LIPPINCOTT’S 
NURSING MANUALS 
HOW WE RESIST 
DISEASE 
By 
JEAN BROADHURST, Ph. D. Lippincott’s Nursing 
Manuals 
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HOW WE RESIST 
DISEASE 
AN INTRODUCTION TO IMMUNITY 
• BY 
JEAN BROADHURST, Ph.D. 
■-M-V 
ASSISTANT PROFESSOR OF BIOLOGY, TEACHERS COLLEGE, 
COLUMBIA UNIVERSITY 
138 ILLUSTRATIONS AND 4 COLOR PLATES 
PHILADELPHIA AND LONDON 
J. B. LIPPINCOTT COMPANY 
1923 COPYRIGHT, 1923, BY J. B. LIPPINCOTT COMPANY 
PRINTED BY J. B. LIPPINCOTT COMPANY 
AT THE WASHINGTON SQUARE PRESS 
PHILADELPHIA, U. S. A. TO 
VERANUS A. MOORE OF CORNELL UNIVERSITY 
AND 
C.-E.-A. WINSLOW OF YALE UNIVERSITY 
TO WHOM I OWE MY 
INTRODUCTION TO IMMUNITY ACKNOWLEDGMENTS 
Grateful acknowledgment is made of the helpful criticism 
of Miss Alice C. Evans, U. S. Hygiene Laboratory, Washington, 
I). C., and I)r. Jane Berry, of the Research Department of the 
Bureau of Laboratories, New York City Board of Health. Sev- 
eral students and other friends have also generously contributed 
their aid during the two years this text has been tried out in 
typewritten form in our Teachers College classes, special 
recognition being due to Miss Jane Williamson, Carnegie Fel- 
low at Aberdeen University; Miss Sylvia Griswold, Miss Mary 
S. Skinker, and Miss Marion Mills. Many authors, publishers 
and institutions have very kindly granted the use of illustra- 
tions, all of which are definitely credited to them in the text 
itself. Of the original illustrations, the more elaborate drawings 
were made by Mrs. Ivan G. Doubble. PREFACE 
This book, designed as a brief introduction to the exceedingly 
technical and apparently limitless field of immunity, has been 
prepared with special reference to nurses and general college 
students whose programs, ordinarily afford opportunity for hut 
a single brief course in bacteriology, the needs of medical 
students and those able to devote more time to the subject being 
already well met by the several excellent and comprehensive text- 
books on bacteriology and immunology. 
Experience has shown, however, that there is no relation be- 
tween the time allotted this subject and the range of student 
interest. This is especially true with regard to nurses, who are 
interested in so many practical applications of the subject. The 
aim has been, therefore, to put into fairly simple language the 
main principles of immunity, covering in a general way the 
most important preventive and curative practices. To attain this 
end briefly, without affording opportunity for a large number of 
attendant misconceptions, is no simple task; realizing this 
keenly, much attention has been given to the illustrations, not 
only their number, variety, and range, but their legends as well. 
It has thus been possible to present a few of the more difficult 
topics in two—sometimes three ways—the text, the illustration, 
and the description used with the illustration. 
A minimum of space has been given to historical sequences 
of accumulated facts, except where such treatment emphasized 
the central or fundamental idea involved, e.g., under vaccines 
or anaphylaxis. Wherever possible general descriptions of 
processes, reactions, etc., have been used rather than exact de- 
tailed descriptions of the technique involved, as for example in 
the Wassermann reaction. In all cases, however, the aim has 
been to give enough detail to enable the student to picture the 
process or the phenomenon under discussion; this explains such 
apparent inconsistencies as omitting all mention of the various 
orders of receptors although complement is discussed in con- 
siderable detail. 
The terminology has been made as non-technical as possible, 
9 10 
PREFACE 
many of the scientific terms being used parenthetically only. 
Where the avoidance of a technical term would cause a lack of 
clearness or necessitate the repeated use of a wordy circumlocu- 
tion such terms have been used, brief characterizations being 
given in the glossary at the end of the hook. 
An elementary text is not the place for the weighing of all 
the various and conflicting theories, such as those advanced 
with regard to anaphylaxis. While every effort should be made 
to have the student realize that we are dealing with a growing, 
developing subject, we must, in such a limited presentation as 
this, select the theories most generally accepted or the “ most 
workable ”—those, which, to the best of our judgment, lead the 
student most directly and rapidly into this new field, and yet 
give the beginner a minimum of material which must be un- 
learned as he advances. This lack of space explains many neces- 
sary omissions, such as the interesting theories of Turck regard- 
ing the role of tissue destruction in disease. 
The study suggestions at the end of each chapter are sug- 
gestions only, not lesson assignments. In each chapter the 
memory or review questions might be selected for general class 
use, the other questions divided among the students Avho are 
more interested or have more time at their disposal. 
Jean Broadiiurst. 
New York, 1923. CONTENTS 
CHAPTER PAGE 
Acknowledgments 7 
Preface 9 
I. Bacteria and Their Effect upon the Human Body. ... 17 
II. Active Immunity 47 
III. Passive Immunity 66 
IV. Toxins and Antitoxins 86 
V. Agglutinins and Precipitins 109 
VI. Opsonins 128 
VII. White Corpuscles 140 
VIII. Lysins • 153 
IX. Vaccines 169 
X. Anaphylaxis... 190 
Glossary 214 
List of Infections and Causal Organisms 230 
Advanced References on Immunity 234 
Index 235 FIG. PAGE 
1. Streptococcus pyogenes 18 
2. Streptococcus pyogenes Destroying Red Blood-cells 19 
3. Section of Necrotic Tonsil 20 
4. Same, Enlarged 21 
5. Entameba histolytica 23 
6. Bacterial Disintegration of Bone 24 
7. Tuberculosis of Synovial Membrane 25 
8. Trypanosoma Brucei 26 
9. Ingestion of Blood-cells by Trypanosomes 22 
10. Extracellular Toxin 27 
11. Bacterial Cell-forming Enzymes 28 
12. Two Types of Protein 29 
13. Protein Disintegration 30 
14. Curve for Acidophilus Organisms 31 
15. Same, with Milk Diet 32 
16. Same, with Lactose 33 
17. Lactobacillus acidophilus 34 
18. Lactobacillus bulgaricus 35 
19. Negative Result of L. bulgaricus in Diet 36 
20. Corynebacterium xerosis 37 
21. Tuberculosis Organisms 38 
22. Peyer’s Patches 39 
23. Pneumococcus Masses 40 
24. Diplococcus pneumonice 41 
25. Rontgenograph of Tooth Lesion 42 
26. Streptococcus viridans 42 
27. Cancerous Disintegration 43 
28. Streptococcus pyogenes 44 
29. Streptococci in Peritoneal Fluid 44 
30. Bacillus anthracis 45 
31. Diagram of Cell’s Combining Power 51 
32. Same, Cell B 52 
33 Toxin Resembling Food 53 
34. Cell and Food Combination 54 
35. Increased Combining Power 55 
36. Toxin Combination with Cell 56 
37. Receptor Formation by Toxin .• ... 57 
38. Antibody Production and Immunity 58 
ILLUSTRATIONS 
13 ILLUSTRATIONS 
FIG. PAGE 
39. Deficient Antibody Response 59 
40. Bacillus anthracis in Liver 61 
41. Bacterium typhosum 64 
42. Malaria Organisms 67 
43. Same, Infection of Erythrocytes 67 
44. Same, Crescent Stage 68 
45. Sporotrichum 68 
46. Temperature Curve in Poliomyelitis 69 
47. Micro-organisms of Infantile Paralysis 70 
48. Inoculated Nerve Tissue 71 
49. Filtering Serum 72 
50. Section Through Filter 73 
51. Filter “Candle” Broken Across 74 
52. Shiga’s Dysentery, Broth Culture 75 
53. Meningitis Organisms in Spinal Fluid 76 
54. Neisseria catarrhalis 77 
55. Pleomorphic Influenza Bacilli 78 
56. Spinal Fluid in Meningitis 79 
57. Jars for Collecting Serum 80 
58. Apparatus for Injecting Serum 81 
59. Tip of Syringe Needle, Magnified 82 
60. Dark Field Photograph 83 
61. Tetanus Organisms 87 
62. Toxin and Toxoid 88 
63. Clostridium botulinum 89 
64. Diphtheria Organisms 90 
65. Diphtheria Throat Smear (Fifth Day) 91 
66. Diphtheria Throat Smear (Twelfth Day) 92 
67. Dialyzing Antitoxic Globulin 94 
68. Drying the Precipitate 95 
69. Intravenous Injection 96 
70. Antitoxin and the Death-rate 104 
71. The Gas Gangrene Bacillus 106 
72. Malignant CEdema Organisms 107 
73. Agglutination no 
74. Paratyphoid B Bacteria hi 
75. Bacterium coli 112 
76. Proteus vulgaris 113 
77. Slide with Hanging Drop 114 
78. Single and Agglutinated Bacteria.. - 114 
79. Precipitin Test for Glanders 115 
80. Precipitin Reactions Against Pneumococci 116 
81. Typhoid Colonies...’ * 117 ILLUSTRATIONS 
15 
FIG. PAGE 
82. Bacterium coli 119 
83. Encapsulated Pneumococci 121 
84. Precipitation Tests for Human Blood 124 
85. Immune and Normal Opsonins 129 
86. Disproportional Antibody Increase 130 
87. A Centrifuge 131 
88. Blood After Centrifuging 132 
89. An Opsonic Pipette 133 
90. Opsonic Index Determination 133 
91. Opsonic Activity in Fatal Erysipelas 134 
92. Same, Recovery 135 
93. Tuberculous and Gonorrheal Opsonic Index 136 
94. Formation of Specific Opsonins 137 
95. Staphylococcus aureus 138 
96. Polynuclear White Corpuscles 141 
97. Amebas 142 
98. Ameboid Ingestion of Food 143 
99. Ameboid Movement 144 
100. Phagocytes Invading Nerve Tissue 145 
101. Neisseria intracellularis 146 
102. Types of Corpuscles 146 
103. Phagocytosis 147 
104. Streptococcus mucosus 148 
105. Blood-counting Slide 150 
106. Spinal Fluid in Meningitis 151 
107. Increase in Bactericidal Power 154 
108. Lysis of Cholera Organisms 155 
109. Source of Complement in Normal Blood 159 
no. “Locking” of Immune Body and Organism 160 
in. Complement Combination 161 
112. Absence of Immune Substance 162 
113. Tubes in Wasserman Test 163 
114. Negative Result with Excessive Complement 164 
115. Syphilitic Human Brain Tissue 165 
116. Syphilitic Human Liver Substance 166 
117. Drying Spinal Cord 173 
118 a. Rabies Organism - 175 
118 b. Same in Brain Film 176 
119. Immunity Curves of Pneumococcus Vaccines 177 
120. Agglutination with Single and Multiple Vaccines 178 
121. Fusiformis acnes 180 
122. Vaccine Syringe 181 
123. Rabies Vaccine Treatment Scheme 182 16 
COLOR PLATES 
FIG. PAGE 
124. Slide Showing Chance of Undercount 183 
125. Capillary Tubes for Vaccine 184 
126. Filling the Tubes 185 
127. Filling Bottles with Vaccine 186 
128. Typhoid Fever and the Army 187 
129. Plague Bacilli., 188 
130. Tubercles on the Omentum 205 
131. Section of Lung with Tubercles 206 
132. Tuberculous Lesions in Cow’s Brain 207 
133. Temperature Curves in Tuberculin Test 208 
134. Protein Splits 209 
135. Same, Incomplete 210 
136. Same, Incomplete (Two Kinds) 211 
137. Skin Tests with Pollens 212 
138. Same, with Timothy Pollen 212 
COLOR PLATES 
PLATE PAGE 
I. Reactions in Skin Tests ioo 
II. Blood Changes Due to Pyogenic Organisms 146 
III. Blood Tests 156 
IV. Serum and Complement Fixation Tests 158 HOW WE RESIST 
DISEASE 
CHAPTER I 
BACTERIA: THEIR ENTRANCE INTO THE BODY AND 
THEIR EFFECT UPON IT 
Destruction of body tissue 
Toxins 
Poisonous split-proteins 
Ptomaines 
Effects 
Fever 
Preparatory relations 
Mechanical in jury 
Bacteria 
and 
their 
effects 
upon 
the 
body 
Indirect effects 
Safeguards of skin and body openings 
Multiplication and growth requirements 
of bacteria 
Distribution of bacteria 
Preferred method of entrance 
Initial number and virulence 
Normal protective agencies 
Conditions 
controlling 
infection 
Although this text presupposes an elementary knowledge of 
bacteria and their activities, it may be an advantage to introduce 
this discussion of immunity with a brief summary of the main 
effects of bacteria upon the body tissues. The efforts of the 
human body to maintain itself in a state of health, whether by 
resisting the entrance of such micro-organisms, or by overcoming 
them after their successful invasion, depend upon and vary with 
the characteristic activities of the attacking organisms. As indi- 
cated in the preceding tabulation bacteria affect the body in 
many ways; the three most important of these effects are (1) the 
17 18 
HOW WE RESIST DISEASE 
destruction of body cells or tissues, (2) the formation of toxins, 
and (3) the formation of “poisonous split-proteins/’ 
Destruction of Tissue.—Bacteria and other micro- 
organisms may actually destroy or disintegrate the body cells or 
tissues. This action is illustrated by some streptococci which 
• dissolve red blood cells (Figs. 1 and 2); by staphylococci, com- 
mon pus organisms in boils and abscesses, which injure the 
white corpuscles; and by the “gas bacillus,” so prominent in 
wound infections in the recent war, which destroys muscle tissue 
very rapidly. Another manifestation of such injurious power 
is the ability of some intestinal bacteria, such as the dysentery 
Fxo. 1.—Streptococcus pyogenes, from chronic suppurating sinus in the upper part 
of the nose, (x 1200) Lewis, Journal of Pathology and Bacteriology 
or cholera organisms, to destroy patches of the mucous mem- 
brane lining the intestine, and so allow the absorption of their 
poisons, which otherwise might pass on out of the body without 
injury to the individual; this has been demonstrated by experi- 
ments in which the animals having uninjured intestinal walls, 
have been given several hundred times the fatal dose of either 
live or dead cholera organisms without any ill effects. 
Just how these destructive effects are produced is not always 
demonstrable. Some may be due to specific enzymes. In some 
cases the effects may be shown to be related to the presence of BACTEEIA 
19 
toxins and are then attributed more specifically to the toxins, 
ignoring their probable enzyme character. We are still very 
far from an adequate comprehension of the activities of bacteria, 
but it seems legitimate to suppose that enzymes play as varied 
and important a part in the various powers and manifestations 
of bacterial cells as in any other plant or animal cells. (See also 
aggressins, p. 56.) 
2. Toxins.—In the ordinary processes of growth of a few 
kinds of bacteria we are able to demonstrate the formation of 
Fia. 2.—Two views of the same region of a blood agar plate showing the power 
of streptococcus bacteria (Streptococcus pyogenes) to destroy the red blood cells. The 
amount of destruction is indicated by the clear or dissolved area (white in photograph) 
surrounding each colony. (Horse blood agar plates; Right, longer growing period 
than Left) Brown, Monograph, Rockefeller Institute. 
special poisonous substances called toxins. These toxins are 
formed inside the bacterial cells but are soluble and are freely 
excreted from the cells, so that they pass promptly into the sur- 
rounding area (Fig. 10). 
The toxins may be locally destructive, destroying the sur- 
rounding tissues; or they may be absorbed by the blood circu- 
lating through that area and carried through the whole body, 
irritating or destroying one or more of the more distant body tis- 
sues. Less often, as in lockjaw or tetanus, the toxins are 
absorbed by the nerves rather than by the blood. 
Toxins differ from each other not only in the method or path 
of absorption but also in the tissues they affect. In lockjaw and 
in botulism the characteristic effects of these organisms are pro- 20 
HOW WE RESIST DISEASE 
duced through the nervous tissue. An illustration of more 
wide-spread effects is provided by diphtheria, in which, besides 
the local effect—the well-known sore throat—there may be de- 
generative changes in the liver, supra-renal glands, and the nerve 
centres combined with extensive changes in the circulatory 
organs, with the consequent characteristic drop in blood pressure, 
hemorrhages of the serous membranes inside the body cavity, and 
degeneration of the heart muscle itself. 
Fig. 3.—Section of tonsil, showing the bacterial layers and necrosis in tonsilitis 
(Vincent’s angina). A, external necrotic layer containing practically no bacteria; B, 
bacterial layer and necrosis with masses of fusiform bacilli and spiral forms: C, spiral 
forms in still living tissue. (x90)—Tunnicliff, Journal of Infectious Diseases. 
3. Poisonous Split-Proteins.—The two effects (destruction 
of tissues and toxins) described above are characteristic 
of but a minority of the organisms connected with ordi- 
nary human diseases. Nearly all pathogenic bacteria owe 
most of their injurious effects to another cause. In dis- 
ease these bacteria multiply in uncountable numbers BACTERIA 
21 
before our body defenses gain control. Then later as these 
myriads of invading bacteria are killed and disintegrated, their 
cell substance is broken down as any protein substance (milk, 
egg, meat) might be broken or split in ordinary digestion 
into smaller and still smaller particles. Whether the disinte- 
grating bacteria are in the blood or in tissues richly supplied 
Fig. 4.—Section through the inner edge ot B in previous figure (tonsil infection 
in Vincent’s angina) showing more clearly the invasion of living tissue by the spiral 
organisms. (x575) The organisms are more numerous at D. Tonnicliff, Journal of 
Infectious Diseases. 
with blood, this disintegration goes on. In this splitting process, 
certain parts or substances which are poisonous to us are split off 
or set free. If these poisonous particles (C in Fig. 12) are not 
themselves neutralized or are not further split or broken up 
into less irritating ones, they accumulate in the body and poison 
us, being carried everywhere by the circulating blood. Some of 
these split-proteins irritate one tissue or set of tissues (Fig. 13), 
some another; therefore, when typhoid bacteria are disinte- 22 
HOW WE RESIST DISEASE 
grated we have one set of symptoms, and another set of symptoms 
characterizes tuberculosis infections (See p. 211). 
These substances may correspond to what were formerly 
called “ endotoxins,” to distinguish them from the toxins readily 
excreted from the cell, the extra-cellular toxins already dis- 
cussed under toxins. While very recent investigations indicate 
the possible existence of such endotoxins, many of the effects 
formerly attributed to endotoxins are doubtless due to the dis- 
integration of the bacterial cell proteins—the split-proteins. 
Vaughan’s most extensive experiments with these split-pro- 
Fig. 9.—Stages in the ingestion and digestion of red blood cells by trypanosomes 
(T. Brucei) isolated from blood of a rat (1250 x ). The resulting reduction in the number of 
red blood cells and in the quantity of hemoglobin is clearly associated with the anemia 
characteristic of trypanosome infections. Seidelin, Journal of Pathology and Bacteriology. 
teins indicate that they may be obtained from any protein—not 
only from non-pathogenic bacteria, as well as pathogenic ones, 
but from ordinary food proteins (eggs, milk) and even from 
such plant proteins as seeds, by special treatment with acids, 
alkalies, alcohol, etc. These disintegration poisons or poisonous 
split-proteins it is clear, then, are not the same as the specific 
toxins formed by certain bacteria themselves during their 
ordinary life or metabolic processes (See p. 87). 
Though chemists have not yet been able to reduce either the 
soluble toxins or the poisonous “split-proteins” to exact chemical 
formulas, there are at leastfour decided differences between them: 
(a) True toxins are formed by living cells; poisonous split- BACTERIA 
23 
proteins only on the death and disintegration of the bacteria 
or of similar non-living proteins. (b) True toxins are produced 
by but few species of bacteria, but the poisonous split-proteins 
may be obtained on the decomposition of any kind of bacteria or, 
apparently, any protein substance. (c) True toxins, being 
soluble and therefore extra-cellular, are found in the filtrate of 
bacterial cultures, while the poisonous split-proteins are lib- 
erated only on the destruction of the cells themselves. 
Fig, 5.—Destructive action of Entameba histolytica, showing three amebas in 
cavity caused by their action. (x350) E, ameba; G, disintegrating glandular tissue. 
We are indebted for the use of this figure to the publishers of “ The Essentials 
of Tropical Medicine,” Bale, Sons & Danielson, Ltd., London. 
(d) Toxins stimulate the animal body to produce antitoxins 
(See p. 48); but the poisonous split-proteins, on the contrary, 
do not excite such antibody reactions. The most that is claimed 
for the split-proteins 1 is a kind of tolerance, not definite im- 
munity (See p. 207). 
4. Ptomaines.—There is still a fourth way in which bac- 
teria are related to disease. Protein foods, in preliminary prepa- 
1 No attempt has been made to cover in this brief discussion 
Vaughan’s further differentiation of his split-proteins into “crude soluble 
poison” and the insoluble non-poisonous “residue,” with the differing 
filterability, of these two parts or fractions. 24 
IIOW WE RESIST DISEASE 
ration stages or under storage conditions in the shop or home, 
as well as protein foods actually in the intestine, may be partly 
digested or broken down by bacteria and ptomaines formed. 
Most ptomaines are not poisonous; but some of them are very 
poisonous, and since the power of utilizing protein is a very 
common one among bacteria, it sometimes happens that the 
bacteria that happens to get into such protein foods as milk, 
veal, cheese, fish, and oysters form sufficient ptomaines to poison 
us. Reliable authorities consider it “ doubtful if ptomaines in 
noticeable quantities are produced within the living in- 
fected body.” 
Fig. 6.—A tuberculosis focus or lesion in the 
head of the femur, illustrating bacterial disintegra- 
tion of bone tissue. Ely. International Clinics, 
J. B. Lippincott Co. 
Ptomaine poisoning is much less frequent than people 
formerly supposed. Acute intestinal disturbances are more often 
due to toxic substances produced by the dysentery bacterium or 
its relatives working in the intestine than to preformed 
ptomaines in the food eaten. (See auto-intoxication following.) 
It was once thought that ptomaine poisoning could be dis- 
tinguished from bacterial infections in the intestines by the 
time elapsing between the eating of the suspected food and the 
development of the attack. Cases developing rapidly (within 24 
hours) were classed as due to ingested ptomaines, the ptomaine 
having been formed before the food was eaten; and the slower BACTERIA 
25 
cases were attributed to the taking in of bacteria which con- 
tinued to develop in the intestine, the symptoms appearing when 
the bacteria had multiplied sufficiently. Recent experiences 
indicate, however, that this is not a certain method of differ- 
Fig. 7.—Tuberculosis of a synovial membrane magnified about 20 diameters. 
A indicates an area of necrosis or tissue destruction ; at B, note the “giant cells” 
which ate characteristic of certain healing conditions. Ely, International Clinics, 
J. B. Lippincott Co. 
entiation, for the rate of multiplication may be surprisingly 
rapid; the dysentery bacterium, for example, may be responsible 
for illness developing only f> to 8 hours after eating food con- 
taining these organisms. 26 
HOW WE RESIST DISEASE 
Ptomaines are probably more often responsible for less acute 
and chronic types of intestinal disturbances, auto-intoxication, 
etc., than for the more acute indispositions such as dysentery and 
diarrhoea. In such chronic affections, an effort is made to dis- 
place the undesirable organisms which continue forming these 
ptomaines by other organisms; this is often brought about by 
(1) changes in the diet (feeding milk or lactose, dextrin, etc., 
Figs. 14, 15, 16) which favor the development of acid-loving 
organisms such as Lactobacillus acidophilus (Fig. 17) normally 
found in the human intes- 
tine, or (2) by using sour 
milk drinks containing acid- 
forming organisms, such as 
the lactic acid bacilli or even 
yeast. Recent experiments 
indicate that Lactobacillus 
acidophilus, Fig. 17, is much 
more efficient in this respect 
than the formerly popu- 
lar Lactobacillus bulgaricus 
(See Fig. 18), as it readily 
becomes the most prominent 
resident of the alimentary 
canal and Lactobacillus bul- 
garicus does not. Any increase in the acid content of the 
intestines by either of the above methods, makes the intestines 
temporarily less alkaline and less favorable for some of the 
putrefying, ptomaine-forming bacteria. 
Ptomaines differ from both of the bacterial poisons, toxins 
and split-proteins, already discussed, in several ways: (a) The 
bacterial poisons come from the bacterial cell itself, while the 
ptomaines are the results of bacterial action on their food material 
still outside the bacteria, material which has never been part of 
the bacterial cell, but which is being broken down for use in the 
cell, (b) The bacterial toxins are all poisons, but most of the 
ptomaines are not poisonous at all. (c) The chemical structure 
of the toxins is not known, but the ptomaines are known to be 
nitrogen compounds of carbon and hydrogen, their poisonous 
quality varying with their complexity; in the most poisonous ones 
Fig. 8.—Protozoan parasites, Trypanosoma 
Brucei, from blood of a rat. (x!500) BACTERIA 
27 
we find oxygen as a fourth element. (Putrescin, C4H12N2, for ex- 
ample has usually but a locally destructive effect, while sepsin, 
C6H14N202, is a powerful poison.) (d) No antibodies are stimu- 
lated by ptomaines. Therefore, no real immunity can be 
developed against them, as is the case with toxins. Since the 
body reactions leading to immunity are our main interest, the 
ptomaines and their effects will not be further elaborated in 
this volume. 
Other Effects.—To some, this list of bacterial effects would 
seem incomplete without adding a fifth, namely, fever. Fever, 
Fio. 10.—A diagrammatic illustration of extracellular toxin in relation to the cell 
producing it: five toxin particles (T) have passed outside the cell membranes, and two 
are still retained within the cell. 
however, must be considered as itself a result of other effects. To 
prevent the irritation and poisoning already described, the cells 
of the body react, forming substances to neutralize or destroy 
the irritating causes. This increased work may be very heavy, 
and means, of course, increased utilization of food and increased 
heat production. That in turn demands increased circulation 
which means still more work with its added heat production. The 
body temperature changes with the work being done; the rise 
in temperature is therefore not itself the evil, but an indication of 
how hard the body is working to overcome the difficulties, to 
make and distribute the necessary reacting and neutralizing sub- 
stances. Fever is, therefore, but an index of the patient’s 
condition, and not itself the condition2 from which he 
is suffering. 
2 Extremely high temperatures, of course, do fix or coagulate cell 
proteins and it is conceivable that while the fever temperatures fall 
short of this coagulating point, the cells may be much less plastic or 
“alive” in the rising temperatures that obtain in high fevers. 28 
HOW WE RESIST DISEASE 
Preparatory Relations.—Another important though less di- 
rect effect of micro-organisms is shown by a few organisms, which 
may or may not be harmful themselves, but which act as primary 
invaders and break down our resistance to other organisms. Recent 
experiments with rabbits have shown that when influenza exudate 
from affected rabbits is injected into other animals it may cause 
lesions in the lung, and may make such animals more susceptible 
not only to the influenza organisms but to pneumococcus bacteria 
as well. 
Fig. 11.—-Diagrammatic representation of a bacterial cell forming various enzymes, 
E, which are attacking a given protein molecule, P. M. in the surrounding food material, 
causing it to break down into a variety of substances as shown by the diversified drawing 
on the right; among them may occur one or more ptomaines, which we may assume 
to be the black products in the right hand figure. This contrasts ptomaines with toxins 
which, like enzymes, are formed inside the bacterial cells themselves. 
To such preparatory action by the influenza organism, or pos- 
sibly to an as yet undetermined filterable organism :i occurring in 
influenza infections, is attributed the highly variable character of 
the recent outbreaks of “ influenza ” in our country during the 
Avar, the number and severity of the cases developing in any lo- 
cality depending not only upon the resistance to the primary 
invader but upon the coincidence and virility of other organisms, 
3 Since this manuscript was prepared, a filterable organism, named 
Bacterium pneumosintes, has been isolated by Olitsky. BACTERIA 
29 
such as the pneumococcus and streptococcus bacteria. This ex- 
plains such statements as, “ Influenza alone is not serious; those 
Fig. 12.—Two types of proteins, Pi and Pi, showing that each may be broken into 
various substances, with a similar central core, C, the “poisonous core of Vaughan. 
who die have influenza plus a lung infection usually a strepto- 
coccus or a pneumococcus infection.” 
Among other bacterial effects which cannot be discussed here 
is mechanical injury, due to masses of bacteria or bacteria and 
fibrin which may clog the smaller capillaries and form emboli 
interfering with the circulation. (See also aggressins, p. 56.) 
Paths of Entrance.—The very serious and far reaching 
effects just described make us ask how it is that our bodies have 
escaped complete destruction. The answer is that although hac- 30 
HOW WE RESIST DISEASE 
teria are very numerous and very widely distributed in nature, 
relatively few of them really get into the body itself—into the 
body tissues. The main paths of entrance are the broken skin, 
the respiratory tract, including the mouth and nose membranes, 
the conjunctiva and the genital tract, and the alimentary canal. 
In infections described as originating in the blood stream the 
primary invasion is really by one of the paths just listed—an 
unsuspected focus in the tonsils, an unnoticed scratch in the 
skin, etc. 
Fig. 13.—The disintegration of a protein may free the “poisonous core completely, 
as indicated by the upper left figure. Less complete disintegration might give such results 
as in the other figures. These differing substances would have varying chemical affinities 
and so unite or combine with different body substances. This affords an explanation of 
the specific effects characteristic of the respective bacterial diseases. 
The Skin as a Protective Covering.—While such parasites 
as wriggling hookworms readily penetrate the skin the unbroken 
skin is not easily invaded by bacteria and protozoa. There is little 
reason to think that such invasion takes place with ordinary 
disease organisms unless there are slight lesions or injuries in the 
skin. Even in animal experiments where bacteria have been 
proven to enter after being rubbed on the shaven skin, entrance is 
probably effected through skin lesions that escape the ordinary 
eye, or through other more or less injured areas, such as might 
be found in connection with the hair follicles or sebaceous glands. BACTERIA 
31 
Without the existence of such lesions bacteria remain on the sur- 
face of the skin, entering only when a cut or injury affords 
them entrance. As some one has well phrased it, “ The skin is 
inhabited but not infected/’ 
Safeguards at Entrances into the Body.—Special safe- 
guards are provided at the places where the ordinary outer skin is 
replaced by more delicate and thinner coverings, such as the eye 
and mouth. In each of these areas there are usually present one 
Fig. 14.—This curve indicates the percentage of acidophilus organisms appearing 
in the fecal specimens of human subjects on ordinary diet plus a milk culture of acido- 
philus, 1000 c. c. Notice after 20 days, the drop when ordinary diet was resumed. 
Rettger and Cheplin, Intestinal Flora, Yale University Press. 
or more characteristic types of bacteria, apparently (or at least 
usually) harmless ones, which very rarely penetrate below 
the surface. 
The mouth has many characteristic organisms, streptococci, 
and other cocci being the types most commonly present, probably. 
A diphtheria-like bacillus, Corynebacterium xerosis (Bacillus 
xerosis, Fig. 20), is characteristically present in the conjunctiva 
of normal eyes; and similarly other harmless bacilli may be ex- 
pected in the genital area. Such organisms may possibly help 
by interfering with the multiplication of ordinary pathogenic 
bacteria; for instance, the presence of staphylococci in the mouth 
has been thought somewhat incompatible with that of diphtheria, 
and some doctors have used staphylococcus in efforts to replace 
the diphtheria organisms in diphtheria carriers. These regionally 
characteristic organisms may, however, be disregarded at least 32 
HOW WrE RESIST DISEASE 
as far as definite immunity is concerned, and our attention may 
he turned to the special conditions that safeguard such delicate 
membranes from definitely harmful organisms. 
The Eye Safeguards.—The eye membranes are very sus- 
ceptible to infection at and for a few days following birth. Later, 
they are much less easily invaded by ordinary bacteria; one has 
only to recall their exposure to dust, and the very common habit 
of rubbing the eyes with unwashed or soiled fingers, to be sur- 
prised at the comparative infrequence of eye infection. This 
Fig. 15.—Curve indicating the percentage of acidophilus organisms appearing in 
human subjects on ordinary diet, (C), and with ordinary or untreated milk added to the 
diet, (D). Note the drop when milk is no longer added. Rettger and Cheplin, 
Yale University Press. 
freedom is mainly due to constant washing of the eye by the 
tear fluids, which mechanically remove organisms from its sur- 
face. This fluid has besides a slightly germicidal power. 
Recently, the eye has been described as a possible route for 
infections of the nasal tract, including the naso-pharynx. This 
theory is of special interest in connection with the spread 
of influenza. 
Safeguards in Connection with the Respiratory Mem- 
branes.—Besides the varied and more or less resident flora in the 
healthy mouth, the mouth, nasal and lung membranes are subject 
daily to the additions of large numbers of bacteria from infected 
teeth and tonsils, only too often more numerous than it is pleas- 
ant to contemplate. (Most of these pass with the saliva into the 
stomach, but small quantities must be constantly distributed over 
the mouth and throat membranes.) Both the saliva and the 
nasal secretions are weakly germicidal. These liquids constantly 
wash the adjacent membranes, mechanically removing accumu- BACTERIA 
33 
lating bacteria. The fetid condition obtaining in the mouth, 
when the salivary how is diminished, may be due as much to 
the lessened mechanical removal of bacteria, as to the in- 
hibitory effect of the saliva. It has been estimated, however, that 
over 300,000 bacteria are daily taken into the lungs under 
ordinary conditions. Caught on the moist lung surface, all bac- 
teria must remain there; yet very few lung infections develop 
compared with the total of daily opportunities. 
This is no doubt in great part due to the fact that some of 
the alveolar cells resemble the 
white corpuscles in their power 
of surrounding and destroying 
bacteria. (See also p. 141.) 
Then, too, when bacteria do 
penetrate this thin alveolar 
membrane, they find them- 
selves immediately in the 
blood stream, in contact with 
white corpuscles and special 
blood substances (antibodies) 
both of which, as will be shown 
later, have the power to destroy 
bacteria. 
Resistance of the Alimentary Canal.—The alimentary 
canal furnishes a most striking example of the protective function 
and resistance of delicate epithelial cells, for surgical work on 
the mouth and anus heals satisfactorily without the use of dis- 
infectants, in spite of the fact that these regions are constantly 
exposed to infections. 
It is stated that bacteria compose fully one-third of the fecal 
matter excreted daily. The inner surface of the intestines must be 
thickly coated with bacteria, even when the intestines are empty 
of food. Yet in health, the thin lining layers successfully with- 
stand the invasion from the intestine into the deeper tissues 
of the body cavity. True, these absorbing areas of the intestine 
are richly supplied with blood containing antibodies, but their 
success as protective agents is none the less wonderful. One has 
only to compare the flavor of a freshly killed chicken with a 
cold-storage one to realize how effective these lining layers are 
Fig. 16.—Typical curve indicating the 
percentage of acidophilus organisms in the 
fecal specimens of a human subject fed on 
ordinary daily diet plus 300 grams of lactose. 
Rettger and Cheplin, Intestinal Flora, 
Yale University Press. 34 
HOW WE RESIST DISEASE 
during life, for the problem of “cold storage chickens” is how 
to prevent intestinal bacteria from passing through into the 
flesh, and causing the changed flavor we all know too well. 
Further illustration of such difference in resistance between 
living and dead cells is found in the digestion of a given tissue 
by the normal digestive juices of that region after death; e.g., in 
life the mucous membrane of the stomach resists the action of 
pepsin in the gastric juice, but after death this stomach mem- 
brane may be digested by pepsin. 
Protective Action of Digestive Juices.—In addition pro- 
Fig. 17.—Lactobacillus acidophilus, 48 hours, glucose broth culture, showing great 
range in size and chain formation (xlOOO), Rettgeb and Cheplin, Intestinal Flora, 
Yale University Press. 
tective effects are claimed through the action of such digestive 
juices as the hydrochloric acid of the stomach, and the intestinal 
juices, including the bile. The protective action of these juices 
has probably been overrated, and many reliable authorities ascribe 
little or no germicidal value to the intestinal secretions. With 
regard to the acid content of the stomach, the short period of con- 
tact, since food may begin to leave the stomach in twenty minutes 
and water almost immediately, makes it improbable that objec- 
tionable bacteria are necessarily subjected for a sufficient period to 
the hydrochloric acid. Besides, the acid occurs in very dilute 
amounts—only two-tenths of one per cent.—and experimental 
work has shown that such organisms as streptococci can with- 
stand at least six times that concentration (one and two-tenths BACTERIA 
35 
per cent.) for over an hour. Experiments have established that 
the organisms of tuberculosis, typhoid and dysentery readily pass 
beyond the stomach when swallowed with food. Bacterial inhibi- 
tion, rather than destruction, is all that it is safe to claim for 
hydrochloric acid in the stomach. 
There are, however, other protective influences to be attrib- 
uted to the stomach region, for although some poisons, such as 
those found in decayed meat, are not destroyed in the stomach, 
the poisons of organisms such as tetanus and diphtheria are 
Fig. 18.—Lactobacillus bulgaricus, 48 hour whey broth culture, showing close 
similarity to Lactobacillus acido-philus. Rettger and Cheplin, Intestinal Flora, Yale 
University Press. 
changed by gastric juice. This may have a bearing on the relative 
freedom of the stomach from bacterial inflammations. 
Although the bile is considered somewhat germicidal, disease 
organisms (typhoid, in typhoid carriers) have been found grow- 
ing in the bile ducts and gall bladder; the antagonistic action of 
the bile, therefore, can not be so great or so universal as once 
thought. Nevertheless, the gastric and intestinal juices including 
the bile, may have an inhibiting action on the growth of many 
organisms, and the alternation of an acid and an alkaline medium 
(stomach to intestine) is thought to be somewhat helpful in 
reducing the kind and number of bacteria found in the intestine. 
The preceding paragraphs have indicated the difficulties met 
by organisms in getting past the external barriers into the tissues. 
But even when they do succeed in effecting an entrance, infection 36 
IIOVV WE RESIST DISEASE 
does not always follow. There are two possible reasons for this: 
(1) The bacteria may not find conditions there that favor their 
growth or (2) they may be met by definite antagonistic substances 
that destroy them. 
Multiplication Necessary to Establish Infection.— 
Ordinarily very few pathogenic bacteria enter the body at any one 
time—in a glass of water, in human-polluted air, on handled food, 
or through a cut. One or even a few bacteria can not cause in- 
fection usually. (See p. 43.) They may be disposed of at once by 
the protective forces (white corpuscles and antibodies) to be dis- 
cussed later. Even if the few 
organisms entering escape 
destruction, multiplication is 
also necessary for infection 
to develop. This means that 
the environment must be 
favorable for the invading 
organism—that it must find 
itself supplied with the right 
food materials, suitable 
amounts of oxygen, favor- 
able temperature, etc. 
While the human body 
has been aptly called “ the 
greatest living culture medi- 
um and incubator,” most of 
the hundreds of types of bacteria known to us do not find 
it favorable for their growth and multiplication. 
Microscopic observation has shown that under favorable con- 
ditions, some organisms may grow to full size and form two new 
ones in twenty minutes. At this rate one organism could produce 
over 2,000,000 bacteria in eight hours. It has been estimated 
that if streptococci multiplied in our bodies without hindrance, 
one initial organism could cause death in 18 hours; a single 
tuberculosis cell, in three weeks. Fortunately, disease organisms 
rarely advance at such rates, and as mentioned earlier, many 
bacteria fail to multiply in the body at all. Out of several 
thousands of bacteria and protozoa known to science, apparently 
less than a hundred kinds can grow in the human body with 
sufficient ease to he considered causes of disease. 
Fig. 19.—-Compare this typical result 
when broth cultures oi the bulgaricus bacillus 
are fed with ordinary diet and note that, unlike 
acidophilus, the bulgaricus organism produces 
no apparent change in the intestinal flora. 
Rettger and Cheplin, Intestinal Flora, Yale 
University Press. BACTEKIA 
37 
How sensitive bacteria are to environmental conditions 
such as temperature, oxygen and food supply is shown in the 
following illustrations: 
1. Temperature.—The various types of tuberculosis organisms 
(Fig. 21) have very different temperature requirements. On 
culture media the human type grows best at 37° C. and growth 
ceases at 40° to 41° C.; the avian type requires a higher tem- 
perature than the human, multiplying rapidly at 45° or even 
higher. As might be expected, therefore, human tuberculosis does 
not develop in fowls, which have an average temperature much 
higher than in man, 40° or even higher; and avian or fowl tuber- 
culosis with its higher temperature requirement does not develop 
in man. 
2. 0 x y g e n—T e t a n u s 
develops best in regions poorly 
supplied with oxygen, and so 
ordinarily multiplies in areas 
poorly supplied with the oxy- 
gen-carrying blood, such as the 
subcutaneous tissue. 
3. Tissue Conditions of 
Host Cells.—Experiments have 
shown that bruised tissue is 
especially susceptible to bac- 
terial invasion and sometimes, 
apparently is absolutely neces- 
sary for the development of 
infection. Tetanus bacteria 
spores may be injected into the blood vessels of a guinea pig 
without causing disease, and spores can be demonstrated in such 
tissues as the liver and spleen, thirty and even fifty days after- 
ward. But if the tissues are bruised, tetanus develops promptly, 
beginning in the bruised tissues. (See also resistance, p. 53.) 
Any necrotic area, or even a blood clot or bruise, may provide 
the necessary nutritive conditions for the development of tetanus 
organisms. This may be not only a question of food material, 
but rather of breaking down the natural cell resistance, for the 
normal cell resistance is typically high. As Zinsser expresses it, 
“Invasion of one cell by another is not Nature’s plan.” The 
resistance to bacterial invasion shown by cells such as those 
Fig. 20.—A diphtheria-like bacterium 
Corynebacterium xerosis (Bacillus xerosis) 
frequently found in normal eyes, (x) Hiss 
and Zinsser, Textbook of Bacteriology, 
Appleton. 38 
HOW WE RESIST DISEASE 
lining the intestine is illustrated by the resistance to decay in 
unprotected living eggs, such as those of the frog. This normal 
resistance of living tissues is emphasized by the rapid decay 
which takes place when such eggs die. 
Saprophytic and Parasitic Organisms.—The various types 
of organisms (e.g., staphylococcus) commoidy found on the skin 
are of little importance except as their persistence may afford 
opportunity for their later entrance into the body, e.g., through 
a break or cut in the skin. 
It is customary to speak of bacteria as either parasitic (de- 
Fig. 21.—Left to right, bovine, (5) human, (//) and avian, (A) tuberculosis organ- 
isms, egg-agar cultures. (xl500) Sands. 
riving their food materials from living animals or plants) or as 
saprophytic (deriving their sustenance from non-living things 
such as dead animals or plants, milk, bread, leather, etc.). Many 
of the kinds of bacteria found in the human intestines are not 
really living on the body tissue, hut on the foods they contain, 
just as they would live and multiply on such foods before they 
were eaten if the temperature were favorable. It is not always 
easy, therefore, to know when the terms parasite and saprophyte 
should be used in speaking of organisms obtained from the body. 
Distribution of Bacteria in the Body.—The effects brought 
about by bacteria are more clearly understood if we know 
something of their distribution in the body. Though their location 
may be limited to a very small area, as in small skin boils or 
abscesses or the throat patches in diphtheria, the infected area BACTEKIA 
39 
is often a much larger or a more general one, such as the lungs, or 
the peritoneum. 
Even in disease they may be located only in what are really 
surface tissues. In suppurating tonsils, stomach ulcers and even 
in the typhoid invasion of glandular areas of the intestine 
(Fig. 22) the organisms have not penetrated far into the body 
tissues. Organisms do penetrate into the body, however, some- 
times making their way inward by continued disintegration from 
a surface lesion. 
Organisms from a localized site or focus may find their way 
into the blood stream in considerable numbers. This is true in 
Fir,. 22.—Peyer’a patches, from intestine of typhoid patient. The swollen patches 
and nodules are necrotic (disintegrated) tissue except at their edges, the central portions 
being ** ragged sloughs,” Delafield and Prudden, Text book of Pathology, Wood. 
diphtheria, where a very definite localized area is ascribed to 
the causal organisms; similarly, typhoid bacteria are commonly 
found in the blood in the early stages of typhoid fever. This 
condition is termed a bacteremia, and the presence of the organ- 
isms in the blood is temporary only, for they are soon destroyed by 
the protective agencies also present in the blood. Pyemia is used 
to indicate the condition when the organisms thus discharged into 
the blood and distributed by it cause several different foci. Some- 
times the organisms multiply in the blood stream itself (septice- 
mia, Figs. 23, 24). A heavily discharging focus may, of course, 
approximate this last condition, septicemia, and be difficult to 
distinguish from it, both in the blood picture presented and the 
condition of the patient. 
In health, occasional bacteria are doubtless constantly making 
their way into the blood stream, not only from an adjacent focus, 40 
HOW WE RESIST DISEASE 
such as an infected tonsil, but through apparently healthy mem- 
branes or tissues such as the intestinal wall; but finding no 
favorable site do not produce infection (See p. 43) before they 
are destroyed by the white corpuscles or specific antibodies. The 
white corpuscles are themselves sometimes responsible for this 
transfer of bacteria to new areas, for they sometimes carry bac- 
teria with them as they occasionally make their way through the 
capillary walls into the surrounding tissues. Usually, however, 
they destroy all ingested bacteria and no infection occurs. 
The extent of the focus does not necessarily correspond to the 
effects caused. A very small focus, such as an infected tooth 
(Figs. 25, 26) may have serious 
systemic effects. In tetanus, 
where we often find but a small 
focus at the point of infection, 
this disparity is still more 
strikingly illustrated, due 
mainly to the very toxic char- 
acter of the poison produced by 
the tetanus bacilli. 
Neither is the size of the 
focus related to the rapidity 
with which a cure may be 
effected. A very small or local- 
ized infection may be very 
difficult to cure. This may be 
due to the slight amount of 
irritation it causes and the 
consequent fact that it arouses very little general body reaction, 
(See Vaccines, p. 186), or to the completeness with which the 
lesion has been closed off from the rest of the body. In tubercu- 
losis, for example, the tubercle wall which is formed around 
the lesion not only protects the body from the organisms, but 
protects the organisms in that lesion from the blood anti- 
substances which might destroy them. Similar conditions 
obtain in meningitis, where the organisms in the meninges 
of the spinal canal are very slowly affected by the anti- 
substance of the blood, because of the relatively meagre blood 
supply of that area. 
Fig. 23.—Large masses of pneumo- 
cocci in the blood vessels of a rabbit dying of 
severe pneumococcus septicemia. Bull. BACTERIA 
41 
Preferred Method of Entrance.—Usually infection occurs 
only when bacteria enter by certain preferred routes or channels. 
For some organisms the “channel of infection ” is very definitely 
fixed. Typhoid, for example, must begin its development in the 
alimentary canal and one usually contracts typhoid by swallow- 
ing the typhoid organism in infected food or water, there being 
little chance of contracting typhoid infection in any other way, 
such as through the air. (Recently the tonsils have been shown 
to be possible, though less probable portals of entry, than the more 
common path, the intestinal membranes.) 
Sometimes the preferred 
method of entry se e m s 
wholly unrelated to the final 
site of the organisms. This 
is strikingly illustrated by 
hookworm, in which 90 per 
cent, of the infection is 
through the skin, and the 
hookworms make a circu- 
itous route through the fiesh 
to lymph vessels, and by the 
thoracic duct to the heart 
and to the lungs; from the 
lungs they are coughed up 
into the throat and being 
swallowed make their way 
to the intestines, their 
real habitat. 
More often in other infections it is a question of being carried 
from the port of entry by the circulating blood until a susceptible 
area is found, where the organisms may continue to develop after 
they have disappeared from the conveying blood. Despite these 
vagaries, the initial point of entrance is very important in de- 
termining whether or not infection shall occur. 
Experiments may be performed to illustrate preferred 
methods of entry. As described by Park, if virulent strepto- 
coccus (Fig. 28), typhoid, and diphtheria organisms respectively 
are rubbed into abrasions of the skin of laboratory animals the 
typhoid produces no lesion, and the diphtheria but a very minute 
Fig. 24.—Blood smear showing the 
invasion of the blood by pneumococcus 
organisms, (Diplococcus pneumonia). The 
characteristic capsules are very evident 
here. Williams, Brown and Earle. 42 
HOW WE RESIST DISEASE 
infected area, but the streptococcus may produce severe cell 
destruction or even fatal blood poisoning (Fig. 29). When 
placed on a similar area of the throat, the typhoid is again 
harmless, the diphtheria produces a typical inflammation and 
characteristic toxic poisoning (p. 87), and the streptococcus 
may cause an infection, or even blood poisoning. If the three 
kinds of organisms are passed into the intestines, it is the 
typhoid organism which develops, while here the streptococcus 
and diphtheria are harmless. 
Fig. 25.—X-ray photograph 
of a tooth showing a definite disin- 
tegration area at the apex of the 
tooth. Such abscesses often fur- 
nish an illustration of very unto- 
ward effects from a very small focus 
of lesion. 
Fig. 26.—A pure culture of Streptococcus 
viridans, taken from a root apex of a tooth; 
this tooth had a good root-filling and the X-ray 
examination did not show decay. 
Machat, Dental Cosmos. 
As stated on p. 36, bacteria that enter the body may fail to 
develop even when the growth conditions are apparently favorable. 
When such organisms as streptococci or staphylococci which can 
grow in the body fail to cause infection, after gaining entrance 
through a cut or bruise, or cause but a slight temporary infection, 
what is the explanation? It is because there was in the blood 
of the body more than a sufficient number of white corpuscles 
to take care of the invaders, and the circulating blood finally 
accumulated in that region enough white corpuscles to dispose 
of them; or else the liquid antibodies in the blood dissolved or 
otherwise affected the bacteria, as will be described in the 
next chapter. BACTERIA 
43 
Number and Virulence Related to Resistance.—There 
is, of course, a limit to the counteracting effect of these protective 
agencies of the normal healthy body. The minimum number of 
bacteria which is necessary to run the gauntlet of these guarding 
agencies explains such statements as “ ten tuberculosis bacteria 
are necessary to inoculate a rabbit.” 
Fig. 27.—Disintegration due to cancer; a, cancer nest-cells with extensive 
inflammatory infiltration of muscle bundles, b. Kelly, Johns Hopkins Bulletin. 
This minimum number depends on the kind of organism as 
well as the natural resistance of the individual. The minimum 
may be very low, indeed; for anthrax (Fig. 30), it has been stated 
that one organism is enough to cause infection in a suscep- 
tible animal (See p. 36). 
In other cases the number necessary for infection is very great, 44 
HOW WE RESIST DISEASE 
and the type of infection may vary with the number inoculated; 
e.g., when a few streptococci pathogenic to man are inoculated 
into a rabbit, they may cause no effect at all, and a few million 
may cause merely local abscesses, while a hundred million will 
usually cause septicemia (general blood poisoning). 
The number necessary for infection varies also with the 
strength and virility of the organisms (See p. 58). If a strain of 
pneumococcus organisms is cultivated in two different ways— 
Fig. 28.—A long-chained streptococcus, 
Streptococcus pyogenes; notice the relationship 
of many of the organisms in the chain, often 
present in this genus. Williams, Brown and 
Earle. 
Fig. 29.—Streptococcus growth in peri- 
toneal fluid freshly drawn from a fatal case of 
peritonitis. Note the heavy growth of bacte- 
ria. 
(1) in a series of tubes of artificial media, such as serum-agar, 
and (2) in a series of living mice—the organisms from the last 
mouse will be much more powerful than the organisms from the 
last serum-agar tube. It may take one-tenth of a cubic centimeter 
of the agar strain to kill a mouse, but it may take only .000001 of 
a cubic centimeter or even less of the mouse strain to bring about 
the same result. 
There is also a great initial difference even in freshly isolated 
strains of a given kind of bacteria. One culture is often fifty or 
more times as virulent as another; experiments have shown that 
a less virulent diphtheria culture may require .1 c.c. for a fatal 
dose, but .022 of a c.c. of a virulent culture of diphtheria may be 
equally fatal. BACTERIA 
45 
Infection and Immunity.—A slight infection, such as a tiny 
abscess around a splinter, may develop even though the body 
as a whole really has sufficient protective or immunity-yielding 
substances, because such substances have not yet been marshalled 
to that area in sufficient quantities. Serious infections, however, 
occur when, because of the 
low level of normal protec- 
tive agencies, or the high 
virulence of the invasive 
bacteria, or both of these 
conditions, the body is for 
the time being relatively 
unprotected. More white 
corpuscles have to be manu- 
factured and special new 
antisubstances have to be 
formed in the body before 
an individual so infected 
can overcome the invading 
organisms; in doing so he develops an active or “ acquired ” im- 
munity to such organisms. This definite or specific immunity is 
the subject of the following chapter. 
Fig. 30.—Anthrax (BaHUvs anthracis). 
Vegetative form on the left, spores on the 
right. Williams, Brown and Earle. 
STUDY SUGGESTIONS 
1. List and describe the various effects of micro-organisms upon the 
human body. 
2. Consult texts describing specific diseases to find specific illustrations 
of each of the various effects of bacteria or protozoa upon the 
human tissues. 
3. Find in a text book of bacteriology a comparison (bulk or weight) 
of the killing strength of a strong drug such as strychnine and a 
given preparation of tetanus, botulinus or other bacterial toxins. 
4. Explain why fever may be considered a symptom rather than the 
disease itself. 
5. Describe the passive body defences against bacterial invasion. 
6. Find an illustration emphasizing the importance of cell vigor in 
resisting disease. 
7. Illustrate “preferred methods of entrance for diphtheria, for typhoid, 
or for tetanus. 
8. Copy the skeleton outline of the contents of this chapter (p. 17) on 
a large sheet of paper and elaborate each of the sub-topics so as 
to cover the subject matter given in the chapter. 46 
HOW WE RESIST DISEASE 
9. It has been demonstrated that such conditions as shock, thirst, 
starvation and collapse can cause disintegration of cell tissue. 
Which of the results of bacterial action would the accumulation 
of such disintegration material parallel or resemble? How would 
such conditions affect the subject’s resistance to bacterial infection? 
10. An investigator reports that one-ten-billionth of a loop of some cul- 
tures of the hemorrhagic septicemia organism kills a rabbit in 
24 hours, at which time bacteria can he demonstrated on every 
drop of blood or body fluid examined. Can you express definitely 
the “minimal lethal dose” of such an organism? 
11. It has been calculated that some bacteria can divide into two new 
ones every twenty minutes. If such multiplication is unchecked 
by body reactions, etc., how many organisms could be formed in 
24 hours from a single initial bacterium? 
12. Look up, in U. S. Public Health-Service Reprint 436, the mode of 
transmission of the diseases described there. In how many of 
the diseases listed are there evidently “preferred methods of en- 
trance?” In how many must the causal organism be inserted 
directly into the tissues (insect bite, etc.) ? 
13. The mode of transmission of leprosy is described as “close, intimate 
and prolonged contact with infected individuals.” Can you ex- 
plain this on the basis of the size of the minimal lethal dose, 
variations in individual resistance, or both? 
14. Stillman (Health News, Sept. 1921) says that “careful histories of 
patients with lobar pneumonia show that about 40 per cent, of 
the cases give a history of coryza or other mild infection of the 
respiratory tract preceding the onset of pneumonia.” What two 
reasons—one direct and one indirect—can be advanced to explain 
the importance of such mild or unrecognized infections? CHAPTER II 
ACTIVE IMMUNITY * 
Sources or origin of protective substances 
' Toxin 
Types of reaction against 
Bacteria - 
Acting alone 
Acting with 
white cor- 
puscles 
Nature of reactions 
Chemical in character 
Graphic illustrations 
Active Immunity 
In recovery from disease 
In death 
Length of immune period 
Variations in bacteria 
virulence 
Disease and the balance 
of bacterial action and 
body reaction 
Types of active immunity 
(Racial, natural etc.) 
Substances used to induce 
immunity 
(Introductory to vaccines) 
Live organisms 
Dead organisms 
Toxins 
It is said that over 1900 years ago Mithridates the Great 
secured immunity against certain poisons hy subjecting himself 
to gradually increased doses of those poisons. The “ Mithridatic 
antidote,” according to Pliny, was composed of sixty-four in- 
gredients, some of them used in infinitesimal amounts, as small 
as one-sixtieth part of a drachm, which is about one-five- 
hundredth of an ounce (apothecaries’ weight). With these sub- 
stances he “ mixed the blood of Pontic ducks, because they lived 
on poisons.” Despite this early essay in immunity production 
it is only in the last generation, except for the preventive methods 
in relation to smallpox, that any practical methods of acquiring 
immuidty to disease have been developed. 
* This chapter, with the following, Chapter III, forms a general in- 
troduction to the subjects of active and passive immunity, the mecha- 
nism of which is discussed much more in detail in the subsequent 
chapters on antitoxins, vaccines, etc. 
47 48 
HOW WE RESIST DISEASE 
Reactions to Bacterial Poisons.—As shown in the preceding 
chapter, bacterial poisons irritate or destroy one or more of the 
body tissues. The normal individual responds to such irritation, 
accumulating in his blood and lymph (1) an increased number of 
white corpuscles, and (2) special antisubstances, or antibodies as 
they are commonly called, formless substances which are con- 
tained in the liquid part of the blood and lymph. 
Sources of Protective Substances.—The white blood cor- 
puscles are formed in the bone marrow and the lymph nodes or 
glands. The antibodies are probably formed mainly in these same 
places, and in the spleen as well; in fact, many believe there is 
no evidence to indicate that these antibodies may not be formed 
anywhere in the body. In some cases they are evidently formed 
quite locally, by the tissues directly affected by the disease 
organisms. This it is thought may explain why in a prolonged 
attack of boils the latest boil always breaks out in a new spot, 
or why erysipelas spreads only to new regions, avoiding previously 
inflamed or affected areas; it is quite evident in these cases that 
the local immunity is greater than any general bod}'' immunity. 
Two Types of Reaction.—It has already been shown 
(p. 18) that the effects of bacteria are mainly due to two causes: 
(1) to the toxins they form, and (2) to the poisons formed from 
the bacterial cells themselves as they are disintegrated in our 
bodies. It is to be expected, therefore, that the body will respond 
or react in two different ways:— (1) to neutralize or destroy the 
bacterial toxins and (2) to destroy the bacteria themselves. This 
last response would be the most effective, of course; for it would 
be final; with the destruction of the bacteria would cease their 
production of toxins. But in some diseases, toxins are excreted 
very rapidly. Since toxins are injurious in very small amounts, 
(1 c.c. of tetanus toxin can kill 75,000 guinea pigs), bacteria 
may give out dangerous amounts of such toxins very early in the 
disease—before the bacteria begin to disintegrate sufficiently to 
stimulate the body to react against their disintegration products, 
i.e., the split-protein poisons. (See p. 21.) The first response 
mentioned above, producing antibodies against the toxin, is there- 
fore a necessary one when toxin-producing bacteria cause the 
disease, as in diphtheria and tetanus. However, even in these 
diseases, reactions inimical to the bacteria themselves are also ACTIVE IMMUNITY 
49 
essential. And since the destruction of these bacteria involves 
more or less irritation due to their split-protein disintegration 
products, it is essential that the bacteria be destroyed as promptly 
as possible. The more prompt such body reactions, the fewer 
bacteria there are to be thus destroyed, and the less split-proteins 
are set free in the body. The body responses to all bacterial 
infections are thought to be “ essentially antibacterial in 
character: that is, by the development of specific antibacterial 
antibodies and their action, as well as by the activity of the 
phagocytic cells.” 
Tabulation of Reactions to Bacteria.—The antibodies vary 
in their way of attacking the bacteria or neutralizing their 
products. Some kill the bacteria directly, others help the white 
corpuscles destroy them; and, as just described in the preceding 
paragraph, other antibodies are effective only against the toxins. 
The following tabulation of these reactions may be helpful in 
visualizing these distinctions. 
Increase in white corpuscles 
against toxins (antitoxin) 
Reactions 
to 
Infection 
acting alone—dissolving bac- 
teria (lysins) 
Production of 
antibodies 
against 
bacteria 
clumping 
bacteria 
(agglutinins 
and 
precipitins) 
digesting 
bacteria 
(opsonins) 
acting with 
white corpuscles 
In most diseases, probably more than one reaction occurs, 
though one is always much more prominent than the rest. In 
diphtheria, for example, there is a lysin formed which helps kill off 
the bacteria, but it is so much less important than the other anti- 
bodies, including antitoxin, that the blood of animals immune to 
diphtheria may fail to show any lysin at all when tested for lysin. 
The relative unimportance of the lysins in diphtheria is also shown 
by the fact that in experimental animals inoculated with living 
diphtheria organisms, there may be recovered from the scabs 
at the site of the injection live diphtheria bacteria after the 
animals have become immune to diphtheria; bacterial lysins, 50 
HOW WE RESIST DISEASE 
therefore, cannot be the most important factor in diphtheria 
immunity. In discussing any particular disease, it is, therefore 
common to emphasize one reaction, antitoxins for example in 
diphtheria. That means only that this is apparently the most 
important of the reactions, or the one most readily measured or 
determined, and does not necessarily imply that it is the only 
reaction made against the disease. 
Theories of Cell Relations to Foods and Toxins.—Toxins 
injure certain cells because they have the power of chemically 
uniting or combining with these cells; they lack such chemical 
attractions or affinity with other cells and so those cells are not 
directly affected. The difference in chemical affinity explains 
why it is mainly nerve tissue that is destroyed in lockjaw 
(or tetanus) and infantile paralysis; diphtheria toxins, on the 
other hand, are much more catholic in their tastes and, as 
already described (p. 20), combine with many different types 
of cells. 
This chemical affinity is doubtless the same type of selective 
affinity that influences the cell in its selection and utilization 
of food materials. One food element can be combined with a 
given cell and utilized; a second food element cannot combine 
and never enters into intimate association with that cell. It is 
doubtless just such selective differences that make possible the 
differentiation of the cells into such specialized types as muscle 
cells, gland cells and nerve cells. 
Since toxins are more or less protein in character, it is 
conceivable that a given toxin may have the same chemical 
affinity as a given food protein. If then, such a toxin combined 
with a cell, it would have two undesirable or injurious effects 
upon the cell: (1) it would prevent the normal combination with 
the special food element whose place it had usurped; and (2) its 
chemically irritating poisons would be brought into intimate 
association with the cell, irritating or destroying it. 
Graphic Illustrations of Chemical Reactions.—While, as 
described above, these combinations and processes are chemical 
ones, so many people are eye-minded that students often find it 
helpful to have these combinations of food and toxins with the 
cell represented pictorially or diagrammatically. Some modifi- 
cations of the diagrams in common use are given below, with the ACTIVE IMMUNITY 
51 
warning that those representations are purely imaginary, and that 
the reader must remember that the combinations and activities 
they illustrate are really chemical, and that such static mor- 
phological structures must not be allowed to supplant in our 
minds dynamic chemical processes. Eecently something of a 
revulsion against this “ side-chain theory/’ as it is called, has been 
evident; and the student is therefore encouraged to emphasize 
constantly the actual affinities and activities themselves, remem- 
bering that the chemical processes these illustrations depict are 
really much more wonderful and mysterious than the compli- 
cated system of dia- 
grams people have 
elaborated to help ex- 
plain them. 
Cell and Food 
Relation s.—T h e 
chemical affinities of 
the cell for food mate- 
rials may be partly 
illustrated by the 
diagram (Fig. 31) 
in which are shown a 
cell and above it five 
types of food mate- 
rials ; these are lettered 
to indicate hypothetical molecules of a sugar (S), a fat (F), 
and three different proteins (PI, P2, and P3). Note that the 
following illustration (Fig. 32) shows one food (P3) not 
utilizable by Cell A. This food, P3, may he utilized by another 
cell, as illustrated by cell B, which may in turn lack the power 
to use one or more of the foods usable by cell A. 
Suppose that a toxin particle by virtue of its protein char- 
acter, resembles PI in its chemical affinity—in its attachment 
structure (Fig. 33). 
It could then attach itself to the cell just as Pi would. 
The cell would suffer in the two ways already mentioned (p. 50) : 
(1) It would lose the food that might satisfy the combination, 
and (2) it would be irritated or damaged by the chemical action 
of the toxin. Instead of cell action on the usual food material, 
we might have toxin action on the cell. 
Fig. 31.—A diagrammatic representation of a 
given cell’s power to utilize four of the five food parti- 
cles shown above it. 52 
HOW WE RESIST DISEASE 
When a cell is well nourished and vigorous, it gains the power 
of caring for or utilizing more food material. When food material 
is made over into cell substance the cell can be pictured as a 
stronger or even larger cell, and, therefore, having increased 
affinities for the same kind of food substances. The more it 
utilizes, the more it can use. This may be illustrated by an in- 
crease in the attachment points or receptors, as they are called, 
showing that when food occupies all the receptors on a cell 
(Fig. 34) it is then stimulated to form more receptors to which 
food may be attached (Fig. 35). 
Cell and Toxic Rela- 
tions.—Tf toxins were pres- 
ent in the neighborhood of 
such cells e.g., in the cir- 
culating blood, these extra 
resources if toxins do begin 
be a disadvantage, unless 
they could be satisfied more 
promptly by food than by 
toxins. 
However, the body is not 
wholly without protective 
resources if toxins do begin 
to combine with the cells 
(Fig. 36). The cells form 
extra receptors just as when 
food particles are the stimulating factors; but instead of keeping 
these chemically-combining factors as parts of the cell, they 
are thrust away from the cell, into the surrounding blood or 
lymph, (every living cell being bathed by blood or lymph on one 
or more sides). Thus these receptors or combining factors meet 
the toxins before they reach the cells and combine with them 
while they are still in the blood or lymph; the living cells are 
thus protected by outlying guards of the substances they have 
formed, the extruded or thrust-off receptors (Fig. 37). When 
as just described, such receptors neutralize or combine with 
toxin, they are called antitoxins. Similar substances combining 
with bacteria themselves might be given a general descriptive 
name such as antibacterins to indicate that they act on bacterial 
cells, not merely on their products, the toxins. Ho such general 
Fig. 32.—Cell B, having the power to 
use P S, which Cell A lacked. ACTIVE IMMUNITY 
53 
term is in common use, however, and the substances formed 
against the bacteria are given special names depending upon 
the way they affect the bacteria: lysins, or bacteriolysins, if they 
dissolve bacteria; agglutinins, if they clump the bacteria 
together, etc. (See p. 49.) 
The cell-food and cell-toxin combinations described in the 
preceding paragraph are the simplest of the series of the combi- 
nations we shall discuss in this volume. But even these may seem 
impossible and fantastic. That there are, however, such relation- 
ships, and that the food-attaching and the toxin-uniting powers 
are somewhat similar and interchangeable is indicated by several 
interesting bits of evidence, among which are the following 
variations in susceptibility to disease. 
When individuals are in a well nourished 
condition they are much less susceptible to disease. 
When even temporarily less well nourished they 
may come down with a disease to which they had 
reason to consider themselves immune, e.g., nurses 
and physicians through overwork or after a sudden 
nervous shock often succumb to epidemics they 
have successfully faced for weeks or months. A 
lack of properly digested food, whether due to 
actual lack of food, or incomplete digestion of 
a plentiful diet, related to overwork, fear, worry or any type 
of nervous strain, may leave unoccupied or unsatisfied the cell 
affinities or combinations by which toxins or other bacterial 
products may unite with the cell. This same idea underlies such 
common expressions as "If you are afraid of such and such 
a disease you’ll get it,” or “She worried herself into it,” or 
“She broke down nursing the rest of the family and then she 
took it.” 
Disease and the Balance between Bacterial Action and 
Body Response.—Tn disease, the bacteria multiply rapidly 
until their toxins or disintegration products stimulate the tissues 
capable of definitely reacting against them to form extra white 
corpuscles or special antibodies, or both. The bacterial growth 
may be represented by the line be in Figure 38, b representing 
the entrance of the bacteria into the body. Finally the body 
responds, beginning to develop antibodies at a; and if the indi- 
Fig. 33.—Toxin 
resembling such 
a food as PI in 
the cell-combin- 
ing power. 54 
HOW WE RESIST DISEASE 
vidual reacts vigorously, the increase in antibodies may be as 
rapid as represented by the abrupt rise of the dotted line a-c. 
The symptoms or set of symptoms evident to the patient or 
doctor may appear before or after the time the protective 
internal reaction begins. They are indicated afterward here, 
by s; b to s then represents what is called the incubation period 
which may range from two or three days to two or three weeks, 
or, rarely even longer, as in rabies. (See p. 59.) At the crisis c, 
the patient’s reaction as shown here is balancing the bacterial 
action. This reaction, however, continues for some time as 
indicated by the extension of the dotted line beyond c to o. 
Finally, however, the overproduction lessens, for the bacterial 
irritation is decreasing rap- 
idly as shown by the decline 
in bacteria or toxin produc- 
tion, the line c-e, and finally 
at e the bacteria and their 
poisons have all been elim- 
inated from the body. The 
antibodies are not elim- 
inated so rapidly, though 
they, too, gradually dis- 
appear from the blood; in 
the diagram above, their dis- 
appearance is indicated at i, 
and the patient is then no longer immune to that disease. 
If the patient described above had responded less vigorously 
the lines starting from b and a might not have met as soon, or, as 
shown in Fig. 39, they might not have met at all. In that 
case the protracted bacterial irritation indicated by the 
continuation of the b-c line would finally cause the death of 
the patient. There would be no “ turning point in the disease.” 
This whole situation has been ivell described by Park: “ It 
is the united skirmish between the two [invading germ and in- 
vaded subject] which determines whether or not a foothold shall 
be gained upon the body of the subject and an infection thus 
established; and it is the balance between them which decides 
the eventual outcome of recovery or death.” 
Length of the Immune Period.—The length of the immune 
Fig. 34.—Diagrammatic representation 
of cell and food combination. ACTIVE IMMUNITY 
55 
period (e to i in Figure 38 following) depends upon how 
vigorously the individual reacted, how much excess antibody 
material was made, and upon how rapidly it was eliminated 
from the body. After smallpox, immunity usually lasts through- 
out life; after vaccination against smallpox it usually lasts 
several years, and in one known case it was demonstrated by 
Jenner that smallpox vaccination gave immunity lasting at least 
fifty years. In such a case the line o-i in our diagram would 
be a very long line indeed. In some diseases immunity lasts 
hut a short time; that is noticeably true in common colds, where 
one sometimes contracts a fresh cold before the last one is over. 
In such cases the line o-i would almost coincide with the line c-e. 
T h e immune' 
period, as intimated 
above, varies greatly 
also with the indi- 
vidual. A reliable 
authority some time 
ago reported a child of 
eleven who had had 
several attacks of three 
diseases, each of which 
ordinarily yields an 
immunity lasting at 
least several years; the 
record was diphtheria 
three times, measles three times, and scarlet fever twice. In each 
attack this child had evidently made very little overproduction 
of immune substances, or else she had eliminated such immune 
substances with unusual rapidity. In either case her line, o-i, 
in the diagram (Fig. 38) corresponds very closely to the line c-e. 
Elimination of Antibodies.—The rate of disappearance of 
antibodies as above described varies with the disease, and with the 
individual. How such elimination takes place is not definitely 
known; the liver and spleen and also the urine have been suggested 
as possibly connected with the elimination of such substances. 
Antibodies as Aids in Diagnosing Disease.—As long as 
antibodies remain in the blood in any considerable amount their 
presence there may be detected by bacteriological methods, as 
described later for each type of antibody in its respective chapter. 
Fig. 35.—Diagrammatic representation of 
the increased size and vigor of a food-satisfied cell, 
and its consequent increased power of utilizing 
more food material. 56 
HOW WE RESIST DISEASE 
These antibodies are specific. That is, the antitoxin for diph- 
theria neutralizes diphtheria toxin and not other toxins, such 
as botulinus toxin; the opsonins for staphylococcus organisms 
aid white corpuscles in disposing of staphylococcus organisms 
and do not help in gonorrheal or tubercular infections. The 
occurrence of such antibodies is therefore taken as an indication 
that the individual has or has had the related disease. 
Variations in Virulence.—Among the organisms which 
can grow in our tissues some are much less irritating than others 
(See p. 211). This difference is partly accounted for by attributing 
to some bacteria the power to form definite substances (aggressins, 
p. 150), which help them invade the tissues, while other bac- 
teria evidently lack such power. Lessened virulence may also be 
explained by considering that such organisms form very small 
amounts of poisons or very 
mild ones, or that they are 
very like the cells of our own 
bodies in their metabolic 
processes, and that their 
action, therefore, is not very 
irritating to us. Such organ- 
isms would not arouse de- 
cided or marked reactions, 
and might continue to 
develop in the body for 
years, even throughout life, 
without at any time causing a condition serious enough to pro- 
duce death, as is sometimes true of tuberculosis. Such bacteria 
have been spoken of as “ successful germs.” They are so adapted 
to body conditions, that they develop without arousing violent 
antagonisms and also without destroying the host on 
which they depend for their existence. In carriers, such as 
typhoid carriers, where typhoid organisms have been known 
to persist in the intestinal membranes of an individual for over 
45 years, there is a similar adaptation between the organism 
and the host. Such adaptation, as might he expected, is not 
uncommon in protozoan diseases, for the causal micro-organisms 
are animal cells and naturally more like our human cells in 
general metabolism. Syphilis and malaria are common examples 
of such “ successful germs ” among protozoa. 
Spurring Body Reactions.—In certain more or less chronic 
Fig. 38.—Diagrammatic representation 
of toxins (T) combining with the cell. ACTIVE IMMUNITY 
57 
diseases such as the above, treatment is sometimes based on the 
theory that an increased or heavier dose of the slightly irritating 
substances will “ jog ” the system into a more pronounced re- 
action with a consequent overproduction of antibodies and thus 
give the individual a definite immunity—at least for a short 
period. Boils sometimes occur in a prolonged series extending 
over months, and treatment on this basis—with injections of large 
numbers of dead bacteria of the kind which are found in the boils 
—has seemed helpful in many cases, being followed by an immune 
period of several months, or complete recovery. (See Vaccines.) 
Variation in a Given Species.—A given disease organism 
does not always have the same degree of virulence. (See also 
p. 44.) We recognize this 
when we say “ J ust a 
light attack of measles, 
the kind all the children 
are having,” or “ Influ- 
enza seems to be of a 
particularly virulent type 
this winter.” 
Causes of Variation. 
—Organisms are affected 
by such outside conditions 
as cold and lack of mois- 
ture in the atmosphere. (See also p. 37.) Organisms weakened 
or attenuated by such unfavorable conditions may, on entering 
the body, multiply less rapidly and produce less injurious and 
irritating conditions. But probably the conditions met by the 
organisms in the last host or individual often have even more 
to do with the vigor or strength of the organisms eventually 
passed on to the next individual. It is easy to understand that 
a vigorous reaction on the part of an individual having the 
disease might not only so affect or weaken the organisms while 
in his body that he had a mild attack of the disease under 
consideration, but might so affect the organisms that when such 
weakened organisms were passed on to the next individual, they 
would cause only a mild or light form of the disease. An attack 
of scarlet fever, for example, contracted from such a mild case 
is more likely to be a mild attack than one contracted from 
a severe case. 
The above does not always follow, of course. A severe case 
Fig.37.—The toxin has stimulated the cell 
to produce other receptors, which neutralize the 
arriving toxins and prevent further toxin-cell 
combinations. HOW WE RESIST DISEASE 
58 
may be contracted from a mild case. The most likely explanation 
of this is that the person having the severe case had very little 
individual resistance, and that even the mild organisms passea 
on to him made relatively greater inroads than with the first 
more vigorous individual who had the mild case. (See also 
p. 59.) 
The severity of a disease may, therefore, be expressed as a 
balance between the resistance of the individual and the virulence 
of the organisms. This may be graphically represented by the 
following equation: Resistance—Virulence=Body Condition. If 
the virulence is greater than the individual’s resistance we have 
a negative result, a state of disease. The degree to which the 
Fig. 38.—Diagrammatic curves showing antibody production and immunity with 
relation to disease. As described in the text, b indicates the entrance of the bacteria; a, the 
beginning of the formation of antibodies, with an increasing rate of production as shown by 
the broken line (o-c,) where bacterial production (b-c) and antibody production (a-c) meet 
mfght be termed the crisis; at c, bacterial production falls off, with a final elimination of the 
organisms at e; antibody overproduction, however, continues to o, and the immune condition 
of the patient persists until these too disappear, e to i representing the immune period. 
resistance overbalances or exceeds the virulence determines the 
health of the individual. 
Virulence Increased by Animal Passage.—The virulence 
of an organism may he increased by growing it in a “ favorable 
animal ” or in a series of such animals. For example, the viru- 
lence of rabies organisms may be greatly increased by so “ pass- 
ing ” them through rabbits. If organisms from the first rabbit 
are inoculated into a second, and then from the second into the 
third, very virulent rabies organisms may be secured from the 
third rabbit. Many other examples could be given of such in- 
crease in virulence by animal passage: notably, streptococcus and 
pneumococcus organisms in rabbits and glanders and diphtheria 
in guinea pigs. The selection of the animal is important; e.g., ACTIVE IMMUNITY 
59 
passage through monkeys decreases the virulence of the rabies 
organism, while, as described, passage through rabbits increases it. 
The accidental transfer of organisms from person to person 
may produce organisms of increased virulence. How far the 
severe forms or types of organisms characterizing certain epi- 
demics, such as the infantile paralysis epidemic of 1916, are due 
to more favorable external conditions, and how far to such a chain 
of perpetuating individuals we cannot say. 
It may not be as simple as we have just implied. Unfavorable 
atmospheric conditions may decrease the number of living 
organisms and therefore one’s chance of infection; but the 
organisms which survive, survive because they are the most vigor- 
ous and resistant, and the cases subsequently caused by them 
Fig. 39.—When the antibody responses do not exceed the irritating or toxic effect 
of the bacteria, the antibody line beginning at a cannot cross the bacterial line at c, as in 
the previous illustration, and there is no marked crisis change, and no recovery followed 
by an immune period. 
may be more severe for that very reason. Then, too, it is quite 
possible that where “ animal passage ” causes an increase in viru- 
lence, it may not be simply because the animal is susceptible, but 
because the animal is resistant, and while the weaker organisms 
are killed off, only the stronger and more resistant ones survive, 
and so a race of more virulent organisms is bred and passed on. 
Relation of Virulence to the Incubation Period.—While 
the incubation period of most diseases is quite definitely known, 
it is usually expressed with a margin of one to three days, e.g., 
yellow fever three to five or six days. This range is more or 
less explained by such variations as the size of the causal dose, the 
initial number of organisms infecting the individual. Other im- 
portant factors are the individual’s degree of resistance, and the 
virulence of the organism. A shortened incubation period, there- 60 
HOW WE RESIST DISEASE 
fore, is often characteristic of the more severe attacks of any 
given disease. 
A short incubation period is similarly characteristic of some 
of the most dreaded diseases, e.g., yellow fever three to five days, 
gonorrhea one to eight days, and diphtheria two to six days. This 
is not an invariable rule, however; there are many exceptions, 
such as smallpox with a two-week incubation period, and 
rabies writh an incubation period varying from two weeks to 
several months. 
Natural Immunity.—Certain types of variation in suscepti- 
bility to disease are usually discussed under such headings as 
natural immunity, racial immunity, and resistance due to age. 
These variations include such differences as the relative prevalence 
of yellow fever in the white and negro residents of a given region, 
or the proportion of diphtheria cases in the adult and infant 
population of a community. For some diseases, this reputed dif- 
ference in susceptibility may be supported by blood tests, such as 
the Schick test by which the individual susceptibility to diph- 
theria may be determined (See p. 100). 
Some of these so-called differences in susceptibility are doubt- 
less due to differences in the opportunities for infection or to 
differences in resistance dependent upon the hygienic character 
of the surroundings. Tt is very evident that when two races so 
compared represent different economic levels, racial differences in 
susceptibility can not be demonstrated unless both races have an 
equally satisfactory environment with regard to all essential 
details—ventilation, methods of waste disposal and other phases 
of sanitation, as well as the character and quantity of the food 
supply and freedom from over-exposure and over-exertion. 
Occasionally, the advantage may seem to be with the race of 
lower economic status, as in malaria or other tropical diseases. 
This is not because environmental conditions are unimportant, 
but because selection through many generations has eliminated 
in the more resistant race the individuals specifically less resistant 
to any given disease, and bred up a race tolerant or even immune 
to the disease in question. 
Racial Immunity.—Variations in susceptibility to disease 
have been noted in different breeds of the same kind of animal, 
such as sheep, and in the different human races. A well-known ACTIVE IMMUNITY 
61 
illustration of such racial differences is the immunity of Algerian 
sheep to anthrax (Fig. 40) while ordinary sheep are susceptible. 
Similarly, pigeons are immune to anthrax (Fig. 30) while most 
birds are susceptible. Field mice are very susceptible to glanders, 
while white mice are immune. Among insects, mosquitoes afford 
similar parallels; the genus Anopheles being the common host of 
the malarial organism, while the genus Culex rarely serves in this 
Fig. 40—B. anthracis with capsules from liver of guinea pig. (x 1500 ) 
Muir, Journal o/ Pathology and Bacteriology. 
way. For man, similar variations are found in comparing the 
negro and white races; the negro, for example, being less sus- 
ceptible to yellow fever and more susceptible to tuberculosis 
and pneumonia. 
Natural Immunity.—Individuals differ in their suscepti- 
bility to disease. These differences may he temporary only, such 
as the variations a given individual might show depending 
upon his physical condition. As might be expected susceptibility 
increases with fatigue, over-exertion, worry, undue exposure to 
chill, overheated or badly ventilated rooms, retention of body 62 
HOW WE RESIST DISEASE 
excretions (e.gfeces), the accumulated effects of a previous 
disease, and with alcoholism. 
Individuals often claim a natural immunity for what is really 
an acquired immunity to a given, disease. Such immunity may 
be due to what is practically a previous but very slight attack of 
the disease—to the earlier unrecognized entrance of a small num- 
ber of the organisms in question, through such membranes as 
the respiratory or intestinal tract, which stimulated the produc- 
tion of sufficient ‘protective substances. Dysentery and typhoid 
may be cited as illustrations of such a condition, appropriate 
antibodies (agglutinins) having been demonstrated in the blood 
of individuals who-are known to be immune but for whom we 
have no records of the disease in question. 
Besides these variations there are differences somewhat more 
predictable, which are generally considered to be related to the 
age, race, or species of the individual. There are, for example, 
certain diseases commonly classed as children’s diseases, partly 
because children are more susceptible to those diseases than adults, 
and partly because, since most adults have had such widely spread 
diseases when children, they are afterward more or less immune 
to them, and therefore most of the cases in any period occur 
among the children. Ringworm and thrush are infections to 
which children are very susceptible. As contrasts one might cite 
diphtheria and typhoid as diseases to which very young children 
seem immune (See p. 102); such “natural immunity” may be 
a transferred immunity—a passive immunity due to sub- 
stances transferred from the mother before birth—or, less often, 
with the milk. 
As these gradually disappear, the child becomes more sus- 
ceptible ; the most susceptible period for diphtheria, for example, 
follows very closely upon the period of inherited immunity,— 
between the ages of one and four years. 
The immunity that sometimes comes with age cannot always 
be explained as due to recovery from an attack of the disease. 
Many individual instances are doubtless due to recovery from mild 
and unsuspected cases of the respective disease; for example, what 
is thought to be an attack of dysentery may be a typical typhoid 
fever, yielding the usual evidences of immunity: agglutinins in 
the blood, and resistance to later typhoid infections. The phe- ACTIVE IMMUNITY 
63 
nomenon of increased resistance with age, is too common to be 
explained on this basis, however, and is generally ascribed to the 
invasion of a few of the micro-organisms through the mucous 
membranes, such as the tonsils, nasal membranes, or intestinal 
linings, and the consequent arousing of the usual immunity 
responses in effective though relatively low amounts. 
There is still a great deal that is unexplained in this question 
of natural immunity; and in this connection we must not lose 
sight of the fact that the chemical conditions -or balance of the 
body cells or tissues are of fundamental importance. Slight dif- 
ferences in chemical structure or composition favor or resist the 
combining effects of the various bacterial products. To such 
unascertained differences we must attribute differences in variety 
resistance, such as the resistance shown by certain strains of wheat 
to rust, certain species of sheep to anthrax, or different races of 
man to yellow fever and tuberculosis. 
Practical Methods of Inducing Active Immunity.— (For 
a more detailed discussion of this phase of active immunity see 
Vaccines.) Since, when one recovers from a disease, he usually 
has secured immunity to that disease for a period of time, it 
would naturally occur to any one interested in the health of a 
people that it would be an advantage to give well people a mild 
attack of a given epidemic disease and thus prevent serious cases. 
Several of the ancient Asiatic peoples recognized this, and prac- 
ticed it with smallpox. Indeed, in some parts of China to-day the 
natives put pus from the eruptions of mild smallpox cases on 
cotton or wool plugs and insert them in the nose. The cases thus 
caused are usually light cases and give immunity for life. But as 
shown earlier in this chapter (p.58) severe cases may result from 
light ones. One can never tell just how virulent such organisms 
are, nor just how much resistance the next individual will have. 
It will be much safer, therefore, if some definite attempt is made 
to weaken the organisms before they are inoculated. 
Several different methods may be used for this: (1) growing 
the organisms in a less favorable animal; (2) growing them 
under unfavorable laboratory conditions, such as too high a tem- 
perature or in unfavorable food materials; or, (3) subjecting 
them after growth to unfavorable conditions, such as drying, 
chilling, or the addition of chemicals. Such weakened organisms 64 
HOW WE RESIST DISEASE 
are very unlikely to cause very serious attacks of their respective 
diseases. In such diseases as typhoid, however, where bacteria 
may so accustom themselves to the body, that they continue to live 
and multiply in the intestine after the individual has apparently 
recovered, there would be a risk in giving live organisms, no mat- 
ter how weakened, for the individual might thereby become a 
“ carrier ” for that disease. In diseases where the infection may 
be transferred by the body excretions (nasal excretions, fece's, 
etc.), it is, therefore, undesirable to give any individual live 
organisms, no matter how weakened, if a better plan can be found. 
-Fortunately, in diseases like typhoid (Fig. 41), good results 
are obtained if the bacteria 
are first actually killed. The 
bacteria are killed by heat, 
by chemicals such as car- 
bolic acid, or less often by 
grinding. Broth or agar cul- 
tures of the bacteria are 
usually used in this work. 
This material contains the 
same irritating substances 
that would follow the devel- 
opment of live bacteria in 
the body: toxins, poisonous 
split-proteins (See p. 173), 
and the body is stimulated 
therefore, to produce the necessary antisubstances. 
In a few diseases, it is not necessary to give the bacterial cells 
themselves. In diphtheria, for example, immunity can be secured 
by filtering the broth culture of bacteria, and inoculating the 
filtrate which contains the diphtheria toxins without any organ- 
isms at all, not even dead ones. A very small amount of this 
diphtheria toxin injected into the arm of a child will give 
immunity to diphtheria. (See p. 99.) 
In all these cases of immunity described, the body reacts 
much as if the disease had been contracted “ naturally.” The 
laboratory part of the process is concerned only with the careful 
preparation of the material to be injected: to obtain pure culture 
of the desired organism only, and to make sure that it has been 
Fia. 41. — Broth culture of Bacterium 
typhnsum, the typhoid organism. Williams, 
Brown and Earle. ACTIVE IMMUNITY 
65 
sufficiently diluted or weakened, thoroughly killed, etc. The 
resulting protection or immunity following the inoculation of 
such substances is due entirely to the reaction of the person 
inoculated, and we therefore speak of the immunity thus gained 
or acquired as active or “ acquired ” immunity. 
STUDY SUGGESTIONS 
1. What are the main types of body reaction to disease organisms? 
2. Consult other texts and find a disease where increase in the white 
corpuscles is commonly associated with that disease. 
3. Classify the antisubstances aiding in the destruction of bacteria. 
4. Consult text books of bacteriology (or later chapters in this book) 
and list the diseases in which the body responds to the infection 
by making (a) antitoxins; (b) agglutinins or precipitins; (c) 
opsonins; and (d) lysins. 
5. Prepare a list of diseases common in school children (or in adults 
in industrial concerns, etc.) and tabulate them according to the 
incubation period. What rules can you formulate to insure the 
welfare of the people associated in the group you selected ? 
6. Consult such a source as U. S. Public Health Service Bulletin 436 and 
list the diseases for which a definite period of immunity is known. 
Do your state laws for smallpox vaccination, typhoid vaccination, 
etc., recognize these facts? 
7. What factors may affect the virulence of an organism? Illustrate 
two. 
8. Support the old saying “Like cures like” in the treatment, often suc- 
cessfully tried in treating such infections as “chronic boils” due to 
staphylococcus infections. 
!). Plot, as on page 58, the body and bacterial relationship in the last 
disease of a given member of your family, showing in days on the 
base line the length of the incubation period, the immune period 
following the infection, etc. 
10. Recently, experimental work with animals demonstrated the reduction 
or disappearance of various bacteria deposited into isolated or 
tied off loops of the intestine; for example, typhoid bacteria were 
greatly reduced in number in five hours; spores of the hay bacillus 
disappeared completely in twelve hours. Can you cite any other 
antibacterial mechanism of the body not explainable by the res- 
ponses described in this chapter? 
11. Wright once said: “The physician of the future will be an immuni- 
zator.” With regard to what disease has that been practically 
true for a generation ? How far is it at present true for typhoid ? CHAPTER III 
PASSIVE IMMUNITY 
(And Antiserums) 
Passive Immunity 
Drugs and immunity 
Blood of 
other 
animals 
Normal blood 
Whole blood 
Modified forms of antiserum 
Types (antibodies 
prominent) 
Dosage 
Standardizing 
Specificity 
Present status of various 
antiserums. 
Immune 
blood 
Serum 
(Antiserum) 
Drug Treatment.—Certain diseases may be prevented or 
cured by drugs. Eor example, quinine may be used very success- 
fully in treating human malaria (Figs. 42, 43) as it kills all forms 
of the malaria organisms, except perhaps the crescent stage 
(Fig. 44). 
When drugs are so used they are usually injected into the 
blood (intravenously) or into the tissues (subcutaneously) where 
they are quite promptly absorbed into the circulating blood 
stream. In certain diseases, however, as in malaria, satisfactory 
results may be obtained by simply swallowing the drug, quinine 
being absorbed from the alimentary canal readily enough to 
secure the desired effect. 
Drugs may be used against a variety of types or classes of 
micro-organisms: iodine compounds against a fungous infection 
(sporothrichosis, Fig. 45); emetin against protozoa (amebic 
dysentery) or arsenic-benzol compounds against syphilis, an- 
other protozoan disease; chaulmoogra oil against the leprosy 
bacteria, and iodine, aniline dyes, etc., against various bacteria 
found in wound infections. 
66 PASSIVE IMMUNITY 
67 
Most of the diseases in which drugs are used effectively 
are caused by protozoa. Bacteria are apparently much more 
resistant to most drugs than our own body tissues are. Good 
results have been claimed in human anthrax through the same 
arsenic-benzol compound that is used in treating syphilis, and 
bacteria-infected wounds are undeniably treated advantageously 
with such drugs as the modified hypochlorites used in the Carrel- 
Dakin method, or ordinary wound disinfectants. Nevertheless, in 
the body itself, chemical treatment against 
bacteria is not yet satisfactorily established. 
Amounts too small to kill bacteria may affect 
the body tissues—ultimately if not directly. 
The treatment of syphilis affords an illus- 
tration of such indirect interference in the 
effect on the teeth following the continued 
use of mercury. 
Recently much time and money have been 
spent in trying to find drugs which are 
effective in the animal body against such 
bacteria as the streptococcus and pneumo- 
coccus organisms. For these investigations many new drugs 
were made—absolutely new chemical substances never before 
seen, even as laboratory curiosities. The negative results obtained 
in these exhaustive studies have been most disappointing, indi- 
cating that drugs cannot be satisfactorily used in such infections. 
Fig. 42.—M alaria 
organisms (59) tree in 
blood stream, sestivo- 
autumnal malaria. 
Lawson Journal if 
Experimental Medicine, 
Rockefeller Institute. 
Fig. 43.—Malaria organisms, showing multiple infection of red blood corpuscles 
Lawson, Journal of Experimental Medicine, Rockefeller Institute. 
Drug Prevention not True Immunity.—While suitable 
dosage with a drug may prevent or cure a given disease, the sub- 
sequent freedom from infection thus obtained is not due to the 
internal processes or mechanism understood by the term im- 68 
HOW WE RESIST DISEASE 
munity. It does not depend upon the presence or increased 
development of antibodies or white corpuscles. 
Immunity by Transfer of Blood Substances.—Since the 
blood of a person recovering from a disease usually contains a 
Fig. 44.—Crescent stages of aestivo-autumnal malaria organisms, 
seen lying in the blood between the red corpuscles. 
Lawson, Journal of Experimental Medicine. Rockeller Institute. 
superabundance of special antibodies as described in Chapter II, 
it is to be expected that immunity thus actively acquired by one 
individual could be transferred to a second individual by trans- 
Fig. 45.—A mold, Sporotrichum, showing branching mycelium and spore clusters 
photographed from an old agar plate culture. (Wolbach, Sisson and Meier, Journal 
of Medical Research.) 
ferring to him a sufficient amount of the blood containing these 
antibodies (Fig. 46). The second individual thus gains im- 
munity through no activity of his own tissues, and his immunity PASSIVE IMMUNITY 
69 
is therefore described as passive immunity to distinguish it from 
the active immunity of the first individual whose blood was 
so transferred. 
Active immunity is always due to the reactions of the indi- 
vidual’s own body against organisms (live or dead) or their 
products (toxins, poisonous split-proteins), while passive im- 
munity is always due to the introduction of blood or serum from 
another animal which has previously developed an active im- 
munity. In other words, vaccines or actual attacks of disease 
excite active immunity, while antiserums give passive immunity. 
To be exact, however, the second individual rarely, if ever, 
fails to make some active 
response to the invading or- 
ganisms himself. The blood 
transferred, contains suf- 
ficient antibodies to counter- 
act or destroy most of the 
organisms and their poisons, 
and therefore lessens mark- 
edly the active reactions the 
second individual must make 
to recover from the disease. 
It is, however, quite cus- 
tomary to speak as if passive 
immunity were the only con- 
sideration ; whereas it really 
only supplements the in- 
jected individual’s efforts to 
develop active immunity. Indeed, some bacteriologists go so far 
as to say, “We never by drugs or antiserums cure any disease; 
we can only help the body cure itself.” 
Immune Substances in Normal Serum.— (See also p. 45.) 
The serum of a normal individual who has not had a given disease 
contains so little of any antisubstances per cubic centimetre that 
it is, of course, rarely used to combat any specific infection. In 
the recent infantile paralysis epidemic of 1916 (Fig. 47) normal 
serum was tried in many instances because blood from recovered 
or known immune cases could not be procured in sufficient 
amounts. The blood used was taken from normal adults on 
Fig. 46.—Typical temperature curve in 
case of poliomyelitis, in which immune serum 
was given, and which ended in complete re- 
covery: B marks the twoinjections of 15 c. c. 
immune serum. 
Zinoher, Collected Studies, Bureau of Labor- 
atories, Health Department of the City of 
New York. 70 
HOW WE RESIST DISEASE 
the theory that since adults were on the whole much less sus- 
ceptible and since the adult members of the patient’s family 
had not contracted the disease, the blood of such adults probably 
contained enough immune substances to benefit the child ill 
with infantile paralysis (See also Fig. 46). 
Since antibodies may accumulate in almost unbelievable 
amounts in the blood of immune animals (as high as 200,000 
times the amount present in normal blood), every effort is made 
o F'°-,47•—Micro-organisms causing infantile paralysis. Separate globoid bodies, 
•>: paired globoid bodies with long and short chains of Streptococcus pyogenes for con- 
trast, 7; chains and pairs of globoid bodies, 5. (x 1000) Flexner and Noguchi 
Journal of Experimental Medicine, Rockefeller Institute. 
to secure blood known to be immune—and it is only in emer- 
gencies that normal blood * would be tried at all. 
Difficulties Attending Transfer of Whole Blood.—When 
whole blood is transferred to another individual clots may 
be formed, clogging the capillaries or exerting pressure upon 
delicate nerve areas. When the blood so transferred belongs to 
another animal species, other undesirable results may also occur: 
(1) the transferred blood cells may be treated as foreign material 
and digested or destroyed; or, (2) some of the blood proteins— 
* This discussion, of course, does not refer to ordinary transfusion 
of normal blood where increasing the antibodies is not the chief con- 
sideration, but where the aim is to replace the loss of large amounts of 
blood, injured red cells, etc. PASSIVE IMMUNITY 
71 
even in the liquid serum itself—may be digested as foreign pro- 
teins, liberating poisonous substances (See p. 193). All of these 
possibilities—or rather probabilities—make it desirable to lessen 
the amount of foreign substances injected; therefore, when blood 
is to be transferred to give immunity not only are the corpuscles 
first removed from such immune blood, but the fibrin also is 
removed from the plasma, leaving the serum only to be used for 
injection (Fig. 49). This immune serum, since it contains the 
desired antibodies is called antiserum. Quite commonly, how- 
ever, the shorter and less accurate term serum 
is used for an immune serum. Serums are, 
as might be expected, much less irritating 
than whole blood; a discussion of serum sick- 
ness is given in the chapter on anaphylaxis, 
but at present it is sufficient to say that the 
fever, rashes, etc., are much less common and 
less severe than formerly when whole blood 
was used for injection. 
Modified Serums.—It is an advantage 
to remove not only the corpuscles and fibrin 
as described above, but as much as possible 
of the protein substances still unavoidably 
left in the serum. This is done in diphtheria 
antiserum by precipitating out some of the 
proteins with special chemicals such as salts. 
(See p. 94.) While some of the antibodies 
are lost in such modification of the serum, 
the remaining antibodies are concentrated to 
such a degree that the resulting fluid con- 
tains four to six times as much in a given bulk, and any irritation 
following the injection of the necessary dosage is much less 
than when the greater volume of whole serum is used. Diph- 
theria antiserum is practically the only serum greatly modified 
before it is injected; other serums such as pneumonia serum, 
are merely filtered to remove small particles, such as broken 
corpuscles or shreds of fibrin. (See p. 93.) 
Antibody-Extracts.—Decently a complicated and ingenious 
technic perfected by Huntoon has made it possible to obtain 
Fig. 48.—Film from 
central nervous tissue 
of monkey inoculated 
with human virus: this 
shows pairs of globoid 
bodies similar to those 
in the preceding figure. 
Flexner and Noguchi 
■Jon rnal of Experimental 
Medicine, Rockefeller 
Institute. 72 
HOW WE RESIST DISEASE 
antibodies practically free from the usual accompanying proteins. 
This process may be very roughly described by saying that a 
given antiserum is mixed with its related bacteria (for example, 
pneumococcus antiserum with pneumococcus organisms) to allow 
Fig. 49.—Filtering serum to remove broken cells, shreds of fibrin etc. before injection: 
T, immune serum; F, a porcelain filter (see following illustrations!: and S, the filtered 
serum, ready to bottle for use. H. K. Mulford Co. 
them to absorb out the allied antibodies. Then this bacteria- 
antibody combination is treated to disassociate the bacteria from 
the antibodies. This disassociation and removal may be accom- 
plished by proper treatment with salt solutions, dextrose solu- 
tions, or even distilled water. On centrifuging, a clear or water- 
white solution or antibody-extract is obtained wdiich is almost PASSIVE IMMUNITY 
73 
free from serum proteins and therefore strikingly free from the 
usual more or less irritating effects connected with antiserums. 
(See p. 71.) 
Some of the antibodies are 
“ lost ” in this method of treatment 
(all are not disassociated from the 
bacteria, etc.). But the concentrated 
antibody-extract thus obtained is 
very readily available in the body; 
and surprisingly small amounts (50 
c.c. in human cases) have given very 
promising results; for example, a 
prompt initial drop in temperature 
(from 104° F. or 107° F to 98° F. 
in 8 to 12 hours), and a decided 
shortening of the period of illness— 
both in the pre-crisis interval and in 
the total period of illness. Encour- 
aging results of this kind were 
recently reported in fifty hospital 
pneumonia cases, and extensive trials 
of pneumococcus antibody-extracts 
are now being made in various hos- 
pitals in the eastern United States. 
Terminology Relating to Anti- 
serums Misleading.—Such a modi- 
fied or concentrated serum as diph- 
theria antiserum is primarily an 
antitoxin, and so is usually called 
diphtheria antitoxin rather than 
diphtheria antiserum. In such anti- 
serums as tetanus antiserum, or gas 
gangrene antiserum, no such modi- 
fication or reduction in bulk takes 
place, and whole serum is used. 
Each of these, too, however, is called 
antitoxin simply because its main action is antitoxic, acting 
against the tetanus or the gas bacillus toxin. 
Then, too, the first antiserums of practical use were mainly 
antitoxic in their action, and it was therefore natural to use the 
Fig. 50.—Section through a 
porcelain or clay filter showing the 
outer metal case, the space into 
which the substance is poured (S) 
the porous clay or porcelain filter 
(C), and the outlet for the substance 
which has passed through the por- 
ous filter (0). See following illus- 
tration. 74 
HOW WE RESIST DISEASE 
two terms interchangeably. All this often leads to a confusion 
regarding the terms antitoxin and antiserum. Antiserum is the 
larger term; some antiserums contain antitoxins, and some do 
not, but owe their value to antibodies other than the antitoxins, 
such as the opsonins. 
Types of Antiserums.—The blood of immune animals con- 
tains more than one reacting substance or antibody, each of 
which is discussed separately in the following chapters. In 
immune blood or serums, as already described (p. 49), one anti- 
Fig. 51.—A porcelain filter “candle” broken across to 6how relative thickness of the 
filtering “candle”, its porous character and the opening through which the filtered liquid 
passes into the vessel beneath. Heins. 
body is usually much more important than the others; sometimes 
so much so that little attention is paid to any of the other anti- 
substances as in the case of the antitoxin in tetanus antiserum. 
Antitoxins, as stated in a previous paragraph, are the most 
prominent antibodies in the immune serums used in treating 
tetanus, diphtheria and gas gangrene infections. 
Opsonins, which aid the white corpuscles in their work, are 
very important in most of the other antiserums now in use. 
Meningitis, pneumonia and streptococcus antiserums have re- 
markable stimulating effects upon the action of white corpuscles, 
though meningitis antiserum is partly bactericidal (lysins) and 
pneumonia antiserum has also definite bactericidal and anti- 
toxic values. Recently, very different substances, anti-endotoxins PASSIVE IMMUNITY 
75 
or anti-split proteins, have been advanced as “ exceedingly 
important in pneumonia, meningitis and streptococcus im- 
mune serums/’ 
Despite the high amount of agglutinins developed in certain 
diseases, such as typhoid and dysentery (Fig. 52), there are as yet 
no established antiserums where the passive immunity obtained 
is claimed to be mainly due to agglutinins. 
The efforts to secure antiserums for use in protozoan diseases 
have been much less successful than with diseases of bacterial 
origin. The most effective so far is probably antirabic serum, 
where a slight inhibiting 
power is granted. In scarlet 
fever and measles, for both 
of which protozoan origin 
has been claimed though not 
proven, beneficial results are 
reported from serum treat- 
ment, but such treatment 
has not advanced beyond an 
experimental stage in these 
diseases. In most of the 
human protozoan diseases, 
including syphilis, no ben- 
efit has yet been demon- 
strated from the use of anti- 
serums. 
Other Antiserums.—Fairly successful antiserums have been 
obtained against other substances not of bacterial origin, such as 
cobra and rattlesnake poisons. Flower pollens have been less suc- 
cessfully used in producing an antiserum for curing or preventing 
hay fever. 
Dosage.—The dosagevaries considerably with the aim in view, 
a much smaller dose being given to protect against possible infec- 
tion than to cure disease when already established. For example, 
nurses and others in contact cases of plague are given immunizing 
doses of 20 c.c., while the patients themselves may be given five 
times that amount, 100 c.c. 
The amount of anti-serum necessary to give protection de- 
pends upon such different factors as (1) the stage and virulence 
Fia. 52.—Shiga’s dysentery, broth culture, 
(x 1500). (Sands.) 76 
HOW WE RESIST DISEASE 
of the infection, (2) the concentration of the antibodies m the 
serum, and (3) the method by which the antiserum is injected 
(directly into a vein, into subcutaneous tissue, etc.). 
The importance of the first factor may be illustrated by such 
a statement as the following: Four times as much rattlesnake 
antiserum is necessary for protection one hour after the person 
has been bitten as if administered at the time of the bite. 
Or, the initial dose of diphtheria antitoxin varies from 5,000 to 
10,000 units (See p. 97), and in pneumonia from 60 to 100 c.c., 
depending upon the condition of the patient and the stage of 
the infection. 
The second factor, concen- 
tration of the antibodies in the 
serum, varies with the antibody 
strength of the original serum 
itself, and with the degree of 
later modification of the serum. 
The serum as obtained from 
the horse varies from 150 to 
1,000 units per c.c., although 
but a small fraction of the 
horses yield as much as 800 
units per c.c. When modified 
as described for diphtheria 
antiserum, the decreased bulk 
means a strength of from 4 to 
6 times the original number of units. It would, therefore, be 
quite possible with some antitoxin to give an ordinary dose, 
5,000 units, in less than 1 c.c. of modified serum. 
The third factor, method of injection, modifies very greatly 
the amount necessary for protection. In tetanus, for example, the 
New York Research Laboratory recommends 5,000 units intra- 
spinally or 10,000 units intravenously. This difference in amount 
is due mainly to the relative rapidity with which the immune sub- 
stances can reach the critical areas, in this case the central 
nervous system. If given intramuscularly or subcutaneously still 
larger doses would be necessary, 100,000 units or more. There 
would, of course, be some doubt as to whether even such an 
increase in the amount injected could adequately compensate 
for the slower absorption rate. 
Fig. 53.—Spinal fluid showing menin- 
gitis organisms and white corpuscles. Bull, PASSIVE IMMUNITY 
77 
Standardizing Antiserums.—The value or strength of an 
antiserum depends, of course, upon the antibodies it contains. 
Although the action of these in the body may not be proportional 
to the measurement standards that we can apply in the labora- 
tory, we are nevertheless often dependent upon such labora- 
tory procedures. 
Measuring Protective Values Directly.—Where serums can 
be definitely standardized the strength is usually estimated by de- 
termining how much is necessary to destroy or neutralize the 
known fatal dose of the 
related toxin or bac- 
teria. In diphtheria, 
for example, the 
amount to protect a 
medium-sized (250 
gm.) guinea pig 
against the known 
fatal dose of diph- 
theria toxin is deter- 
mined by inoculating 
each of a series of 
guinea pigs with vary- 
ing combinations of 
the antiserum to be 
tested and the known 
fatal dose of diph- 
theria toxin. This pro- 
tective amount is very 
small—but a small fraction of a cubic centimetre—and not nearly 
enough to protect a human being; therefore 100 times the minute 
amount that protects a guinea pig is used as the standard diph- 
theria antitoxin unit. This insures a workable unit—one that 
can be handled with greater facility and accuracy. 
In tetanus the unit is 1,000 times the amount needed to pro- 
tect a larger (350 gm.) guinea pig against the known fatal or 
lethal dose of tetanus toxin. The strength of pneumococcus anti- 
serum is determined by finding its protective value against pneu- 
mococcus organisms when both are injected into mice. 
Measuring Specific Antibody Content.—Besides determin- 
Fig. 54.—Neisseria catarrha/is ( Micrococcus ca- 
tarrhalis) from a nasal suppuration, one of the 
organisms sometimes causing meningitis (k 1200). 
Lewis, Journal of Pathology and, Bacteriology. HOW WE RESIST DISEASE 
78 
ing the protective values, some idea of the strength of a given 
antiserum may be obtained by testing it for its relative 
abundance of the antibodies known to be prominent in that 
particular kind of antiserum—by determining, for example, the 
agglutinin content of dysentery antiserum. 
In this method, the laboratory processes are not so simple 
nor, apparently, so parallel to what takes place in the body. 
Nevertheless, the determination of the relative abundance of 
opsonins, agglutinins, etc., present in a given antiserum consti- 
tutes the only definite standard in sight, and, therefore, we 
endeavor to determine in 
different antiserums the rel- 
ative amounts of the most 
prominent antibodies pres- 
ent. Such laboratory meas- 
urements are usually made 
for one type of antibody 
only, such as opsonins; and, 
obviously, the results ob- 
tained tell us nothing of the 
possible aid rendered by the 
other antibodies, such as 
agglutinins, or lysins. 
Other Methods of 
Estimating Values. — The 
strength of some antiserums 
can not be accurately de- 
termined by either of these 
two methods, and we are compelled to use such admittedly 
imperfect standards as their transparency when diluted in cer- 
tain proportions. 
Since most antiserums have not yet been satisfactorily 
standardized, the treatment varies with the patient’s reaction or 
condition after a trial dose of a few cubic centimetres has been 
given. This is, of course, very unsatisfactory, as the actual bulk 
means very little without some way of determining the antibodies 
present in a given volume. Probably the dosage is usually too 
small, and the promising effects recently obtained in treating 
pneumonia are attributed to the greatly increased amounts of 
antiserum given, sometimes over 100 c.c. at a time. 
Number of Doses.—While a single dose is usually sufficient, 
Fig. 55.—Smear of spinal fluid sediment 
showing pleomorphic forms of the influenza 
bacillus (x 1200) from a case of meningitis. 
Abt and Tumpeer, American Journal of 
Diseases of Children. PASSIVE IMMUNITY 
79 
as in diphtheria, we are not yet able to measure the strength of 
other antiserums definitely enough (See standardizing anti- 
serums following) to calculate the required dosage so exactly; 
then, too, we have not yet accumulated such a wealth of experi- 
ence with them. The practice, therefore, in such cases, is to 
give one large dose (10-25 c.c. for meningitis, 100 c.c. for pneu- 
monia) and base the later dosage upon the patient’s subsequent 
condition. Doses may be repeated every 10 or 12 hours until 
improvement is evident, or they may be repeated daily for as 
long as 4 to 6 days. Occasion- 
ally, the treatment may con- 
tinue for as long as two weeks. 
In the preventive use of 
antiserums, the repetition in- 
tervals are based on the rate 
at which the injected serum 
substances are eliminated from 
the body. Nurses in contact 
with diphtheria cases may be 
given diphtheria antitoxin 
every 8 to 10 days, and wounds 
likely to be infected with teta- 
nus organisms may be so treat- 
ed at similar intervals. 
Variations in Disease 
Organisms.—Difficulties often arise because organisms enough 
alike to be given the same name and enough alike to cause the 
same general clinical symptoms, are not, nevertheless, exactly 
alike in all their effects on the body. There are, for example, 
several types or varieties of the pneumococcus organism (Diplo- 
coccus pneumonice) responsible for pneumonia, and, similarly, 
several varieties of paratyphoid organisms, Bacterium paraty- 
phosum, which cause intestinal disturbances. Even more varie- 
ties are probably represented in streptococcus infections. It is 
thought that such variations in pneumococcus organisms may be 
responsible for second attacks of pneumonia. An individual 
recovering from one variety of pneumococcus has made anti- 
substances against that type only, and is not fully protected 
against a second or different type. Nor would his blood confer 
Fig. 56.—Spinal fluid showing heavy 
invasion of spinal fluid in meningitis. Bull. 80 
HOW WE RESIST DISEASE 
complete protection upon another having an attack of pneumonia 
due to different types of pneumococcus. 
In producing antiserums, therefore, some attention must be 
paid to the varieties of the organism responsible for the disease or 
infection. If it does not mean too great a delay, the type of such 
organisms as pneumococcus and dysentery is first determined by 
such procedures as obtaining from the patient pure cultures of 
the organism and finding its reactions in various media and 
against various blood serums. (See also p. 122.) This may make 
Fig. 57.—Bleeding jars for collecting serum. A, tube for re- 
ceiving blood; C and D, device for allowing fall of weight, if, and 
causing the depression of the clot. Serum is then withdrawn through 
A. This method yields about 50% serum. Avery, Chickering, 
Cole and Dochez, Monograph, Rockefeller Institute of Medical 
Research. 
it possible to select an antiserum made in response to the patient's 
own type. Such antiserums are by far the most satisfactory. Even 
with pneumococcus, however, where at present the most definite 
“ typing ” lias been done, effective antiserum has been produced 
for but two of the four recognized types of pneumo- 
coccus organisms. 
Since in most cases such “ typed ” antiserums are not avail- 
able, a choice must be made between two other procedures. First 
we may ignore variety or type differences and select the most viru- 
lent or the most common type of an organism with which to inocu- 
late an animal for the production of antiserum. The use of such PASSIVE IMMUNITY 
81 
Adapter for 
Syringe 
Three-way 
stop-cock 
Glass tube/ 
for window / 
. /» 
Adapter for 
Needle 
18 gauge 
Needle 
Needle 
holder 
Fig. 58.—Apparatus for injecting serum, showing the bottle of serum, suspended 
from the bed or wall. The serum may be drawn into the syringe and so injected 
through the needle into the vein, or the syringe may be left out of the scheme and the 
serum allowed to flow from the bottle into the vein by gravity. The serum can be 
kept at a body temperature by placing the tubing between two hot water bags. Avery, 
Chickeking, Cole and Dochez. Journal of Experimental Medicine, Rockefel’ir 
Institute. . , 82 
HOW WE RESIST DISEASE 
an antiserum for an infection due to another type of the same 
organism is based upon the hope that because of the general like- 
ness between the types the antiserum thus obtained may contain 
antibodies so closely approaching the kinds desired that they will 
aid in overcoming the infection. By the other method of pro- 
cedure we may prepare a polyvalent serum as described in the 
next paragraph. 
Polyvalent Serums.—To obtain a poly- 
valent serum an animal is inoculated with 
several varieties of the same organism. 
An animal may thus be made immune to 
several different varieties or types of a given 
organism such as the dysentery bacteria. 
This means that its blood contains anti- 
bodies against all the varieties or types with 
which it was inoculated, and is of value in 
infections due to any one of the several 
varieties. Such an antiserum is called a 
polyvalent serum; literally it means a 
serum of many powers or much strength or 
a serum of many combining powers. Poly- 
valent serums are used more in dysentery, 
meningitis and gonococcus infections than 
in other diseased conditions. While such 
polyvalent serums have a wider range, there 
is of course an accompanying disadvantage 
in that this very range of contained anti- 
bodies may mean an increase in the unneces- 
sary foreign proteins injected. Then, too, there is always the 
possibility that such “ polyvalent ” antiserums are not truly 
polyvalent—that the animal producing the antiserum did not 
react to all of the varieties with which it was injected. 
Mixed Antiserums.—Antibodies can even be produced 
simultaneously in the same animal against a group of quite 
distinct organisms, such as pneumococcus, streptococcus and 
influenza organisms, or against typhoid, dysentery and the 
“ colon ” bacteria. Such antiserums would—because of their 
wider range—have a wider margin of possibly unnecessary sub- 
stances and they are, therefore, open to the same objections 
given above for polyvalent serums. While a few mixed anti- 
Fig.59.—Tip of syringe 
needle, magnified to show 
that it is a hollow tube, 
with a bevelled point. This 
general type of point is 
used both for drawing 
blood or serum, and for 
injecting vaccines and se- 
rums. H. K. Mulford Co. PASSIVE IMMUNITY 
83 
serums are on the market, there is none of undisputed value, 
and the production of mixed antiserums must be considered as 
still in the experimental stage. 
Present Status of Antiserum Treatment.—It is clear from 
the preceding discussion that the value of antiserum treatment 
depends upon three 
things: (1) the accu- 
racy with which the 
causal organism is 
determined, enabling 
thereby the selection of 
the corresponding anti- 
serum; (2) the 
promptness with which 
such determination can 
be made, for to be 
effective an antiserum 
must be administered 
before the tissues are 
too greatly injured, 
and (3) whether a 
potent antiserum has 
yet been prepared. 
In both meningitis 
and pneumonia the 
situation is compli- 
cated by the fact that 
the causal organism 
may he of a wholly 
different type (Figs. 
53 to 56) from the one 
usually present in such 
infections: Neisseria 
meningitidis (Diplococcus or Micrococcus meningitidis) in 
meningitis and Diplococcus in pneumonia. It is hardly neces- 
sary to state that antisubstances formed by the horse against 
the coccus organisms ordinarily causing meningitis cannot be 
expected to counteract the conditions found in meningitis due 
to tuberculosis organisms; similarly, a serum successfully used 
in combating pneumonia due to one of the types of pneumo- 
Fig. 60.—Dark field photograph of a “filterable 
virus”, Leptospira icteroides, the causal organism of 
yellow fever, from a two-week culture on semi-solid 
rabbit serum agar, (magnified 3000 x). Noguchi, 
Journal of Experimental Medicine, Rockefeller Institute. 84 
HOW WE DESIST DISEASE 
coccus, Viplococcus pneumonice, will be less or not at all helpful 
when the pneumonia is due to streptococcus bacteria. It is to 
meet such difficulties that mixed antiserums are tried. 
At present there are but four infections in which antiserum 
treatment is on a practical and unchallenged basis. For two of 
these diseases the antiserums are antitoxic—diphtheria and 
tetanus. For the other two diseases the serums are antibacterial 
—the antiserums used in treating meningitis and (two types 
of) pneumonia. 
Although the results obtained are less uniformily successful, 
antiserums are prepared and used for several other infections. 
Dysentery, especially the Shiga type of dysentery (Fig. 52), 
often responds very favorably to antiserum treatment. Good 
results are reported with anthrax and plague, both fortunately 
uncommon in our country. 
Benefit has been obtained from appropriate antiserums 
against uncomplicated cases of “ gas gangrene ” or wound infec- 
tions so prominent in the recent war. In certain types of strepto- 
coccus infections some aid may be gained by the use of antiserums. 
Whole blood from scarlet fever convalescents has been used 
in scarlet fever with apparent advantage, although as before 
stated, this treatment is still in the experimental class. Neither 
blood nor antiserum seems to give definite aid in treating in- 
fantile paralysis. (See p. 69.) 
More detail concerning antiserums—their contained anti- 
bodies and the diseases in which they are most helpful—is given 
in the several chapters following. In each case the discussion 
includes also a brief mention of the days in which the antibodies 
may be used as aids in diagnosing disease. 
STUDY SUGGESTIONS 
1. List tlie diseases, with the causal organisms in each, in which drugs 
afford helpful treatment. How many of them are of protozoan 
and how many of bacterial origin ? 
2. What is passive immunity? Give an example of active and also 
passive immunity against diphtheria or against meningitis. 
3. What antibodies may be important in the antiserums given to afford 
the patient passive immunity? 
4. Show why the whole blood of an immune animal may be more irri- 
tating when transferred to a patient than the serum of that 
immune animal. PASSIVE IMMUNITY 
85 
5. Show that antiserum is a broader or more inclusive term than 
antitoxin. 
6. Describe one way of standardizing or determining the strength of 
an antiserum. 
7. List the antiserums in a commercial catalog of such biological prod- 
ucts; how many of them are used in the hospital or by the 
physician you know best? Can you cite one instance probably 
indicating too conservative an attitude on the part of the medical 
authorities? Cite one, indicating the sale of a preparation not 
yet certainly past the experimental stage. 
8. “Disinfection, isolation, and the widening of the danger space between 
the sick or infected and the well is the chief occupation of 
modern sanitation,” according to Dr. Theobald Smith. After 
reading Chapters II and III name the practices of preventive medi- 
cine which widen the danger space. 
9. Difficulty in finding animals sufficiently susceptible to human disease 
organisms has limited our ability to prepare antiserums for 
human protection. To what human diseases is the horse suffi- 
ciently susceptible to aid in this way? 
10. An early report (October, 1921) by Noguchi contrasts the usual 
mortality of yellow fever, 50 to 60 per cent, with that obtained 
in 152 cases treated with an antiserum, with a mortality of but 
9 per cent. How does that compare with the helpful results 
obtained with diphtheria antitoxin? 
11. In a record of 1200 cases of meningitis the death rate varied with 
the promptness with which treatment was begun as follows: 
1-3 days, 18 per cent, died; 4-7 days, 27 per cent, died; and after 
7 days, 36 per cent. Since among the untreated, the deaths are 
80 per cent., work out for each group the treated child’s chance 
of recovery when compared with the untreated child. CHAPTER IV 
TOXINS AND ANTITOXINS 
Definition Bacterial toxins 
Double toxins 
Modified toxins or toxoids 
Production requirements 
Animal 
Plant 
Excite antitoxins against. 
Poisonous 
substances 
Toxins 
Non-poisonous substances 
Production of antibodies 
Modification of 
antiserums 
Standardization 
Dosage 
Toxins and Antitoxins 
Produce antitoxins for man 
in other animals 
Antitoxin modification 
(Toxin-antitoxin) 
Treatment of infants 
Efficiency of toxin-anti- 
toxin treatment. 
Uses 
Produce antitoxin 
human beings 
Typical and pseudo- 
reactions 
Value of the Schick test 
Test of susceptibility 
(Schick test) 
Present status of antitoxins 
Diphtheria 
Tetanus 
Other diseases 
86 TOXINS AND ANTITOXINS 
87 
Toxins.—Bacterial toxins have already been described briefly 
in the first chapter of this text. Toxins of such organisms As 
tetanus and diphtheria are obtained by filtering a broth culture of 
the respective organisms. The filtrate contains the toxins; it is 
spoken of as toxin, as if it were toxin only, although its chief 
bulk consists of water and soluble food substances. 
This filtrate may contain more than one kind of toxin. For 
example, two distinct toxins are quite constantly formed by the 
tetanus bacillus (Fig. 61) : one, affecting mainly the motor 
nerves and associated with 
the characteristic lockjaw or 
tetanus convulsions; and a 
second, causing a dissolution 
of the red blood cells. Simi- 
larly the filtrate of diph- 
theria cultures contains not 
only the specific diphtheria 
toxin which is the cause of 
the usual acute symptoms of 
diphtheria, but also a second 
toxic substance or toxon, 
slower in its action and 
responsible for the paralysis 
which sometimes occurs in 
the late stages of diphtheria. 
In an elementary text 
such as this, little emphasis can be placed upon these separate 
toxins, and the term toxin is used in a general inclusive sense. 
The same is true of the related term antitoxin; no recognition 
is here given to the fact that the protective antitoxic action of 
the blood in a recovered diphtheria case, for example, is due 
to at least two antitoxins, each acting against its respective 
diphtheria toxin. 
Toxon.—A secondary or lesser toxin is sometimes termed 
toxon, to distinguish it from the better known, stronger or more 
typical toxin. More than one such toxon may be produced by the 
bacteria during their development, whether growing in the body 
or in ordinary culture media. 
Toxoids.—Another similar-sounding term sure to occur in all 
Fig. 61.—Lockjaw or tetanus organ- 
isms most of which have formed spores, the 
lighter bodies at the swollen end of the cell. 
Wiliams, Brown and Earle. 88 
HOW WE DESIST DISEASE 
reference books on immunity is the word toxoid. Toxoid is quite 
consistently used for toxins that have changed with age, tempera- 
ture conditions, etc., thereby becoming less poisonous, but not 
losing their power of chemical combination with the body cells 
or with antitoxins (Tig. 62). Such changes may be con- 
siderable; toxin but a few months old may lose more than 
half its strength by conversion to toxoids. 
Toxoids are mentioned here because their presence may affect 
the amount or bulk of a given antitoxin which it is necessary 
to give for protection, as in the toxin-antitoxin treatment de- 
scribed on page 98. Apparently, when antitoxin is injected into 
the body it first combines with the toxoid present, then with 
the toxin and last with the toxon. If a large amount of changed 
toxins or toxoids is present, 
such unsuspected toxoids may 
thus combine with the anti- 
toxin, leaving too much free 
active toxin. A similar dif- 
ficulty may be met in attempt- 
ing to arouse active immunity; 
the individual receiving a tox- 
in-antitoxin mixture contain- 
ing such toxoids might not be sufficiently protected against the 
contained toxins even though the mixture contains only the usual 
amount of toxins. 
Non-bacterial Toxins.—Since bacterial toxins have never 
been satisfactorily analyzed and no chemical formulas can be 
given for them, it is natural that the term toxin should be given 
to substances from very different sources if they are like bacterial 
toxins in the two most striking characters: (1) in having very 
irritating or toxic effects and (2) in exciting the production 
of antibodies. 
From this point of view we may have several different types 
of toxins. Some of these are commonly recognized as poisons, 
such as the poisons formed by certain species of snakes, fish, eels, 
spiders, etc. Another type is illustrated by the characteristic 
substances found in certain plants, such as the poisonous ricin in 
the castor oil seed, or abrin in the Indian licorice bean. As a 
third illustration of the substances against which antitoxins may 
Fig. 62.—Left, a toxin particle; and 
right, a toxoid or changed toxin which has 
lost part of its toxic quality but still retains 
its ability to combine with tissue cells. TOXINS AND ANTITOXINS 
89 
be formed we have substances not ordinarily toxic or poisonous, 
such as the normal body enzymes (pepsin, trypsin, steapsin, 
and lactase). 
Our interest, however, attaches mainly to the toxins formed 
by common human disease organisms, such as tetanus and diph- 
theria. Therefore, unless otherwise specified, antitoxin as used 
hereafter refers to the antibodies formed against such bac- 
terial toxins. 
Usually the diseases due wholly or in great part to bacterial 
toxins occur only when the appropriate bacteria develop in the 
body: e.g., in the intestine 
in Shiga's type of dysen- 
tery ; in the throat mem- 
branes in diphtheria; and 
in wound areas in gas gan- 
grene infections. A notable 
exception to this is found in 
botulism (Tig. 63); in this 
disease, most if not all of 
the cases recently studied 
have been due to the eating 
of foods which had already 
undergone considerable de- 
composition and in which 
the accumulated toxin had 
not been destroyed by the final heating process. (See glossary.) 
Antitoxins.—Our main interest in toxins, however, lies not 
in such modifications or differences but in their common pos- 
session of the power to stimulate the production of antibodies. As 
we have already seen we make practical use of this power on a 
large scale by injecting appropriate toxins, such as diphtheria 
toxin, into other animals, so that the blood of such infected 
animals may later be drawn off to aid human beings (See p. 90). 
All of the available antitoxin in the blood of such immunized 
animals is contained, not in the blood corpuscles but in the serum. 
Using the serum only, therefore, as in the preceding chapter, 
eliminates the corpuscles and fibrin and so decreases materially 
the amount of foreign protein substances that must be introduced 
when an animal’s blood is transferred to give passive immunity. 
Fro. 63.—Clostridium botulinum, the or- 
ganism responsible for botulism, a type of food 
poisoning. Reddish. HOW WE DESIST DISEASE 
90 
Occasionally this elimination of unnecessary protein substances 
can be carried still further and the serum itself can be modified. 
Modified Antiserum or Antitoxin.—As described in the 
preceding chapter the only antiserum in which this treatment or 
modification of the serum does not occasion too great loss of pro- 
tective substances is diphtheria antiserum. All the other so- 
called antitoxins (tetanus, gas gangrene and Shiga’s dysentery) 
are really antiserums, but as before explained, such antiserums 
are often called antitoxins, because their main action is antitoxic. 
Preparation of Diphtheria Antitoxin in Horses.—The 
animal phases of antiserum production were almost ignored in 
the preliminary discus- 
sion of the production of 
antiserum in Chapter 
III. It may be of inter- 
est here, therefore, to be- 
gin with the horse and 
give a little more in de- 
tail the whole process of 
producing antitoxin. For 
this discussion we have 
selected diphtheria anti- 
toxin, partly because it is 
historically the most in- 
teresting, as diphtheria 
antitoxin was the first antitoxin to be placed upon an un- 
challenged basis. Diphtheria antitoxin is also more popularly 
and widely known than any other. The process of production, 
as described, is, only in a general way, true for other antiserums, 
as there is, of course, considerable variation in such details as 
the following: 
(1) Method of inoculating the animal which is to produce the 
antiserum—e.g., with dead bacteria or only their toxins; (2) the 
dosage: amount of material inoculated at a time and the number 
of inoculations; (3) the time period that elapses before sufficient 
antibodies are formed to make the use of the animal’s serum 
really helpful. 
The preparation of diphtheria antitoxin may be discussed 
under three headings : (1) The animal phase, beginning with the 
Fig. 64.—Rod-like diphtheria organisms, 
magnified more than 1000 times, showing dis- 
tinctly the characteristic unequal staining. 
Emerson, Clinical Diagnosis, J. B. Lippincott Co. TOXINS AND ANTITOXINS 
91 
inoculation of the animal and extending to the withdrawal of 
blood containing the helpful antisubstances; (2) the separation 
of the serum from the other elements of the blood; and (3) any 
further modification of the serum itself. 
(1) The Animal Phase.—The horse selected for the produc- 
tion of antitoxin is injected at short intervals, (every two days) with 
diphtheria toxin. This toxin is nowadays partly neutralized with 
some diphtheria antitoxin previously made by another horse. As 
explained on page 99, this makes it possible to give a large dosage, 
and so secure a greater 
or stronger reaction by 
the horse—more anti- 
toxin in each cubic- 
centimetre of his 
blood. Beginning with 
a dose of about 3,000 
units of toxin, or 10 
minimum lethal doses 
for the guinea pig, the 
dose is gradually in- 
creased until on the 
last injection the ani- 
mal may be given 
about 500,000 units. 
(It is impossible to 
describe the dosage or 
treatment accurately 
in ordinary terms of 
bulk, because the strength of the toxin varies greatly; those 
who need some such term of measurement to help them to 
visualize the process, may picture the initial injection as prob- 
ably ranging from 10 to 15 c.c.). By the sixth to eighth 
week the horse is usually producing enough antitoxin to make it 
worth while to withdraw blood for use in the protection of 
human beings. 
The blood is drawn from one of the prominent surface veins in 
the neck of the horse, in which the blood is flowing downward on 
its way back to the heart. Aseptic methods are used both to keep 
the drawn blood sterile and to prevent the horse from becoming 
Fig. 65.—A throat smear from a case of diph- 
theria, fifth day, showing much the same range in the 
diphtheria organisms, Corynebacterium diphtheriae, as 
the pure culture in the preceding illustration. Cave, 
Journal oj Pathology and Bacteriology. 92 
HOW WE DESIST DISEASE 
infected. The skin is cleansed (usually shaven and washed with a 
disinfectant), and a slender, sharp-pointed metal tube is thrust 
upward into this vein, the metal tube being connected by means 
of a sterile rubber tube with a large sterile bottle held below. 
Eight to ten quarts are often taken at a time. When the bleeding 
tube is withdrawn the skin is pinched together by the fingers to 
slow the flow and allow a clot of blood to form at the small punc- 
ture made by the tube. 
The surface is again 
washed with carbolic 
or a similar disinfect- 
ant, and the horse, 
weakened but usually 
without other ill ef- 
fects, is allowed to 
“rest” for several 
weeks before another 
bleeding is made. 
Horses may be bled in 
this way throughout a 
period of two years or 
even longer. Ad- 
ditional doses of diph- 
theria toxin are given 
the horse from time to 
time to increase the 
rate of production of 
antitoxin or to 
lengthen his productive period. During most of this period the 
horse seems quite normal, giving little or no evidence of dis- 
comfort, and may be used for light work at the station or given 
other suitable forms of exercise. In one city laboratory a diph- 
theria antitoxin horse has been used in emergencies for ambu- 
lance work. 
(2) Separation of Serum.—The immune blood drawn into 
sterile bottles is next treated to separate the white and red cor- 
puscles as well as the fibrin from the resulting liquid or serum. 
One of the simplest ways of doing this is to allow the blood to 
stand for twelve to twenty-four hours, in which time it will clot, 
the corpuscles and fibrin forming a reddish jelly-like mass, leav- 
Fig. 66.—The presence of diphtheria-like bac- 
teria, such as the shorter, plumper and more uniform 
“Hofmann’s bacillus” often lead to incorrect diag- 
nosis or interpretation. The above smear made on 
the twelfth day shows the so-called pseudo-diphtheria 
onlv, while the earlier smears, one of which is pictured 
in the preceding figure, showed true diphtheria organ- 
isms. Cave, Journal of Pathology and Bacteriology. TOXINS AND ANTITOXINS 
93 
ing a colorless liquid, the serum, above and around the clotted 
mass of corpuscles and fibrin. 
Quicker results may be secured by means of a beating arrange- 
ment of twisted wires, extending down into the bottle, which is 
placed in it before it is sterilized, lifter the blood is collected 
this beater is twirled by means of the handle extending through 
the neck of the bottle. This motion hastens the separation of the 
fibrin, a large mass of stringy fibrin collecting on the beater, and 
enmeshing most of the white and red corpuscles. 
Up to this point it is relatively easy to handle the blood 
aseptically and maintain its sterility. Filtration through the best 
types of filters is often added, and if further treatment is neces- 
sary to insure sterility, disinfectants may he added. Preference 
is often given to such volatile substances as chloroform which 
evaporate and do not, therefore, complicate matters by intro- 
ducing salts, etc., into the blood. Ultra-violet rays are recom- 
mended by some because they, too, add nothing to the serum. 
When as described in the next paragraph the antiserum is still 
further modified, the treatment (filtering, adding chemicals) to 
insure sterility is deferred until such modification has 
been completed. 
Modified Serums.—The preparation of most antiserums— 
practically all with the exception of diphtheria—stops at this 
point. In all cases where it is practicable, however, further 
treatment should be undertaken to concentrate the antitoxin and 
thus lessen as far as possible the unfavorable effect produced by 
the introduction into the body of foreign proteins from another 
individual. There is a loss of “ protective principles” during 
this process which prohibits such modifying or concentrating 
processes with almost all serums, diphtheria antiserum being the 
outstanding exception. One form of tetanus antitoxin may be 
somewhat modified, but tetanus antitoxin in common with other 
antiserums is generally used as “ straight ” antiserum. ( See also 
Antibody Extracts, p. 71.) 
(3) Further Modification of Diphtheria Serum.—The 
antitoxic qualities of this antiserum are very intimately associated 
with the globulins (euglobulins, pseudoglobulins) in the serum. 
Although TTuntoon has recently shown (See p. 73) that antibodies 
themselves are not euglobulins or pseudoglobulins, it is neverthe- 94 
HOW WE RESIST DISEASE 
less necessary in the ordinary modifications of antiserums to keep 
this association in view; and in each process of the preparation 
of diphtheria antitoxin, such as filtering, the worker must retain 
the part which contains the globulins, especially the pseudo- 
globulins. In some methods there are several different filterings, 
the desired pseudoglobulins being sometimes in the liquid filtrate, 
Fig. 67.—At the right, dialyzing the antitoxic globulin in running water to separate 
from it the inert soluble salts. At the left, one of these parchment bays, through which 
water has passed during its stay in the running water, is being emptied into a receptacle, 
previous to the final filtering and bottling. H. K. Mulford Company. 
sometimes in the solid precipitate. The recent method described 
below is one of the simplest. 
The immune serum is diluted with an equal amount of water 
and a very large amount of ammonium salt (ammonium sul- 
phate) is added until the material is about one-third saturated 
with the ammonium sulphate. This mixture is then heated 
(61° C.) for two hours, and filtered through filter paper. This 
leaves the antitoxin globulins in the precipitate. The liquid fil- 
trate is therefore discarded and the grayish-white precipitate • TOXINS AND ANTITOXINS 
95 
scraped off the filter paper and compressed between many thick- 
nesses of filter paper until most of the liquid is absorbed. This 
also removes much of the salt which was used to precipitate the 
antitoxin. The rest is removed by dialyzing, the nearly dry pre- 
cipitate being placed in a large parchment bag (Fig. 67) and sus- 
pended in running water (flowing tap in a sink) for several days, 
during which time the salts are dialyzed out through the parch- 
Fig. 68—Drying the precipitate containing the antitoxic globulins, by pressing out the 
water. The precipitate is placed between many thicknesses of absorbent filter paper: several 
lots of such precipitate (separated by boards) may be pressed nearly dry in the same press 
as shown in the accompanying illustration. H. K. Mulford. Co. 
ment. Meantime some water passes through into the parchment 
bag, and the putty-like precipitate gradually changes to a brown- 
ish liquid, the modified anti-serum or the antitoxin. (This 
antitoxin may be still further diluted with water, and salts like 
those in human blood added to make it similar to the blood in 
salt content [isotonic].) 
Owing to the long period of treatment just described it is now 
necessary to make sure that no micro-organisms are present in the 
finished antitoxin. Sterility is obtained (1) by using such dis- 
infectants as the cresol compounds or chloroform and (2) by 
filtering. Paper pulp, glass wool, etc., may be used to remove 96 
IIOW WE KESIST DISEASE 
the coarser debris, after which the filtration is completed by 
means of a Berkefeld filter. The antitoxin is now free from 
micro-organisms and also from shreds of fibrin and broken cells 
which might cause death if they passed into the finer capillaries. 
This modified antiserum retains about 70 per cent, of the 
original antitoxic power of the 
original whole serum. Al- 
though some of the antitoxic 
power is thus lost, the resulting 
liquid is so concentrated that a 
cubic centimetre of the original 
blood may be represented by 
but V4 or 7, of a cubic centi- 
metre. Antitoxin given in this 
form, therefore, contains much 
less of the various serum or 
blood proteins per cubic centi- 
metre, and is therefore less 
irritating when injected. 
This antitoxin is stored 
aseptically in large sterile 
bottles until its strength can be 
determined. It is then put 
into small bottles, or preferably 
into syringes ready for indi- 
vidual use, each bottle or 
syringe containing a little more 
than the usual protective dose. 
The amount is indicated by a 
label, which gives the total 
value contained in the bottle or 
syringe, and often also a graduated scale for convenience in 
measuring the proportion of the contents given a patient. If 
kept sealed in a cool dark place diphtheria antitoxin can be kept 
for months without appreciable loss of strength. 
Standardization of Diphtheria Antitoxin.—The strength 
of the antitoxin secured from the horse is determined by 
finding how much of it is needed to protect a medium-sized 
guinea pig against a fatal dose of diphtheria toxin. When that 
amount is determined, it is used as a basis for estimating how 
Fio. 69.—Intravenous injection of 
drugs, serum, etc., is done as shown here. 
In subcutaneous or intramuscular injec- 
tion, no effort is made to strike a blood- 
vessel. Thomas and Ivy, Applied Immu- 
logy. J. B. Lippincott Co. TOXINS AND ANTITOXINS 
97 
much is necessary to protect human beings. For such a large 
animal as man several hundred, or even thousand, times as much 
are necessary, as there is so much more tissue throughout which 
the antitoxin must be distributed to make sure no part is left un- 
protected against the diphtheria toxin, which is being rapidly 
distributed by his circulating blood from the infected area in 
his throat. 
The first step in the process of determining the strength of a 
given antitoxin consists in placing in each of a series of about 
ten test tubes just enough diphtheria toxin to kill a standard-sized 
guinea pig (250 grams) on or by the fourth day. This is often 
spoken of as the minimal lethal dose (M.L.D.) and may be as 
small an amount as 5/100o one cubic centimetre, a very small 
amount indeed. To each of this series of tubes is added progres- 
sively increased amounts of the antitoxin to be standardized. 
The combined contents of each tube is then inoculated into a dif- 
ferent guinea pig, each properly labeled to. correspond to the 
tubes so that we can tell by the fate of the guinea pigs exactly 
where in the series the antitoxin just neutralized the toxin. All 
the guinea pigs having enough or more than enough antitoxin 
will recover. (Care is taken, of course, to use healthy guinea pigs 
of the same relative size, vigor, etc.) 
This amount of antitoxin that will protect a guinea pig is 
much too small for a workable unit (speed and accuracy of meas- 
urement, etc.), and since man will need so much more antitoxin 
than that minute amount we use one hundred times the guinea 
pig amount as a “ unit ” of diphtheria antitoxin.* Even this 
makes too small a bulk for a satisfactory working basis, for horses 
may yield one thousand or more such units of antitoxin to one 
cubic centimetre of blood, though 800 units is considered high. 
(See p. 76.) 
Dosage.—The amount of diphtheria antitoxin given a person 
varies with such conditions as the age or size of the individual, 
the stage of the disease, and its relative severity; and the dose also 
varies in size, depending upon whether it is given to aid an indi- 
vidual actually ill with the disease or merely to prevent him from 
contracting the disease. 
*A unit of tetanus antitoxin is 1,000 times the amount needed to 
protect a large guinea-pig (350gin.) against one fatal dose of tetanus toxin. 98 
HOW WE RESIST DISEASE 
As a preventive only, the usual dose varies from five hundred to 
one thousand units for an adult; this gives an immunity 
lasting about two weeks, though it may last 30 days. In 
epidemics, the fact that injected antibodies disappear rather 
rapidly from the body makes it advisable to repeat the treatment 
for nurses or others subject to re-exposure every 10 to 14 days 
until the danger is past. (See p. 201.) 
In treating actual cases of diphtheria the dosage is larger, 
especially if treatment has been delayed. A delay of even a few 
hours only may be serious, for toxin makes very stable combina- 
tions, and once it has combined with the tissues, the results can- 
not he neutralized by increasing the amount of antitoxin given. 
The amount of antitoxin given varies also with the method of ad- 
ministering it—intravenous injection being 500 times as effective 
as subcutaneous injections would be, consequently the latter 
method is no longer recommended. Doses usually vary from 5,000 
to 10,000 units when given on the first day of the disease; in the 
very severe attacks 15,000 to 20,000 units might be used, but 
extremely large doses (100,000 units) are not now considered 
advisable; if beneficial results with the smaller doses are not 
evident in a short time (eight hours) the treatment is repeated. 
Preventive Treatment Using Toxin.—The protection ob- 
tained by injecting a toxin is due to an active immunity produced 
in response to toxin stimulation. This is, of course, essentially the 
same process as when the results are obtained by giving an ordi- 
nary vaccine made of living or dead bacteria, and therefore pro- 
tection against diphtheria by the injection of toxin would be 
properly discussed under vaccines, page 174. 
This toxin treatment, however, is now commonly spoken of as 
a toxin-antitoxin treatment; and since the word antitoxin in this 
connection always raises a question in the student’s mind, it is 
described here to explain the antitoxin part of the procedure. 
On page 91 note that the horse was not given toxin only—but 
a combination of toxin and antitoxin, for the reasons stated there. 
Students often find this difficult to understand. What, they say, 
is the use of adding antitoxin if it only neutralizes part of the 
toxin particles—why not give only the toxin represented by the 
difference, omitting the antitoxin altogether? 
Here we come to one of the weak places in the receptor theory TOXINS AND ANTITOXINS 
99 
—of which the student was warned. According to Bordet, the 
combination of toxin and antitoxin is probably more like the 
well-known combination seen when starch and iodine are mixed 
together. A large amount of iodine can be used, combining with 
each starch grain, and making the grains blue black in color. If 
less iodine is used each grain combines with less iodine, becoming 
merely blue in color; if still less iodine is used, each grain again 
has correspondingly less iodine combining with it and becomes 
only light blue or pale lavender in color. 
In toxin-antitoxin mixtures, the antitoxin seems to combine 
with toxin in this same way, each toxin particle being slightly 
modified by the relatively small amounts ©f antitoxin present 
(See Fig. 88?); therefore, in a toxin-antitoxin mixture in which 
the antitoxin is not great enough to neutralize all of the toxin, 
the toxic effects are due not to a small unneutralized or uncom- 
binecl excess of the original toxin but to the very large amount of 
weakened toxins at work. It is possible—to carry on our illus- 
tration—to use so little iodine or so much starch that some of the 
starch grains are wholly unaffected. This would be true with 
toxin and antitoxin combinations, of course, and in such treat- 
ment the relative amounts of toxin and antitoxin given must be 
very accurately determined; with too little antitoxin the indi- 
vidual is not properly protected, and with too much antitoxin, 
the mixture is too inert—not sufficiently irritating to arouse the 
active immunity responses for which it was given. 
This toxin-antitoxin treatment, it is evident, causes the indi- 
vidual to make his own protective substances just as the horse 
does, and is used only where it is probable that there will be 
sufficient time for the individual to make his own antibodies. 
In actual illness we cannot wait for the individual to develop 
active immunity, and therefore passive immunity is secured by 
giving antitoxins. In sudden outbreaks the children or other 
individuals directly exposed should receive antitoxins, the toxin- 
antitoxin treatment being given them later when the immediate 
danger of direct infection is at an end. Those less directly in 
contact with the first case or cases will, as implied in the beginning 
of this paragraph, be given the toxin-antitoxin treatment. 
When time is not an important consideration it is much 
cheaper and much simpler to have each individual make his own 100 
HOW WE RESIST DISEASE 
antitoxins, for all that is needed is to inject into each individual 
a little diphtheria toxin, using with it but a fractional amount of 
the expensive antitoxin that would otherwise he required to give 
passive immunity. This is not only cheaper, hut infinitely 
better in every way as the passive immunity conferred by anti- 
toxin lasts but two to four weeks oidy, whereas the active im- 
munity resulting from toxin-antitoxin treatment persists for 
years and perhaps for life. 
The Schick Test.— It is possible to determine by a skin test 
whether or not an individual is susceptible to diphtheria— 
whether or not he has antitoxin in his blood that will protect him 
against an attack of that disease. This test, which is called the 
Schick test (PI. 1) is made by injecting a tiny amount of diph- 
theria toxin (about one-tenth of a cubic centimetre, or more 
definitely, 1/50th of a minimal lethal dose for a 250-gram guinea 
pig) beneath the outer layer of the skin of the forearm. If there 
are no antitoxins present to neutralize the toxins injected, the 
tissues round about will be irritated by the toxins as shown by the 
formation of a red, inflamed area (Plate I), which appears in 12 to 
48 hours, and is at its height in three to four days; this lasts from 
one to two weeks, and as the inflammation gradually disappears, 
there is a superficial scaling and a characteristic browning of the 
area. But if the individual is immune to diphtheria the antitoxin 
present in his blood will neutralize the injected toxins before they 
can so affect the tissues, and the characteristic swollen red area 
will not be formed; we say, therefore, that this individual gives 
a negative Schick test, indicating that he is immune to diphtheria. 
Pseudo-Reactions in the Schick Test.—In order to interpret 
correctly the result of the Schick test it is necessary to differ- 
entiate carefully between a true Schick reaction and the false (or 
non-specific protein) reaction which appears in some cases. This 
pseudo-reaction seen in persons unusually sensitive to the irritat- 
ing effect of foreign proteins develops in consequence of the 
minute amount of foreign protein necessarily introduced with the 
toxin. The pseudo-reaction may appear alone or in combination 
with the Schick reaction, and it is entirely without significance 
except as a possible source of error in interpreting the Schick test. 
(An irritation due to proteins as such and not to the diphtheria 
toxin may be mistakenly interpreted as due to the toxin.) To Plate I A.—Shick test. Positive reaction of moderate severity 72 hours after intra- 
cutaneous injection of 1/10 of minimal lethal dose of diphtheria toxin. Later, this pa- 
tient’s blood serum was tested and found to contain no antitoxin. When this test is 
negative, no change is noticeable in the skin, for the injected toxin is neutralized, and 
therefore, fails to act as an irritant. Craig and Speese, International Clinics. 
“ r 
Plate I B & C.—- Abraded skin on which was placed one drop of egg albumen; six 
minutes afterwards the area showed as pictured a white wheal K inch in diameter with 
the encircling reddened area. This reaction increased up to 15 minutes; the entire re- 
action in this case disappeared in less than two hours. A control test is shown in C. 
Hess and Levinson, International Clinics. 
Plate I D.—The luetin test for syphi- 
lis. showing (1) a typical reaction (a large 
reddish indurated papule measuring about 
5mm. in diameter) as it appears hours after 
the injection of luetin or killed syphilis or- 
ganisms. 
Hess and Levinson, International 
Cl in ics 
Plate I E.—Cutaneous test for horse 
asthma, showing typical reaction obtained 
with horse dandruff protein; the barely 
perceptible whiter spot above is the nega- 
tive control. 
Courtesy of the Arlington Chemical 
Company. TOXINS AND ANTITOXINS 
101 
guard against this danger a control test should be made on the 
opposite arm at the same time that the Schick test is made, using 
for this control diphtheria toxin which has been heated to destroy 
its toxin content, leaving the inert protein as the only irritat- 
ing substance present. 
Value of the Schick Test.—The Schick test, it can be readily 
seen, is a very helpful one. In epidemics it enables one to pick 
out promptly the susceptible children or nurses and other at- 
tendants and protect them by giving them antitoxins—or if time 
allows, the toxin-antitoxin treatment—thus making the control 
of diphtheria much more possible. Since many people are im- 
mune to diphtheria, it also enables us to save large sums of money 
by determining which individuals do not need treatment, vari- 
ously estimated as 30 to 50 per cent, of babies under two, 40 to 
70 per cent, of the children from 2 to 4 years, 45 to 75 per 
cent, from 4 to 6 years, 45 to 80 per cent, from 6 to 12 years, 80 
to 85 per cent, from 15 to 18 years, 85 to 95 per cent, of adults. 
Zingher states that in institutions and schools the susceptible 
children may be but 20 to 25 per cent, of the total. 
Recent tests with large numbers of public school children in 
several eastern cities have indicated that 30 to 80 per cent, of the 
various school populations were susceptible to diphtheria. With- 
out a word of explanation such a wide range in susceptibility 
might seem to indicate a lack of reliability in the Schick test. 
Age differences as shown by the figures in the preceding para- 
graph enter in; the proportion of girls and boys also affects the 
total percentage for the group, as girls are more susceptible to 
diphtheria than boys. An analysis of the Schick results has 
shown, however, an interesting relationship between the percent- 
age of susceptible children and the general social status of the 
group tested. In New York City institution and school groups 
from the poorer and more crowded areas showed 10 to 20 per 
cent, susceptible children. In other more favored areas the per 
cent, of susceptible children was higher, representative schools 
containing 29 per cent., 41 per cent, and even 67 per cent, sus- 
ceptible children. In three private schools of New Jersey the 
Schick test showed the presence of 73 per cent., 79 per cent, and 
85 per cent, susceptibles, respectively. Children subject to con- 
stant or repeated exposure apparently develop a natural immunity. 102 
HOW WE RESIST DISEASE 
The high susceptibility in the richer schools and neighborhoods 
is explained on the basis of a segregation of the children remain- 
ing susceptible because protected from exposure. 
Toxin-Antitoxin Treatment of Infants.—Since children 
between one and five are more susceptible to diphtheria than any 
other age group (80 to 85 per cent, of the cases and deaths) 
immunity should be developed as early as possible by giving the 
toxin-antitoxin treatment to all children yielding a positive 
Schick test. It was at first thought that this might be done ad- 
vantageously by giving the treatment during the least susceptible 
part of the infant’s life—the first six months. Later work with 
several thousand infants has shown, however, that the toxin- 
antitoxin treatment has very little effect upon very young infants, 
as the presence of the antitoxin derived from the mother pre- 
vents or limits the excitation of such antibodies in the child. This 
inherited immunity (85 per cent, of the newborn give negative 
Schick tests) is usually lost during the first six to nine months, 
though it may persist six to nine months longer. By the second 
year, therefore, children should be actively immunized against 
diphtheria by the toxin-antitoxin treatment, thus forestalling 
the possibility of infection during the most susceptible part of the 
pre-school period. 
Results of Toxin-Antitoxin Treatment.—The results are 
most satisfactory, both with regard to the higher degree of im- 
munity developed and the total lack of untoward results, even 
where many thousands of children have been so treated, as in New 
York City. The doses are small in bulk, consisting of one or two, 
or less often, three injections of one cubic centimetre of the toxin- 
antitoxin mixture given subcutaneously in the arm. The mixture 
is so slightly toxic that when five cubic centimetres are given a 
guinea pig there results a local induration at the injection site, 
which is followed by a later paralysis, but never by the “ acute 
death ” of the animal. 
Immunity develops in three to twelve weeks, varying with the 
dosage—that is, with number, size, and proportions of toxin- 
antitoxin doses. If individuals do not yield negative Schick tests 
after the first treatment, full immunity is usually developed by a 
second series of treatments. As high as 85 to 100 per cent, im- TOXINS AND ANTITOXINS 
103 
munity has been obtained with a single series of injections. In 
one institution of over 1,000 children 81 per cent, gave negative 
Schick tests after single injections. 
The immunity thus developed is quite lasting. Eetests on 
thousands of children in New York City have shown the im- 
munity still present after 3, 4 and even 5 years, and experienced 
workers in this field feel that the immunity thus developed will 
probably persist throughout life, and that there is every hope 
that diphtheria may be eradicated as completely as smallpox. 
Diphtheria Antitoxin.—During the period of forty years 
that diphtheria antitoxin has been in use there has been more or 
less discussion of the ill effects following its use. These reports of 
ill effects have been greatly exaggerated. According to Park, in 
140,000 cases so treated in New York City, there have been but 
two deaths which were due to the antitoxin; and only about one 
in 10,000 treated individuals develops alarming symptoms. 
Disturbances following the use of diphtheria antitoxin are 
due entirely to the effect of the foreign protein in the horse serum 
and not to the antitoxins it contains. For “ serum sickness ” and 
the occasional ill effects of antitoxins as they are prepared to-day 
see the chapter on Anaphylaxis. 
Diphtheria antitoxin has reduced the mortality from diph- 
theria at least 60 per cent. (Fig. 70). In the pre-antitoxin days, 
according to Zingher, the mortality w~as 70 to 75 per cent.; with 
the introduction of antitoxin in 1894 the mortality has gradually 
been reduced to 10 per cent., a more or less constant figure for the 
past eight to ten years. Diphtheria antitoxin has been called “ a 
specific and sovereign remedy/’ and deservedly so, for if used 
during the first twenty-four hours of the disease it is almost uni- 
formly successful. The persistently high mortality of 10 per cent, 
is explained as due to “ delayed application for treatment on the 
part of the patient, delayed recognition of the disease on the part 
of the physician, or to both of these factors.” 
Tetanus Antitoxin.—Tetanus antitoxin is, as described on 
page 93, usually whole serum, though a modified (or globulinized) 
serum is also commercially available. Tetanus antitoxin is pro- 
duced in horses, which are injected much as is the case with the 
diphtheria antitoxin horses, with gradually increasing doses, until 104 
HOW WE RESIST DISEASE 
ill a few months the horse is being given 100 c.c. of strong tetanus 
toxin, a surprisingly large amount when one considers that 
tetanus toxin is one of the most poisonous substances known— 
6/i,ooo,ooo °f a gram killing a large (350 gram) guinea pig. Be- 
Fig. 70.—The effect of antitoxin upon the diphtheria death rate in New York State. 
Health News, 1914, completed through 1921 by information supplied by New York State 
Department of Health. 
cause tetanus toxin is such a strong poison, horses are not bled 
until at least two weeks after the last injection of toxin, so as to 
make sure that all the injected toxin has disappeared from the 
blood and cannot therefore he transferred to man. 
Treatment.—Since tetanus antitoxin is absorbed slowly, and 
since, to be effective, it must reach the central nervous tissues, it TOXINS AND ANTITOXINS 
105 
is better to give it intraspinally or at least intravenously, in treat- 
ing actual cases of infection. 
At present tetanus antitoxin is used mostly as a preventive, 
in the treatment of wounds which are likely to contain tetanus 
organisms. In treating such wounds two things must be kept in 
mind: (1) that the intestines of the larger domestic animals 
harbor tetanus organisms, and that, therefore, street, road and 
farm soil is very likely to contain tetanus spores; and (2) that the 
tetanus organisms grow best where little oxygen is present, and 
that spores left in the recesses of jagged wounds made by ex- 
plosives (fireworks, explosives used in modern warfare) are often 
sealed up in such recesses by the clotting blood forming little 
anerobic pockets favorable for their development. The present 
low rate for tetanus following Fourth of July accidents, and the 
relative absence of tetanus in the Allied forces in the recent war 
are both due to the early or prompt use of tetanus antitoxin. As 
a matter of routine, soil-infected wounds were treated with anti- 
toxin, at least 1,000 units (See p. 97) being injected in the wound 
region. Since tetanus antitoxin disappears quickly from the 
body (8-10 days), a second treatment is given at the end of a 
week, and another usually during the third week. 
A very large part of the tetanus antitoxin used abroad during 
the first part of the recent war was made in the United States, 
some by commercial laboratories, but a very large part by the 
Department of Health Laboratories of New York City. Soon, 
however, hundreds of horses were manufacturing tetanus anti- 
toxin on the other side of the Atlantic, using for the purpose the 
more productive tetanus cultures sent by the New York 
City Department. 
In ordinary civil practice, where wounds are usually more 
promptly cared for, the preventive treatment, 1,500 units, is 
usually given subcutaneously or intramuscularly. 
Antitoxin against Gas Gangrene.—Occasionally soil-borne 
organisms other than tetanus cause serious wound complications. 
One of the worst offenders is Welch’s bacillus (Fig. 71), or the gas 
gangrene bacillus, which forms a virulent toxin or poison, de- 
stroying muscle tissue and causing a gangrenous condition of 
the area infected. Against this organism, an antitoxin (anti- 106 
HOW WE RESIST DISEASE 
serum) has recently been prepared which has been successfully 
used in many cases. Where wounds are infected with other septic 
organisms (malignant edema organism, Fig. 72; Pasteur’s 
“ vibrion septique ”) the appropriate antitoxin should he used. 
Unfortunately infections are not always due to a single type of 
such organisms. Besides, various aerobic organisms, such as 
hemolytic streptococci, are often important disintegrating or 
toxic agents, and their presence often adds greatly to the diffi- 
culty in securing effective antiserums for treatment. 
The so-called antitoxins used in this connection are anti- 
serums—whole serums; and 
are given in preventive work 
much as tetanus antitoxin is 
used — intravenously and 
also in frequent injections 
around the wounded area. 
In treating infected war 
wounds, more use than usual 
was made of the microscope 
findings, for the microscope 
was used not only to aid in 
determining the type or 
types of organisms present, 
hut to show the progressive 
changes in the infected 
areas; these findings were 
made not only to determine the subsequent antiserum dosage, 
but to indicate when such areas were sufficiently free from organ- 
isms for open wounds to be closed with safety. 
The relative infrequence of such wound infections in civil 
life and the variety of organisms related to all such infections 
make it unlikely that we will ever have—in this connection—any- 
thing like the satisfactory results now obtained with diph- 
theria antitoxin. 
Other Antitoxins.—Antitoxins against botulism (See p. 89) 
have not been put upon a successful basis. 
Shiga’s dysentery bacillus (Fig. 52), the most toxic of the 
dysentery and para-dysentery group, forms a toxin against which 
Fig. 71.—The gas gangrene bacillus, 
Clostridium Welchii (Barulus Welchii) from 
tissue. Bull. TOXINS AND ANTITOXINS 
107 
an antitoxic horse serum is produced, which has reduced the mor- 
tality of that type of dysentery in Japan from about 30 per cent, 
to about 10 per cent. AVhile Shiga’s dysentery is less common in 
the L nited States than in J apan, it is one of the two most common 
Fio. 72.—A three-day culture of malignant oedema organisms; most of the 
spores are centrally placed, causing a bulged appearance. Adamson, Journal of 
Pathology and Bacteriology. (Photograph by C. Powell White). 
types of dysentery here; there have been recent indications of 
an increase in this type of dysentery, especially in the south- 
ern States. 
STUDY SUGGESTIONS 
1. Wliat are toxins? 
2. How do old or changed toxins affect the strength or toxicity of a 
toxin? How would the presence of toxoids in toxin preparations 
affect the determination of the strength of an antitoxin? 
3. Name three diseases which are characteristically toxin diseases, 
giving one definite associated effect or symptom for each. 
4. Describe the method of producing diphtheria antiserum in horses. 
5. Describe one preparation used in treating disease in which immune 
blood undergoes special treatment—something more than clotting 
and drawing off of the serum. 
6. Give two ways in which immune serums may he made sterile without 
any attendant formation or retention of solid particles. 
7. How is diphtheria antitoxin standardized? 
8. Describe the Schick test. 
0. Describe the toxin-antitoxin treatment for diphtheria. 
10. Write in semipopular form (for parents of school children) a state- 
ment presenting the advantages to be gained by the toxin-anti- 
toxin treatment against diphtheria. 108 
HOW WE RESIST DISEASE 
11. In a family containing two young children who slept together and a 
third older child who was away on a visit, one of the younger 
children “came down” suddenly with diphtheria. W’liat treat- 
ment would you advise for each? If the absent unexposed child 
returned during the illness, what protective or preventive treatment 
should be given him? 
12. In the City of Washington there were one year 143 cases of lockjaw 
or tetanus from Fourth of July wounds; in the ten years follow- 
ing when the sale of fireworks was prohibited no cases developed 
following the Fourth of July celebrations. Explain the difference 
in these figures, including in your answer the probable relationship 
of (1) the actual number of surface or skin breaks made on 
the Fourth, (2) the type of wounds formed, and (3) the sub- 
stances gaining entrance into the body. 
13. If the blood taken from a horse shows 700 diphtheria antitoxin 
units to a cubic centimetre of serum, and if the modified form of 
the serum (described on page 93) retains 70 per cent, of the 
original antitoxic power, how many cubic centimetres would have 
to be injected into a patient needing 10,000 units? CHAPTER V 
AGGLUTININS AND PRECIPITINS 
General character of agglutinins 
Specific and group agglutinins 
Relation to other antibodies 
Agglutinins and Precipitins 
Methods of demonstrating- 
Visible to naked eye 
(macroscopic) 
Agglutination 
Precipitation 
Microscopic agglutination 
' Agglutinins present in blood of patient 
Types - 
Agglutination of or- 
ganisms obtained 
from body of pa- 
tient 
Methods 
Difficulties 
Disease 
Negative results 
Diseases so tested 
Tests 
Relation to serum standardization 
Animal relationships 
Blood transfusion 
Legal applications 
Protein differentiation 
Although bacterial agglutination by the blood (or serum) of 
immune animals has been known for about thirty years, it is only 
recently that it has been positively demonstrated that such agglu- 
tination really takes place in the body (Fig. 73) and is not merely 
a laboratory phenomenon. And although agglutination tests have 
for years been a routine laboratory procedure of undeniable value 
in diagnosing disease, especially typhoid, it is only within the last 
few years that we have had incontrovertible evidence that aggluti- 
nation is a most important preparatory step in the destruction 
and in the elimination of bacteria from the body. 
According to Bull, “ in order that the bacteria may be 
promptly removed from the blood stream it is requisite that they 
be first agglutinated, which condition is also required in order 
109 110 
HOW WE RESIST DISEASE 
that they he destroyed en masse within the organs, a process 
achieved, apparently, chiefly through phagocytosis.” 
Bacterial Agglutination.—When a loopful of bacteria, of a 
given kind such as cholera, is properly diluted and mixed with 
a drop of the blood of an individual recently recovered from that 
disease, the bacteria show two distinct changes: (1) All move- 
ment ceases—true motility as well as Brownian movement; and 
(2) all the organisms stick together in clumps or small 
masses, as if they have become sticky or glutinous, hence the 
term, agglutination. 
Fin. 73.—These photographs show that agglutination is not merely a laboratory phenom- 
enon but actually occurs in the animal body. A rabbit previously made immune to typhoid 
by injections of Bacterium typhosus was later given a heavy injection of the same organism. 
The left photograph of blood taken from the heart 30 seconds later shows clumps of bacteria 
and indicates how rapidily agglutination took place. The agglutinated cocc in the photo- 
graph on the right were from the blood of a rabbit treated similarly with pneumococcus 
organisms. Photograph, Bull; Broadhurst, Home and Community Hygiene. 
This clumping or agglutination is not a vital phenomenon or 
response because it takes place with dead as well as live bacteria. 
It is a delicate phenomenon occurring in very weak dilutions, and 
the real cause is far from clear. It may be hastened or inhibited 
by very slight chemical differences, such as variations in the 
amount of salts, acids or alkalies present, and is usually vaguely 
described as a “ chemical-physical process involving the bacterial 
cell and an agglutinating factor present in the serum,”oi\ some- 
what similarly, as an electro-chemical phenomenon. AGGLUTININS AND PRECIPITINS 
111 
Agglutination itself does not kill bacteria, though it does lead 
to their destruction, because these agglutinated clumps do not 
make their way so readily through the tiny capillaries, and are, 
also, filtered out or held back in such glands as the lymph nodes 
and spleen, being therefore, much more rapidly captured and 
destroyed by the white corpuscles. 
Agglutination a Specific Phenomenon.—One of the oldest 
facts known about these agglutinating substances or agglutinins is 
that they are specific; for example, the blood of a person having 
typhoid fever will agglutinate typhoid bacteria and not cholera 
organisms; while the blood of a cholera patient will agglutinate 
cholera bacteria, and not typhoid. 
This specificity makes it 
possible to diagnose disease 
by testing for agglutination. 
If the bedside or clinical 
symptoms of the patient 
indicate typhoid fever, the 
diagnosis can be made cer- 
tain by showing that the 
blood of the patient agglu- 
tinates typhoid bacteria. 
(See p. 114.) 
Group Agglutinins.— 
While this action is specific, 
related organisms, such as 
the various typhoid types, 
are enough alike to respond 
in a general way to the agglutinins made against any one of 
the related group. For example, in paratyphoid fever due to 
the so-called paratyphoid B organism (Fig. 74), the blood of the 
patient not only agglutinates the paratyphoid B organism, but 
may also agglutinate paratyphoid A and ordinary typhoid as 
well. (See also p. 112.) 
This group relationship does not, however, make diagnosis 
impossible, for though as described in the paragraph above the 
blood of the paratyphoid B patient may agglutinate all of the 
three types of bacteria, it does so in varying degrees; this blood 
Fio. 74.—Para-typhoid B bacteria broth 
culture (x 700). Sands. 112 
HOW WE RESIST DISEASE 
may agglutinate the “ paratyphoid B ” organism although it is 
diluted as much as 5,700 times, but it will not certainly aggluti- 
nate typhoid organisms in dilutions of more than 120, or “ para- 
typhoid A ” in dilutions of more than 10. Similarly, the blood of 
an individual immune to typhoid may agglutinate typhoid bac- 
teria in dilutions of 10,000 or more, while the dilutions causing 
the agglutination of related organisms may he as low as one to 
1,000 for the paratyphoid organisms, or one to 100 for the 
colon bacterium. 
There are occasional exceptions to these differential results; 
e. g., the serum of a horse immunized to one of the dysentery 
organisms also possessed the power of agglutinating the colon 
bacillus when diluted 10,000 times. Less often still such excep- 
tions may he found as the 
agglutination of unrelated 
organisms, illustrated by the 
agglutination of a variety 
of Proteus vulgaris (B. pro- 
teus vulgaris) (Fig. 76), by 
the blood of typhus fever 
patients. (Seep. 123.) Such 
exceptions are, however, not 
common, and diagnosis 
based on agglutination can 
safely be made by using 
dilutions higher than the 
group or cross-agglutination 
strength, e.g., dilutions 
above 1,000 for the typhoid 
serum described in the pre- 
ceding paragraph. 
The agglutinating action of immune blood or serum is re- 
markably prompt and vigorous. That, in fact, is one reason why 
experimenters did not earlier demonstrate that agglutination does 
occur in the body. The second reason is that the white corpuscles 
take in and destroy these clumps with remarkable celerity, and 
therefore the agglutinated clumps as such were not found by 
workers, because they waited too long (hours or even days) for 
the clumping to take place before drawing blood for examination. 
Fig. 75.—Bacterium co'i, an organism 
common to the intestinal floralof man and the 
larger domestic animals. Williams, Brown and 
Earle. AGGLUTININS AND PRECIPITINS 
113 
The accompanying photograph (Fig. 73), shows typhoid bacteria 
clumped by the blood of a rabbit which had been made immune 
to typhoid by several earlier injections of typhoid bacteria; after 
immunity had thus been established, the rabbit was injected with 
a heavy dose of typhoid bacteria which were immediately ag- 
glutinated as shown by this photograph of blood drawn thirty 
seconds after the bacteria were injected. 
No practical modification or concentration of antiserums con- 
taining agglutinins has yet been made for therapeutic work, 
although the ag- 
glutinins may be 
present i n almost 
unbelievable 
amounts. (See,how- 
ever, p. 124.) This 
remarkable agglu- 
tinin content of im- 
mune blood can be 
illustrated in several 
different ways. For 
instance, one cubic 
centimetre of pneu- 
mococcus antiserum 
can agglutinate ten 
million bacteria. 
The antiserum 
obtained from ani- 
m a 1 s immunized 
against the Shiga 
dysentery bacteria 
may be active when diluted at least 20,000 times. Recently 
Bull showed with a horse immunized against typhoid that one 
drop of the horse serum could agglutinate all the billions of 
typhoid bacteria grown on four agar slants even when they were 
suspended or diluted in a whole litre of salt solution. 
Agglutinins Not Related to Lysins.—While the action of 
agglutinins is a preliminary step in the destruction of bacteria by 
the white corpuscles, these agglutinins are not to be confused with 
lysins (See p. 49) which acting alone can dissolve and destroy 
Fig. 76.—Proteus vulgaris, much enlarged, (x 2000) 
showing incidentally the flagella which give the power of 
independent movement. Many of the other rod and spiral 
organisms pictured in this text have similar appendages, 
but they have not been stained with the special technic 
necessary to show the flagella. Vincent, American Jour- 
nal of the JJiseases of Children. 114 
HOW WE RESIST DISEASE 
bacteria. Agglutinins may exist in an antiserum independent of 
lysins, and lysins independent of agglutinins, or both may be 
found in the same antiserum. 
Visibility of Agglutination Outside the Body.—Usually, 
as, in typhoid agglutination, the clumps are not distinguish- 
able without the aid of a microscope, and the mixture of 
Fig. 77.—A hanging drop, showing the drop suspended in the chamber under the 
coverglass: to keep the drop from drying up, the contact surface of cover glass and slide are 
sealed with vaseline. 
antiserum and bacteria is made as a hanging drop (Fig. 77), as 
described on page 110 and page 118, and examined with the high 
power of a microscope (Fig. 78). 
Fio. 78.—Left: A hanging drop showing single free-swimming typhoid bacteria. Right: 
the same, except the addition of serum of a typhoid patient has caused the agglutination 
of the typhoid organisms. Thomas and Ivy, Applied Immunology, J. 13. Lippincott Co. 
Sometimes, however, as with meningitis, the clumps of bac- 
teria are large enough to be seen with the naked eye, and the 
mixture is made upon an ordinary flat microscopic slide, which 
is then held between the eye and the light, to enable the worker 
to distinguish the whitish “flakes ” or agglutinated masses. This AGGLUTININS AND PRECIPITINS 
115 
slide-agglutination may also be demonstrated with typhoid, 
cholera, paratyphoid and dysentery organisms. 
In some cases, such as glanders, the results are more easily 
determined when much larger amounts of each material are used; 
test tubes containing the antiserum and bacteria are examined 
for turbidity changes and the final flaking or precipitation of 
the bacteria as they fall out of the solution to the bottom of the 
tube. (See Pig. 79.) This precipitation and the resultant clear- 
ing of the tube contents is essentially the same as the agglutina- 
Fio. 79.—Precipitin test for glanders. Serum from a normal horse was added to the 
glanders bacteria suspension in tube A, negative reaction. Positive results are shown in B, 
(occult glanders) V (nasal glanders) and 1), (chronic farcy or glanders), where as indicated by 
arrows, a cloudy ring is seen at the point of contact of the bacterial suspension and the 
serum. Mohler and Eichhorn Bureau An. Ind., U. S. Dept. Agriculture. 
tion observed in the minute amounts used on microscope slides. 
As used in routine test work it may be a much slower process, 
however: one to three hours in the precipitin test for typhoid, 
and seventy-two hours in the usual routine precipitin test 
for glanders. 
Precipitins.—The action of agglutinins and precipitins is es- 
sentially the same; the effect on large particles, such as bacteria, 
is visible as agglutination, and the effect on small particles, such 
as colloid particles or proteins in solution is indicated by the 
resulting clouding and precipitation. Precipitins like agglutinins 
are specific; a precipitin formed against a given protein, such as 
human milk, for example, causes precipitation with human milk 116 
HOW WE IIESIST DISEASE 
and not with other proteins or even other kinds of milk, such as 
cow’s milk. 
While the principal theories and procedures accepted for ag- 
glutinins are applicable to precipitins, there are, nevertheless, 
important differences which can not be completely described here. 
The most important for our purposes are the two following: 
(1) To demonstrate precipitins we must be able to secure a clear 
fluid containing the related protein ; this is not always possible, 
and limits decidedly the number of diseases in which precipitin 
tests can be made. (2) Another reason that precipitins are less 
used in diagnosis is that precipitins are not easily demonstrated 
Fig. 80—A series of tubes showing precipitin reactions against 
pneumococcus organisms ; left negative; to right, varying degrees of pre- 
cipitation with varying dilutions of immune serum. H. K. Mulford Co. 
ill the serum of the sick, being apparently a much slower response 
than the formation of other antibodies. 
When demonstrable this precipitating effect may be observed 
with bacterial extracts as well as with whole bacteria. It is com- 
monly obtained with “ unformed proteins ” or non-cellular pro- 
teins, such as milk or serum. For further discussion of precipi- 
tins see Fig. 8b and page 126. AGGLUTININS AND PRECIPITINS 
117 
Tests Based on Bacterial Agglutinins and Precipitins.— 
Tests for agglutinins (and precipitins) may be used to show sev- 
eral different things: (1) That an individual is developing a given 
disease, having already begun to form agglutinins against that 
particular species of bacteria; there may be a gain of several days 
by using this method of diagnosing a disease. (2) Agglutinin 
tests are also valuable during the active stages of a disease, par- 
ticularly in cases where the disease develops atypically, as often 
occurs in typhoid, thus delaying the possibility of' diagnosis by 
the usual clinical evidences. (3) Agglutination tests are also made 
to identify the type or variety of organism causing the disease. At 
Fio. 81.—Plate3 showing typhoid colonies. A diluted sample of human feces was 
added to these two plates, containing the usual agar plus a dye, brilliant green, which allows 
typhoid to develop while inhibiting most of the other intestinal bacteria. Even in these 
some of the inhibited effects may be seen,as the typhoid colonies are much smaller in the 
right hand plate containing the larger amount of green dye. Photographs by Heins from 
plates made by the Bureau of Laboratories, Health Department of the City of New York. 
least four distinct types of pneumococcus organisms are recog- 
nized in pneumococcus infections. If an antiserum is to be given, 
it should be an antiserum made in response to and against that 
particular type of pneumococcus. (See p. 80.) (4) In carriers, 
such as typhoid carriers, the immunity and continued good 
health of the carrier is no doubt partly due to the antibodies he 
continues to produce during the persistence of the typhoid bac- 
teria in the intestinal tissues, bile duct, etc. Suspected carriers 
may be cleared—or the suspicions concerning them may be con- 
firmed—by such agglutination tests, even months or years after 
apparently complete recovery (See p. 56). 
The tests (See also p. 121) involving the use of specific agglu- 118 
HOW WE BESIST DISEASE 
tinins or proteins are of two different kinds: (1) In the first 
kind the individual’s blood is examined to see if it will agglutinate 
or precipitate a known species of bacteria. The presence of such 
reacting substance in his blood is taken as evidence that the spe- 
cific causal organisms are or have been present and are responsible 
for the production of those reacting substances. (2) In the second 
kind of test, the suspected organism is isolated in pure culture 
(Fig. 81) from the infected area (throat, feces, blood, etc.), and 
its identity is proved by its agglutination or precipitation with 
known antiserums—antiserums obtained from another known to 
have that particular disease. 
Each of these two kinds of tests is obviously just the reverse 
of the other. In the first kind as described above, the serum of 
the patient is the unknown factor and the laboratory organism is 
the known factor. In the second kind, the serum is the known 
factor and the organism of the patient is the unknown. These 
two types of tests may be more briefly contrasted as 
(1) Patient’s or unknown serum against known organism. 
(2) Patient’s or unknown organism against known serum. 
Both kinds of tests may be made in a given disease, as in 
typhoid. The blood is examined to see if typhoid agglutinins are 
present. Blood is collected from the ear lobe, finger or any con- 
venient place, in capillary tubes and allowed to stand until the 
serum has separated; or, more simply, a few drops of blood may 
be dried upon a clean glass slide, though this cruder method is 
questioned by many. The blood or serum thus obtained is diluted 
with physiological salt solution, and typhoid bacteria are added 
to see if agglutination occurs. If the result is positive (the 
typhoid bacteria being agglutinated), no other test is necessary. 
Should the result be negative, the second kind of test should also 
be tried. In that test a small amount of the fecal discharge is 
diluted, and varying amounts spread over agar plates to allow the 
typhoid bacteria to develop (Fig. 81). Their detection is often 
aided by adding to the agar such a dye as “ brilliant green,” which 
inhibits most types of intestinal bacteria, while allowing typhoid 
to develop. The colonies developing on such agar plates are 
studied, and those having the characteristic typhoid appearance 
are selected for testing against known agglutinins; bacteria taken 
from these colonies are mixed with an antiserum known to contain AGGLUTININS AND PRECIPITINS 
119 
agglutinins for typhoid bacteria. If the bacteria thus obtained 
are agglutinated it is thereby demonstrated that the individual 
is harboring typhoid bacteria. If, in any given case, negative 
results are obtained by this test also, one or both tests must be 
repeated as long as any doubt exists as to the cause of the disease, 
more conclusive evidence ordinarily being obtained as the 
disease progresses. 
Negative Results.—Negative results here as elsewhere, are 
never conclusive. The blood will not give a positive test for 
agglutinins until a certain 
borderline of agglutinin pro- 
duction has been reached. 
A negative result may mean 
only that the individual has 
not yet formed enough ag- 
glutinins to show up in such 
a test. Since people vary 
greatly in their degree of 
resistance to invading or- 
ganisms, an individual may 
continue to give negative 
results day after day—and 
even throughout the attack. 
It is not difficult to under- 
stand that even in serious 
illness the agglutinin tests 
sometimes give only nega- 
tive results; the agglutinins 
formed are insufficient to protect the individual or to show up 
in such laboratory tests. 
The tests depending upon the isolation of the causal organism 
have their special difficulties also. Other organisms present in 
the material examined (sputum, feces, etc.) may outgrow the 
ones searched for. The causal organism may not be present in the 
very small amount necessarily used in making the agar plates 
(Fig. 82). Sometimes, as in typhoid, where the organisms de- 
velop in glands in the lining layers of the intestine, and are 
irregularly ejected into the intestinal cavity, they may not show 
up in the fecal material even though samples are taken on several 
Fig. 82.—This plate, made from the 
same fecal sample as the preceding, shows 
only Bacterium coli, because such a weak dilu- 
tion was made that only the more numerous 
Bact. coli were represented in the amount used. 
(Endo’s medium). Photograph by Heins from 
plate made by the Bureau of Laboratories, 
Health department of the City of New York. 120 
HOW WE RESIST DISEASE 
successive days, and examined by the most careful and elab- 
orate technique. 
Other Difficulties of Technique.—As mentioned earlier, 
group agglutinations may mislead the investigator unless the dilu- 
tions are properly made (p. 111). Slides and other materials 
should be carefully prepared or cared for, as slight amounts of 
acids, alkalies, and salts may mislead the worker by inhibiting 
agglutination or causing a false agglutination. Besides, laboratory 
or stock cultures of bacteria often lose their agglutinating power, 
or vary markedly in the dilution showing agglutination and 
should be checked by known antiserums at intervals; for example, 
one strain fell suddenly from 8,000 to 4,000 in the dilution 
capable of causing agglutination. 
Occasionally non-agglutinable strains of organisms are ob- 
tained even in diseases where agglutination is characteristic; e.g., 
non-agglutinating strains of typhoid have been isolated from the 
spleen, gall-bladder, etc. This resistance on the part of the 
organism probably has a definite relation to its invasiveness or 
virulence, making it less easily affected by the protective sub- 
stances in the body as well as under laboratory conditions. 
Normal Agglutinins.—Another difficulty to be considered in 
such tests lies in the fact that “ normal agglutinins ” may occur, 
as shown earlier for antibodies in general (See p. 62). The new- 
born child often possesses such normal agglutinins, probably due 
to substances transferred with the mother’s blood, as they tend 
to disappear later. Adults may also possess “ normal aggluti- 
nins,” probably explainable by the well-known fact that even in 
health, bacteria may invade the tissues (e.g., the intestinal 
environs, or the portal circulation) and so, probably, excite the 
production of a small amount of agglutinin or other antibodies 
before the invading organisms are wholly overcome and destroyed. 
(See p. 62.) 
All the foregoing difficulties make it necessary that such tests 
as these agglutinin and precipitin tests should be made by re- 
sponsible and experienced people, carefully checked or controlled 
wherever possible. It is also essential that the result of such tests 
should be considered in combination with the physical or 
clinical evidence. 
Diseases Diagnosed by Agglutination Methods.—Among AGGLUTININS AND PRECIPITINS 
121 
the diseases involving agglutination are such intestinal infections 
as cholera, typhoid, paratyphoid and dysentery. Of these, the 
typhoid test is the most common in our country, and the test 
oftenest used is the first one described on page 118, the direct 
examination of the blood for agglutinins—commonly known as 
the Widal test. Often, however, in typhoid, and very commonly 
in the other intestinal infections named above, the second kind of 
test is used, in spite of the difficultv often incurred (p. 119) in 
isolating the specific causal 
organism. This second test 
may succeed when the other 
fails because agglutinins do 
not always appear early in 
the diseases; they naturally 
follow rather than precede 
the development and multi- 
plication of the invading 
organisms. In typhoid, for 
example, the agglutinins 
rarely appear before the end 
of the first week and often 
not till well toward the end 
of the second week. On the 
other hand, the typhoid 
bacillus is isolated from the 
blood oftener early in the disease than in the later stages. 
Attempts to obtain the organism in culture are often unsuc- 
cessful by the end of the second week or even earlier. 
Agglutinin Tests for Respiratory Diseases.—Three dis- 
eases which affect the respiratory areas—pneumonia, meningitis, 
and glanders—may be diagnosed by agglutination. In pneumonia, 
sputum or material from the naso-pharynx is usually examined 
for pneumococcus organisms, and the type determined by aggluti- 
nation so as to aid in selecting the type of antiserum to be given 
the patient. (See also p. 80 and p. 122.) 
Meningitis carriers are picked out by isolating from the nasal 
cavities meningitis bacteria, which agglutinate when mixed with 
known anti meningitis serum. In actual cases of meningitis, 
serum is drawn from the spinal canal to determine the presence 
Fig. 83.—Pneumococcus organisms, 
stained by Huntoon’s method to show the 
capsules. Huntoon, Journal of Bacteriology. 
Photograph by Dunn. 122 
HOW WE RESIST DISEASE 
of meningitis bacteria, which are positively identified by finding 
that they are agglutinated by antimeningitis serum. Corrobora- 
tive tests (cloudiness, white corpuscles count, sugar, albumin) arc 
also made on the spinal fluid; the spinal fluid and the blood are 
apparently not rich enough in agglutinins to use them in tests 
against known meningococcus organisms. 
In pneumococcus infections, as described elsewhere (p. 80) 
it is important to determine early the type of pneumococcus. This 
may be done in several ways: (1) One method depends upon 
isolating the organism from the sputum, lung exudate, etc., and 
testing small amounts of the pure cultures thus obtained against 
the different types of antiserums—antiserums made by different 
horses against the respective types of pneumococcus. Rapid 
methods of isolation, using special media such as rabbit’s blood, 
have been developed to utilize this method. 
(2) A second method takes advantage of the fact that such 
exudates as the sputum contain substances that can be precipi- 
tated when brought into contact with pneumococcus antiserum. 
In other words, instead of using the bacteria in agglutination 
tests as described in the preceding paragraph, we use liquid ob- 
tained from the areas affected by the bacteria. The sputum is 
treated (heated in normal salt solution, alkaline hypochlorite 
solution, etc.) and a clear fluid is finally obtained. This fluid is 
added to the respective types of antiserum, precipitation occur- 
ring only in the tube containing the related antiserum. This may 
be indicated by a general cloudiness or precipitation or as a 
definite precipitated area, or contact ring ” where the added fluid 
comes in contact with the serum, (much as in Fig. 79). 
(3) The third method of diagnosis is called the mouse inocula- 
tion method. Sputum, containing the pneumococcus organisms, is 
injected into a white mouse (peritoneum) where the organisms 
multiply for 5 to 8 hours. The exudate then obtained from the 
peritoneal cavity is specially prepared (centrifuged, etc.), after 
which the sediment and the supernatant fluid are tested against 
the different pneumococcus antiserums in various ways; the clear 
fluid being used to show precipitation with the different types of 
serum aa described in the preceding paragraph, or the bacterial 
sediment may be used with the serums to show agglutination. 
The glanders test is chiefly made by the first of the above AGGLUTININS AND PRECIPITINS 
123 
methods. To the diluted serum of the horse to be tested dead 
glanders organisms are added. Kesulting precipitation of bac- 
teria (Fig. 79), and final clearing of the supernatant fluid in 72 
hours or less is taken as a positive result. Although glanders is 
usually an infection of horses, the disease may occur in other 
domestic animals and also in human beings. 
As stated earlier, Proteus vulgaris, (B. proteus), an organism 
apparently not at all related to typhus fever, may be used to 
diagnose typhus fever. Since the causal organism of typhus fever 
has not yet been definitely determined this is a fortunate coinci- 
dence, and the Proteus organism (strain 19), in dilutions of 1 to 
50 or over, is at present satisfactorily used with the patient’s 
serum in testing for typhus fever. 
Whooping cough is not diagnosed by agglutination tests, 
although the pertussis bacterium can be readily agglutinated by 
rabbit antiserum. This is due to the fact that the blood of human 
cases is not rich in agglutinins. The opposite form of the test— 
the patient’s organisms tested against antiserums known to be 
rich in agglutinins, such as the rabbit antiserum—is not generally 
used either, because the pertussis bacterium is only with difficulty 
distinguishing from other bacilli common in sputum. (See lysin 
test for whooping cough.) 
Agglutination Tests in Other Diseases.—Agglutination 
tests are used for certain diseases in addition to those just de- 
scribed. In Malta fever, the patient’s serum is tested against 
cultures of thecausal organism,Bacterium melitensis (Micrococcus 
melitensis) ; agglutination when the patient’s serum is diluted 
1000 or more times indicates Malta fever. 
In tuberculosis, agglutination tests have not been found of 
any real value; the dilutions used are much lower than with any 
other infection—but one to 10 or 15. In gonococcus infections 
agglutination tests are not used for diagnosis, though the various 
strains of gonococcus may be differentiated by such tests in much 
the same way as we type the pneumococcus strains. We are, how- 
ever, just attacking the immense task of typing the various 
disease organisms. 
Standardization of Antiserums.—While the abundance of 
agglutinins in a given antiserum is indication of good body re- 
action, the amount of agglutinin bears no definite or constant 124 
HOW WE RESIST DISEASE 
relationship to other anti-substances, and measurement of the 
agglutinins present is not an exact measurement of the whole or 
total protective value of a serum. However, in diseases in which 
agglutinins are characteristically developed, a good antiserum is 
rich in agglutinins;.and in treating such diseases, it would there- 
fore be sensible to discard any antiserum not coming up to a 
given agglutinin titer or strength. Commercial typhoid, men- 
ingitis, and dys- 
entery anti- 
serums may, 
therefore, be 
described in 
terms of ag- 
glutination 
strength, espe- 
cially dysentery 
antiserums (See 
p. 138). 
Agglutinins 
Against Other 
Types of Cells. 
—Bacteria are 
not the only 
cells which can 
stimulate the 
production of 
agglutinins and 
orecipitins. 
Practically any 
foreign cells 
(e.gwhite corpuscles, red corpuscles, gland cells) can cause the 
production of such antibodies when injected into other kinds of 
animals. Indeed the production of such antibodies may be taken 
to indicate that the cells inducing it are foreign. To illustrate: 
a guinea pig will not form antibodies if injected with any of his 
own tissues (except possibly the eye lens protein), nor, normally, 
if injected with red blood cells or other tissues of other guinea 
pigs. But antibodies are formed by the guinea pig following 
the injection of red blood cells or other tissues of other kinds 
Fig. 84.—Precipitation tests for human blood. Tubes 
1 to 10 (top row) showing positive reactions, contain human 
blood, each specimen dried for one month on various material, 
(1 silk handkerchief; 2, tweed cloth; 3; black dress fabric; 4, 
dark green cloth; 5, coarse green cloth; 6, coarse red cloth; 7, 
kid glove; 8, blanket; 9, very coarse material; 10, flannel). 
The controls, tubes 11 to 20, with negative reactions contain 
the same series of blood samples, but have yielded negative re- 
sults because they were tested against anti-ox serum instead of 
anti-human serum. The slight cloudiness of the lower tubes 
is not true precipitation. Nuttall, Immunity and Blood 
Relationships, Macmillan and Cambridge University press. AGGLUTININS AND PRECIPITINS 
125 
of animals such as man, horse and sheep. In fact, the amount 
of reaction of injected animals gives a basis for judging the 
degree of relationship between the injected animal and the 
animal providing the blood for injection. 
Relationship in zoological families (horse, dog, rabbit) is sup- 
ported by such agglutinin tests. These tests support the acknowl- 
edged relationship of the horse and the ass, the fox and the dog, 
the sheep and the goat and the domestic and the wild pig. In 
monkey groups interesting support has been found with regard 
to the degree of relationship between the various groups of 
monkeys: orang-outangs, chimpanzees and gorillas; and man has 
been shown by agglutinating blood tests to be more closely related 
to one group, the chimpanzees, than some of the monkey groups 
are to each other. 
Agglutinin Tests for Blood Transfusion.—Human blood 
differs somewhat in different individuals and four distinct types 
have been observed, when tested by the tendency to form ag- 
glutinins against other specimens of human blood. One of these 
four groups is very large, containing nearly 50 per cent, of all 
human beings. It is fortunate that so many people fall into one 
group, as emergencies sometimes occur where it is not possible to 
test blood before using it for transfusion. Agglutinin tests are 
made by adding red corpuscles from the volunteer to a sample of 
the serum of the patient. If the red corpuscles added are aggluti- 
nated or precipitated it shows that the patient’s serum treats them 
as foreign; and it would be dangerous to transfuse the blood of 
that volunteer into the patient, for it is only when tests show 
such agglutination that the red corpuscles are destroyed by the 
white corpuscles of the patient. Transfusion of such blood would 
be dangerous because it would mean caring for a lot of disinte- 
grating foreign protein (See p. 193); and it would not, of course, 
accomplish the usual aim in transfusion—the addition of active 
oxygen-carrying red corpuscles. (See also red corpuscle lysins 
and blood transfusion.) 
Blood Tests as Legal Aids.—The reaction of one animal to 
the red blood cells of another kind of animal is usually so specific 
that the serum of small laboratory animals (rabbit, guinea pig) 
may be used to identify the kind of blood with which they have 
earlier been injected or sensitized. If the blood cells are intact 126 
HOW WE RESIST DISEASE 
this identification can be made by means of a hemolysis test. 
(See p. 156.) Often, however, the only blood in question is in a 
blood stain; but even so, a definite conclusion can be reached by 
means of a precipitation test. The broken-down blood washed out 
of the stain with salt solution is floated over a given immune 
serum in a test tube; a definite ring at the point of contact 
(much as in Fig. 79) identifies the blood cells in the stain as 
the kind used to produce the immune serum. 
By this means, in such situations as a murder trial, a blood 
stain can be shown to have been caused by human blood, and not, 
as the defendant claims, by the blood of some other animal, as for 
example, a horse. Fresh serum from an animal sensitized against 
human red cells properly diluted is put into a test tube and to it 
are added some of the red blood cells washed out of the stain. If 
they are precipitated they are human cells, and the stain in ques- 
tion was, of course, made by human blood. Whether or not the 
stain is horse blood, may be shown by the same kind of a test, sub- 
stituting, of course, for this part of the test, the serum of an 
animal sensitized to horse red blood cells. 
These blood cells reactions are so reliable that they may be 
used to determine the kind of meat present in such preparations 
as sausage and “ chopped beef,” though a modified method is 
necessary with meats that have been heated. Even dried blood 
soaked from boards and chopping blocks has beeen successfully 
used in this way as legal evidence. The age of the blood stains 
affects these tests less than one would suppose. In one case a blood 
stain sixty-six years old gave satisfactory results when so tested; 
so did embalmed or mummified blood forty years old. Similar 
claims have been made for very old mummy blood—for one 
sample two thousand years old, and for another five thousand 
years old. 
Precipitins Against Unformed Proteins.—Such proteins 
as milk, serum and white of egg are called unformed or non- 
cellular proteins. Sensitized animals may also be used to identify 
these substances; the precipitin reactions of these animals are so 
delicate that their serums may be used to determine whether a 
given substance is the white of a hen’s egg or a duck’s egg; 
whether it is human milk or cow’s milk. The possibility of the 
application of such tests to food adulteration is at once evident. AGGLUTININS AND PEECIPITINS 
127 
These reactions are so similar to the phenomena discussed under 
Anaphylaxis that the reader is here referred to Chapter X, where 
human sensitiveness to such food proteins as milk and eggs, and 
to such foreign cells as horse skin cells and cat hairs, and pollen 
(hay fever) is briefly discussed. 
STUDY SUGGESTIONS 
1. In what ways may agglutinins help the body in overcoming 
bacterial infections? 
2. Describe a test for disease in which the patient may he shown to 
have specific agglutinins present in his blood. 
3. Describe a disease test in which the organisms obtained from the 
patient’s blood, mouth or nose exudate or intestinal discharges 
are identified by showing that they are agglutinated by a given 
or known antiserum. 
4. What diseases are satisfactorily tested for by agglutinins or precipi- 
tin tests? 
5. Show how agglutinins or precipitins may be used to identify blood 
in meats, blood stains, etc. 
6. How could such adulteration as horse meat for beef be detected? 
7. How could you determine whether hen eggs or duck eggs were being 
used in a given egg powder, icing preparation, etc. ? 
8. Tests_ showing agglutination of red blood cells give results in 15 
to 30 minutes; how does this compare with the time interval in 
tests involving the presence of lysins which dissolve the red 
corpuscles (see Chapter VIII) ? 
9. How can we use the blood content of mosquito stomachs to determine 
the animals mosquitoes feed upon? Of what use might such 
knowledge be in controlling a disease spread by an insect feeding 
upon other hosts besides man, as in malaria or in sleeping sickness? CHAPTER VI 
OPSONINS 
(Tropins) 
Comparison with agglutinins 
General technique 
White cor- 
puscle aid 
Tests proving 
Opsonic index 
How deter- 
mined 
Reliability 
Necessary 
factor 
Destruction by white corpuscles 
Final destruction by “fixed” cells 
Opsonins 
Related to 
disease 
Types 
Stages 
Variations 
in amount 
Massage 
Vaccination 
Increased by 
treatment 
Anti-serum 
values 
Opsonins described on page 49 as aiding the white corpuscles 
in the destruction of foreign organisms, are so named (from the 
Greek opsonium, a relish) because of the greater avidity or relish 
with which white corpuscles take in and digest bacteria, when these 
substances are present. At least as early as 1895, Metchnikoff 
noticed that the serum of immune animals aided white cor- 
puscles in the destruction of bacteria, the number of bacteria 
ingested and destroyed being greater than when normal blood or 
serum was used with the white corpuscles (Fig. 85). Tropins 
and the less definite term stimulins, are other names for such 
substances. (See p. 129.) 
Agglutinins and Opsonins.—Like agglutinins, opsonins can 
not single handed bring about destruction of bacteria; each of 
these antisubstances acts as an aid to the white corpuscles in this 
work. Neither opsonins nor agglutinins have any definite quan- 
titative relation to any other antibodies, such as the bactericidal 
substances or lysins which may be present in an immune serum 
(Fig. 86). Opsonins, like agglutinins, are specific for the organ- 
128 OPSONINS 
129 
isms which excite or stimulate their production, anti-staphy- 
lococcus opsonins aiding in staphylococcus destruction and 
anti-tuberculosis opsonins acting in tuberculosis (Fig. 94). 
Although normal blood may be shown to contain varying 
amounts of normal opsonins, these normal opsonins are, however, 
unlike the specific opsonins formed during disease or after vacci- 
Immune OpSemns 
TlormaJ Opsonin5 
Fig. 85.—A chart showing the great amount of immune opsonins in btood when 
compared with normal opsonins of a second or control animal; AT indicates the injection of 
killed tuberculosis organisms in the first animal. Meakins, Journal of Experimental 
Medicine. 
nation. The normal opsonins are not only less abundant, hut they 
differ also in being less resistant to heat than the opsonins of 
immune blood. Workers who emphasize the difference between 
normal and immune opsonins designate the latter as tropins. In 
this respect opsonins differ from agglutinins and lysins, for both 
normal agglutinins and lysins apparently differ from immune 
agglutinins and opsonins mainly in amount, not in kind. 
Tests for Opsonins.—Meningitis and streptococcus anti- 
serums have a marked opsonic effect and opsonins may be the most 
valuable antisubstances present. Opsonins also play an important 130 
HOW WE RESIST DISEASE 
part in the body reactions against staphylococcus and tuberculosis 
infections, and aid substantially in combating pneumococcus and 
gonococcus infections. 
It might be expected therefore, that in a given disease or in- 
fection, a measurement of opsonins present would give some indi- 
cation as to how vigorously the body is reacting (See p. 135). The 
Opsonins 
BattericiAa.) Power 
'A%%] utimmS 
Fio. 86.—This chart shows that the various antibodies do not increase 
proportionally against a given organism; tests were made for each of the three anti- 
bodies shown every 5 to 9 days for 97 days. Meakins, Journal of Experimental 
Medicine. 
presence and relative abundance of opsonins in a given blood or 
serum, is demonstrated by showing how the addition of such blood 
or serum affects the white corpuscle destruction of bacteria. 
While this determination is far from simple, it is not really 
difficult to understand, either in theory or as a matter of lab- 
oratory practice. To determine how much aid such opsonins are 
giving to a tubercular patient, for example, we add a little of his OPSONINS 
131 
serum to a mixture of white corpuscles and tuberculosis organ- 
isms. The serum is obtained by taking a small amount of blood 
from the patient (e.g., ear or finger prick) ; after it has clotted, 
a little of the serum is drawn off into a specially marked or gradu- 
ated capillary pipette (Fig. 89). Similar carefully measured 
amounts of tuberculosis organisms and of washed white corpuscles 
from a non-tubular source (a normal human or such laboratory 
animals as a guinea pig or rabbit) are measured off, and all three 
are well mixed together to 
insure the uniform suspension 
of the opsonins, bacteria and 
white corpuscles. (The cor- 
puscles are washed to make 
certain we are dealing with 
only the patient’s opsonins— 
not opsonins from the blood 
furnishing the corpuscles for 
the test.) This mixture is 
allowed to stand (fifteen min- 
utes) at body temperature, 
thus providing favorable con- 
ditions for white corpuscle 
action. A little of this triple 
mixture is then spread upon a 
glass slide, stained, and ex- 
amined under a microscope to 
determine the extent of the 
white corpuscle ingestion of 
bacteria. This may be measured in two ways: (1) by counting 
the total number of bacteria ingested by the first hundred cor- 
puscles seen, or (2) by estimating what per cent, of the first 
hundred white corpuscles seen have ingested bacteria. Results 
are more easily estimated by the second of these two methods, as 
it may be “ impossible to count the bacteria ingested by even one 
cell for the leucocytes simply gorge themselves.” 
The Opsonic Index.—Since normal serum has some opsonic 
power, exactly how much special opsonins are going to help a 
patient combat a disease, such as tuberculosis, could be deter- 
mined only by comparing the results obtained with the patient’s 
F,ig. 87.—A centrifuge, with a re- 
volving shaft, R, which spins rapidly and 
whirls the tubes into a horizontal position, 
the heavier part of the contents (such as 
corpuscles in blood) being thrown outward 
(centrifugal force) to the bottom of the tube. 132 
IIOW WE EESIST DISEASE 
serum and with normal serum. A control test is, therefore, made 
by repeating exactly the same procedure described in the preced- 
ing paragraph, substituting a non-tubercu- 
lar normal serum—often the worker’s own 
serum—in the place of the patient’s serum. 
Wright, who did much to develop the 
technique of opsonin measurement, used 
a mixture of five normal serums for this 
control part of the test, thus securing a 
less variable normal serum for the control. 
Any difference in the white corpuscle 
activity is attributed to the difference be- 
tween the normal serum and the patient’s 
serum. If, for example, in the normal 
serum mixture, the first hundred white 
corpuscles counted showed ten white cor- 
puscles containing bacteria, and the tu- 
bercular serum yielded a count of twenty- 
one containing bacteria, the relative power 
of tubercular serum to the normal serum 
would be as twenty-one to ten, or |A. 
These relative values may be expressed as 
2.1, and would technically be spoken of as 
an opsonic index of 2.1, the interpretation 
being that the patient’s serum is more 
than twice as efficient as the normal serum 
in destroying the invading organisms. 
• Results are given in such “ index ” terms. 
To quote, for example, from hospital re- 
ports, the opsonic index of one patient’s 
serum against staphylococcus infection 
causing a series of boils was but 0.62, 
much less than normal. Another patient 
who had been vaccinated with staphylo- 
coccus organisms to increase his resistance 
against a similar condition showed an 
opsonic index of 2.4 (Fig. 90). 
Difficulties in Determining the Opsonic Index.—The 
technique employed demands very careful work. The amounts 
Fig. 88.—Tube of blood, 
after centrifuging, to sep- 
arate the white corpuscles 
for making opsonic tests. S. 
serum; W. C.white corpus- 
cles; R. C. red corpuscles. 
After Thomas and Ivy, 
Applied Immunology, J. B. 
Lippincott Co. OPSONINS 
133 
measured in the capillary pipettes are very small, and slight 
differences in bulk might mean a big difference in the relative 
number of bacteria and white corpuscles. Any variation of this 
kind would mean a similar difference in the opportunities or 
Fig. 89.—An opsonic pipette, with a marked tip by which are measured the 
bacterial suspension, white corpuscles, and the patient’s serum which are drawn in 
separately, a little air separating them as indicated. These three substances are then 
mixed and kept at body temperature (15 to 30 min.), when slides are made, stained, 
and ingestion of bacteria noted through the microscope. 
chances for bacterial ingestion, and would yield unreliable re- 
sults. Recently important differences have been shown to be 
due to such matters of technique as slight variations in the 
acidity of the liquid used in washing the white corpuscles or 
making up the final suspension. Most workers feel that about 
OPSONIC INDEX DETERMINATION 
Bacteria 
Bacteria 
Patient’s serum 
Tlormal (control) serum 
White corpuscles 
White corpuscles 
Percentage corpuscles 
ingestmo bacteria. 
Patients Opsonic Index 
Fig 90.—Method of determining a patient’s opsonic index. 
10 per cent, error is to be expected. It may be several times 10 
per cent., and it is claimed that even the results of experts may 
not agree; in one instance, working on the same case, one expert 
showed that the patient had an opsonic index lower than normal, 
while another estimated the osponic index to be higher than nor- 
mal. There is, however, a great difference in the chances of error 134 
HOW WE RESIST DISEASE 
in the several special methods for determining the opsonic index, 
and the method to be used should be carefully considered. (See 
also p. 138.) Besides these mechanical difficulties, the patient’s 
physical condition (fatigue; loss of blood, as in hemorrhage) 
affects the results obtained. 
Opsonins as Aids in Pre- 
scription.—Other mechanical 
difficulties affect the value of 
opsonic tests in treating a 
patient. The time involved in 
making such counts is also an 
important consideration affect- 
ing the adoption of opsonic 
tests in determining the prog- 
ress of disease. The prep- 
aration, separation, washing 
and proper dilution of the 
white corpuscles is itself no 
small task. Several hours are 
not too much to allow for all 
the details involved in compar- 
ing the patient’s opsonic activi- 
ty with that of a normal indi- 
vidual. This means that in 
medical practice, the observa- 
tion of clinical or physical 
symptoms and the determin- 
ation of the opsonic index can 
not be really contemporary. 
Only under the best hospital 
or sanitarium conditions can the clinical and opsonic reports be 
less than a few hours apart, and often they are twenty-four, 
or even several days apart. This means that an opsonic index is, 
therefore, often valuable only in corroborating the physician’s 
diagnosis or treatment rather than in aiding him in making his 
decisions or prescribing treatment. 
One of the most useful applications of the opsonin tests is in 
conditions such as joint infections, where there are no open 
lesions to aid in diagnosis. An example very widely quoted in 
Fig. 91.—The heavy line indicates 
the opsonic activity of a patient against 
Streptococcus pyogenes on the 7th to 14th 
day of an attack of erysipelas. This curve 
shows quite typically the early period with 
the opsonic index below normal (0.2 to 
0.7), the rise in this index (average 2, 0, 
ranging from 1.4 to 4.4) with a falling 
temperature and improvement, and the ab- 
rupt fall to normal in 1 to 3 days. (The 
light line is the temperature record.) 
Tunnicliff, Journal of Infectious Diseases. OPSONINS 
135 
this connection was the case of a patient having a swollen wrist 
joint. (Fig. 93.) To determine whether the inflammation was 
due to gonorrhoea or to tuberculosis the opsonic index test was 
taken both for gonococcus and for tuberculosis organisms, under 
varying conditions; throughout, the tuberculosis index remained 
about normal, 0.94 to 1.1, while the gonococcus index ranged 
from 1.3 to 2.4, thus indicating 
that the inflammation was due to 
gonorrhea and not to tuberculosis. 
Aside from this diagnostic 
application of the opsonic tests 
little practical value attaches to 
their use in the actual treatment 
of disease, and while variations in 
the opsonic index are used in 
special investigations, they are 
not used as a routine guide for 
the administration of treatment. 
Relation of Opsonins to 
Final Bacterial Destruction.— 
Quite recently it has been claimed 
that the fixed body cells are more 
important in bacterial destruction 
than the white corpuscles—that 
the white corpuscles hold the bac- 
teria but temporarily, their ulti- 
mate destruction occurring main- 
ly in the spleen and lymphatic 
areas. If this is so, the rate at 
which opsonins aid the white cor- 
puscles in ingesting bacteria, 
would be an important initial 
factor, but would give no accurate 
measure of the actual rate of bac- 
terial destruction, and an opsonic 
index could not be an exact index of the patient’s resistance. 
Variations in Opsonic Index Related to Types of 
Disease.—A low index is often associated with a definitely local- 
ized infection, as a gland or a joint, or with a quiescent focus. 
The explanation of this is that in such instances relatively small 
Fig. 92.—Here the opsoniacurve 
is measured against Streptococcuspyog- 
enes in a fatal case of erysipelas. Note 
the contrast to the curve of recovery in 
the preceding figure. The light line 
represents the temperature changes 
during thejsame interval. Ttjnn:cliff, 
Journal of Infectious Diseases. 136 
HOW WE RESIST DISEASE 
amounts of irritating substances are distributed from the focus, 
and so, little body reaction (opsonins) results. A low index may 
also be found in more or less chronic or at least long continued 
infections, such as acne or boils, where the opsonins are often 
considerably below normal (.4 to .8). 
A high index is often associated with active lesions, especially 
Gonorrhea Index 
Tuberculosis Index 
Fig. 93.—An increased opsonic index obtained by bandaging the infected 
area. The tuberculosis index remained the same, while the gonorrheal index va- 
ried, as shown, thus indentif.ving the infection as gonorrheal. Redrawn from 
Wright, Studies in Immunisation. Constable. 
iii pulmonary tuberculosis, and probably indicates that the body 
is being forced to do its utmost to overcome the irritat- 
ing organisms. 
Increasing the Opsonic Reaction.—In cases with a low 
index, the body may be stimulated to increased reaction by an in- 
crease in or by greater distribution of the irritating factors. In 
more or less chronic cases (boils, acne, tuberculosis) this may be 
done in two ways: First, by massage or pressure of the localized OPSONINS 
137 
infection (such as tubercular joint) thus distributing the irritat- 
ing organisms and exciting more general and greater body re- 
action (Fig. 93). This method may, of course, be actually 
dangerous, distributing too much irritating material, thus over- 
reaching the mark, injuring the body tissues and failing to pro- 
duce a compensatory increase in opsonins or other antisubstances. 
The second method of increasing the opsonic reaction is by 
repeated injections of killed bacteria or vaccines. In staphylo- 
coccus infections, such opsonin increase may be readily demon- 
strated. To illustrate, a patient suffering from “ chronic ” 
boils was found to have an op- 
sonin index for staphylococcus 
(Fig 95) considerably below nor- 
mal—about .6. He was vacci- 
nated with a few billion killed 
staphylococcus organisms, and 
(after the usual brief drop) his 
opsonic index became established 
at about 1.3. A few days later he 
was again vaccinated, reaching an 
opsonic index of about 2.0 which 
was followed by complete re- 
covery. (See p. 132.) 
Zinsser, summing up the re- 
sults and conclusions of several 
workers in this field says that, 
“ in many of the infections of 
man the resistance of the patient 
is roughly proportional to the 
opsonic index—and that properly 
spaced inoculations with suitable quantities of dead bacteria 
(vaccines) will raise the opsonic index and lead to the recovery 
in many of the localized subacute and chronic conditions.'” 
Other Tests Based on Opsonins.—Besides the more or less 
successful method of estimating an individual’s body reactions to 
disease by measuring the opsonic value of his serum, opsonins 
are capable of another important laboratory application. The 
value of curative meningitis antiserum— 
may be measured in terms of opsonin values. While the United 
Fig. 94.—Diagrammatic represen- 
tation of the formation of specific 
opsonins adapted to different bacteria, 
but alike in their power of working 
with the white corpuscles, as indicated 
by the similarity of the immune body- 
corpuscle juncture. 138 
HOW WE RESIST DISEASE 
States Public Health Service does not use the opsonic reactions 
of any serum as an official standard, the opsonic value may be 
used as an aid in deciding whether a given serum should be 
passed. (See p. 124.) For example, a given anti-meningitis 
serum, which is questionable according to the agglutinin or com- 
plement-fixation tests, may be passed on its opsonic rating. 
Opsonin values are quoted more often for anti-meningitis serum 
than for any other serums. Investigators have reported the 
presence of opsonins in a 1: 5,000 dilution of meningitis serum; 
this is apparently high, for 
reliable workers make such 
statements as a “ commer- 
cial serum having tropins 
for the two main groups of 
meningococci in a dilution 
of 1:4,000 is considered 
excellent.” 
Besides the difficulties 
already mentioned (p. 132) 
which are experienced in 
securing accurate and con- 
sistent results in measuring 
opsonins, another objection 
to using opsonins as a basis 
for the standardization of 
serums has been the fact that opsonin values do not correspond 
to the protection values of a given serum. Recently Evans with 
improved (Neufeldt) technique, has shown for each of a series 
of antiserums, a surprising correspondence between the opsonic 
strength and the protective value. While the protective value 
of a given serum does not lie in its opsonic value only, it is 
possible, however, that the measurement of antiserum strength 
may be much more definitely established by these newer methods. 
Fig. 95.—Staphylococcus aureus, a 
common pus organism. Williams, Brown and 
Earle. 
STUDY SUGGESTIONS 
1. What are opsonins? 
2. What three substances are used in testing for opsonins? Why 
should a control test be made? 
3. Show how opsonins may aid in diagnosis of one disease. OPSONINS 
139 
4. Give the difficulties which may affect the accuracy of determining 
a patient’s opsonic index. 
5. Explain why variations in a patient’s condition in a given infection 
(tuberculosis, boils) might be expected to correspond to changes 
in his opsonic index. 
6. Find in a text book on bacteriology or immunology a series of opsonin 
tests made on one individual, and chart the reactions obtained 
as in Fig. 85. 
7. List from an advanced text in bacteriology the human diseases in 
which opsonins are thought to be important body aids. CHAPTER VII 
WHITE CORPUSCLES 
Primitive rather than 
specialized function 
Dependence on opsonins 
Relative activity of types of 
white corpuscles 
Phagocytic activity 
White Corpuscles 
Increase in number—Phases and types of disease 
Other variations 
in activity 
Health and disease 
Age 
Different types of animals 
Extracts 
Capsule relations 
“Virulence” 
Aggressins 
Bacterial resistance 
Number related to specific diseases 
Progress during disease 
Tests 
As early as 1870, bacteria were seen in white corpuscles, but 
strange as it seems to us now, their presence in the corpuscles was 
thought to indicate that the bacteria were extending their de- 
structive influence to the blood cells. Later, the theory of the 
protective activity of the white corpuscles was advanced, in a 
speculative way, but it was not until 1883 that Metchnikoff first 
showed experimentally, that white corpuscles both ingest and 
digest bacteria (Fig. 96). He and his associates also showed 
that this activity was greater in the presence of immune serum. 
(See Agglutinins and Opsonins.) 
Phagocytic Action a Digestive Process.—It is not uncom- 
mon to find that the phagocytic action of white corpuscles is 
viewed by the layman as a very unusual type of cell activity, 
indicative of a high degree of specialization in the white cor- 
puscles. Phagocytosis is, however, essentially the same process 
that occurs constantly in one-celled animals, protozoa, as they 
engulf and digest food particles. 
140 WHITE CORPUSCLES 
141 
This type of cell activity is not only characteristic of small 
protozoa, such as the ameba (Fig, 97), but may be demonstrated 
in favorable tissues in many higher animals as well (Fig. 98). 
As illustrations of such tissues the following may be mentioned: 
(1) The lining cells of the intestines of certain blood-sucking 
worms or leeches which engulf and digest red blood cells; (2) the 
intestinal lining cells of mollusks which similarly ingest food 
particles; (3) various gland cells in the human body—lymph 
Fig. 90.—Numerous polynuclear white corpuscles from pus; two near 
the centre have ingested numerous gonococcus bacteria, (Neisseria gonor- 
rhese). Adami and McCkae, Textbook of Pathology. Lea and Febiger. 
nodes, liver and spleen—which are constantly causing the de- 
struction of red blood cells; (4) the alveolar cells of the human 
lung which surround and destroy foreign particles, including 
bacteria brought to them in the inspired air; and (5) the bac- 
terial destruction due to the lining cells of the blood vessels and 
the abdominal cavity. 
From these illustrations, therefore, we may conclude (1) 142 
HOW WE RESIST DISEASE 
that phagocytic activity of the wdiite corpuscles is far from 
peculiar and may be interpreted as a retention of a very primitive 
characteristic rather than the development of a highly special- 
ized power; and (2) that phagocytosis is not limited to the 
motile white corpuscles, but is a function of many fixed cells. 
Phagocytosis by Fixed Cells.—The importance of certain 
fixed tissue cells in bacterial removal has been shown by several 
investigators in various animal experiments, and includes the 
Fig. 97.—Three different amebas showing the irregular body or cell outlines; changes 
in these projections allow movement and the engulfing of food particles. (N. nucleus: c v., 
contractile vacuole.) Schafer, Ameboid Movement, Princeton University Press. 
activity of the liver in pneumococcus infections in guinea pigs, the 
spleen and liver in typhoid infections in rabbits, and the spleen, 
liver and lungs in streptococcus infections in rabbits. Such 
activity on the part of the fixed tissues may lessen the im- 
portance attaching to the opsonic index, and some writers have 
claimed for these fixed cells greater results than those achieved 
by the white corpuscles themselves. 
Against this last opinion must be balanced the fact that in 
the tissues, such as the spleen, where the white corpuscles are 
temporary agents, they are none the less important ones; for 
whether the white corpuscles are the final destructive forces, or WHITE CORPUSCLES 
143 
mainly temporary agents transferring their ingested bacteria to 
the spleen and the lymphatics for final destruction, they are 
necessary to the phagocytic process. (See p. 145.) 
The Factors Involved in Phagocytosis.—It will probably 
be best to discuss phagocytosis under three headings: (1) The 
part played by serums, (2) the role of the white corpuscles, and 
(3) the bacteria exciting or stimulating this white cor- 
puscle activity. 
Fig. 98.—Diagrammatic representation of the stages (a-e) in the movement of an 
ameba, and the ingestion of food. Schafer, Ameboid Movement, Princeton University 
Press. 
Serum Factors in Phagocytosis.—While investigators dis- 
agree as to the rate at which white corpuscles alone can ingest 
bacteria, they all agree that such ingestion is much more rapid 
when immune serum substances, agglutinins and opsonins, 
are present. 
The importance of the preliminary action of agglutinins as 
an aid to phagocytosis has been discussed in the chapter on 
Agglutinins and Precipitins. Opsonins, in the chapter preced- 
ing this, have been shown to be necessary not only for the in- 
gestion but also for the complete digestion of any considerable 
number of bacteria; without such opsonins the ingested bacteria 
may retain life and sometimes full virulence. (See also p. 145.) 
Nevertheless, the great importance of these serum substances 
should not blind us to the fact that though the white corpuscles 
can not complete these destructive processes unaided, they are 
themselves nevertheless indispensable to the process. How in- 
dispensable, may be seen from the fact that bacteria such as Fig. 99.—Three units, from a moving picture film,_ 
showing the same ameba in movement at intervals of 15 
seconds. The photographs are placed to show movement 
toward the right. Ricker, U. S. Public Health Service. WHITE CORPUSCLES 
145 
pneumococci (Diplococcus pneumonia) may multiply rapidly in 
the most potent immune serum after the mechanical destruction 
of the white corpuscles. .Similarly, pneumococci multiply in 
defibrinated human blood or serum because few or no phagocytes 
are present after defibrination. Anthrax apparently offers 
another illustration of the importance of white corpuscles with 
relation to opsonins, for while dogs are very resistant to anthrax, 
the organisms multiply rapidly in normal dog serum. 
White Cor- 
puscles and 
Phagocytosis. 
—It is sufficient 
for our purpose 
to consider only 
the two main 
types of white 
corpuscles: (1) 
The polynuclear 
leucocytes, which 
have two or more 
nuclei, marked 
ameboid activity 
(Fig. 99) and 
ingestive power 
and which are 
produced mainly 
in the hone marrow, and (2) the lymphocytes, with less ameboid 
and ingestive power, having but a single nucleus, and produced 
mainly in the lymph nodes. 
Most of the ingestion and destruction of bacteria is done by 
the polynuclear leucocytes. With regard to the role of the 
lymphocytes, investigators are less in agreement. It is probably 
safe to attribute to the lymphocytes the following activities: 
(1) They accumulate in localized or early infections apparently 
forming an important initial stage of the white corpuscle re- 
action; (2) they are important in the final disintegration of 
broken down cells and foreign substances; (3) they may help in 
chronic infections or in infections due to very resistant bacteria, 
Fig. 100.—Nerve tissue showing the invasion of phag- 
ocytes which are surrounding the ganglion cells undergoing 
disintegration. . 
Neal, International Clinics, J. B. Lippincott Co. 146 
HOW WE EESIST DISEASE 
such as the tuberculosis and leprosy organisms; and (4) consid- 
erable importance has also been ascribed to these single-nucleated 
white corpuscles in protozoan infections. 
Number Changes in White Corpuscles.—Tt is, however, 
the activities of the more-numerous polynuclear 
corpuscles (60-75 per cent, of the total number 
of white corpuscles) which are most marked 
and most easily studied and measured. These 
corpuscles show marked variation, not only in 
activity, but often in number. (Plate 2.) In 
general, it may be said that the polynuclear 
corpuscles increase in number as immunity 
develops—increasing most rapidly in acute 
infections. If the disease progresses too rapidly 
—indicating insufficient or little body re- 
sistance, these white corpuscles may show a 
decrease. They also tend to decrease as a given 
attack declines. In mild attacks or chronic infections there is 
often a similar decrease. 
The increase obtained in white corpuscle counts may be to 
Fig. 101.—S pi na 1 
fluid showing 
Neisseria iniraceU 
lularis and several 
polynuclear leucocy- 
tes, the white corpus- 
cles most active in 
ordinary bacterial 
destruction. Sutter, 
International Clinics, 
J. B. Lippincott Co. 
Fig. 102.—Types of corpuscles frequently found in microsopic exami- 
nation of spinal fluid. Cells 1-4 are small lymphocytes, No. 4 being a poorly 
staining type not uncommon in pathological conditions; 5 is an old red blood 
cell; 6 is a large lymphocyte; 7-10 polynuclear leucocytes. 
Sutter, International Clinics, J. B. Lippincott Co. 
some extent due to a change in distribution, but it is mainly due 
to an actual increase in number—the addition of newly formed 
corpuscles to the total number already present in the body. This 
increase may be due to the irritation or stimulation of bacterial 
substances or proteins. Injected proteins not of bacterial origin 
(albumoses, etc.) cause a similar increase, page 177.* In sterile 
injuries, such as may occur occasionally with a splinter, there 
* In connection with this increased production of white corpuscles 
there is room for interesting speculation regarding its possible relation 
to the role physiologists assign to white corpuscles—the regulation 
of the protein content of the blood. Plate II.—Changes in blood picture due to pyogenic organisms. Upper, blood 
smear from normal monkey; lower, blood smear from monkey inoculated with pyogenic 
organisms. Note especially, the difference in number and proportion of the polynuclear 
white corpuscles. Sellards, Johns Hopkins Bulletin. WHITE CORPUSCLES 
147 
may also be an increase in the number of white corpuscles. This 
has been attributed to the irritating substances resulting from 
the destruction of the tissue cells. Such responses are less marked 
than the responses made to bacterial stimulation. 
White Corpuscle Changes in Specific Diseases.—While 
the white corpuscle count may, as described, show variations 
during the course of a given attack or infection, it may vary also 
with the kind of disease. This is readily understandable as the 
relative importance of the other reactions of the body, such as 
Fig. 103.—A blood smear showing phagocytosis; the large white 
corpuscle in the centre has ingested or swallowed pneumonia organisms. 
(Photograph by Bull.) Broadhubst, Home and Community Hygiene, 
J. B. Lippincott Co. 
lysins or antitoxins, would affect the need for extra corpuscle 
activity. Normally the white corpuscle count is about 5,000 
to 9,000 per cubic millimetre. Increase in the number of white 
corpuscles is characteristic in pneumonia, while a decrease is 
more often found in influenza. (See also p. 151.) 
White Corpuscles as Carriers of Infection.—White cor- 
puscles have, by virtue of their ameboid activity, the power 
of migrating through the capillary walls and into the tissues. 
This is doubtless often an advantage in the rapid movement of 
these phagocytes to the infected focus, but it is conceivable that 
it may increase the number of local infections, as white cor- 
puscles are not always able to digest or destroy all the bacteria 148 
HOW WE RESIST DISEASE 
they have taken in. In such a situation resistant bacteria may be 
transported to a new area, and undeterred by the white corpuscle 
that conveyed them, set up a new focus of infection. Such trans- 
fer is not easily demonstrated, as the surface allowing the passage 
is not always inflamed. The location of infections, otherwise 
difficult to account for, as in osteomyelitis and tuberculosis, are 
sometimes attributed to such white corpuscle transfer. This 
method, of course, is the exception rather than the rule, and 
should not detract from our conception of the white corpuscles 
as important protective agents. 
Variations in Normal 
Phagocytic Activity.— 
White corpuscles vary not 
only in their relative abun- 
dance, but in the vigor of 
their activity. Their phag- 
ocytic power varies in health 
and disease in a given indi- 
vidual. Age differences have 
also been noted, the activity 
of the white corpuscles of 
new-born children being less 
than that of adults. Cor- 
puscles from normal indi- 
viduals differ somewhat in 
their power to dispose of 
such bacteria as the staphy- 
lococcus and tuberculosis organisms. In the lower animals, 
there is great difference in the relative activity of the normal 
white corpuscles; the white corpuscles of the frog, for example, 
aiding greatly in destroying injected anthrax bacteria, while 
the corpuscles of guinea pigs and rabbits show very little power 
of this kind. 
White Corpuscle Extracts.—Much of the white corpuscle 
activity is explained on the basis of the enzymes they contain. 
Different protein-splitting enzymes have been studied, these 
enzymes being held accountable for such activities as dissolving 
of fibrin (clotted blood) or the disintegration of bacteria. 
Experimental work has been done following this general 
Fig. 104.—Streptococcus mucosus, stained 
to show the capsule so characteristic of this 
species. (Photograph by Dunn.) Huntoon, 
Journal of Bacteriology. WHITE COEPUSCLES 
149 
line, in an effort to demonstrate that similar results 
may be obtained by white corpuscle extract (obtained by sub- 
jecting washed white corpuscles to distilled water). Ex- 
perimental animals and infected human beings have been treated 
with such white corpuscle extracts, and beneficial effects claimed 
in infections due to streptococcus, staphylococcus, pneumonia, 
influenza and meningitis organisms. Horse blood may be used 
for preparing such white corpuscle extracts, and a rather large 
dosage may be given, as much as 100 c.c. every four to six 
hours. This treatment is not yet practically established, and its 
value, at present, seems greatest in localized infections. 
Relation of Bacteria to Phagocytosis.—The phagocytic 
powers of the white corpuscles are not exercised against all kinds 
of bacteria; diphtheria bacteria, for example, are little affected by 
this activity. Phagocytosis may occur with some members of a 
group of organisms, and not with others, e.g., a capsulated species 
of streptococci resists the phagocytes, while the uncapsulated 
types are readily engulfed. This same difference is seen within 
a given species of bacteria, where there is a difference in indi- 
viduals in capsule formation; white corpuscles have been seen 
to select uncapsulated anthrax bacteria from masses of capsulated 
ones. Often the formation or presence of a capsule (Fig. 104) 
parallels the possession of greater virulence or pathogenicity, thus 
supporting the view that the capsule is an “ earmark of viru- 
lence.” According to Zinsser, “ Habitually capsulated bacteria, 
like the Eriedlander bacillus and Streptococcus mucosus, are of 
fairly consistent virulence, while in other microorganisms like 
the pneumococci, anthrax bacillus, plague bacillus, and certain 
other streptococci, the formation of a capsule goes hand in hand 
with an increase of virulence.” 
The waxy capsule of tuberculosis organisms may help account 
for the fact that their destruction is not so great as their rapid 
ingestion by the white corpuscles would lead us to expect. This 
resistance, it is claimed, may be due to the lipoids prominent in 
the capsule. 
In other cases definite bacterial resistance exists without the 
presence of capsules; in explaining these cases refuge is usually 
taken in the vague term “ virulence ” which covers not only 
this resistant quality but also actual invasive properties. 150 
HOW WE RESIST DISEASE 
Another way of explaining the resistance of bacteria attrib- 
utes to them the power to form special substances—enzyme- 
like substances—which neutralize or destroy the reacting 
substances of the body, or paralyze the polynuclear white cor- 
puscles, and so give the bacteria a relative immunity to the white 
Fig. 105.—Part of a specially marked blood-counting slide 
showing the red corpuscles. Moving the slide as indicated by the 
arrow makes it possible to count all the organisms in a representative 
number of the marked spaces, without repetition. There are slight 
variations in the technique used (dilutions etc.) for estimating red 
corpuscles, white corpuscles, and bacterial vaccines, but the general 
principle is the same. After DaCosta. 
corpuscles, lysins, etc., and aid the bacteria in their invasion of 
the tissues. These special substances are called aggressins (See 
p. 56); and belief in their existence has been supported by ex- 
periments showing increased virulence in experimental infec- 
tions, if sterile material from an abscess is inoculated in addition 
to the related type of bacteria. To these aggressins have been 
attributed also other powers, such as the paralysis of the phago- 
cytic white corpuscles. 
Tests Based on White Corpuscle Counts.—In spite of the WHITE CORPUSCLES 
151 
fact that white corpuscles and opsonins are interdependent, we 
have not yet demonstrated any definite parallel or ratio in these 
two responses to infection. Indeed, there may exist definite con- 
trasts in these two responses in a given case, such as a low 
opsonic index with a high white, corpuscle count in a staphylo- 
coccus infection. It may well be that our present methods of 
determinating such values are not delicate and accurate enough 
to show the real relationship that exists—or that these differences 
may be due to a more or less temporary overproduction in one 
reaction in the effort to 
compensate for the delayed 
manifestation of the other 
reaction. 
However that may be, 
white corpuscle counts and 
their variations can be used 
as laboratory aids much 
more readily than opsonin 
determinations. This may 
be due to the greater ease 
with which accurate white 
corpuscle counts are deter- 
mined. 
The diagnosis of disease 
is sometimes materially aid- 
ed by making blood counts, 
thus securing evidence of the marked reduction of overpro- 
duction of the white corpuscles already mentioned on page 147. 
Reduction (leucopenia), for example, is characteristically found 
in uncomplicated typhoid, and in influenza and, often, in tuber- 
culosis; a marked increase in the white corpuscles (leucocytosis) 
is equally characteristic of pneumonia, streptococcus and staphy- 
lococcus infections, especially in deep-seated abscesses. As char- 
acteristic comparison illustrating these differences we might cite 
the following counts from reports on individual cases in recent 
medical journals: Leucopenia: typhoid, 2,000; measles, 3,600; 
influenza, 2,800; tuberculosis, 1,000. Tor leucocytosis: erysip- 
elas, 20,000; cerebral meningitis, 34,000 and 47,000; severe 
Fig. 106.—Spinal fluid from a case of 
meningitis, showing white corpuscles and pneu- 
mococcus bacteria. ( x 700 ). Schoening, 
Photograph by Sands. 152 
HOW WE RESIST DISEASE 
diphtheria, 30,000, and pneumonia, 56,000, 115,000, 151,000 
and 245,000. 
There are not, however, many human diseases in which such 
blood counts prove practical aids; and, as might be expected, 
such indications are lacking in the diseases, such as diphtheria, 
in which phagocytosis plays little or no part. Death often occurs 
even when the white corpuscle count indicates a high degree of 
reaction against the invading bacteria. Too much importance 
must not be attached to the count alone, for as Emerson well 
states it, a high count simply means that the patient is putting 
up a vigorous fight. 
Variations in the number of the white corpuscles are not, on 
the whole, so helpful in making the diagnosis of the disease itself, 
as in determining an individual’s progress during an attack of 
a given disease or in ascertaining his response to prolonged vac- 
cine treatment and, thereby, the most favorable dosage. 
STUDY SUGGESTIONS 
1. Show that the phagocytic power of white corpuscles resembles the 
activity of many other kinds of cells. 
2. What three factors enter into phagocytosis? 
3. Describe the probable relationship of agglutinins and opsonins to 
phagocytosis. 
4. Consult a text book on pathological bacteriology or diagnosis and 
calculate for one or more diseases the per cent, increase recorded 
for the patient’s white corpuscle count. 
5. Some twenty years ago a doctor recommended that small abscesses 
be treated by local injections of distilled water; what possible 
connection is there between this recommendation and the belief 
that the phagocytic action of white corpuscles is due to the 
enzymes they contain ? 
6. What reasons are advanced to explain the variation in the suscepti- 
bility of different bacteria to phagocytosis ? CHAPTER VIII 
LYSINS 
(Including Complement Fixation Tests) 
Action 
Methods of demonstrating lysins 
Sources 
General characters 
Kinds 
Types of cells dissolved 
Normal and specific 
Lysins 
Double factors of lysins 
Specificity 
Effect of heat 
Principles 
involved 
Wassermann test 
Other tests 
Reliability of tests 
Tests based 
on lysins 
Diseases so 
tested 
Syphilis 
Protein tests 
Other diseases 
In 1886, Nuttall showed that normal blood contains special 
substances, lysins, which destroy bacteria. When bacteria are 
acted upon by lysins they become granular and swollen, and are 
finally completely dissolved. This result must not be confused 
with the destructive action of white corpuscles, for, as was later 
shown, this type of dissolution takes place without the presence of 
white corpuscles, that is, by the action of the serum alone. Later 
work showed, also, that these lysins are much greater in immune 
serum (Fig. 107) than in normal serum, most normal serum 
having, in comparison, very little destructive power. In one of 
Nuttall’s early experiments he demonstrated that one cubic 
centimetre of rabbit’s blood contained enough lysin to destroy 
over 50,000 anthrax bacteria, causing their complete disap- 
pearance in four minutes. 
Methods of Showing Lysin Action.—The presence of 
lysins may be demonstrated by making slides at intervals from 
a mixture of bacteria and immune serum and comparing the 
number of organisms visible with the aid of a microscope. In 
another method the serum and bacteria are mixed in larger 
amounts in a test tube, and at intervals, small but definite 
153 154 
HOW WE RESIST DISEASE 
amounts are taken out and used in making agar plates to de- 
termine how many live bacteria remain. After these plates have 
been incubated to allow the live bacteria left in each amount to 
develop into colonies, the colonies are counted, the difference in 
Increase in. Bactericidal Po^er 
Fig. 107.—On the second day, the subject was inoculated with ty- 
phoid vaccine. After the initial drop, the bactericidal power reached normal in 
about a week, and continued to rise during the three-week observation period 
that followed the inoculation, Redrawn from Wright. British Medical 
Journal. 
the counts of the various agar plates made including the rate 
at which the bacteria have been killed off. 
Source of the Lysins.—The production or action of lysins 
has no relation to the presence of opsonins or white corpuscles. 
As indicated in the opening paragraph, this dissolving power of 
the serum is not to be confused with the similar destructive action 
of white corpuscles. The end results are the same, but the LYSINS 
155 
process is very different—so different that the claim that the 
serum lysins are formed in the white corpuscles cannot be ac- 
cepted. One of the most striking differences is that the action 
of the serum lysins can be destroyed by heating the immune 
serum (60° C.) and then renewed by adding a little normal 
blood, although normal blood itself lacks this destructive power; 
white corpuscles or their extracts cannot be reactivated in 
this way. 
White corpuscles are therefore evidently not the source of 
the lysins. Some investigators have, on the basis of their experi- 
Fig, 108.—Stages in the lysis or dissolution of cholera organisms (left to right) 
before final dissolution occurs. Karsner and Ecker, Principles of Immunology, 
J. B. Lippincott Co. 
merits, designated the liver or the thyroid as the lysin producer, 
but as yet we can not positively attribute to any special gland 
or tissue the production of lysins. (See p. 48.) 
Red Corpuscle Lysins.—Lysins are formed not only against 
bacteria but against other foreign cells. Most of the experi- 
mental and laboratory work with other than bacterial cells, has 
been done with red blood corpuscles. If the red corpuscles of 
one animal such as the cow, are injected into an animal of 
another species, the guinea pig, for example, the injected animal 
develops lysins to aid in disposing of the “ foreign ” red cells 
injected. Whether or not such lysins have been formed, may be 
demonstrated (Plate 3.) by mixing together in a test tube the 
serum of the injected animal (guinea pig in the above discus- 156 
HOW WE RESIST DISEASE 
sion) and washed red corpuscles of the same species as those 
with which the animal has previously been injected (cow). 
If no lysins have been formed, the red blood corpuscles in the 
mixture finally settle by gravity to the bottom of the tube, leav- 
ing a colorless liquid above them. If lysins are present, they 
dissolve out the red coloring matter, and the colorless remnants 
of the corpuscles settle to the bottom of the tube, but the hemo- 
globin being now in solution, does not settle with the corpuscles, 
and the liquid in the tube does not clear but remains red through- 
out. Lysins that affect red corpuscles and their contained 
hemoglobins in this way, are called hemolysins in contradistinc- 
tion to those affecting bacteria (bacteriolysins). 
Specific Character of Lysins.—Lysins are specific, whether 
formed against bacteria, or against other types of cells, such as 
red corpuscles. For example, lysins formed by a guinea pig 
against the red blood cells of a cow do not hemolyze human red 
cells, and vice versa. It is therefore possible to test the blood 
serum of such injected animals against samples of blood (obtained 
from meat, blood stains, etc.), and so determine the kind of 
animal from which the meat or blood originated. 
To illustrate, a man accused of murder may be cleared or 
convicted by a study of the blood stains that led to the charge, 
and which he claims were caused by an animal other than man. 
In such a test, the blood corpuscles are washed out of the stain, 
and then they are tested against the serum of a laboratory animal 
(e.grabbit) which has been injected at suitable intervals with 
human red corpuscles. If the corpuscles washed out of the stain 
are human corpuscles, the serum of such a rabbit will dissolve 
them and the test tube contents will remain red (PI. 3.). If the 
corpuscles from the stain are not human, they will not be dis- 
solved by the serum and will settle unbroken to the bottom of 
the tube, and the contents will gradually clear (See Plate III). 
The results are evident in one to three hours; (an additional 
period of 12 to 24 hours at ice box temperature often aids 
in interpretation). 
It is, of course, also easy to prove or disprove the defendant’s 
statement regarding the kind of blood (cow, pig, dog, etc.) in the 
stain under investigation, by using in a similar way, the serum Plate III A.—Tube showing dissolving (lysis) of red corpuscles; the red coloring 
matter has escaped from the corpuscles, and such tubes will therefore not clear 
on standing. 
Plate III B.—Human blood stains give a positive test (right tube) with the serum 
of a laboratory animal which has been injected with human red cells and negative 
results (left tube) with the serum of a laboratory animal injected with red cells of a 
dog, pig, etc. LYSINS 
157 
of a laboratory animal which has been injected with the cor- 
puscles of the animal the defendant mentioned. 
Blood tests of this kind—both in murder trials and in other 
legal situations, such as determining the type of meat sold—are 
more commonly used in European countries than in the United 
States. In this country more dependence is placed on delicate 
chemical tests (substances present, types of crystallization) as in 
the heinin test. (See also blood tests under agglutinins 
and precipitins.) 
Long-dried blood stains do not lend themselves so well to this 
test, as the red cells may be already broken up. In such cases 
the precipitin test (p. 126) would be employed to ascertain the 
kind of blood in the stain. 
Normal Lysins for Human Red Corpuscles.—The blood 
of one person may contain lysins against the red corpuscles of 
another individual. If time allows, tests are made before trans- 
fusing blood from one person to another, in order to make sure 
that the blood to be transfused is not too “ foreign ” to yield the 
expected benefits. (See also p. 125.) In cases of anemia or 
where much blood has been lost, as in severe wounds or hemor- 
rhage, no benefit would result from transfusing blood corpuscles 
that are straightway destroyed, for if the transfused corpuscles 
are to serve as “ carriers of oxygen ” they must remain intact in 
the blood stream of the patient. Whenever possible, therefore, 
the blood offered for transfusion, is first tested against the 
patient’s serum to see if the serum contains any lysins against 
the volunteer’s red corpuscles. Usually samples are taken from 
several volunteers, and tested at the same time, to avoid unneces- 
sary delay in finding suitable blood for transfusion. The blood 
selected for transfusion, will, of course, be that in which the 
corpuscles were so like the patient’s that no lysis takes place, the 
whole or unbroken corpuscles settling to the bottom of the tube 
and the liquid becoming clear. (See also p. 125.) 
Bacterial lysins, because of their specific character, lend them- 
selves to diagnosis of disease, and tests based on their presence 
are now used in several diseases (See p. 159), the patient’s serum 
being tested against the suspected organism to see if special 
lysins for those organisms are present. Unlike the case with red 
corpuscles, such mixtures of serum and bacteria give no color or 158 
HOW WE RESIST DISEASE 
other visual evidence regarding serum lysins. The microscopic 
and plate count methods described on page 153 were developed 
for indicating and measuring bacterial lysins. At present, how- 
ever, a peculiarly complicated but interesting method of dem- 
onstrating their presence or absence has been devised (to be 
described later, p. 160), which is based on one of Bordet’s contri- 
butions to the subject of lysins, i.e., that a lysin is not a single 
but a double substance or factor. 
Lysins not a Single Factor.—A puzzling inconsistency be- 
tween the results obtained with immune serum in living animals 
and in test tube experiments, led to the discovery that a lysin is 
made up of two substances: one substance common to normal as 
well as immune blood, and the other a special immune sub- 
stance specific for the organism which called it into existence. 
In early guinea pig experiments with cholera, it was found 
that the immune serum formed by a guinea pig against cholera, 
contained a lysin for cholera organisms. This lysin killed cholera 
organisms equally well, whether used in test tube experiments or 
injected with virulent cholera organisms into a guinea pig. If the 
immune serum were heated to 60° C., however, it lost its power to 
act in test tube mixtures with cholera organisms, but strange to 
say, still protected a guinea pig as effectively as the unheated 
immune serum. 
This inconsistency was explained by Bordet when he showed 
that a lysin contains two substances. One substance is common 
to normal as well as immune serum and is very susceptible to 
heat, being destroyed at 60° C. or even lower temperatures. The 
second substance is the immune part of the lysin; this is usually 
found only in immune serum, and is quite resistant to heat, sur- 
viving 60° C. 
Both of these substances are necessary for the lysis or disso- 
lution of bacteria. In the test tube mixture of cholera and serum, 
therefore, no action takes place if heated serum is used. Since 
heating the serum, however, destroyed only a substance with 
which the normal guinea pig is well supplied, but left the im- 
mune part of the serum, the heated serum was therefore as 
effective in protecting a guinea pig, as the unheated serum. 
But if, to the test tube containing the bacteria and heated 
immune serum mixture, a little normal guinea pig serum is added, 
the action will now be exactly as effective as if unheated immune Plate IV A.—Results using the heated and the unheated serum of laboratory animal 
(guinea pig) injected with red blood cells of another animal (rabbit). The unheated serum 
(right tube) contains both the immune bodies and complement, therefore can dissolve rabbit 
red blood cells; the heated serum (left tube) has had its complement destroyed and cannot 
complete the combination (P. lo8) necessary to dissolve the red blood cells, and they 
have settled to the bottom unbroken. 
Plate IV B.—In a comp'ement-fixation test, such as the Wasserman test, a com- 
p'etely positive result is shown in 1, a wholly negative one in 4; grades between the 
two are shown in 2 and 3. Patients improving under treatment progress from 1 to 4, 
intermediate grades being recognized ( + + + +. + + + &c. of laboratory reports). LYSINS 
159 
serum had been used, showing that the normal serum has com- 
pleted or complemented the action of the heated serum. The 
constituent supplied by normal serum is therefore termed 
complement. 
Complement not Specific.—As stated above the comple- 
ment factor is not specific, but is found in normal blood. The 
same complement aids in complementing the action of the im- 
mune substances formed in the blood of such widely differing 
animals as man and the guinea pig; and normal guinea pig 
complement is commonly used to complete the action of human 
serum in many w'ell established tests. 
And the kinds of cells which are destroyed 
by the aid of the complement include the 
greatest possible range, for normal com- 
plement from the same animal can be 
used satisfactorily in tests against bacteria 
(pertussis, in whooping cough tests, or 
gonococci, in gonorrhea); against pro- 
tozoa (the spirochagtes of syphilis); and 
against red blood corpuscles (of man, 
cow, sheep, rabbit, etc., in blood tests). 
The preceding examples are given in 
an attempt to illustrate how a single type 
of complement can bind together many 
very different kinds of immune bodies and 
invading organisms. (Complement itself 
is probably a double substance, but since we are here interested 
only in the general phase of the subject, it is not possible to 
consider the lesser differences that do exist in various comple- 
ments). Complement is apparently not increased during disease, 
after vaccination, etc. While the source of complement has not 
been demonstrated, it may, as some workers believe, be formed 
in the white corpuscles. It is quite possible that complement 
plays a very important role in the normal body, e.g., in the 
utilization of foods (Fig. 109). At any rate, its importance in 
the destruction of foreign cells is as great as if it were as specific 
as the other antibodies, for the immune part of the lysins cannot 
work without complement. 
Diagnosis of Disease.—Blood determination tests by means 
of lysins have already been described (p. 157). Lysins may also 
Fig. 109.—Wholly dia- 
grammatic representation of 
the source of complement 
present in normal blood. 
Ordinary “metabolic” proc- 
esses such as cell utilization 
of food probably account for 
the presence of complement 
in normal blood. 160 
HOW WE RESIST DISEASE 
be used to prove that an individual has or has had certain dis- 
eases by showing that his serum contains special or specific lysins 
against the disease in question, just as described on page 155 
for cholera guinea pigs. 
A special technique has been developed for demonstrating 
the presence of these serum lysins which is both quicker, more 
exact, and more delicate than the microscope or plate count 
method described at the beginning of this chapter. This special 
technique utilizes four of the principles 
already discussed: (1) a lysin is a double 
not a single substance; (2) the comple- 
ment part of the lysin is readily destroyed 
by heat and the immune part is not; 
(3) complement is but slightly or not at 
all specific in its binding power; and (4) 
complement combinations once made are 
stable. Let us briefly describe in a general 
way an early form of the lysin or comple- 
ment-fixation test for syphilis in which 
the complement is combined or fixed 
(complement fixation test),and the reader 
may afterward locate for himself these 
four principles. 
General Description of Complement 
Fixation Test.—A sample of the patient’s 
serum is heated to 60° C. This destroys 
the complement always present in blood or serum, but leaves in it 
the specific immune part of any contained lysin against syphilis. 
This (1) heated serum of the patient is put into a test tube 
with (2) syphilis organisms (a culture of syphilis organisms 
or a piece of syphilitic tissue such as the liver containing syphilis 
organisms) and (3) a limited amount of complement from 
normal blood, e.g., a guinea pig. If the patient has syphilis, 
the immune part of the lysin in his serum will unite with the 
syphilis organisms, and both of these substances will be bound 
together by the guinea pig complement. 
All this has been described before. The new and ingenious 
part of the test consists in adding at this stage red blood cor- 
puscles to show whether or not the three substances have been 
bound together—whether or not the complement has been used. 
Fig. 110.—Diagrammatic 
representation of the com- 
bination of a given organism 
and the specific “immune 
body”, held together by the 
“locking” complement. 
The joining surfaces of the 
syphilis organism and the im- 
mune body formed against 
syphilis are matched to indi- 
cate the specific character of 
the immune body. After 
Zinsser, Infection and Re- 
sistance, Macmillan. LYSINS 
161 
To the test tube, therefore, are now added two more things which 
are themselves also capable of using the complement, and which 
need it to complete their combination: the red blood cells of a 
sheep, and the heated serum of another animal, a guinea pig, 
immunized against sheep cells and which therefore contains the 
stable immune part of the lysins the guinea pig has made against 
the sheep corpuscles. The guinea pig serum is heated to destroy 
its own complement; that means that these last added substances 
(sheep corpuscles and heated guinea pig serum) will have to 
depend on the complement already in the tube for their com- 
plete combination. 
Fig. 111.—Complement making the left hand combination is not able to make the 
right hand one also. In such cases the red corpuscles will not be dissolved, and the tube 
will clear as the unbroken cells settle to the bottom. After Zinsser, Infection and Resis- 
tance, Macmillan. 
If the patient has syphilis, and, therefore, lias the immune 
part of the lysin in his serum, the limited amount of comple- 
ment present in the test tube mixture will all be combined in 
the first part of the above test, and, therefore, will not be free 
to unite with the red corpuscles and the specific immune part 
of the guinea pig serum or lysin which were added afterward. 
The red corpuscles will, therefore, sink unbroken to the bottom 
of the tube. In other words, the complement having made the 
first or syphilis combination, as indicated by the heavy arrow in 
(Fig. Ill) above, cannot also make the red corpuscle combi- 
nation indicated by the dotted arrow. 
If the patient’s serum does not contain the immune body for 
syphilis, the syphilis organisms alone will not he able to hold 
the complement in combination, and the complement will there- 162 
HOW WE RESIST DISEASE 
fore be free to make the second combination with the red cor- 
puscles indicated by the dotted arrow. 
In this event the hemoglobin will be dissolved out of the red 
cells, the liquid becoming red throughout. And, having thus 
demonstrated that the patient’s serum lacks the reacting lysins 
for syphilis, we conclude that he has not syphilis. Such colora- 
tion of the tube is therefore called a negative test or result for the 
Fig. 112.—If the immune substance which helps hold the complement is lacking, the 
complement will be free to dissolve the red cells. A flushed or reddened tube indicates the 
lack of such specific immune substances in the patient’s serum, and is termed, therefore, a 
negative test. After Zinsser, Infection and Resistance, Macmillan. 
disease organism represented in the first combination in the tube 
mixtures. A clearing tube, as described in the preceding para- 
graph, indicates on the contrary, that the patient did have syphi- 
lis and is therefore termed a positive test * or result. (PI. IV.) 
* The degree of reaction of any individual in a given infection 
may be gauged in a general way at least by the amount of antibodies 
produced. Since acute or serious infections would demand a plentiful 
supply of the specific antibodies, it is natural to consider a higher 
production of lysins, for example, as indicating a greater need for such 
lysins, and therefore implying a more serious or intense form of 
the disease. 
Positive tests for syphilis often show a great variation in the 
amount of lysin present as judged by the red color changes in the 
Wassermann test (PI. IV). Serum containing a high production of lysin 
would use up all the complement and therefore the tubes would remain 
absolutely clear. Serum low in lysin antibodies might not use it all, 
and would therefore leave some complement for combination with the 
red cells. The serum of such a patient would be described as weakly 
positive. In ordinary practice, four grades of positive results are usu- 
ally recognized and the degree of each indicated by + or positive signs, 
—]-+,+++)++) and +. As a patient improves under treatment 
his reactions change from + + H—b to -j- types and finally, on recovery, 
to wholly negative (—) results. LYSINS 
163 
Such tests, it is evident, must be very carefully made. For 
example, if too much complement is put into the tube in the first 
part of the experiment, enough will be left over to make the 
second combination, and so a colored liquid will result—giving 
an apparently negative test—even when the patient has syphi- 
lis (Fig. 114). 
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RSer. 
Comp. 
S.Oro. 
R Ser. 
Fig. 113.—Tubes showing the substances used in the Wasserman test, the order in 
which they are mixed, and the fate of complement in negative and positive cases, as described 
in the text and in the preceding illustrations. 
Modifications of the Wassermann Test.—The test just 
described gives in a general way an early form of the complement 
fixation test for syphilis, known as the Wassermann test. Many 
modifications have since been made in this test, such as the use of 
other kinds of red corpuscles; for example, in one method 
human red cells and serum from rabbits injected with human 
red cells are used to make the second part of the combination. 
The most notable modification is perhaps one by Noguchi. 
Instead of the syphilitic organisms themselves may be substituted 
other reacting materials or antigens, such as heart muscle extracts 
(cow, guinea pig). These extracts (acting through their pecul- 
iar lipoid or protein-lipoid content probably), make surprisingly 164 
HOW WE RESIST DISEASE 
satisfactory substitutes for the syphilitic mate- 
rial or antigen, as it is called. In certain stages 
of syphilis the results with these antigens cor- 
respond more nearly to clinical diagnoses than 
when the syphilitic material itself is used in 
the test. 
Such substitutions make these tests seem 
much more complicated—and very much more 
difficult to describe in a noil-technical way, but 
very often simplify greatly the preparatory work 
involved in such a test; for example, it is a 
much simpler matter to secure a heart muscle 
extract than satisfactory syphilitic material. 
Descriptions of such tests sound complicated 
because we have really two overlapping tests 
made in one tube; the ingenious part of the test 
lies in using, for the second part of the test, 
a combination yielding color changes, so that 
one can judge by the visible results of the second 
part what did or did not take place in the first 
part of the experiment. This red corpuscle 
method of indicating the presence or absence 
of lysins is superior to the slower method of 
making, incubating, and counting agar plates 
(p. 154), not only in regard to time but also 
with regard to the delicacy and accuracy of the 
results obtained. Where it is difficult or impos- 
sible to cultivate the organisms under laboratory 
conditions, as with syphilis, this red corpuscle 
method is the only one that can be used. 
Reliability of Complement Fixation 
Tests for Syphilis.—In such tests, as with the 
tests for agglutinins or all other body reactions, 
early or incipient stages of disease are not 
always correctly diagnosed. If the tests fail in 
these advanced stages the clinical symptoms are 
usually strongly indicative. Other diseases 
such as malaria, scarlet fever, leprosy, and sleeping sickness may 
interfere with the proper diagnosis of syphilis and misleading 
TtoCor. 
GP.Ser. 
\CoTTip. 
fComp. 
S.Oro. 
iRSer. 
Fig. 114.—If an 
excessive amount 
of complement 
is present, there 
may be enough to 
make the red blood 
cell comb i n a t i o n 
indicated b y t h e 
upper brace in the 
tube, even though 
the patient had 
syohilis and the us- 
ual amount of com- 
plement was used 
in the first part of 
the procedure. 
This would lead to 
a false conclusion 
of “negative.” This 
shows how carefully 
the measurement of 
the respective sub- 
stances must be 
done and how im- 
portant it is that 
such tests should be 
made by r e 1 i a b le 
laboratories. LYSINS 
165 
positive results may he obtained. Treatment with certain curative 
preparations containing mercury and salvarsan may cause nega- 
tive results, even though the patients are not yet cured; and 
after such treatment, repeated negative tests for a long period 
(three at intervals of six months) should he obtained before the 
Fig. 115.—Human brain tissue, (congenital syphilis) containing syphilis 
organisms, Treponema pallidum, (x 960). Leo M. Powell. 
individual is considered free from disease. Alcohol, too, may 
weaken the reaction in such tests, and anaesthetics may give false 
positive reactions. 
Nevertheless, the many years of experience with this test, indi- 
cate that the tests of the blood or spinal fluid if properly carried 
out give accurate results in 80 to 88 per cent, of the cases in all 
except the early stages (first five to six weeks). Some workers 
claim a still higher per cent, of accuracy—90 per cent, or more 
in all active general infections. 166 
HOW WE KESIST DISEASE 
Other Diseases Diagnosed by Complement Fixation 
Tests.—Complement fixation tests are used in several other 
diseases. In each the serum of the patient is tested with known 
bacteria—one or more strains of the suspected bacteria being used 
in various forms: alcoholic and ether extracts of dried bacteria, 
emulsions of centrifuged residue of washed cultures, etc. 
In typhoid infections 
the complement fixation 
test is used mainly to 
corroborate the agglu- 
tinin results. In whoop- 
ing cough, the pertussis 
bacillus, considered by 
many the causal organ- 
ism, has given positive 
reactions in about 50 per 
cent, of a large number 
of cases in which the 
serum of the patients was 
tested by this method. 
For glanders, the Hew 
York City Health De- 
partment finds the com- 
plement fixation test less 
reliable than the agglu- 
tination test in very acute 
cases because the agglu- 
tinins are the most abun- 
dant antibodies in the 
early stages. For more chronic cases the complement fixation 
test is considered best. Used together, it is claimed that these 
two will give a correct diagnosis in 99 per cent, of the cases. 
The complement fixation test is used by most workers to corrobo- 
rate the agglutinin test and has not supplanted it. 
In meningitis, the results by the complement fixation test are 
satisfactory, but the diagnosis of meningitis can be too satis- 
factorily and quickly made by microscopic and chemical exam- 
ination of the spinal fluid to make it worth while to fully develop 
Fig. 116.—Disintegrating effects of the 
syphilis organism, Treponema pallidum; the liver 
substance (new-born child) in which these organ- 
isms are living is wholly unrecognizable. ,(x880). 
Adami and Me Crab, Text Book of Pathology, 
Lea and Febiger. LYSINS 
167 
this method. This test is, however, used when it is desired to 
distinguish the types of meningococcus from each other. 
In tuberculosis, the outlook is very encouraging; investi- 
gators showing that while the complement fixation test does not 
show up incipient cases, it does give positive reactions in “ 75 
per cent, to 95 per cent, of clinically active pulmonary ” cases. 
It is also stated that, unlike the much-disputed tuberculin re- 
action, it gives positive reactions in active cases only and not in 
healed lesions. Contrary to the statements of early investigators 
in this field, this test is specific, and gives a positive reaction in 
tuberculosis only. 
The complement fixation test is an accepted test in gonorrheal 
infections. Though not reliable in the early stages (before the 
fourth week) and though it sometimes fails to give positive 
reactions in certain types of gonorrheal infection, such as acute 
vulvovaginitis, when positive reactions are obtained they are con- 
sidered reliable, if it is remembered that the positive reactions 
may continue one or two months after a cure has been effected. 
It may well be, that as encouraging data can be given for these 
five diseases as for syphilis, when a corresponding amount of 
work has been devoted to them. Recent work indicates the prob- 
ability that similar tests may be applicable to malignant tumors. 
Complement Fixation in Standardizing Serum.—An im- 
portant though relatively recent use of the complement fixation 
test is made in standardizing immune serums, measuring the 
strength of serum by the power of varying dilutions or amounts 
of the serum to fix or combine with known amounts of comple- 
ment and standard preparations of bacteria. 
After these three substances (serum, complement and bac- 
teria) have been properly diluted and mixed, red corpuscles and 
an immune red corpuscle serum are added—the usual comple- 
ment fixation test. The principal serum tested in this way is 
meningitis antiserum. (See also p. 124 and p 138.) 
Protein Tests.—The complement fixation method affords a 
more delicate test than the precipitin tests for detecting foreign 
proteins or differentiating between various proteins. The un- 
known protein is tested against the serums of different animals 
each injected with a special protein. The method is essentially 
that already described for diagnosing disease, the results being 168 
HOW WE RESIST DISEASE 
made visual in the same way by later additions of red corpuscles 
and an immune red corpuscle serum. By this method it is pos- 
sible to detect foreign proteins when the amount present is too 
small to be visible by the simpler precipitation methods. 
STUDY SUGGESTIONS 
1. What are lysins? Give four diseases against which lysins are im- 
portant aids. 
2. Explain why we think lysins are “double” substances. 
3. Show how lysins may be used in identifying samples of blood. 
a. Contrast complement and the immune part (immune body or ambo- 
ceptor) of lysins in specificity, resistance to heat, and their 
presence and absence in normal and immune individuals. 
5. Consult an advanced text on bacteriology or pathological diagnosis 
for a more complete description of the Wassermann test and 
write up a negative and a positive test as simply and as briefly 
as you can. 
ti. Compare the Wassermann test with a very different test such as 
the “colloidal gold” test for syphilis, showing the difference in 
theory or principle in each test. 
7. Among the directions for treating an animal to cause it to produce 
lysins for use in blood tests we find: 
(1) Wash and centrifuge the blood cells to be injected in 
salt solution. 
(2) Inject 5 to 20 c.c. of the washed blood cells at intervals 
of 5 or 6 days. 
(3) Blood may be drawn six or more days after the third 
injection. 
Answer as many of the following questions as you can: 
(a) Why are the blood cells washed? 
(b) Why are three sets of injections used instead of one? 
(c) If it is desired to continue to obtain blood through 
a period of several months wliat supplementary direc- 
tion should be added to the above? CHAPTER IX 
VACCINES 
Unchanged and similar organisms 
Attenuated organisms 
Killed organisms 
Main types 
Extracts 
Toxins 
Bacterial products 
Partly neutralized 
Sensitized vaccines 
Toxin-antitoxin 
Autogenic 
Xon-specitic 
Polyvalent 
Mixed 
Vaccines 
Specificity variations 
Terminology 
Vaccine, virus, bacterin 
Antigen 
Preparation 
Dosage 
Standardization 
Present status 
Treatment 
The oldest field of bacteriology is that of vaccines, for the 
control and prevention of disease by the direct use of micro- 
organisms began centuries ago. But despite the fact that the 
period of investigation along this line is measured by centuries, 
while that of antitoxins and other phases of immunity is measured 
by decades only, the most important modifications and advances in 
vaccines have been made in the last few years. 
Early Methods of Transferring Smallpox.—Even cen- 
turies ago, several of the Asiatic peoples purposely transferred 
smallpox by such practices as wearing the clothing or sleeping 
in the beds of people recovering from light cases of smallpox. The 
Chinese transferred smallpox still more collecting pus 
from smallpox pustules on bits of wool, etc., and placing them in 
the nostrils of the person who wished to contract the disease. In 
Turkey, a still more direct method of transferring smallpox 
169 170 
HOW WE RESIST DISEASE 
organisms was practiced, the pus from a mild case being inserted 
into or under the skin. 
An individual inoculated in any of these ways from a mild 
case was likely to have a similarly mild attack. While this did 
not always prove true, the risk was a slight consideration in an 
age when the only choice was—not whether one would contract 
smallpox or not—but when one would have it; under such con- 
ditions it was wiser to endeavor to contract a mild form of the 
disease, than to take one’s chances in the next epidemic. 
Control by Inoculation.—The Turkish method of direct 
inoculation was introduced into Great Britain in 1718 by an 
English woman, Lady Montague, who had had one of her chil- 
dren inoculated during a short residence in Turkey. This method 
was continued in England for over a century—until forbidden 
by a special act of Parliament, owing to the perfection of 
.Tenner’s new and more reliable method of preventing small- 
pox. (1840) 
In our own country the inoculation method was practiced 
much longer, however; as late as 1863 the people of Richmond, 
Va., were besought by a house to house canvass to have their 
children inoculated that the scabs containing smallpox organisms 
might be collected to provide material for the inoculation of 
soldiers in the Confederate army. 
Protection by Using Similar Organisms.—There was cur- 
rent among English dairy people the opinion that those who had 
had cowpox did not later develop smallpox. Acting on this idea, 
a farmer named Jesty, in 1774, inoculated his wife and two sons 
with pus from a cow having cowpox, and to this he attributed 
their later immunity to smallpox. 
Real proof, however, that cowpox protects against smallpox 
was first given by Jenner, a doctor, who inoculated with small- 
pox pus, ten people who had previously had cowpox, the interval 
between the earlier attack of cowpox and the inoculation with 
smallpox ranging from nine months to fifty years. Not one of 
the ten contracted smallpox. For further proof, in 1796, Jenner 
inoculated a boy with pus taken from the hand of a dairymaid 
who had become infected with cowpox. Six weeks later, and 
again several months afterward, Jenner inoculated the boy with VACCINES 
171 
real smallpox pus, but both times the boy proved resistant to the 
smallpox thus inoculated. 
The explanation accepted for the resistance to smallpox in 
all these instances, is that cowpox organisms are so like smallpox 
organisms, that the body reacts against them in practically the 
same way as against smallpox, and therefore, each person recover- 
ing from cowpox has in his body reacting substances that fully 
protect against the smallpox organisms when he is later exposed 
to smallpox. 
Since in these cases the infectious material came from a cow, 
it was called vaccine (from vacca, a cow). The original vac- 
cines were. (1) living organisms, and (2) cultivated in the body 
of a living animal, the cow. It will be interesting to trace in the 
following pages the changing meanings attaching to the 
term vaccine. 
Protection by Weakened Organisms.—Cowpox and small- 
pox organisms may be considered as similar organisms. More 
general, however, is the feeling that cowpox is a modified or atten- 
uated form of smallpox—that the disease was originally a human 
disease which has been transferred to cows by human contact and 
the less virulent character of cowpox is due to the fact that the 
original smallpox organisms have been weakened by the period 
spent in the cow’s tissues. (See p. 63.) 
It was Pasteur, however, who first developed a method of 
weakening or attenuating organisms by laboratory procedures, 
so that they might be used as vaccines. 
In 1880, while Pasteur was working on fowl cholera, by an 
accident some hens were inoculated with an old culture of fowl 
cholera organisms made a few weeks before, instead of a fresh 
culture but a day old such as he had been using for that pur- 
pose. The hens sickened, but contrary to all of Pasteur’s pre- 
vious results, afterward recovered. Later, when these recovered 
hens were inoculated with fresh cultures of fowl cholera, they 
proved to be immune while the control hens died. 
Pasteur properly interpreted this as indicating that the hens 
survived because they had been sufficiently irritated by the age- 
weakened organisms to produce enough reacting substances for 
full protection against the fresh, vigorous organisms used in the 
later or second inoculation. 172 
HOW WE RESIST DISEASE 
It was essentially the same situation as when the cowpox 
organisms were used to protect against the more virulent small- 
pox organisms. The only difference was that the fowl cholera 
organisms had been weakened by unfavorable laboratory condi- 
tions, while the cowpox organisms had been affected by the 
conditions met in the living tissues of the cow. 
Pasteur and his associates included in their study of weakened 
organisms, the effects of other laboratory conditions besides age: 
unfavorable temperatures, chemicals, etc. Pasteur’s best known 
contribution in this line, however, was made with rabies, the 
rabies organisms being attenuated by drying. In this case, the 
organisms themselves not having been isolated, they were weak- 
cned by drying the brain (medulla) and spinal cord of rabid 
animals, as it Avas found that these tissues contained 
the organisms. 
With such dried tissues Pasteur demonstrated that by grad- 
ually using organisms that Avere less and less Aveakened (dried 
for relatively shorter periods), he could protect dogs from rabies 
if they were later bitten by rabid animals or inoculated by him 
with saliva or brain tissue containing rabies organisms. lie also 
proved that it was possible to protect dogs in the same Avay even 
if they were bitten or inoculated before he began treatment with 
the Aveakened organisms. The explanation is that rabies organ- 
isms develop very sloAvly, and therefore, before the feAV organ- 
isms entering when the dog is bitten can multiply sufficiently to 
produce rabies, the dog forms sufficient protecting antibodies 
against the numerous weakened organisms given in the series 
of inoculations. This method is now commonly used to protect 
people who have been bitten by rabid animals, but it Avas first 
tried by Pasteur in 1885, on an apparently hopeless case, a little 
boy terribly bitten (hand, legs and thighs) and covered Avith blood 
and saliva. Although the child Avas not brought to Pasteur until 
two and one-half days after being bitten, Pasteur undertook the 
case, beginning the treatment with spinal cord dried (Fig. 117) 
for fourteen days. On the tenth day he gave the last inoculation 
with spinal cord dried but one day. The successful outcome of 
this and another apparently hopeless case, in which treatment 
had been deferred for six days, brought Pasteur international 
reputation, (Four children from the United States Avere sent by VACCINES 
173 
a New York newspaper to Pasteur for treatment) and firmly 
established the use of attenuated organisms as vaccines. Now our 
large cities have “ Pasteur Institutes ” or similar divisions of 
the Health Department for developing immunity to rabies by the 
use of weakened organisms.» 
Killed Or- 
ganisms as Vac- 
c i n e s . — As 
shown above, 
weakened organ- 
isms arouse 
much the same 
reactions as or- 
dinary live or- 
ganisms. In the 
first dose given 
in rabies treat- 
ment, most of 
the organisms 
(Pig. 118 a, b.) 
have doubtless 
been killed by 
the long drying 
period just de- 
scribed. These 
dead organisms 
contain or are 
composed of 
much the same 
irritating sub- 
stances as the live 
ones, and so 
begin the stimulation of the same reactions which the live 
organisms induce much more vigorously. Each succeeding dose 
in the series of inoculations given in treated rabies, contains 
relatively more and more live organisms; this is necessary be- 
cause dead organisms alone do not arouse sufficient body reactions. 
In many diseases, however, dead organisms are sufficient. If 
the bacterial effects are due mainly to the toxins which they 
Fig. 117.—Method of drying sections of spinal cord 
before injection as vaccine; two pieces of cord are shown 
suspended over a water-absorbing chemical. Stimson, U. 8. 
Bureau of Animal Industry. 174 
HOW WE KESIST DISEASE 
form, these same toxins are sufficiently represented in the broth 
in which the bacteria are grown. If the effects are due to the 
disintegrating proteins of the bacterial cells, this disintegration 
may take place even more rapidly when dead bacteria are used 
than when live cultures are inoculated. There is often a great 
advantage in using killed organisms, for though the protecting 
substances they excite may not be so lasting, it is possible to 
measure the doses much more accurately and to predict their 
effect much more definitely. It is possible also to give with safety, 
relatively much larger doses than when live organisms are given, 
for the effects of killed bacteria are limited, since they can not 
multiply in the body. 
In the United States the most widely used vaccine made of 
killed bacteria is typhoid vaccine. Staphylococcus vaccine (boils, 
skin eruptions) probably ranks second. 
Bacterial Extracts as Vaccines.—Bacterial extracts (alco- 
holic or glycerine extracts or emulsions of broken or disinte- 
grated bacteria) may be used instead of killed bacteria as vaccines. 
All vaccines—even living ones—contain some disintegrated bac- 
terial substances. Bacterial extracts have been advocated for 
two reasons: (1) Such extracts contain relatively more of the 
toxins or other characteristic irritating substance. Since all 
foreign protein is irritating when injected in this way, it would 
be a great gain if only the necessary irritating substances could 
be given. (2) Another reason advanced is the more rapid ab- 
sorption * of such bacterial extracts or partly digested bacteria. 
This absorption, however, may be too rapid; instead of causing 
the quicker response desired, it may overpower the body before 
the responses are aroused. Little if any practical use is, as yet, 
made of such bacterial extracts. 
Toxins as Vaccines.—It is not the custom to speak of 
toxins as vaccines, but there is no real reason why toxins should 
not be included as a fifth of the series of substances we have been 
* This difference in the absorption rate is illustrated by Vaughan’s 
experiments with three types of preparations of the colon bacterium— 
live bacteria, killed ones, and his specially prepared extract (split- 
proteins) of the colon organism. The guinea pigs injected with the 
living organism showed no symptoms for five to twelve hours, and death 
occurred in one and a half to two days; inoculations with the killed 
bacteria caused death in six to twelve hours, and the guinea pigs 
receiving the extract died in thirty to sixty minutes. VACCINES 
175 
discussing: (1) Live organisms; (2) attenuated organisms: 
(3) killed organisms; (4) extracts; and (5) toxins. 
(See also p. 98.) 
Such toxins are ordinarily obtained by filtering the broth 
cultures of the desired bacteria, e.g., diphtheria. These filtrates, 
loosely called toxins, contain much besides the soluble toxins— 
such as the broth itself and other products of ordinary growth 
and metabolism. 
When these toxin filtrates are injected into the body, the soluble 
toxins are carried by the blood stream throughout the body, just 
Fig. 118 A.—Rabies organism or Negri bodies. Nucleated bodies from cultures 
are shown in 1, 11 and 12. 
as they would be distributed from a disease focus in the body, e.g., 
the throat patches in diphtheria. Toxins are given horses to cause 
them to produce antitoxin for diphtheria or tetanus. It is only 
recently—to prevent diphtheria—that toxins have been injected 
into human beings to stimulate their own production of antitoxins. 
“ Sensitized Vaccines ” and “ Toxin-Antitoxin.”—A 
vaccine is sometimes modified by allowing it to stand for some 
hours mixed with the antiserum formed in response to that par- 
ticular organism, e.g., Shiga’s dysentery organism. Such modi- 
fied vaccines are termed “sensitized vaccines” or “sero-vaccines.” 
Much the same result is secured by injecting a vaccine and its 
respective antiserum simultaneously. 
Antitoxins may similarly he used to modify toxin, in the same 
way as antiserum and its respective vaccine are combined. (See 
p. 98.) Diphtheria toxin, when it is used to produce immunity 
to diphtheria, is thus modified by the addition of antitoxin. This 
combination is called “ toxin-antitoxin.” In both the “ sensitized 
vaccines ” and the “ toxin-antitoxins,” larger doses may be given 
than if simple vaccines or simple toxins are used. As explained on 176 
HOW WE RESIST DISEASE 
page 99, the antitoxins or antibodies apparently do not neutralize 
part of the vaccine,leaving the balance unaffected, but instead tend 
to distribute themselves over the whole amount of toxin or vaccine 
weakening every particle of it, thus making it possible to give a 
larger dose of stimulating but somewhat less irritating material. 
The desired body reactions are, therefore, aroused with much 
less “ shock ” or other undesirable symptoms. 
Autogenous Vaccines.— 
Since there are many closely 
related species and even dif- 
ferent varieties of some organ- 
isms, it is evident that a person 
vaccinated with one species or 
variety of a bacterium, such as 
streptococcus, may not gain 
full protection against a re- 
lated species or variety. Some- 
times, therefore, an effort is 
made to secure the individual’s 
own variety of organisms, and 
use that to make the vaccine 
and so bring about his recov- 
ery. This takes time, for it is 
necessary to spread the pus, 
nasal excretion or other mate- 
rial containing the organisms, 
out on a special medium (e.g 
agar plates), and Avait until 
the organisms have developed, to secure the organism responsible 
for the infection. Broth or agar cultures are then made of the 
organisms thus isolated; these cultures are examined for purity, 
type, etc., and also tested for strength (See p. 183) before they 
can be used as vaccines. Such preparation takes several days 
at least, a delay advisable only in chronic or mild cases. In 
acute cases, the delay may not be compensated for by the differ- 
ence between the ordinary laboratory or stock organisms and the 
individual’s own variety. In streptococcus, pneumonia and simi- 
lar infections, therefore, a stock vaccine is sometimes given until 
the individual’s own variety can be isolated and made into a 
vaccine—an autogenous vaccine. 
Fig. 118 B.—The arrows indicate the 
Negri bodies seen in a brain film or smear. 
(The large black bodies at the corners of 
No. 14 are nerve cell nuclei.) Noguchi, 
Journal of Experimental Medicine, Rocke- 
feller Institute. VACCINES 
177 
Treatment with Non-Specific Vaccines.—Beneficial re- 
sults from closely related organisms (such as cowpox in preventing 
smallpox) have been already discussed, hut benefit from the 
use of widely differing protein substances—not necessarily bac- 
terial in their origin, for example, albumose in typhoid fever, is 
IMMUNITY CURVES. 
PASSIVE IMMUNITY with IMMUNE SERUM 
PASSIVE IMMUNITY with SENSITIZED VACCINE 
ACTIVE IMMUNITY w.th UNSENSITIZED VACCINE 
Fig. 119.—A comparison of the results obtained with two types of pneumococcus vaccines 
with mice. The sensitized vaccine, like immune serum, gives high initial immunity; and 
it arouses, later, a higher active immunity than ordinary (unsensitized) vaccine. Corsa, 
H. K. Mulford Co. 
more difficult to understand. More than one factor is doubtless 
involved in this protective response; an important one doubtless 
is the effect of such injected substances, as albumose, on the tis- 
sues which form the various antibodies, causing a rapid increase 
of typhoid antibodies and white corpuscles. The fact that the 
amount or strength of these responses is greatest if the injections 
are begun some days after the disease organisms begin to develop 
in the body (about the tenth day in typhoid, for example), seems HOW WE RESIST DISEASE 
178 
to indicate that such increases are due to the liberation of anti- 
bodies already formed—that the response is not an increase in 
specific reactions but a stimulation of the tissues concerned, to 
release the antibodies already formed. Such non-specific results 
do not lessen the value of the ordinary specific vaccines in com- 
mon practice, however, for in most cases specific stimulation is 
necessary to increase the actual formation of protective sub- 
stances. Neither do the results with non-specific substances war- 
AGGLUTINATION 
single and multiple vaccines 
■Results using single vaccine 
■Results using two va.ccmes 
■Results using three, vaccines 
Fia. 120.—Result with one, two, and three vaccines (typhoid alone, or 
typhoid with coli or pseudo-dysentery organisms or both) with regard to the re- 
action aroused against typhoid, justifying the use of mixed vaccines. Redrawn 
from Huntoon (after Castellani), Journal oj Immunology. 
rant the general or indiscriminate use of mixed vaccines (p. 179) 
or of other non-bacterial or “ non-specific ” proteins, for the 
increase in the irritating material thus injected has its attendant 
disadvantages (See p. 192 and p. 193). 
Polyvalent Vaccines.—Two or more strains, e.g., of staphy- 
lococcus, may he mixed together and used as a vaccine, the design 
being to he sure to include the particular strain against which the 
individual needs increased resistance, without the delay caused by 
preparing an autogenous vaccine. In such polyvalent vaccines 
there is a great increase in the amount of foreign protein injected, VACCINES 
179 
and a corresponding increase in the work to be done by the body 
when it can least afford such expenditures of energy. 
Mixed Vaccines.—In certain diseases where the causal 
organism is not definitely known, as in colds, or where more than 
one organism is frequently associated with the disease, as in 
influenza, a mixed vaccine is sometimes given. In influenza, 
such a mixed vaccine may contain influenza, streptococcus and 
pneumococcus organisms. Such treatment is open to the same 
objections as in the case of “polyvalent vaccines.” 
Slightly different, however, is the simultaneous injection of 
two or more different vaccines each of which is necessary to pro- 
tect against a possible infection and where, therefore, each type 
of body response is needed. In the recent war, such protection 
had to be developed in a very short time, and it was necessary to 
give the requisite vaccines simultaneously. Our own army used 
for such purposes a triple vaccine containing typhoid, para- 
typhoid and dysentery organisms. In the Eussian army a tetra- 
vaccine was used, cholera being the fourth kind of organ- 
ism included. 
Vaccine, Virus and Bacterin.—The original vaccines were 
live organisms which were grown in the body of a living animal. 
Most of our vaccines are now cultivated in laboratory media and 
are used after they have been killed. For these killed organisms 
the word bacterin has been tried but has never come into popular 
use. Though dead and though cultivated under very different 
conditions, they are after all like the original smallpox vaccine 
in the one essential—they cause the reqiiired body reactions. 
Virus is a term used by some writers to designate living vac- 
cine material and vaccine for killed forms. This is a shifting of 
the term vaccine which seems unjustified, for if any distinction 
of this kind is to be made, the word vaccine should be retained for 
the class of living vaccines in which smallpox vaccine, the first 
known vaccine, still belongs. 
The word virus is more justifiably used in another sense—to 
indicate the infectious organism when the speaker does not know 
a more definite name for it, because the organism has never been 
seen (as in smallpox), or because its proper classification is still 
unsettled (e.gthe globoid Flexner-Noguchi organism in in- 
fantile paralysis). 
Because of all these variations in meaning or usage, it seems 180 
HOW WE KESIST DISEASE 
much wiser to avoid over emphasis on the terminology, and accept 
the term vaccine in the broadest possible sense—for organisms 
or their products which are capable of arousing protective body 
reactions; this is especially desirable as the many millions of 
people vaccinated with both live organisms (smallpox) and dead 
organisms (typhoid) during this recent war have used for both 
processes but the one term, vaccination. 
Antigens.—Any substance which stimulates the production 
of antibodies is called an antigen, (anti, against; and gen, pro- 
ducing) ;all vaccines (live cowpox organisms, killed typhoid bac- 
- teria and diphtheria toxin) 
are, therefore, antigens. 
In many laboratories, how- 
ever, it happens that the 
term antigen is rarely used 
for the organisms in ref- 
erence to their part in pro- 
ducing these antibodies in a 
given individual, but rather 
for the organisms (or 
substitutes for them) in 
relation to their power to 
combine with the antibodies 
present in laboratory 
samples of an individual’s 
blood. In other words the 
term antigen is much more commonly used in connection with 
diagnosis—with tests for disease—than in connection with the 
prevention or treatment of disease. For example, we speak of 
the killed typhoid bacteria or the vaccine used to vaccinate 
against typhoid, but we use antigen to indicate the typhoid 
organisms when we test a patient’s serum for agglutinins. The 
expression “ syphilitic antigen ” may mean any of the several 
substances—syphilis organisms, syphilitic tissue or even non- 
syphilitic substances such as heart extracts—which will unite 
with the syphilis antibodies an individual has produced and so 
show up in a laboratory test, such as the complement fixation 
test. (See p. 160.) 
Preparation of Vaccines.—The organisms used in making 
Fig. 121.— Fusiform is acnes (Bacillus 
acnes), a diphtheria-like organism, growing best 
with minimum amounts of oxygen (x 700). VACCINES 
181 
vaccines may be grown in broth or agar. They may be killed by 
disinfectants (carbolic, tricresol, chloroform, alcohol, etc.), or 
they may be killed by heat (about 55° C.); if chemicals are also 
used in preparing heat-killed vaccines, they are added mainly as 
preservatives. In addition, the organisms may be finely ground 
or pulverized; for the lipo-vaccines, they are ground in specially 
constructed apparatus for many hours. The organisms are finally 
made up in liquid form—as normal salt suspensions or as lipo- 
vaccines, in which case they are combined with lanolin and 
cotton seed oil. The oil in the lipo-vaccines is thought to delay 
absorption, making one small dose serve as the equivalent of 
several repeated doses Avith consequently better production of 
antibodies. Our army in the recent Avar used mainly the single- 
dose lipo-vaccine, while the navy used the old three-dose saline 
suspension, as not enough of the newer lipo-vaccines was avail- 
Fig. 122.—Syringe for injecting vaccines. In some syringes the tube is grad- 
uated (see Fig. 58) to guide the physician in calculating the amount to be injected. 
able for both the army and the navy, and the complicated book- 
keeping where three doses were required was more difficult in the 
shifting life of an army in preparation, than in the navy. The 
army has since resumed the old three-dose saline vaccine. Most 
vaccines can he kept at low temperatures for three months or even 
longer without great loss in strength. Lipo-vaccines have a 
longer “ keeping ” period. 
Dosage.—Vaccine dosage varies greatly, both in number of 
doses, and in the size of the dose. In preventive treatment, vac- 
cines are usually limited to one to three doses, as in typhoid. 
When given as a curative measure, as in rabies or staphylococcus 
infections, the doses may be repeated throughout a considerable 
period, for weeks or even months—until definite body reactions 
have been aroused as indicated by special tests for the increase 
of antibodies (e.gopsonins against staphylococcus), or by the 
patient’s physical symptoms. Most vaccines are given with inter- 
vals ranging from two to seven days, though three or four days 
are probably the best intervals—at least for preventive work. 182 
HOW WE RESIST DISEASE 
TWENTY-ONE DAY SCHEME OF RABIES VACCINE 
TREATMENT 
Day 
Days Cord Dried 
No. of 
Injections 
Adults 
Children 
Face Cases 
6 to 10 yrs. 
1 to 5 yrs. 
1 
8-7-6 
8-7-6 
2 
3 c.c. 
3 c.c. 
3 c.c. 
2 
8-7-6 
8-7-6 
2 
3 c.c. 
3 c.c. 
3 c.c. 
3 
5-4 
5-4 
2 
3 c.c. 
3 c.c. 
3 c.c. 
4 
5 
5 
1 
2 c.c. 
2 c.c. 
2 c.c. 
5 
4 
4 
1 
2 c.c. 
2 c.c. 
*lHc.c. 
6 
4 
4 
1 
2 c.c. 
2 c.c. 
*lMc.c. 
7 
3 
3 
1 
2 c.c. 
*l)4c.C. 
1 c.c. 
8 
3 
3 
1 
2 c.c. 
*13^C.C. 
1 c.c. 
9 
5 
2 
1 
2 c.c. 
2 c.c. 
2 c.c. 
10 
4 
4 
1 
2 c.c. 
2 c.c. 
2 c.c. 
11 
4 
4 
1 
2 c.c. 
2 c.c. 
2 c.c. 
12 
3 
3 
1 
2 c.c. 
2 c.c. 
*lHc.c. 
13 
3 
2 
1 
2 c.c. 
2 c.c. 
*lHc.c. 
14 
4 
4 
1 
2 c.c. 
2 c.c. 
2 c.c. 
15 
4 
4 
1 
2 c.c. 
2 c.c. 
2 c.c. 
16 
3 
3 
1 
2 c.c. 
2 c.c. 
*l^c.c. 
17 
3 
2 
1 
2 c.c. 
2 c.c. 
*1J^C.C. 
18 
4 
4 
1 
2 c.c. 
2 c.c. 
2 c.c. 
19 
4 
4 
1 
2 c.c. 
2 c.c. 
2 c.c. 
20 
3 
3 
1 
2 c.c. 
2 c.c. 
2 c.c. 
21 
3 
2 
1 
2 c.c. 
2 c.c. 
2 c.c. 
2/10 per cent, phenol used as a preservative instead of glycerine. 
♦Face cases receive adult doses. 
Fig. 123.—Copy of treatment now given in the New York City Health Depart- 
ment. Face cases may be given treatment with spinal cords dried but two days, or the 
whole twenty-one day treatment may be repeated for such cases. (Bureau of Labora- 
tories, Department of Health, City of New York.) VACCINES 
183 
The doses are often small in actual bulk, for example, they 
may he as small as 1/1000 of a milligram (1/1000 mgm.) in the 
initial dose of tuberculosis vaccine (tuberculin). Most of us can 
visualize better the bulk of the larger but still minute dose used 
for smallpox vaccination; small as it is, less than one-fifth of it is 
composed of the causal organisms themselves. (See next para- 
graph.) A clearer idea of what the dosage means to the body is 
gained from the number of bacteria in a dose. A dose, usually, 
is somewhere between two million and live hundred million bac- 
teria, and it often is as 
high as one billion or 
even ten to thirty billion. 
In most cases, vaccines 
are finally diluted so that 
they range from one hun- 
dred million to five hun- 
dred million per cubic 
centimetre, and the dose 
is administered in cubic 
centimetres or appropri- 
ate fractions thereof. 
Standardization of 
Vaccines.—In the use of 
some vaccines, such as 
smallpox vaccine, where 
the organisms themselves 
cannot be seen to be 
counted, the doses are 
measured in a rather crude way, mainly by bulk or weight. 
In making smallpox vaccine the pulpy exudate containing the 
organisms is scraped off the body of the calf and ground up with 
four times its bulk of glycerine, water, and carbolic acid. This 
glycerinated mixture is distributed for use in tiny glass capillary 
tubes from which it is expelled in minute amounts to vaccinate 
human beings. The potency of the vaccine is proven before 
the preparations are sold or distributed, by showing that a given 
number of vaccinations, usually fifteen, is 100 per cent, suc- 
cessful when used on children who have never been vaccinated. 
Vaccines are sometimes graded more definitely by weight with 
regard to the organisms they contain. The bacteria used in 
Fig. 124.—Part of a slide with a mass of 
bacteria (staphylococci) at the end of a blood film, 
showing why this method of estimating the number 
of bacteria in a vaccine often results in an under- 
estimate (100 to 200%) (x 800). Muir, Journal 
of Pathology and Bacteriology. 184 
HOW WE EES 1ST DISEASE 
making the vaccines represent fixed amounts by weight per cubic 
centimetre; in the lipo-vaccines recently used in the army, men- 
ingococcus organisms represented 1.8 milligrams, and pneumo- 
coccus, 2.5 to 3.5 milligrams, respectively. 
Usually, however, the 
strength of a vaccine is deter- 
mined much more definitely bv 
an actual counting process. 
This may be done by micro- 
scopic determination of the 
number of bacteria present in 
a given bulk, e.g., one cubic 
centimetre. The bacteria are 
usually determined in one of 
the following ways: (1) By 
mixing equal amounts of blood 
and the bacterial culture; for 
since we know the number of 
red blood cells in a cubic centi- 
metre, the proportion of bac- 
teria and blood cells in the 
mixture on the slide tells us 
the number of bacteria per 
cubic centimetre; (2) or, by 
counting the bacteria alone, 
using the well-known blood- 
count slides, and counting the 
bacteria by the aid of the 
markings on such a slide. 
It is not necessary to count 
the bacteria in each batch of 
vaccine. Once the bacterial content of a series of vaccine dilu- 
tions has been determined, it is easy to make up a set of tubes of 
the same range in turbidity, using for this standard turbidity 
set, some finely divided substance such as silica. Once we have 
determined the number of bacteria per cubic centimetre corre- 
sponding with the silica standards, the determination of the 
strength of a new lot is very easily determined, by a simple 
“ matching up ” process. 
Fig. 125.—-Small capillary tubes, 
fused shut at the upper end, standing in 
the container used for filling. The lower 
open end of each comes into contact with 
the vaccine as it runs out of the bottom of 
the large central tube. See next illustration. VACCINES 
185 
Present Status of Vaccines.—At present the results with 
some of the prophylactic vaccines—in preventing disease—are on 
a more unchallenged basis than can be claimed for the curative 
vaccines. In our own country smallpox, typhoid and rabies vac- 
cines (Fig. 128) easily rank first. Diphtheria vaccine, for 
“ toxin antitoxin ” may be so called (See p. 102), has already 
Fig. 126.— Ingenious device for filling thecapillary tube shown in the previous illus- 
tration. Several of the containers are placed in the covered jar on the right. The air is drawn 
out of capillary tubes by establishing a vacuum. The vaccine in the bottom of the small 
containers is forced up into each of the capillary tubes by pressure and the end is fused shut. 
Bureau of Laboratories, Health Department of the City of New York 
established its value beyond question, especially for young 
children. The dysentery vaccines (paratyphoid and Shiga’s 
dysentery), and the vaccines for plague, and cholera, have 
shown their value in emergencies, such as epidemics or crowded 
war time conditions. 
There is still great diversity of opinion Avith regard to the 
value of the vaccines used in preventing or in treating infections 
of the respiratory tract, such as whooping cough, pneumonia, 
influenza, mouth infections, and colds. This is partly explained 
by the fact that many different organisms are usually present in 186 
HOW WE RESIST DISEASE 
the areas affected in each of these diseases. Persistent congestion 
of such areas as the frontal sinuses, the ears, etc., may resist vac- 
cine treatment because such areas are too poorly supplied with 
blood to be greatly benefited by ordinary amounts of the anti- 
bodies formed against the vaccine. 
Fig. 127.—Filling small bottles with finished vaccine. Bureau of Labora- 
tories, Health Department of the City of New York. 
Vaccine treatment foi: meningitis has not been successfully 
established. Curative effects with vaccines are most marked in 
chronic or sub-acute diseases, such as staphylococcus infections, 
of which there is a wide variety, ranging from mild cases of skin 
infections (acne [Fig. 121]) and persistently recurring boils to 
chronic osteomyelitis. For streptococcus and gonococcus infec- 
tions vaccines are much used; they are considered helpful in VACCINES 
187 
treating such conditions -as gonorrheal joints and other localized 
infections or inflammations. 
Vaccines are still used by some physicians in treating tuber- 
culosis, the advantages claimed being that tuberculin vaccine pro- 
motes the healing of existing lesions and lessens the tendency to 
the characteristic relapses in tuberculosis. As Park advises, users 
should realize that such a substance “is not a cure, and should 
he employed as an addition to other recognized methods of 
treatment.” (See discussion in Anaphylaxis chapter following.) 
BANISHING TYPHOID FEVER FROM THE U.S. ARMY 
SINCE THE TPOOPS WEPE VACCINATED 
THE TYPHOID DEATH HATE HAS ALMOST 
D/SAPPEARED 
AHHl/AL DEATH PATE PEP /OO.OOO 
U. S-MMY _ 
,a\/'L h re: 
SANITATION ekot/6HT TH.S DOWN 
£ AN/?<tT/OH AMD VACC 'MAT/OM Ml THIS 
A/OT£ 
P/fvVrS for Cirt/ Life 
O.S. Rejtst ra.tr/on Area. 
Fig. 128.—How do these rates compare with the rate for your state? Vaughan and 
Palmer, Journal of Laboratory and Clinical Medicine, C. V. Mosby Co. 
Recently Calmette has reported successful preventive work 
with tuberculosis vaccine, both with cattle and monkeys. An 
experimental station is now being constructed in West Africa 
to extend the observations of preventive tuberculosis vaccina- 
tion among the man-like apes. 
Objections to the Use of Vaccines.—While the ordinary 
subcutaneous vaccination is considered as without attendant risk, 
the intravenous mode may cause agglutination of the injected 188 
HOW WE RESIST DISEASE 
organisms, resulting in obstructions in the smaller bloodvessels; 
or, if the bacterial substances are too rapidly absorbed “shock” 
may follow. See the following chapter on Anaphylaxis for brief 
discussion of the “ shock ” and the dangers of repeated injections 
of bacterial proteins. 
Other Phases of Vaccines.—The treatment given for hay 
fever, food sensitiveness, or any other form of “ protein sensi- 
tiveness ” is essentially the same as the vaccine treatment for 
bacterial infections. In any bacterial disease the stimulating 
substance given the patient is the specific bacterial protein, 
while for food sensitiveness 
and hay fever patients, the 
related food or pollen pro- 
tein is used. The descrip- 
tion of the treatment in 
such cases is given in the 
following chapter, because 
of the close connection of 
the various phases of these 
problems with anaphylaxis. 
While the substances 
used in the skin tests for 
the presence of diseases as 
tuberculosis, syphilis, and 
gonorrhea, are really the 
killed organisms, we do 
not think of them as vaccines. True, the same bacterial sub- 
stances may be used in both cases, but when used as vaccines 
they are given in sufficient amounts—whether in single or 
repeated doses—to excite an accumulation of helpful body re- 
actions. When they are used to test for the existence of a given 
disease, but a single minute dose is given to aggravate and so 
make evident the sensitive condition of the individual. (See 
tests described on p. 205 and p. 208.) 
Fig. 129.—Plague bacilli, edge oi mass of 
a culture from a flea’s stomach (x 1000) 
Martin, Journal of Hygiene. (Eighth Report 
of Pleague Investigation in India.) 
STUDY SUGGESTIONS 
1. Describe vaccine as first used and compare it with typhoid vaccine 
in origin (or preparation), dosage and results. 
2. Why may we call the toxin-antitoxin treatment to prevent diph- 
theria a vaccine treatment? VACCINES 
189 
6. List the vaccines advertised by a reputable firm; how many are 
bacterial and bow many of protozoan origin? 
4. What is an autogenous vaccine? What advantage may be claimed 
for autogenous over stock vaccines? 
5. How may the strength of a vaccine be graded or measured? 
6. What two vaccines do you consider most successful ? Give support- 
ing figures from army or national statistics. 
7. Recently a large sum has been divided among three well-known 
institutions for the study of common colds. Prepare a list of 
organisms found in or causing diseases of the respiratory and 
adjacent membranes and show why it is improbable that a satis- 
factory preventive vaccine will result. 
8. Killed cultures of Leptospira icteroides have been tried by Noguchi 
in 427 vaccinations with a morbidity of 11 per thousand among 
the vaccinated as compared with a morbidity of 110 per thousand 
among the unvaccinated. Have we in our country any other 
established vaccines for diseases of protozoan origin? 
9. The statement is often made that curative results are more frequently 
obtained with vaccines in cases of localized rather than general 
infection. How may this be explained? 
10. Many investigators recommend the employment of larger doses of 
vaccines than those given in the text of this chapter, e.g., 5,000 
million to 25,000 million in gonorrheal vaccines. Can this be 
shown to be related to the chronic character of gonorrhea? 
11. Karsner states that the “frequent occurrence of pneumococcus septi- 
cemia as a part of the disease makes it unlikely that vaccination 
will be helpful.” Why? 
12. In the city of Tokio 238,936 people were vaccinated against cholera. 
Cholera occurred in 1.85 per 10,000 of the unvaccinated people, 
and in 0.13 per 10,000 of the vaccinated. What was the relative 
morbidity of those not vaccinated? 
13. How can you explain the good effects reported from the use of 
albumin solutions when used as a vaccine to prevent typhoid? 
14. When measles was first introduced into the Faroe Islands, over 6,000 
of the 7.782 inhabitants contracted the disease; why could measles 
not attain that percentage in any of our communities today? 
15. Show what there is in common between diphtheria toxin-antitoxins 
and sensitized- or sero-vaceines. 
16. Tabulate from an advanced text on bacteriology or immunity the 
diseases in which vaccines are used; separate or classify them as 
(1) live organisms, (2) dead organisms, (3) toxins. 
17. The spread of smallpox has been limited so effectively by the “wall 
of the immune” people who have been vaccinated, that most com- 
munities are becoming very careless about enforcement of the 
smallpox vaccination regulations. How many of your community 
group (hospital, college, dormitory, etc.) would surely escape if 
an epidemic started? 
18. Recently killed pneumococcus organisms have been used as a throat 
spray to arouse local reactions in the areas naturally first 
attacked in pneumonia infections. Give one argument in support 
of this method of vaccine administration. CHAPTER X 
ANAPHYLAXIS AND SIMILAR PHENOMENA 
Definition of anaphylaxis 
Historical 
background 
Experimental work 
Underlying principles 
Split-proteins 
Theories of 
anaphylaxis' 
Blood stream 
changes 
Antibody-protein 
combinations 
Cellular theory 
Time and quantity relationships 
Anaphylaxis and 
similar reactions 
Anaphylactic manifestations 
Experimental 
animals 
Man 
Anaphylaxis and protein sensitization 
Vaccines 
Serums 
Foods 
Pollens 
Tests for disease 
Important human relations 
Anaphylaxis and immunity 
Although it is impossible to present the subject of anaphy- 
laxis satisfactorily in one brief chapter of twenty pages, it 
seems desirable to bring together in this final chapter, various 
phenomena commonly discussed in connection with that topic. 
Meaning of Anaphylaxis.—The term anaphylaxis (without 
or against protection) is used to cover a wide range of phe- 
nomena, varying from such slight and local symptoms as an itch- 
ing of the nose and running of the eyes and nose to sudden col- 
lapse and death. (See p. 196.) More specifically it includes such 
widely various phases or occurrences as (1) true anaphylactic shock 
and death, (2) the less fatal “ serum sickness,” (3) the tempo- 
190 ANAPHYLAXIS AND SIMILAR PHENOMENA 
191 
rary discomfort following the second or later injections of vac- 
cines, (4) such skin tests as those used for tuberculosis or 
gonorrhea, (5) the diet idiosyncrasies of certain individuals, and 
(6) the sensitiveness of other unfortunates to flower pollens 
or to epidermal cells of cats and horses. 
Historical Background of Anaphylaxis.—About eighty 
years ago (1839) a French physiologist, Magendie, described the 
sudden death of dogs which had received repeated injections of 
egg albumen. In 1894, Flexner found that animals succumbed 
to the second dose of dog serum, if it was given several days or 
even several weeks after the first dose. The term anaphylaxis 
(without protection) for such susceptibility to proteins, was first 
applied by Richet, who with Hericourt, secured similar results 
with dogs following the second injection of eel serum, which, 
however, is itself a toxic substance. 
With this came the dawning appreciation that (1) this phe- 
nomenon depended upon a previous inoculation with the same 
protein substance, and that (2) a definite time must elapse before 
such sensitiveness developed. In 1903, Arthus, a Frenchman, 
proved that this time interval was important, and that the phe- 
nomenon of anaphylaxis was not merely a matter of accumulating 
a given total amount of the foreign protein—for, while a single 
dose of 40 cubic centimetres of horse serum was not fatal, several 
repeated small doses of 5 cubic centimetres, or even less, caused 
anaphylactic disturbances. 
Arthus also showed that the phenomenon of anaphylaxis was 
due to a general systemic rather than a local condition or sensi- 
tiveness, for the same anaphylactic results occurred even though 
the first and the later injections were in such entirely different 
areas as the skin and peritoneal cavity. 
Much of this earlier work was, however, forgotten, or ignored 
through failure to grasp the essential likeness—the protein 
character of the several substances used in each of the experi- 
ments just described: egg albumen, horse serum, dog serum, and 
the (toxic) eel serum. Therefore, in 1904, when Theobald 
Smith accidentally found that his guinea pigs, which had been 
injected with horse serum antitoxin in some standardizing tests 
on diphtheria antitoxin, were very susceptible to plain horse 
serum when that was injected several days or several weeks later, 192 
HOW WE RESIST DISEASE 
the anaphylactic condition that resulted became widely known 
as the “ Theobald Smith Phenomenon.” The greater promi- 
nence given Smith’s results was due both to the increasing 
opportunities for exchange and diffusion of information con- 
cerning the achievements of the scientific world, and to the 
current wide interest in diphtheria antitoxin. 
Since Smith’s observation in 1904, many important contribu- 
tions have been made to this problem. Very promptly followed 
those of Rosenau and Anderson (190G-08) who showed that 
antitoxin, per se, had no relation to the Theobald Smith Phe- 
nomenon,—for the same result occurred if plain horse serum 
were used in both injections in the experiment. This really 
reduces the Smith Phenomenon to a parallel of Artlius’s results 
with horse serum and even to Magendie’s egg albumen experi- 
ment back in 1839. Among other contributions of Rosenau and 
Anderson to the subject of anaphylaxis are the following: 
(1) The reaction is specific, that is, anaphylaxis is brought about 
by later injections of the same or specific substance (horse 
serum, egg albumen, etc.) used in the first injection. (2) Though 
this phenomenon is an extremely delicate one (for only one- 
millionth of a cubic centimetre may be sufficient to sensitize an 
animal), the susceptibility thus induced may persist for a long 
time, over three years being recorded in some test animals. 
(3) Anaphylaxis can be induced by many other substances, by 
vegetable proteins, including bacterial proteins, as well as animal 
proteins, such as those already described. 
This last fact connects the problem of anaphylaxis with in- 
fectious diseases, and as later shown (p. 193), gives a different 
conception of the relation of the non-toxin-prod .icing bacteria 
to disease. (See p. 22.) 
Anaphylaxis a Protein Reaction.—Further explanation of 
the part played by proteins—not only in diseases, but in diet 
idiosyncrasies, etc., has been given by A7aughan and his co- 
workers. He has shown that widely different protein substances 
(white of egg, milk, peptone, seeds, non-pathogenic bacteria and 
also pathogenic bacteria) have the same fundamental basis of 
structure—a poisonous “ core ” or basic substance which is 
common to all protein substances, and may be obtained from any 
protein by appropriate treatment (with acid, alkali, alcohol, ANAPHYLAXIS AND SIMILAR PHENOMENA 
193 
etc.) which causes the breakage or splitting of the various kinds 
of protein molecules into smaller poisonous ones common to all 
proteins, the “ poisonous split-proteins.” With these split-pro- 
teins, obtained from sources as varied as those listed above, 
Vaughan has been able to demonstrate that by appropriate dosage 
any given type or set of clinical symptoms can be produced; 
these include various types of fevers (acute, relapsing) con- 
vulsions, and death, all of which may be produced in a given or 
predicted time. 
The effects of repeated injections of proteins which have not 
been previously so disrupted or broken, as described earlier in 
the egg-albumen and serum experiments, can be explained in the 
light of these same poisonous split-proteins. When egg-albumen, 
for example, is injected into the tissues, some of it may find its 
way, relatively unchanged, into the blood stream; this is, of 
course, an unusual condition, for though egg substances are com- 
monly used as food, they are then taken into the alimentary canal 
and there digested or broken down into simpler substances before 
passing into the blood itself. The blood does not ordinarily con- 
tain the mechanism (enzymes?) for taking care of the unchanged 
proteins; therefore appropriate substances must be developed 
and finally accumulated in the blood when the foreign proteins 
do find their way there. A first injection of any foreign protein 
may therefore stimulate the production of suitable protein-break- 
ing substances which remain in the blood for some time (See 
p. 192). If during the period they persist in the body, we inject 
a second dose of that same kind of protein that stimulated them, 
it may be attacked at once by these special protein-breaking 
substances, and broken down very rapidly. Poisonous split- 
proteins produced by these processes, and accumulating in the 
blood, may be absorbed by the tissues more rapidly than they can 
be neutralized or further broken down to harmless stages, giving 
the condition known as anaphylaxis, or anaphylactic shock. The 
explanation is, of course, equally applicable to the anaphylactic 
manifestations occurring with other injected proteins—anti- 
serums and vaccines—or to any protein substances such as pollen 
and epidermal cells absorbed through surface membranes rather 
than definitely inserted or injected into the tissues. 
Antibodies and Anaphylaxis.—The explanation of ana- 194 
HOW WE RESIST DISEASE 
phylaxis just given, throws the emphasis upon the digestion 
products derived from the foreign protein. It is the simplest of 
several theories, and for that reason is given the most promi- 
nence in this elementary presentation. 
Many find it, however, inadequate for some of the complicated 
protein relationships occurring in health and disease, and two 
other theories are often advanced to explain anaphylactic phe- 
nomena. According to one of these, the first injection of the 
foreign protein stimillates the production of suitable antibodies 
which combine with it; the second injection of that specific pro- 
tein finds ready an abundance or superabundance of these anti- 
bodies with which it unites, forming thereby irritating or 
toxic products which induce anaphylaxis. Support is given this 
theory by workers who have shown for various bloods a definite 
relationship between the abundance of contained antibodies 
already familiar to us, precipitins, and the power of these various 
bloods to produce anaphylaxis when injected into other animals. 
The Cellular Theory.—A third theory, which is rapidly 
growing in favor, differs from both of those just given, in locating 
the anaphylactic processes in the body cells—in the fixed tissues 
—rather than the blood stream. According to this theory, the 
first dose of protein sensitizes by inducing changes in the body 
cells—changes which make possible the combination of the foreign 
protein with the cells themselves. On the second dose of injec- 
tion of the given protein, it makes ready combination with the 
body tissue cells, by virtue of the changes earlier induced. The 
formation of such antibodies as precipitins would fit into this 
third theory as well as into the second one, discussed in the pre- 
ceding paragraph. Precipitins retained by the cells and not 
discharged into the blood stream would increase the cell sensi- 
tiveness and susceptibility to injury—-through their increased 
combining power with the foreign proteins. The toxic condition 
according to this theory—the cellular theory—emanates from the 
body cells themselves. 
To sum up briefly, we may consider the mechanism of anaphy- 
lactic states as due (1) to the formation of ferments or enzymes 
which digest or split the foreign proteins into harmful sub- 
stances, or as due to the production of “ antibodies,” such as pre- 
cipitins, which injure the animal body by making antibody- ANAPHYLAXIS AND SIMILAR PHENOMENA 
195 
protein combinations—either (2) in the blood stream or (3) in 
conjunction with the body cells. 
Quantitative Relationships: Time and Dosage.—In each 
of the three theories of anaphylaxis thus briefly delineated, we 
have a combination of a specific protein with a reacting sub- 
stance produced in the body, and as one would naturally expect, 
the effect produced in any given instance varies more or less with 
the degree of combination taking place. If the second injection 
or dose of the specific protein is given before a certain necessary 
minimum of the reacting substances has been accumulated, ana- 
phylactic results will not be produced. In man, a period of about 12 
days is necessary for the production of such reacting substances. 
When repeated doses of the same proteins must be given, as in 
serum therapy and in most of the vaccine treatments, the repeti- 
tions are made short of this twelve-day interval; vaccines may 
be given at three-day or weekly intervals; and antiserums are 
usually repeated at very short intervals—such as every eight, 
twelve or twenty-four hours until improvement is assured. 
Size of the Sensitizing Dose.—The amount of the foreign 
protein is also an important consideration—both with regard to 
the initial sensitizing dose, and the amount necessary to induce 
anaphylactic symptoms. Though a very minute amount may be 
sufficient to “sensitize” the animal (See p. 192), there is an 
irreducible minimum for even the first dose of the foreign pro- 
tein ; for some animals the sensitizing dose must be quite large—- 
several cubic centimetres, and some animals, such as rabbits, 
require several repeated doses to really sensitize them. 
Size of the Sensitizing Dose.—The amount of the foreign 
ation with regard to the amount which will cause the appearance 
of anaphylactic symptoms. With guinea pigs it may be but a 
minute amount—as small as 1/1000 of a cubic centimetre. Two 
cubic centimetres is called a “ shock injection ” for a rabbit, and 
20 to 30 c.c. will cause anaphylactic death in dogs. The amount 
of protein injected in the “ shock dose ” naturally limits the 
amount of toxic substances that can be produced, and the degree 
of anaphylaxis can be modified by suitable reductions in the 
protein given; the results may thus be made to vary from a slight 
local symptom, such as reddening or inflammation at the site of 
the injection, to general systemic disturbances, or collapse and 196 
IIOW WE RESIST DISEASE 
death. A very small amount of the protein will produce only 
local reactions, or slight increase in temperature, etc., indicating 
that the animal is sensitive to the protein in question. This is 
the basis of skin tests where minute amounts are used for de- 
termining whether or not an individual is sensitive to the 
respective proteins of such diseases as tuberculosis (See p. 208), 
or whether he will be affected by the usual dose of antitoxin. Not 
only can the degree of anaphylactic reaction be lessened (Fig. 138) 
by reducing the total amount of foreign protein given, but by 
spreading the full amount which would cause anaphylactic re- 
sults, over a longer period—that is, giving it in divided doses at 
short intervals. This probably gives the tissues time to dispose 
of the poisonous products that result so that at no instant 
is a harmful total amount present in the body. Advantage is 
taken of this in giving antiserums to over-sensitive individuals. 
In using diphtheria antitoxin, for example, instead of giving 
the Avhole dose at once, it may be given in very small sub- 
divisions, but 1/10 of a cubic centimetre at a time, at half-hour 
intervals, until the prescribed total has been injected. 
Typical Anaphylaxis in Experimental Animals.—Re- 
cently much discussion has centred around the differences 
between these protein reactions as observed in man and in the 
lower animals used in experimental work. As observed in that 
very susceptible animal, the guinea pig, the anaphylactic condi- 
tion may be described briefly as follows : A few minutes (or even 
as short a time as one-half minute) after the injection of the 
dose causing anaphylaxis, the animal shows a drop in tempera- 
ture, restlessness and difficulty in respiration. The animal may 
then either recover slowly, or grow progressively worse, the 
general weakness increasing so that the animal falls upon its side, 
respiration becoming more difficult and slowed, the condition 
finally ending in convulsions and death. The whole process may 
be extremely rapid, death taking place within one minute after 
the “ shock dose ” is given. 
The effects are attributed to the contracted condition induced 
in the smooth or involuntary muscle tissues, variations in the 
symptoms of the various laboratory animals corresponding some- 
what to differences in the distribution and proportion of this 
sensitive muscle tissue in the affected areas, such as the lungs. In ANAPHYLAXIS AND SIMILAR PHENOMENA 
197 
rabbits, for example, tbe bronchial regions are less well supplied 
with smooth muscle, and the respiratory phases are less marked 
than in guinea pigs; similarly in dogs, the absence of respiratory 
symptoms, such as asphyxia, and the prominence of intestinal 
symptoms may be explained by the relative proportions of smooth 
muscle tissue in those respective areas. 
Anaphylaxis in Man and Other Animals.—In man, symp- 
toms of extreme severity are rarely produced. They occiir but 
rarely even with serum treatment, in which large amounts of 
foreign proteins (See p. 79) are injected. According to Park, 
but one individual in every 10,000 treated with diphtheria anti- 
toxin develops alarming symptoms, and but one in 50,000 dies. 
Most of the human disturbances fall under the less serious mani- 
festations described in connection with serum sickness, food 
sensitiveness and hay fever, in the following pages. 
Anaphylaxis as seen in the ordinary experimental animals, 
is a phenomenon affecting primarily the smooth muscle fibre, 
especially in the respiratory and circulatory areas; in man the 
manifestations are more varied, and the effects most often noted 
are in such areas as the skin or the nose and eye membranes. 
What is apparently the greatest contrast is seen when we state 
that when fatal results do occur in man they follow quickly upon 
the first injection of the protein while anaphylaxis in experi- 
mental animals occurs after one or more preliminary sensitizing 
doses. Then, too, most of the effects occurring in man seem 
more dependent upon systemic peculiarities or inheritable pre- 
dispositions. Individuals supersensitive to antitoxin, for ex- 
ample, are often found to have an individual or family history 
of asthma, food idiosyncrasies, etc. Anaphylactic conditions in 
guinea pigs and other laboratory animals have not yet been found 
to be associated with such inheritable characteristics. 
The differences between man and the usual laboratory animals 
may be more a matter of dosage than is apparent. The rabbit has 
been described as being 400 times as resistant to induced anaphy- 
laxis as the guinea pig, and man may have a similar high coeffi- 
cient of resistance; it may well be that what is considered a 
difference between the human and animal type of such protein 
sensitiveness may sometimes be shown to be really a difference in 
degree. It is quite possible that the size of the final dose pro- 198 
HOW WE KESIST DISEASE 
ducing the symptoms affects the quantitative or relative distri- 
bution of the poisonous substances to the various smooth muscle 
areas, and therefore affects the relative prominence of the respira- 
tory or other regional symptoms. 
.Anaphylaxis, Allergy and Protein Sensitiveness.—Such 
differences as those listed in the preceding paragraph, have led 
some to limit the use of the term anaphylaxis to the acute 
symptoms most characteristically seen in the guinea pig, and to 
adopt for the various less fatal hypersensitive manifestations in 
man, another term, such as Yon Pirquet’s name, allergy (formed 
from alios, change, and ergon, action and indicating the changed 
or altered power of the animal to react). Others avoid making 
a sharp distinction of this kind, and either use (1) the term 
anaphylaxis in the same general way that we have so far followed 
in this discussion, or (2) substitute for it the more inclusive 
term, protein sensitiveness.* 
Protein Sensitiveness.—The term protein sensitiveness 
has been recommended with the idea of avoiding too great em- 
phasis upon differences in the final or outward physical mani- 
festations, and emphasizing by the use of this inclusive term, 
underlying likeness in all such phenomena, the protein sensitive 
condition of the animal. 
Unfortunately, this use of protein sensitiveness, leads to two 
other serious errors, although it does accomplish the immediate 
purpose and emphasizes the common fundamental likeness—that 
the various phenomena are all responses to foreign proteins to 
which the animal is sensitive. The first error involved is that 
such use of the term protein-sensitiveness implies the complete 
separation of these phenomena from all of the antibody reactions 
discussed in the previous chapters of this book, and leads the 
unwary to forget that agglutinins, opsonins, and all other anti- 
bodies are likewise formed in response to bacterial or other pro- 
tein stimulation. The second error involved in this restricted 
use of the term protein sensitization is the implication that pro- 
tein sensitization is essentially harmful and undesirable. This 
blinds the student to the fact that protein sensitization is essential 
* In such a brief discussion many important phases must necessarily 
be omitted, e.g., whether such sensitization really occurs with protein 
substances only, or whether such exceptions as those reported for lipoids 
are really attributable to protein-lipoid combinations. ANAPHYLAXIS AND SIMILAR PHENOMENA 
199 
to the development of active immunity, and that only certain 
incidental or attendant phases of such sensitization are harmful. 
To pick out these isolated and injurious exceptions and call 
them protein sensitization is certainly misleading. It is highly 
desirable that we should refrain from increasing in the slightest 
degree any objections the uninformed may still hold against such 
invaluable preventive methods as those involving the use of vac- 
cines and antiserums. 
Drug Sensitiveness.—Under the term allergy, is sometimes 
included the supersensitiveness of certain individuals to such 
drugs as iodine, quinine, morphine, mercury, turpentine and 
salvarsan; the reactions may be very similar to those observed in 
human hypersensitiveness to proteins, with such symptoms as 
fever, local inflammations, swollen joints and lymph nodes, and 
skin eruptions. With drugs, as in the human reactions against 
pollens and food proteins, a high degree of immunity is not 
developed—the reaction following repeated treatment or vaccina- 
tion being tolerance rather than true immunity (See p. 207). 
Anaphylactic Considerations in Relation to Vaccines.— 
Since bacteria are protein substances, their continued repeated 
injection might be expected to cause anaphylactic reactions. The 
increased temperature, local inflammation, etc., attending the 
later injections of a given vaccine, such as typhoid vaccine, is 
due in part, of course, to the actual increase in total protein, but 
in greater part to the higher sensitive or anaphylactic condition 
of the individual. Vaccination has, therefore, been described as 
“ extended or continued anaphylaxis.” 
Students often ask why vaccines can be given throughout a long 
period of time without risk of causing serious phases of anaphy- 
laxis. Even though the second or even the third dose may safely 
fall within the twelve-day period (See p. 195), why do not the 
later injections cause dangerous anaphylactic symptoms ? After 
any given dose or injection there is a short period—several days 
or even weeks—during which the individual is less susceptible 
to anaphylaxis—during which the ordinary anaphylactic dose 
will not affect the animal. These less sensitive or refractory 
period's are similarly extended throughout the treatment, and 
make possible, therefore, continued injection of vaccines, which 200 
HOW WE RESIST DISEASE 
may be extended through weeks or even months, as in staphy- 
lococcus treatment. 
There is another possible explanation. The first dose of a 
given vaccine may not have been sufficient for a sensitizing dose; 
it may even require—for that individual or for the strength of 
the vaccine used—more than the usual number of injections to 
sensitize that individual. (See p. 195.) 
Vaccines, therefore, are usually given without serious dis- 
comfort and without risk. The discomfort following vaccine in- 
jections is usually greatest after the second dose, and is usually 
limited to soreness in the locality of the injection, pain in the 
adjacent glands, and general indisposition, sometimes accom- 
panied with headache or nausea. 
While vaccine treatment is quite generally approved for 
typhoid, dysentery, smallpox, cholera and also staphylococcus 
infections, many feel that it is less warranted in tuberculosis,— 
both because of the greater length of the period during which 
the vaccine (tuberculin) injections must be continued and because 
of the more damaging effects of the tuberculosis proteins. Since 
clinical symptoms do not always warn us of the erratic changes 
occurring in tubercular people, injections may be given at a very 
inopportune time, when the body is not able to counterbalance 
the effects of the organisms growing in the tissues, and may thus 
add unnecessarily to the work to be done without giving the de- 
sired stimulus or aid. While tuberculin treatment may “ pro- 
mote healing and make relapses less frequent,” it may hasten or 
increase the conditions it is intended to overcome, and experienced 
physicians recognize that “ such a weapon is a two-edged sword.” 
This objection does not, of course, apply to the use of tuberculin 
as a test for tuberculosis (See p. 208), where we use but a minute 
amount in a single injection. 
Serum Reactions in Man.—As seen in human beings there 
are two important types of serum reactions. In the most serious 
type the patient promptly (five to ten minutes or even a shorter 
time after the first injection) experiences collapse, unconscious- 
ness, and great difficulty in breathing. Less than half of such 
collapses result fatally, death occurring, as noted elsewhere 
(p. 103), in but one case in every 50,000 diphtheria patients 
treated with antitoxin. ANAPHYLAXIS AND SIMILAR PHENOMENA 
201 
Serious results are more common with patients who are 
asthmatics, horse-sensitives, etc. (See p. 197). Before injecting 
any antiserum the physicians should ascertain whether the fam- 
ily or individual history indicates such hypersensitiveness, and in 
such cases the risk should be clearly explained, and the dose given 
with appropriate precautions. Among such precautions are the 
following: (1) giving first a trial dose of a very small fraction of 
a cubic centimetre, for even a single cubic centimetre has proven 
fatal in such cases (See p. 200); (2) giving the dose very slowly 
either spacing it throughout several hours, (See p. 196), or 
giving it in oil combinations to insure its slow absorption; and 
(3) having at hand appropriate drugs (chloral hydrate, atropin, 
adrenalin) for lessening the anaphylactic effects on respiratory 
or other smooth muscle tissues (See p. 196). 
Serum Sickness,—The more common after results, but for- 
tunately not fatal ones, are the several effects grouped together 
under the name “ serum sickness/’ These phenomena may appear 
in a few hours, but more often between the third and twelfth day 
following the injection of the antiserum. They include various 
types of skin eruptions, excretion of albumin in the urine, swollen 
lymph glands, especially near the injection site, and painful and 
sensitive joints. The frequency with which such symptoms 
follow treatment depends upon such variables as the size of the 
dose or the amount of foreign protein given and the reduction 
or elimination of the serum proteins. 
Fortunately, the most frequently given antiserum, diphtheria 
antitoxin, is so modified in its preparation (See p. 93) that it 
has a minimum of protein material, and serious after-effects are 
rare. Every effort should be made to insure the general recogni- 
tion of the rarity of serious results accompanying antiserum treat- 
ments, especially in diphtheria, the disease in which antiserum is 
most commonly used. 
Reactions with Initial Rather Than Repeated Doses.— 
Little fear need, therefore, be felt in repeating serum injections 
during any attack, for the doses usually fall well within the 
initial twelve-day period of safety, and when this is not the case 
within the extended refractory period as described earlier on 
page 199. 
As stated above, the serious results attending the use of anti- 202 
HOW WE RESIST DISEASE 
serums occur with the first injection; as commonly expressed, 
“ There is no danger from the second or later injections if the 
first was given with safety.” The preceding paragraph has called 
attention to the fact that the time is too short for the first dose to 
act as a sensitizing dose. What puzzles students is why there 
should be any reaction with the first dose. 
Among the theories extended to meet this situation are the 
following: (1) The irregular absorption of such first injection, 
due to the striking of a small vein, as might occur in a sub- 
cutaneous injection; the first absorbed fraction of the dose might 
act as the sensitizing or first dose, for the more slowly absorbed 
remainder of the dose. Or the injected substance may be virtually 
a second dose, the reaction being due to either of the two follow- 
ing causes: (2) Natural sensitiveness, through substances 
acquired before birth, e.g., from the mother’s blood. (3) Earlier 
absorption of similar substances through the alimentary or respir- 
atory membranes—of substances enough like some of the 
injected proteins to cause typical anaphylaxis. This, of course, 
it is impossible to prove, hut the plausibility of something of this 
kind appears when we recall that serious results, as already men- 
tioned, are more common with people who exhibit other phases 
of protein sensitiveness. Some cross-relationship of this kind is 
also indicated by the fact that individuals injected with egg 
albumen to cure an egg-sensitive condition, may find that horse- 
sensitiveness or other idiosyncrasy disappears with the egg-sen- 
sitiveness. 
Anaphylactic Phases of Serum Treatment.—Antiserums 
may be administered in but single doses; this is commonly true of 
diphtheria antitoxin as used in curative work and in the ordinary 
preventive treatment for tetanus. Where possible, but one dose 
of antiserum is given as in diphtheria treatment; the first dose 
is usually large enough to make repetition unnecessary. In many 
cases, however, more than one dose is necessary; three to five 
doses are often administered in the serum treatment of pneu- 
monia. In the treatment of soil-infected or otherwise evidently 
contaminated wounds in the recent war, three sets of tetanus 
antitoxin injections were given around the outer edge of the 
wound as a matter of routine, one at the time of the first 
dressing, one early in the second week, and one during the third ANAPHYLAXIS AND SIMILAR PHENOMENA 
203 
week. This repetition was necessary because tetanus antitoxin 
is apparently eliminated from the body in eight to ten days. 
Where repeated injections of antiserum are used in other 
diseases they are usually repeated at even shorter intervals: every 
twelve or twenty-four hours in lobar pneumonia, and every 
eighteen to twenty-four hours in meningitis. 
Food Sensitives.—There seems little reason to doubt that 
unusual forms of protein may make their way into the blood 
stream from the alimentary canal. Such absorption seems to 
take place more readily from the large intestine than from other 
parts of the alimentary canal, and in digestive disturbances, in- 
completely digested or unchanged proteins may reach the large 
intestine. Severe operative shock and the attending lack of tone 
in the intestinal region apparently favors such absorption of in- 
completely digested proteins. 
It has been claimed that parents, by giving to a child too large 
an amount at the first feeding of a new food, such as egg, may 
create a sensitiveness to that food, by inducing an overproduction 
of the reacting substances which persist and cause disturbances 
later when that food is eaten. More often, probably, there is a 
family history of asthma, hay fever or similar food sensitive- 
ness that may be a more important consideration (See p. 201). 
Such sensitiveness may appear most erratically, however, and 
without any known family or inherited sensitiveness; for ex- 
ample, in one individual a sensitiveness to strawberries occurred 
for the first time at the age of fifty and lasted throughout an 
entire season. Such sensitiveness to foods is more common for 
milk and eggs than for any other foods. It may evidence itself 
merely by a hive-like or itching rash, or as an eczema, or it may 
be attended by most severe symptoms including respiratory diffi- 
culties and intestinal disorders. It is often inconvenient and 
sometimes quite undesirable to omit entirely from the diet the 
protein irritating to the individual. This is especially true for 
milk and eggs. While with time, improvement may occur with- 
out definite treatment, treatment is often necessary for full or 
permanent relief. This is gained in many cases by giving the 
individual gradually increasing doses of the specific protein. 
Since in food sensitives (PI. I) the absorption seems to be by way 
of the alimentary canal, treatment is most simply accomplished 204 
HOW WE RESIST DISExlSE 
by giving gradually increasing doses of the specific protein by 
mouth—often in gelatin capsules. The initial dose may he as 
small as 1/1000 of a gram, and a few months may suffice to cover 
the entire period of treatment. 
Sensitization Through the Respiratory Membranes.— 
Absorption of foreign protein may occur through the nasal and 
lung membranes as well as through the intestinal membranes. 
Small and easily-floated particles of foreign protein substances, 
such as pollen grains, particles of goose and chicken feathers and 
epidermal cells (hair, dandruff) of horses, cats, dogs, and guinea- 
pigs, are among the irritating substances shown to be absorbed in 
this way. Most of us know of people who cannot work with horses 
or guinea pigs, or who have asthmatic symptoms or hive-like out- 
breaks on the skin if they drive behind a horse even a short dis- 
tance. It is only recently that we have understood the peculiar 
phenomenon of people who are made uncomfortable by the pres- 
ence of cats—who “ know without seeing when a cat has entered 
the room.” 
More common are cases of discomfort due to the absorption of 
plant proteins, such as flower pollens. Ragweed, grasses, such 
as timothy or the staple grains, early flowering trees with 
abundant wind-blown pollen and several plants with more con- 
spicuous flowers, such as daisies and roses, are common causes of 
“hay fever,” “rose cold” or similar respiratory difficulties. 
Goldenrod is probably less important in this connection than 
generally supposed. Very fine particles of other plant parts such 
as dust from broken grass seed or wheat grains may have the 
same effect upon similarly hypersensitive people. (See p. 213.) 
In all these cases the sensitive condition thus provoked is no 
doubt due to earlier and unnoticed absorption of the substance 
the individual finds so irritating. On each later opportunity 
enough is absorbed to produce anaphylactic symptoms. The 
extreme susceptibility of some individuals is attributed to a 
difference in the mucous membranes of the respiratory area—to 
tbe “ peculiarly acute penetrability ” of such membranes. There 
is also evidence that these differences vary in a given individual 
with his physical condition (disease, fatigue, operative shock, 
etc.). This would explain many of the erratic manifestations, ANAPHYLAXIS AND SIMILAR PHENOMENA 
205 
such as the sudden susceptibility of a hitherto immune individual, 
or recovery without treatment. 
The amount of substance which causes these anaphylactic 
symptoms or conditions is usually very slight. Vaughan re- 
ports one individual who on entering the laboratory could tell 
by the presence or absence of disturbing symptoms whether or 
not the cork was out of the peptone bottle. 
Fig. 130.—This photograph with numerous tubercles (T) on the 
omentum oi fat layer shows the reason for the name tuberculosis. 
(External view) Moore, Bovine Tuberculosis. Macmillan. 
Tests to Identify the Specific Causes of “ Hay Fever ” 
and Food Sensitiveness.—In all conditions of food sen- 
sitiveness and sensitization through respiratory membranes, 
the first thing required is to ascertain definitely what protein is 
responsible for the anaphylactic symptoms. This is ascertained 
by means of intradermal skin tests. Minute quantities of dif- 
ferent proteins are introduced beneath the outer skin. (Fig 137.) 
Eight or ten different substances are often injected at the 
same time, one below the other, an inch or so apart, in the upper 
arm or the leg. The relative degree of inflammation at the re- 
spective injection sites, enables the physician to decide which is 
the most irritating substance for that individual. (Fig. 138.) 206 
HOW WE RESIST DISEASE 
Treatment for “ Hay Fever.”—Occasionally an individual 
is able to control his time to such an extent that he can avoid 
the irritating cause, e.g., avoiding ragweed pollen by spending 
the summer in the city, mountains or summer resorts where that 
particular plant does not grow. Often he prefers to “ take treat- 
Fig. 131.—This shows a cross section through the lung tissue 
and so through many of the tubercles. Moore, Bovine Tubercu- 
losis, Macmillan. 
ment,” the treatment consisting of a series of appropriately 
graduated doses of the protein to which he is sensitive; this makes 
him finally less sensitive, probably because the body tissues have 
learned to take care of that particular protein in a different way 
—either gaining the power to break it down without an accu- 
mulation of the poisonous split-proteins, or forming substances 
to protect the tissues against these poisonous split-proteins. 
Treatment may not give the patient complete or permanent ANAPHYLAXIS AND SIMILAR PHENOMENA 
207 
freedom from his difficulties, as he gains tolerance rather than 
complete immunity, apparently. For treatment, an extract of 
the specific irritating substance is used. Pollen, for example, 
may be prepared by drying the pollen from the plant in question, 
Fig. 132.—Lesions (A, B) in brain of cow, due to tuberculosis 
organisms. Moohe, Report New YorJs State Veterinary College. 
and then treating it with a glycerol and salt solution to secure the 
extract needed. 
Tests for Disease.—As already stated (p. 196), bacterial 
proteins, because of their anaphylactic relationships, may be used 
in testing for disease. These tests may be used to show either 
(1) the actual presence or absence of a given disease in the 208 
HOW WE RESIST DISEASE 
tested individual, or (2) the immunity or susceptibility of an 
individual to a given disease. 
The diseases of most interest in this connection are tubercu- 
losis, syphilis (PI. I) and gonorrhea. Since the test for tubercu- 
losis is the one most generally known, that may be described 
as more or less illustrative. The principles underlying such tests 
do not differ from those applying to hay fever and food-sensitive 
tests (p. 205). 
The (Von Pirquet) Tuberculin Test.—The various prep- 
arations of tuberculosis organisms used in the tuberculosis 
Marchis 
March is 
Fig. 133.—The light lineshows fhenormaltemperature of a cow; the 
heavy line shows the greater range in temperature (positive test) 
obtained with the same cow the next day following the injection of tuber- 
culin. Redrawn from Moore, Pathology of Infectious Diseases, 
Macmillan. 
test are called tuberculin. Many different types of tuberculin 
are prepared in the various laboratories—heated and unheated, 
concentrated and not concentrated, broth cultures and emulsions, 
with and without glycerine, etc. 
The various types are indicated by special names, abbrevia- 
tions, etc., such as Tuberculin, B. F., the final initials in this case 
indicating a bouillon filtrate. 
The tuberculin test is made by injecting some of the tuber- 
culin into the individual to be tested, usually into the skin. 
Several methods are used: such as scarifications in the skin 
(cutaneous method), or, inserting the tuberculin into the sub- ANAPHYLAXIS AND SIMILAR PHENOMENA 
209 
cutaneous tissue (subcutaneous method); in the newest and most 
commonly used (intra-cutaneous) method, the material is in- 
serted between the layers of the skin just as in the Schick test. 
Injections in the eye, a method often used with cattle, is rarely 
used in man. 
In a tubercular individual the characteristic skin response 
to tuberculin is a reddening and swelling at the site of injec- 
tion, beginning in about six hours, increasing through the first 
Fig. 134.—A diagrammatic represention of two proteins to show the very diverse 
character due to different secondary (S) or tertiary (T) parts. It is possible to split each 
down to the same poisonous core. (P.C.) See also Fig. 12. 
two days following the injection, and disappearing in six to ten 
days. People who have not tuberculosis, whose tissues are not 
already irritated by tuberculosis organisms, are not affected by 
such small amounts of tubercle bacteria, and do not, therefore, 
show such local irritation. (See also temperature reaction, 
Fig. 133.) 
Positive reactions are obtained only from people who have 
tuberculosis or wbio have recovered from tuberculosis. On the 
other hand, a tubercular individual may not give a positive re- 
action the first time, a second injection being necessary to suffi- 
ciently stimulate such response. Occasionally advanced cases 
fail to give a positive reaction; in such cases, however, the clinical 210 
HOW WE RESIST DISEASE 
or physical symptoms are usually sufficiently indicative. The 
principal argument against the tuberculin test, however, is that 
a positive reaction may be obtained not only from latent but also 
from cured cases, and that, therefore, such reaction is not very 
helpful for adults, since practically all adults have at some time 
had tuberculosis—mainly mild or unnoticed cases. (Sputum ex- 
aminations are, of course, determinative in pulmonary types of 
tuberculosis, and may be used to support the tuberculin tests.) 
Other diseases, such as typhoid and syphilis, 
lessen the diagnostic value of the results 
obtained by tuberculin tests. (See also 
agglutination and complement-fixation tests 
for tuberculosis.) 
For young children, tuberculin tests are 
more decisive and may throw light upon 
otherwise perplexing conditions, such as 
sometimes exist with gland or intestinal 
tuberculosis; in a young child a negative 
tuberculin test would eliminate tuberculosis 
and indicate the cause should be sought 
elsewhere. 
Skin reactions similar to those described for tuberculosis, 
occur with emulsions of Treponema pallidum in skin tests for 
syphilis. Skin tests are also made with typhoid and gonococcus or- 
ganisms in testing for typhoid or for gonorrhea. These tests are 
not nearly so reliable as the tuberculin test—as non-specific reac- 
tions may occur with “ relative frequency,” and many authorities 
consider these tests far from satisfactorily verified or established 
as yet. Illustrations of characteristic reactions in positive skin 
tests, as in gonorrhea and syphilis, may be found in Plate I. 
Symptoms in Disease.—Since one of the theories of the 
poisonous effects of bacteria implies a common poisonous sub- 
stance (See pp. 20 and 192) two questions often arise. One is, 
“Why then do different diseases have different symptoms?” or 
even, “ Why are there different diseases at all ? ” The second is, 
“ ITow can we then test for a given disease; are such tests really 
specific and reliable ? ” 
In answer to the first we may say that although all proteins 
can by laboratory processes be broken down to a similar form, 
it does not at all follow that they are all so broken (Fig. 135) in 
Fig. 135.—Even if the 
splitting is not so com- 
plete, a like body may be 
obtained as shown in the 
following figure. ANAPHYLAXIS AND SIMILAR PHENOMENA 
211 
the body, and in the stages actually reached we may find simi- 
larity without complete likeness. (See Fig. 136; also Fig. 13.) 
Vaughan explains the different symptoms in the various diseases 
by attributing to different bacterial by-products dissimilar chemi- 
cal affinities which cause them to accumulate in different tissues 
of the body, e.g., lungs, kidneys. These varying “ predilection 
centres 7 give us the various symptoms or combination of symp- 
toms associated with the various diseases. 
In answering the sec- 
ond question, “Are such 
tests really specific and 
therefore reliable ?” the 
results compiled show 
that, as described in dis- 
cussing the tuberculin 
test, positive results are 
truly indicative of pres- 
ent or past infection. Neg- 
ative results, here as in 
every other field of science, 
are not positive evidence. 
Anaphylaxis and Immunity.—The sensitiveness which 
produces reactions against bacterial proteins can not be separated 
from the sensitiveness which initiates the production of helpful 
antibodies against them—so alike are the conditions known as 
anaphylaxis and as immunity. The changes upon which the 
development of immunity depend have their attendant dangers; 
in the anaphylactic disturbances we see “ the disadvantages of 
the advantages ” hoped for in immunity. 
This chapter forms but a brief presentation of the varied 
and perplexing phenomena ordinarily discussed in connection 
with anaphylaxis—the most hotly disputed subject in the whole 
realm of immunity. Nowhere do we find agreement or unity— 
with regard to the theory, the terminology, or the manifestations 
of anaphylaxis. In this discussion the aim has been to maintain 
a safe middle course through this perilous region, hoping that 
the beginning student will find herein what seems to him a 
simple, sensible explanation of the situations in his past ex- 
perience, and, also what will prove, later, an easy introduction to 
a real study of this most interesting if complex subject. 
Fig. 136.—Even though proteins can be split 
into the like poisonous substances, proteins prob- 
ably differ with i egard to the ease with which this 
may be done. The formation of such incomplete 
split products, differing slightly from each other, as 
shown here, may explain the different effects and 
symptoms when different bacteria (proteins) in- 
vade the body. See also Fig. 13. 212 
HOW WE RESIST DISEASE 
1. Show that anaphylaxis is a protein sensitiveness. 
2. What is the “Theobald Smith Phenomenon?” 
3. What is serum sickness? 
4. Describe anaphylaxis in an animal other than man. 
5. What human tests to show the presence of, or the susceptibility to, 
disease are based on anaphylactic reactions? 
6. The following is taken from a set of laboratory directions for procur- 
ing serum lysins against rabbit’s red blood cells: 
Inoculate a rabbit with sheep’s cells. 
(1) 1 c.c. 50% cells on first day, (2) 1 c.c. 50% cells on second day, 
(3) 2 c.c. 50% cells on third day, (4) After 5 days repeat series, 
(5) After next 5 days draw 5 c.c. blood from ear of rabbit. 
Through how long a period is the rabbit inoculated with foreign 
cells? Why does anaphylaxis not occur in rabbits so treated? 
STUDY SUGGESTIONS 
Fig. 137—Skin tests to determine the 
individual’s susceptibility to several differ- 
ent pollens; reading down, these are rag- 
weed, sunflower, goldenrod, willow and 
maple. Maple is used as a control since the 
usual results are negative. This individual 
should receive treatment with ragweed and 
willow pollen. Courtesy of Arlington 
Chemical Company. 
Fig. 138—Tests with varying 
strengths of timothy pollen to which this 
individual is sensitive to determine the 
strength with which treatment should 
begin, 1 to 10.000 in this ease. Courtesy 
of Arlington Chemical Company. 
7. How do we explain the different skin reactions obtained in Fig. 137? 
8. In an early discussion of the antibody-extracts, (p. 71), their relative 
freedom from irritating results common to foreign proteins is 
supported by the statement that “even 5 c.c. of the extract only 
irregularly sensitizes.” Show that this does support the claim made. 
9. During the training of one of our men in the recent war he was shifted 
several times from camp to camp, and his records being lost or 
delayed, was repeatedly vaccinated with the (triple) typhoid 
vaccine, receiving in all nine injections in forty days. What is 
the probable explanation of the intense local reaction he experi- 
enced in the latest injections? Explain the lack of general ana- 
phylactic symptoms during this whole period. ANAPHYLAXIS AND SIMILAR PHENOMENA 
213 
10. The intestinal wall of new-born infants (4th to 10th day) has been 
shown to be very permeable to small quantities of white of egg. 
W hat disadvantages may result from too early feeding or even 
giving a small “taste” of such proteins to young babies? 
11. Explain or support the statement often made that for adults only 
negative tuberculin tests are to be relied on, and those only when 
no general malnutrition exists. 
12. A recent article on “hay fever” cites the following list of causes: 
Pollen of birch, maple, roses, goldenrod, asters, daisy, clover, 
corn, timothy, ragweed, alfalfa; epidermal cells (dandruff, hairs) 
of horses, cats, dogs, rabbits, chicken feathers, cotton; insecticide 
powders; powdered orris root (in scented talcum powders) ; and 
broken particles of wheat, straw and cereals. 
Check off those found to be irritants by your acquaintances. 
Which cause is found most freqiiently? Which is not found at all? 
13. Health Neivs (October 1921) gives the following series of positive 
reactions in 100 consecutive asthmatic patients: 
Ragweed. 
Per cent. 
, . . 28 
Dust 
. .. 25 
Orris 
. .. 19 
Chicken epithelium , 
... 19 
Hay 
. . 19 
Cow epithelium . . . 
. .. 16 
Horse epithelium .. 
. .. 14 
Cat epithelium .... 
. . . 13 
Timothy 
. .. 13 
Straw 
Per cent. 
. . . 12 
Rabbit epithelium . 
8 
Dog epithelium .. . 
7 
Dog saliva 
6 
Duck epithelium . . . 
3 
Goose epithelium. . . 
3 
Horse serum 
3 
Cotton 
2 
Le Page (glue) .... 
1 
(Note, as the total of these percents indicate, that some of these 
patients were sensitive to more than one substance.) 
Among your affected acquaintances do these ratios hold? 
How many of them are also sensitive to such foods as egg, milk, 
fish, cereals (wheat, corn and rice) ? 
14. Investigators have found that supersensitiveness to proteins as seen 
in man may be inherited (following Mendel’s law of inherited 
characters). Does this preclude the explanation of such sensitive- 
ness as being due (1) to the chemical sensitiveness of the in- 
dividual’s cells, or (2) to the unusual permeability of the exposed 
or contact membrane (nasal membranes, intestinal linings) ? 
15. Animals repeatedly injected with small doses of proteins may estab- 
lish such a high degree of resistance that they can withstand 
1,000 times the dose usually fatal to that animal. Is this high 
or low compared with the immunity following the use of bacterial 
vaccines, such as given in Fig. 119? 
16. Use Ferry’s characterization that anaphylaxis is “a phenomenon 
rarely seen in the human subject and seldom observed in any animal 
other than the guinea-pig”—a “picture that belongs to the research 
laboratory and not to the bedside,” as a theme for dispelling the 
fears of the public with regard to the use of vaccines and serums. 
17. One investigator succeeded in sensitizing a guinea-pig by such a small 
dose as 0.000,000,05 gm. of crystallized egg albumin. Can you find 
a record of a smaller sensitizing dose than that for any animal? 
18. One firm advertises “No mixed pollen solutions for either diagnosis 
or treatment will be supplied.” Do you approve of this? Why? GLOSSARY 
While it is presupposed that the reader has had an elementary 
course in bacteriology, the scope of the terms herein defined has been 
extended considerably to aid in making the book understandable to others 
who may be interested in the subject of immunity. 
These definitions are, in no sense, complete technical definitions, 
but are designed as brief characterizations to aid beginners in using this 
text. Reference to the index will, in many cases, indicate the various 
passages in the main body of this book where these terms are more 
fully defined. t 
For information regarding the scientific name of a given organism 
consult the list following the glossary. 
Acne. A skin disease, commonly 
affecting the sebaceous glands of 
the face, and characterized by 
such symptoms as dilated blood 
vessels and pustular or other 
types of eruptions. 
Agar. The term agar is used for 
a semi-transparent substance re- 
sembling gelatin in appearance 
which may be expressed from 
seaweed, and also for a combina- 
tion of that substance with meat 
broth to form a solid medium 
suitable for cultivating bacteria. 
Agar Plate. A covered glass dish 
(Petri Dish) containing a layer 
of agar which furnishes food ma- 
terial for the growth of bacteria. 
Agglutinins. Substances accumu- 
lating in the blood, in response 
to the specific irritation or stimu- 
lation caused by many foreign 
cells, such as typhoid bacteria. 
These substances cause the 
clumping together (agglutina- 
tion) of the related bacteria— 
a phenomenon aiding in their 
destruction. The name, agglu- 
tinins, refers to the apparently 
sticky or glutinous condition of 
the cells. 
Aggressins. (Aggressive or at- 
tacking substances.) Enzymes 
or other substances formed by 
bacteria which increase their ef- 
fect upon the host. 
Alexin. Same as complement. 
Allergy. (Working in another 
way.) The altered power of re- 
action occurring in animals as 
the result of inoculating with a 
specific substance; a type of pro- 
tein sensitiveness. (See index.) 
Alveolar. Relating or belonging 
to the alveoli, the air sacs or 
pouches which form the tiny ulti- 
mate subdivisions of the lungs. 
Although the alveolar membranes 
forming these sacs are richly 
supplied with blood, bacterial 
invasion may take place through 
these membranes. 
Amboceptor. See “immune body.” 
(Literally, holding two at once.) 
214 GLOSSARY 
215 
A term used for the “immune 
body” and indicating its power to 
unite with two things at once— 
with another complementary 
blood substance (complement) 
and the irritating factor, (bac- 
teria or other foreign cells). 
Anaphylaxis. (Without protec- 
tion.) A term covering various 
forms or manifestations of un- 
usual or extreme susceptibility 
to foreign proteins; certain un- 
toward phases of protein hyper- 
sensitiveness. 
Antibodies. Protective reacting 
substances formed in response to 
such irritating factors as bac- 
teria or their products. The 
names given antibodies—antitox- 
ins, agglutinins, opsonins, and ly- 
sins—are more or less indicative 
of their action. Moie than one 
kind of antibody may be aroused 
by a single kind of bacterium. 
Antigen. Any substance which 
when present or injected into an 
animal can stimulate the produc- 
tion of (one or more kinds of) 
antibodies. A vaccine is an anti- 
gen ; any substance used to 
arouse sensitiveness (and there- 
fore reacting antibodies) is an 
antigen. In blood tests, such as 
the Wassermann test, the term 
antigen is used for any substance 
capable of uniting with a given 
antibody. 
Antiseptic. Against or preventing 
sepsis (or decay). Gauze used 
for dressings is sometimes made 
antiseptic by impregnating it 
with chemicals which inhibit or 
prevent the development of bac- 
teria in the wounded areas; us- 
ually dressings are merely sterile 
or aseptic. (See Sterile and 
Aseptic.) 
Antitoxins. The specific sub- 
stances or antibodies formed in 
the body in response to the ir- 
ritating or poisonous toxins of 
such bacteria as diphtheria and 
lockjaw are called antitoxins. 
These antitoxins neutralize the 
toxins formed by the related bac- 
teria, but do not destroy the 
bacteria themselves. 
Popularly, antitoxin is often 
used to designate commercial 
diphtheria antitoxin, as produced 
by the horse, ignoring the fact 
that in such a disease the human 
body may itself produce its own 
antitoxins. 
Arthritis. A disease of the joints 
with symptoms resembling rheu- 
matism or gout. Various species 
of bacteria, e.g., Streptococcus 
riridans, are sometimes found 
to be associated with such 
conditions. 
Aseptic. Without sepsis, putre- 
faction or decay. Dressings and 
instruments may be made sterile 
or aseptic by heat. In the effort 
to keep wounds in an aseptic 
condition they are, if possible, 
made surgically clean (removal 
of pus, diseased surfaces), and 
then either sterile or antiseptic 
dressings are used. See Anti- 
septic. 
Auto-intoxication. The digestion 
or breaking down of protein 216 
GLOSSARY 
foods includes many temporary 
or transitional stages, some of 
which are poisonous. Nervous 
or other functional derangements 
of the digestive processes may 
lead to the accumulation and ab- 
sorption of unusual amounts of 
some of these intermediate pois- 
onous stages; this “self-poison- 
ing” is termed auto-intoxication. 
The kinds of bacteria present in 
the alimentary canal vary in 
health and disease; and the 
prominence of one or more un- 
desirable types may be respon 
sible for the development of such 
cases of auto-intoxication. 
Autopsy. An examination of a 
dead body to determine the cause 
of death, the seat of disease, etc.; 
a post-mortem examination. 
Bacillus. (pi. Bacilli.) Rod- 
shaped bacteria; a term used us- 
ually for the rod forms possess- 
ing motility or the power to form 
spores. 
Bactericidal. Able to kill bac 
teria; carbolic acid, alcohol, etc. 
are bactericidal substances. A 
given blood may have a bacteri 
cidal effect upon bacteria through 
the action of the white corpus- 
cles, or the presence of such 
antibodies as lysins. 
Bacteriemia. Bacterial infection 
in which the bacteria escape from 
the more or less localized lesions 
and invade the blood stream. 
Bacterin. Bacterin is a term 
sometimes used as a name for 
killed cultures of bacteria which 
are used to produce immunity to 
a given disease. The vaccine 
used to prevent typhoid is tech- 
nically a bacterin. (See vac- 
cine. ) 
Bacteriolysin. A lysin or dis- 
solving substance formed against 
bacteria, (see Lysin.) 
Bacteriophages. See white cor- 
puscles. 
Bacteriotropins. See Tropins. 
Blood. See Serum; also Whole 
Blood. 
Blood Count. A count of tbe 
total number and proportion of 
white and red corpuscles. This 
count is made by putting a care- 
fully measured amount of ac- 
curately diluted blood on a spe- 
cial slide which holds a given 
amount of blood over a central 
area marked off in tiny squares 
to facilitate counting. See in- 
dex for illustration page. The 
count is made through a micro- 
scope. 
Botulism. Food poisoning due to 
the accumulated toxin of Glos trid- 
ium botulinum. Although sev- 
eral recent workers have obtained 
vigorous growth at body temper- 
ature, it still seems probable 
that few if any cases of botulism 
come from the development of 
the organism in the human body. 
Nevertheless canned or prepared 
food of a suspicious character 
(odor, texture, etc.) should not 
be eaten even if brought to the 
boiling point (or 15 minutes at 
!)0°C.) which destroys the toxin 
accumulated in the food. The 
temperature necessary to kill the 
spores varies with their age, one GLOSSARY 
217 
month old spores being “three 
times as resistant as five months 
spores.” Botulism occurs most 
often after eating foods incom- 
pletely cooked (canned fruits or 
vegetables) or in which the pre- 
paratory processes (chopping 
pickling, ripening, etc.) cover ex 
tended periods as with some meat 
products, “ripe olives,” etc., be 
cause the initial preserving con 
ditions have not killed the 
organism or the later conditions 
have allowed its entrance into 
the food. 
Carrier. A person, who though in 
apparent health, carries the or- 
ganisms of a given disease in 
his body: diphtheria bacteria on 
the throat membranes, typhoid 
bacilli in the intestinal area, or 
malaria organisms in the blood. 
An individual may be a tempo- 
rary carrier following the period 
of convalescence. It is estimated 
that 1 to 5°/0 of typhoid patients 
become more or less permanent 
carriers; records have shown the 
persistence of such conditions 
for forty years and more. Less 
often, normal individuals, not 
known to have had a given dis- 
ease may be found to be carriers 
of the organisms causing that 
disease. 
Centigrade. (centum, one hun- 
dred.) The Centigrade thermom- 
eter has between freezing and 
boiling but one hundred divisions 
or grades, therefore, literally 
centigrade. The cut following 
gives the corresponding Centi 
grade and Fahrenheit tempera 218 
GLOSSARY 
tures with rules for translating 
one scale into the other. 
To convert de- multiply by 9, 
grees Centigrade divide by 5, add 
into degrees 32. 
Fahrenheit: 
To convert de- subtract 32, mul- 
grees Fahrenheit tiply by 5, di- 
into degrees vide by 9. 
Centigrade: 
C.C. (See Cubic Centimetre.) 
Clinical. This term refers to the 
immediate or direct examination 
of a patient; the clinical symp- 
toms are those which might be 
determined by observation at the 
bedside rather than by the micro- 
scopic or chemical findings of the 
laboratory. 
C02- Carbon dioxide. 
Coccus, (pi. Cocci.) Globular bac- 
teria are termed cocci. The va- 
rious bacteria of this general 
character are further differenti- 
ated or classified by other mor- 
phological or by functional char- 
acteristics, such as arrangement 
in chains (Streptococci),arrange- 
ment in packets (Sarcina), form- 
ing red pigment (Rhodococcus). 
Communicable. Diseases readily 
transferred from one person to 
another are now spoken of as 
communicable. This term is 
supplanting the older term con- 
tagious,. 
Complement. A substance pres- 
ent in blood (ordinary or normal 
blood as well as immune blood) 
which completes (complements) 
the dissolution or lysis of bac- 
teria or other foreign cells in- 
vading the body. 
Contagious. (See Communicable 
and Infectious.) 
Cubic Centimetre, (c.c.) A small 
unit of size used in the metric 
system, now almost uniformly 
adopted for scientific measure- 
ments and descriptions. A cubie 
centimetre of water weighs one 
gram; probably a cubic centi- 
metre can be visualized better 
by remembering that a cubic 
centimetre of such liquids as 
water contains about sixteen 
drops. For measuring liquids 
the word mil, (French, mille, a 
thousand) has been suggested as 
a substitute for cubic centimetre, 
as its form indicates its relation 
to the larger liquid unit of the 
metric system, the litre, a cubic 
centimetre or mil being one 
thousandth of a litre. 
Diagnosis. A conclusion based 
upon a careful study of the 
characteristic signs or symptoms 
presented in a given case. Form- 
erly a diagnosis was necessarily 
based upon clinical symptoms 
only; at present an examination 
of bacteriological or pathological 
material (e.g., blood and feces 
in typhoid) is often made to 
confirm the clinical diagnosis. 
Dialysis. The passage of soluble 
substances through membranes, 
either cell membranes, or artifi- 
cial membranes such as dialyzing 
bags. (See Osmosis.) 
Disinfectant. That which can de- GLOSSARY 
219 
stroy infectious matter (bacteria, 
pus, etc.). Germicidal and steri- 
lizing are stronger terms than 
disinfectant. Complete steriliza 
tion of dishes, utensils, bedding, 
etc., by heat or chemical germi- 
cides is rarely necessary as the 
organisms causing the common 
human diseases are usually killed 
long before the common and more 
resistant molds, and such harm- 
less spore-producing bacteria as 
the hay bacillus. (See Germi- 
cidal. ) 
Endemic. (Literally, in or among 
the people.) Applied to any 
disease produced and continu- 
ously propagated by local condi- 
tions; e.g., malaria and hook- 
worm are endemic in certain 
areas of the United States. 
Endotoxins. Toxins of such na- 
ture that they are not freely 
excreted from the living cell. 
(See Toxins.) 
Enzymes. Substances produced 
by living cells which bring about 
definite chemical changes in those 
cells, their stored substances or 
their food materials. The growth 
and metabolism changes of all 
cells are dependent upon the ac- 
tion of such enzymes. 
Epidemic. (Literally, upon the 
people.) Applied to sudden and 
widespread manifestations of 
disease, such as the recent 
“influenza epidemic.” Epidemics 
differ from endemics in being 
sometimes attributable to the 
introduction of more virulent 
or entirely new organisms, 
though physical conditions, fam- 
ine, panic, etc., may be im- 
portant factors in causing an 
“endemic disease to assume epi- 
demic proportions.” 
Eustachian Tube. A tube con- 
necting the cavity between the 
nose and the throat with the ear. 
Infection from the mouth or 
nasal region very often spreads 
into this tube and so into the 
ear, penetrating the spongy 
(mastoid) bone near the ear 
(mastoid abscess). 
Exotoxins. Toxins which are eas- 
ily or readily excreted from 
the cell producing them. (See 
Toxins.) 
Exudate. The more or less liquid 
material found in a lesion or 
exuding from an inflamed area, 
such as the drip from nostrils, 
or the mucus or phlegm so char- 
acteristic of colds. 
Feces. The discharges from the 
intestines or bowels. 
Fibrin. A protein (globulin) sub- 
stance present in the blood which 
helps form the clot in coagulat- 
ing blood. Defibrinated blood is 
termed serum. (See Plasma 
and Serum.) 
Filterable. Capable of being 
passed through a standard filter, 
such as the “porcelain” filters. 
(See illustration of filters 
in text.) 
Food Sensitives. Individuals who 
experience such definite manifes- 
tations as hive-like eruptions, 
breathing difficulties or inflam- 
mation of the eye or nose mem- 220 
GLOSSARY 
branes, following the eating of 
one or more specific food sub- 
stances, such as eggs, shellfish, 
and strawberries. 
Flora. The plants present in a 
given region. A list of the kinds 
of bacteria found in a region, 
such as the mouth or intestine, 
would be termed the bacterial 
flora of that region. 
Focus, (pi. Foci.) Site or seat of 
infection; the area of growth 
and multiplication of the invad- 
ing organism. (See Lesion.) 
Fomites. Substances capable of 
absorbing, holding and transport- 
ing infectious micro-organisms; 
particles of mucus, clothing, etc., 
come under this heading. 
Furunculosis. A technical term 
for boils and similar infections. 
Germicidal. A term used in refer- 
ence to substances or agents 
(acids, heat, etc.) that can kill 
germs or micro-organisms. By 
implication (killing all germs) 
a germicide is a more powerful 
agent than a disinfectant, for a 
germicide must kill even resist- 
ant spores—such as mold spores 
—as well as the ordinarily less 
resistant organisms causing in- 
fection. (See Disinfectant.) 
Germicidal substances, such as 
lysins, are produced by the body 
and may be demonstrated in the 
blood, e.g., lysins against cholera 
organisms. 
Globulin. See Protein. 
Gonorrhea. A dangerous bacte- 
rial disease, affecting such deli- 
cate membranes as those of the 
eyes and the genital area. It 
is sometimes transferred through 
infected towels, bedding, and per- 
sonal articles, as well as by 
personal contact. 
Gram. A unit of weight. One 
cubic centimetre of pure water 
at its greatest density (4°C., or 
39°F.) weighs one gram. The 
weight and bulk units of the 
metric system—gram and cubic 
centimetre—are, therefore, prac- 
tically interchangeable for water 
measurements, but not for liquids 
lighter or heavier than water, or 
for most dry substances. 
Hay-fever. A form of protein- 
sensitiveness, in which the pa- 
tient is very susceptible to the 
presence of such substances as 
the pollen of certain plants, 
grasses, ragweeds, etc. 
Haemoglobin. The compound re- 
sponsible for the coloring matter 
of red corpuscles and important 
as a carrier of oxygen. Ruptured 
or dissolved red corpuscles allow 
the escape of the colored haemo- 
globin; tests involving such dis- 
solution of red corpuscles are 
now in common use, e.g., Was- 
sermann test. (See Lysins.) 
Haemolysins. Lysins formed 
against and dissolving red blood 
cells, allowing the escape of the 
haemoglobin. An animal injected 
with foreign red blood cells forms 
lysins against such foreign cells. 
Some bacteria (Streptococcus, 
Hemophilus) form similar lysins 
and, therefore, have very destruc- 
tive action on red blood cells. 
Hay bacillus. A common spore- 
producing organism, Bacillus sub- 
tilus, quite universally found on 
hay, in soil, water, etc. 
Hemorrhagic. Showing evidence 
of hemorrhage; reddened or in GLOSSARY 
221 
flamed by the accumulation, pas- 
sage, or escape of blood. 
Hookworm. A small round worm 
(Necator) which causes the 
hookworm disease. The hook- 
worm is a many-celled animal as 
contrasted with the one-celled 
bacteria and protozoa with which 
most of this text deals. 
Host. An organism that harbors 
another as a parasite. In ty 
phoid or hookworm, man acts as 
host for the typhoid or hook 
worm organisms. In such dis- 
eases as malaria, man and the 
mosquito are alternately the host 
for the parasite. 
Immune. Free from and resistant 
to disease. (See Immunity.) 
Immune Blood. Blood from a 
person or other animal immune 
to a given disease; that is, bloqd 
from an animal which has recov- 
ered from a given disease— 
•whether contracted “naturally” 
or as the result of the purpose- 
ful inoculation of the causal 
organism.. 
Immune Body. Part of a lysin 
—the “specific” part. Ambo- 
ceptor is often used as a syno- 
nym for Immune Body. (See 
Lysin.) 
Immunity. This is defined as 
freedom or exemption from; the 
literal meaning “not in service 
to,” carries the same implication, 
and gives an interesting parallel 
of the body as the slave of the 
disease organism. Immunity to 
a given type of infection may be 
due to antibodies produced in an 
earlier attack of that same dis- 
ease. This is termed active 
immunity in contrast to passive 
immunity where an individual 
lacking such active immunity 
may secure similar protection by 
injections of blood from another 
individual who is immune. 
Incubation. When bacteria are 
kept at temperatures favorable 
for growth or multiplication, 
they are said to be incubated. 
We also speak of the initial time 
period when bacteria are multi- 
plying in the body as the incu- 
bation period; this period extends 
from the time when the disease 
organism or organisms enter the 
body to the time when the symp- 
toms appear and the patient 
“comes down” with the disease. 
The growth or multiplication of 
the organisms concerned, how- 
ever, continues beyond this time 
—until the protective reactions 
of the body make such multipli- 
cation impossible. 
Inert. Neutral; devoid of active 
chemical properties. 
Infection. Disease organisms that 
multiply in the body cause in- 
fection. Infection may have a 
definite focus or be quite local- 
ized as in a boil or tooth abscess; 
or the infection may be more 
generally distributed, as in blood 
poisoning. 
Infectious. Caused by disease- 
producing organisms; capable of 
producing disease through the 
transfer of such organisms, e.g., 
infectious discharges from a 
wound or abscess. The old at- 
tempt to differentiate between 
infectious and contagious has be- 
come unnecessary since the adop- 
■ tion of the term communicable. 
Inhibited. Prevented from grow- 222 
GLOSSARY 
ing or from multiplying in 
number. Chemicals, unfavorable 
temperatures, eta, may be used 
to inhibit bacterial growth or 
action. 
Inflammation. A tissue reaction, 
of which the main symptoms are 
swelling and reddening due to 
the increased amount of blood 
in a given area; this may include 
the escape of one or more of the 
blood constituents, such as serum, 
into the inflamed tissue. 
Inoculate. To introduce directly 
into the body, as into the skin, 
the abdominal cavity, or a blood 
vessel; used mainly in reference 
to the introduction of micro- 
organisms ; curative substances 
(serum etc.) are more commonly 
• spoken of as injected. 
Intradermal. Into the skin, not 
underneath, as in subcutaneous. 
Lesions. Injuries, diseased areas 
or morbid changes in organs or 
tissues. As examples of lesions 
we may cite an ulcer, a tuber- 
cular nodule, or a hemorrhagic 
area. 
Lethal. Deadly; causing death, 
in a given or prescribed time. 
Leucocytosis. An increase in the 
number of white corpuscles. 
Leucopenia. A deficiency of 
white corpuscles. 
Litre. A metric system unit for 
liquids, slightly larger than the 
quart; it consists of 1000 c.c. 
(See Cubic Centimetre). 
Lymph-nodes. Small lymph- 
glands or collections of lymph 
tissue. Certain types of white 
corpuscles are produced in these 
lymph-glands; the inflammation 
of certain lymph-nodes and the 
attendant pain (pressure) are 
due to the increased activity and 
blood content of such glands 
following infection. 
Lymphocytes. Single-nucleated 
white corpuscles. Though not so 
generally active in bacterial de- 
struction as the white corpuscles 
which have two or more nuclei, 
definitely helpful action is attrib- 
uted to the lymphocytes in cer- 
tain diseases, e.g., tuberculosis. 
Lysins. Dissolving substances or 
antibodies formed in the body as 
a reaction to bacteria (or other 
foreign cells, such as injected red 
blood cells). The action of a 
lysin is best explained by con- 
sidering it as a double agent or 
substance: (1) The immune 
body and (2) the complement. 
Both factors are necessary for 
the lytic or dissolving action on 
foreign cells. Normal blood con- 
tains but one of these two factors, 
the complement; but a person 
recovering from such a disease 
as cholera, has also the second 
type, the “immune body,” and 
therefore his blood can complete- 
ly dissolve the cholera organism. 
(See Haemolysins.) 
Lysis. A dissolving or dissolution. 
(See Lysins.) 
Macrophage. (See White Cor- 
puscles. ) 
Medium, (pi. mediums or media.) 
Substances used to provide nu- 
tritive material for the growth 
and multiplication of micro-or- 
ganisms; milk, beef broth and 
gelatine are examples of common 
mediums. For certain organisms GLOSSARY 
223 
special kinds are used; these may 
contain egg for tuberculosis 
organisms, serum for diphtheria, 
blood for streptococci, etc. 
Meninges. The enveloping mem 
branes of the brain and spinal 
cord. 
Meningitis. A disease of the 
meninges of the brain or spinal 
cord; the causal organism is 
usually the meningococcus organ 
ism but may be one of half a 
dozen other organisms—either 
characteristically disease produc- 
ing organisms, such as the 
pneumococcus or streptococcus 
organisms, or less virulent ones 
such as the colon bacterium. 
Metabolic. (See Metabolism.) 
Metabolism. A comprehensive 
term for all the cell changes, 
including the change of stable 
non-living food substances to 
complex unstable living material 
and the breaking down of that 
living material to simpler and 
more stable substances; metab- 
olism includes all the upbuilding 
and energy-producing changes 
in a cell. 
Metric System. A system of 
weights and measures very com- 
monly used in Europe and now 
generally adopted in this country 
for scientific work. It is much 
simpler than our own systems 
the units being similar multiples 
or divisions of each other, vary 
ing by tens, hundreds, etc. The 
smaller units of the metric sys 
tern are more suitable for the 
finer measurements than ours 
(See Gram, Cubic Centimetre.) 
Micro-organisms. Organisms of 
very small size demanding a 
microscope for detailed study. 
Bacferia and protozoa come 
under this general classification; 
members of many other groups 
(yeasts, molds) are small enough 
to be included. 
Microphage. (See White Cor- 
puscles. ) 
Mil. (See Cubic Centimetre.) 
Minimal Lethal Dose. The 
smallest dose that uniformly 
causes death within a given or 
designated period. 
Motility. The power of locomo- 
tion or moving from place to 
place. Flagella or organs which 
aid in locomotion are shown in 
the illustration of Proteus 
vulgaris. 
Mucus. The viscid secretion of 
certain membranes; we are most 
familiar with it as the excessive 
secretion of such membranes as 
the nose and throat attending 
“colds.” 
Necrosis. The death or gangrene 
of a part of the body. 
Necrotic. Dying; decomposing or 
in a gangrenous condition. 
Non-pathogenic. Not capable of 
causing or producing disease. 
The hay bacillus is a non- 
pathogenic organism. (See 
Pathogenic.) 
Normal Blood. The blood of a 
normal person, or one who has 
not had the disease under consid- 
eration. (See Immune Blood.) 
Opsonic Index. The relative 
abundance of opsonins in an in- 
dividual’s blood as indicated by 
comparing the value of his serum 224 
GLOSSARY 
with that of a normal person. 
(See Index.) 
Opsonins. Antibodies produced 
as a reaction to invading organ- 
isms which aid the white cor- 
puscles in digesting and destroy- 
ing such invaders. 
Optimum. Used to designate the 
condition or combination of con- 
ditions producing the best or 
most characteristic results; we 
speak, therefore, of optimum 
temperatures, optimum growth 
conditions, etc. 
Organic. AH organic substances 
contain carbon as an element; 
the term organic is, however, us- 
ually applied to substances which 
are or have been part of living 
organisms; flour, milk, serum 
and spores are organic substances 
in contrast to iron rust, table 
salt, and air, which are inor- 
ganic. Animals are dependent 
upon organic forms of food ma- 
terials ; while green plants often 
utilize certain organic substances 
formed by plant decay, they can 
exist on inorganic substances 
alone: Soil minerals, C02 and 
water. Most non-green plants 
(molds, bacteria) are, like ani- 
mals, dependent upon organic 
types of food materials. 
Osmosis. The term osmosis is 
now often limited to the passage 
of water through membranes, 
dialysis being used for the pas- 
sage of the substances in solution, 
such as sugars, salts and acids. 
There is a constant exchange of 
substances in and out of all liv- 
ing cells by these two processes. 
Parasite. (Literally, to live at 
another’s table.) An organism 
which lives upon another living 
organism. Tapeworms, the diph- 
theria organism, and such molds 
as those causing thrush and ring- 
worm are examples of “human 
parasites.” 
Paratyphoid. An intestinal dis- 
ease, or the organism's produc- 
ing it; the symptoms and the 
causal organism resemble ty- 
phoid, therefore the prefix, para. 
Passive Immunity. (See Im- 
munity. ) 
Pathogenic. Capable of causing 
or producing disease; the tetanus 
or lockjaw organism is a patho- 
genic organism. 
Pathogens. A term used to des- 
i g n a t e the micro-organisms 
which are capable of causing or 
producing disease. 
Peritoneum. The delicate mem- 
brane which lines the abdominal 
cavity and covers the surfaces of 
the various organs in that region. 
Peritonitis. An inflammation or 
infection of the peritoneum. 
Phagocytes. Cells having the 
power of engulfing and destroy- 
ing foreign matter, including 
bacteria or other foreign cells. 
Generally, when this term is 
used, the several-nucleated white 
corpuscles are meant. (See 
White Corpuscles.) 
Phagocytosis. (See Phagocytes.) 
Plasma. The fluid part of the 
blood, or blood minus the red 
and white corpuscles. (See 
Serum.) 
Plasmolysis. A shrinkage or col- 
lapse of the cell attendant upon 
its loss of water. 
Poliomyelitis. Infantile paralysis. 
A disease with serious lesions in GLOSSARY 
225 
the spinal cord; the typical paral- 
ysis is due to the disintegration 
of spinal nerve cells ordinarily 
controlling the muscles in the 
areas (arm, leg) so paralyzed. 
Polyvalent. (Literally, equal to 
many, or powerful in many 
ways.) A polyvalent serum is 
one which has the power of pro- 
tecting against several varieties 
of organisms, having been pro- 
duced by an animal vaccinated 
with all those varieties (that is, 
with a polyvalent vaccine). 
Precipitate. (Literally, to throw 
or cast down headlong.) To 
cause to fall or settle more rap- 
idly than would otherwise occur 
naturally by gravity. 
Precipitins. Precipitating sub- 
stances or antibodies formed as 
a reaction to the presence of 
foreign proteins in the blood 
stream; bacteria, the blood cells 
of another kind of animal, or 
even various ordinary food pro- 
teins, such as egg, milk, etc., 
may excite the production of ap- 
propriate precipitins. (See Fig ) 
Protein. The most important or 
foundation substance of all cells, 
or organisms, as indicated by the 
literal meaning of the word, 
first in. White of egg probably 
gives us a good common example 
of protein in the semi-liquid con- 
dition in which it exists as the 
ground work of most cells. Pro- 
teins differ in the number and 
proportion of the various con- 
stituents (iron, sulphur, phos- 
phorus, magnesium, carbon, 
nitrogen, etc.), the ways they 
are decomposed, their value as 
cell building material, and their 
solubility in water, etc. Albu- 
mins and globulins are classed 
as simple proteins; peptones as 
derived proteins (decomposition 
products of simple proteins). 
Protein Sensitiveness. Super- or 
hyper-sensitiveness to protein, 
including such varied phenomena 
as the sensitive or sensitized con- 
dition which evokes protective 
antibodies, and the disturbances 
known as hay fever and ana- 
phylaxis. 
Protozoa. The lowest group of 
animals, simple one-celled forms 
(such as amebas and trypano- 
somes ). Protozoa represent the 
lowest animal divisions, just as 
bacteria form one of the lowest 
divisions of plants. 
Ptomaines. These are alkaloid- 
like substances (amino-acids) 
formed in the decomposition of 
organic matter, especially pro- 
teins. Some of them are pois- 
onous, though most ptomaines 
are not. The more complex 
ptomaines, especially those con- 
taining oxygen, are the more 
poisonous ones. The simpler 
ones such as methylamine, 
(CH5N), are not toxic, while 
muscarin (C5H15N03) and sepsin 
(CbH14N202) are very toxic. 
Pulmonary. Relating to or af- 
fecting the lungs, as pulmonary 
tuberculosis. 
Pyemia. The distribution of in- 
fectious material from an initial 
focus by the blood may result 
in the establishment of several 
other infection areas, a general 
pyemia. 226 
GLOSSARY 
Pyogenic. Pus-forming or cap- 
able of causing infection. 
Receptors. Chemical or atomic 
groups which are conceived as 
affording cell combinations not 
only with food but with injuri- 
ous materials, such as toxins and 
split-proteins. Advanced texts 
on immunity classify antibodies 
as falling into three receptor 
groups, varying in their suscep- 
tibility to heat, etc. 
Saprophyte. An organism which 
lives on organic material, but 
not on a living host. Bacteria 
or molds living on bread, dead 
fish, milk, are saprophytes. 
Many parasitic organisms may 
become adapted to a saprophytic 
mode of existence, and, vice 
versa, most disease organisms 
can be grown as saprophytes on 
ordinary laboratory media. 
(See Parasites.) 
Sepsis. (See Septic.) 
Septic. Undergoing or showing 
signs of sepsis or decay. A sep- 
tic wound has decay-producing 
organisms growing in it; pus and 
“proud flesh” are indications of 
such septic conditions. 
Sensitized vaccine. Vaccine mod- 
ified by the addition of its spe- 
cific antibodies or anti-serum 
containing one or more types of 
antibodies. “Toxin-antitoxin” 
used to prevent diphtheria is 
really such a sensitized vaccine. 
(See Index.) 
Septicemia. When the organisms 
causing infection actually mul- 
tiply in the blood stream, the 
condition is called a septicemia. 
(See Bacteria and Pyemia.) 
Sero-vaccine. Vaccine modified 
by the addition of anti-serum, 
a sensitized vaccine. 
Serum. Serum differs from plas- 
ma, the liquid part of the blood, 
in lacking not only the red and 
the white corpuscles but the fib- 
rin of the plasma as well. When 
blood clots the resulting yellow- 
ish licpiid is the serum, the 
solid clot containing the en- 
meshed corpuscles and fibrin. 
(See Whole Blood.) 
Serum Sickness. A term cover- 
ing such manifestations as skin 
eruptions, fever, rheumatic pains, 
and inflammation of the joints 
and glands occasionally caused 
by the injection of serum, such as 
horse serum. 
Species. A group of similar in- 
dividuals, all resembling each 
other, and all differing in the 
same respects from other mem- 
bers or species of the larger 
group or genus to which they all 
belong. The genus Streptococcus 
contains such different species, 
for example, as Str. viridans 
(forming green pigment on blood 
agar), and Str. pyogenes, (dis- 
solving the red blood cells and 
forming a transparent area on 
blood agar). All the members 
of the species viridans resemble 
the rest of the genus in their 
chain-forming method of growth, 
but they differ from them in 
producing the green pigment. 
These green-producing organisms 
may differ from each other in 
minor or less constant ways 
(size, chain length) than they 
differ from the other species; GLOSSARY 
227 
strains showing such lesser dif- 
ferences are spoken of as vari- 
eties. (See Type.) 
Spirillum, (pi. Spirilla.) One of 
the classes of spiral-shaped bac 
teria is called Spirillum; Vibrio 
includes the shorter spirals, 
such as the cholera organism. 
Spirochaeta. The protozoa in- 
clude a group of spiral shaped 
organisms called Spirochceta. 
The spiral protozoa are larger 
and longer—with more spirals 
or turns than the spiral bacteria. 
Syphilis is caused by one of 
these spiral protozoa. 
Spirochetes. Anglicized form of 
Spirochceta. 
Split-proteins. A term used in 
connection with the decomposi- 
tion of proteins, especially bac- 
terial proteins, into irritating 
substances, termed “poisonous 
split-proteins.” (See Index.) 
Spore. Some species of bacteria 
form spores—inactive stages— 
in their life history or develop- 
ment. Spores are quite resistant 
to most unfavorable conditions, 
and are usually formed in re- 
sponse to such environmental 
influences or changes. , 
Sputum. Mucus accumulating in 
or ejected from the mouth or 
throat. 
Stains. Special dyes or stains are 
used to color bacteria so they 
may be seen more definitely. 
No real progress was made in 
identifying bacteria until after 
this application of Perkin’s dis- 
covery of anilin dyes. 
Sterile. Free from micro-organ- 
isms. Substances may be ren- 
dered sterile by the application 
of heat, chemicals, electricity, etc. 
Instruments, bandages, etc., are 
made sterile by such methods. 
It is not always possible to make 
wounds and body tissues sterile. 
In such, cases the growth of un- 
desirable or pathogenic organ- 
isms must be prevented by the 
use of inhibiting or antiseptic 
agentsi. 
Sterilize. To free from all micro- 
organisms by such agents as heat 
or chemicals. A stronger term 
than disinfect, which has as its 
aim only the killing of the in- 
fections or disease-producing or- 
ganisms which may be present. 
Streptococci. Coccus or globular 
bacteria which adhere in chains, 
related to many types of human 
disease or infection, such as 
abscesses, erysipelas and blood- 
poisoning. 
Subcutaneous. Underneath the 
skin. 
Supernatant. Rising or floating 
over or above, as the liquid over 
a precipitate or sediment. 
Symbiosis. A living together of 
dissimilar organisms, each type 
of which contributes thereby 
some necessary factor or condi- 
tion for the welfare of the other. 
Syphilis. The most dangerous of 
the venereal diseases, sometimes 
transferred by common drinking 
glasses, towels, bedding, or per- 
sonal articles, as well as by 
personal contact. 
Tetanus. The lockjaw organism, 
Clostridium tetani, or the dis- 
ease caused by it. 
Toxins. (Literally, an arrow, and 228 
GLOSSARY 
referring to the poison used on 
arrow tips.) Poisons formed by 
bacteria in their ordinary living 
or metabolic processes. In cer- 
tain disease organisms, such as 
diphtheria, these toxins may be 
excreted freely by the bacteria 
(exotoxins) and accumulate in 
the blood; in most organisms 
toxins, if formed, are not liber- 
ated freely from the living cell 
but are freed only on the death 
or disintegration of the cells. 
Toxoid. An altered toxin, having 
less toxic or poisonous effects. 
Toxon. A secondary or less well- 
known toxin, differing from the 
primary or better-known toxin 
formed by a given organism. 
Tropins. A term used to distin- 
guish the opsonins in immune 
blood from normal opsonins— 
or the opsonins present in nor- 
mal blood. 
Trypanosomes. A group of pro- 
tozoan or one-celled animals 
which cause various diseases in 
animals but none common in man 
in this country. 
Tuberculin. A preparation of 
killed tuberculosis organisms 
used chiefly as an exciting agent 
to demonstrate whether or not a 
given individual is sensitive to 
that organism. 
Tuberculosis. A disease of the 
lungs, glands, bones, etc., which 
in man is caused by one of two 
organisms: the ordinary human 
type of tuberculosis, or, a related 
species, the bovine type. 
Type. A characteristic example; 
a specimen that embodies the 
characteristics of the species or 
group. Recently, in bacteriol- 
ogy, the word type has been 
used more in the sense of the 
varieties or lesser groups of a 
given species, especially those 
based upon serum tests (agglu- 
tination, etc.) ; this is the mean- 
ing underlying such expressions 
as “pneumococcus, type 1”. 
Vaccine. (From vacca, a cow, 
because the first vaccine—against 
smallpox—was obtained from 
cows.) Vaccine is a term used 
for substances, such as bacteria, 
which are inoculated into the 
body to excite protective sub- 
stances against the related dis- 
ease. Some vaccines are made 
of living, others of dead organ- 
isms; if living organisms are 
used, they are first weakened in 
some way to lessen their effect 
on the body. Even dead or- 
ganisms may be modified to 
lessen the serious effects upon 
the tissues, to favor absorption, 
etc., as in sensitized vaccines, 
and lipo-vaccines. 
Vibrio. See Spirillum. 
Virulence. Power to produce in- 
jury in a host by growth and the 
production of poisonous sub- 
stances; virulence varies with 
the invasive power of the organ- 
ism as well as the strength and 
kind of injurious substances 
produced. (See Virulent.) 
Virulent. (Literally, full of poi- 
son.) Highly pathogenic or ex- 
tremely toxic or poisonous. 
(See Virulence.) 
Virus. A term often used to in- GLOSSAKY 
229 
elude or designate the causal 
agents of disease, especially if 
the organism has not been seen 
or identified. The material used 
to vaccinate against smallpox is 
commonly spoken of as smallpox 
virus. Similarly we speak of the 
virus of hog-cholera, and of foot- 
and-mouth disease. When the 
causal organism is known, it 
is usually spoken of by its 
group or generic name (Strepto- 
coccus, Trypanosoma, Spirillum, 
etc.) or by such general names 
as bacterium or protozoan,. 
Vital Resistance. The resistance 
of animals or other individuals 
against such untoward agents as 
infection and fatigue. Upon the 
individual’s resistance depends 
his freedom from disease or the 
severity of the attack, and the 
rate or chance of recovery. This 
resistance is in great part de- 
pendent upon the activity of the 
white corpuscles and the produc- 
tion of such antibodies as anti- 
toxins and opsonins. 
White Corpuscles. White cor- 
puscles, though relatively few in 
number when compared with the 
red, are very important; they 
help in blood clotting, in keeping 
a protein balance in the blood, 
etc. The white corpuscles vary 
more than the red in size and 
activity; although several kinds 
of white corpuscles are found in 
all human blood, they may, for 
our purposes, be divided into two 
main groups, those that contain 
but one nucleus and those that 
contain several nuclei. Those 
possessing two or more nuclei 
have the power of surrounding 
or enveloping and finally digest- 
ing bacteria, thus protecting the 
body against invading organisms. 
Sometimes dozens of bacteria 
may be seen inside one white 
corpuscle. Consult the index for 
illustrations of an example of 
this destructive phagocytic ac- 
tion. These smaller white cor- 
puscles are sometimes termed 
microphages or microphagocytes 
to distinguish them further from 
the other larger cells having 
phagocytic action such as 
the single-nucleated lymphocytes. 
White corpuscles active in bac- 
terial destruction are sometimes 
spoken of as bacteriophages. 
This elementary presentation 
does not warrant the discussion 
of the destructive (lytic) 
“bacteriophage principle” dem- 
onstrated by current investiga- 
tions in successive cultures or 
generations of staphylococci, 
typhoid, etc.; this bacterial de- 
struction is variously explained 
as a “bacterial disease,” an en- 
zyme reaction of the host tis- 
sues, and (despite the inhibiting 
and dissolving action on the re- 
spective bacteria) a product of 
the bacteria themselves. 
Whole Blood. Literally whole 
blood, without the corpuscles sub- 
tracted. Blood from which the 
corpuscles have been removed is 
spoken of as plasma; if the fibrin 
is also taken out the resultant 
liquid is called serum. (See 
Plasma and also Serum.) LIST OF INFECTIONS, AND CAUSAL 
ORGANISMS DISCUSSED IN 
THIS TEXT* 
Of Plant Origin 
Acne 
Anthrax 
Bacillus acidophilus 
” acne (See Acne) 
” anthracis (See Anthrax) 
” bulgaricus 
” coli 
” edematis (maligni) (See 
Malignant edema) 
” mallei (See Glanders) 
” pertussis (See Whooping- 
cough ) 
” pestis (See Plague) 
” subtilis 
” typhosus (See Typhoid 
fever) 
Bacterium coli 
” dysenterise (See Dysentery) 
” paratyphosum (See Para- 
typhoid fever) 
” pneumosintes (See Influ- 
enza) 
” pneumoniae (See Pneu- 
monia ) 
Botulism 
Cholera 
Fusiformis acnes (Bacillus acnes) 
Bacillus anthracis 
Lactobacillus acidophilus (Bacil- 
lus acidophilus) 
Lactobacillus bulgaricus (Bacillus 
bulgaricus) 
Bacterium coli 
Bacillus subtilis 
Bacterium coli 
Clostridium botulinum (Bacillus 
botulinus) 
Vibrio cholercc-asiaticce (Vibrio 
cholerce) 
*The bacteria are listed (second column) by the names in the Generic 
Index in the 1920 report of the Society of American Bacteriologists. LIST OF INFECTIONS 
231 
Clostridium botulinum (See 
Botulism) 
” edematis (See Malignant 
edema) 
” tetani (See Tetanus) 
” Welchii (See Gas gangrene) 
Diphtheria 
Diplococcus intracellularis menin- 
gitidis (See Meningitis) 
” meningitidis (See Menin- 
gitis) 
” pneumoniae (See Pneu- 
monia ) 
Dysentery 
Fowl cholera 
Gas gangrene 
Corynebacterium diphtherial 
(Bacillus diphtherias) 
Bacterium dysenteries (Bacillus 
dysenteries) 
Pasteurella cholerce-gallinarum 
Clostridium Welchii (Bacillus 
Welchii) (Other organisms may 
be found in gangrenous con- 
ditions) 
Pfeifferella mallei (Bacillus 
mallei) 
Glanders 
Gonococcus (See Gonorrhea) 
Gonorrhea 
Hay bacillus 
Hemophilus influenzae (See In- 
fluenza ) 
” pertussis (See Whooping- 
cough ) 
Infantile paralysis (See Poliomy- 
elitis) 
Influenza 
Neisseria gonorrhece (Micrococcus 
gonorrhece; Gonococcus gonor- 
rhece) 
Bacillus subtilis 
Hemophilus influenzce (Bacillus 
influenzce) 
Recently a filterable organism 
Bacterium pneumosintes. has been 
found. 
Lactobacillus acidophilus 
” bulgaricus 
Lactobacillus 232 
LIST OF INFECTIONS 
Leprosy 
Lockjaw (See Tetanus) 
Malignant edema 
Meningitis 
Mycobacterium leprce (Bacillus 
leprce) 
Clostridium edematis (maligni) 
(Bacillus edematis [maligni]) 
Neisseria meningitis or intracel- 
lularis-meningitidis (Earlier 
classified under Micrococcus, 
Diplococcus, and Meningococcus.) 
Many other organisms may cause 
meningitis such as the tubercu- 
losis, influenza and typhoid 
organisms. 
Meningococcus (See Meningitis) 
Micrococcus gonorrhea (See 
Gonorrhea) 
” meningitidis (See Menin- 
gitis) 
Mumps (Causal organism uncer- 
tain) 
Mycobacterium leprae (See Leprosy) 
” tuberculosis (See Tuber- 
culosis ) 
Neisseria gonorrhese (See Gonor- 
rhea) 
” meningitidis (See Menin- 
gitis) 
Paratyphoid fever 
” A 
” B 
Pasteiirella pestis (See Plague) 
Pertussis (See Whooping-cough) 
Pfeifferella mallei (See Glanders) 
Plague 
Pneumonia 
Bacterium paratyphosum var. A 
or B, (Bacillus paratyphosus 
var. A or B). 
Pasteurella pestis (Bacillus pestis) 
Bacterium pneumonice (Formerly 
usually classed, under Diplococ- 
cus, Micrococcus or Pneumo- 
coccus.) Many other organisms 
may cause pneumonia, notably 
Streptococcus pyogenes and Hem- 
ophilus influenza. LIST OF 
INFECTIONS 
233 
Poliomyelitis 
Proteus vulgaris 
Staphylococcus . 
Streptococcus 
Tetanus 
Tuberculosis 
Typhoid fever 
Whooping-cough 
“Globoid bodies” of Flexner (Clas- 
sification as plants uncertain) 
Proteus vulgaris 
Staphylococcus aureus 
Staphylococcus pyogenes-aureus 
Streptococcus mucosus 
Streptococcus pyogenes 
Streptococcus viridans 
Clostridium tetani (Bacillus 
tetani) 
Mycobacterium tuberculosis (Ba- 
cillus tuberculosis) 
Bacterium typhosum (Bacillus 
typhosus) 
Hemophilus pertussis (Bacillus 
pertussis) 
OF ANIMAL ORIGIN (Mainly Protozoa) 
Hookworm 
Malaria 
Measles (Causal organism un- 
known ) 
Nagana 
Negri bodies (See Rabies) 
Rabies 
Smallpox (Causal organism un- 
known) 
Syphilis 
Spirochseta pallida (See Syphilis) 
Treponema pallidum (See Syph- 
ilis) 
Trypanosoma (See Nagana) 
Yellow fever 
Anchylostoma americanus (Necator 
americanus) 
Plasmodium malarias 
Trypanosoma Brucei 
“Negri bodies” 
Treponema pallidum (Spirochceta 
pallida) 
Leptospira icteroides BOOKS ON IMMUNITY 
Bolduan and Koopman. Immune Sera. Wiley, New York, 1917. 
Bordet and Gay. Studies in Immunity. Wiley, New York, 1909. 
Jordan. General Bacteriology. Saunders, Philadelphia, 1921. 
Karsner and Ecker. The Principles of Immunology. J. B. Lippincott, 
Co., Philadelphia, 1921. 
Kolmer. Infection, Immunity and Serum-therapy. Saunders, Phila- 
delphia, 1917. 
Metchnikoff. Immunity in Infective Diseases. Macmillan, New 
York, 1917. 
Nuttall. Blood Immunity and Blood Relationships. Macmillan, 
New York, 1904. 
Park, Williams and Krumwiede. Pathogenic Microorganisms. Lea 
and Febiger, Philadelphia, 1920. 
Thomas and Ivy. Applied Immunology. J. B. Lippincott Co., Phila- 
delphia, 1914. 
Vaughan, Vaughan and Vaughan. Protein Split Products in Relation 
to Immunity and Disease. Lea and Febiger, Philadelphia, 1909. 
Wright. Studies on Immunisation. Archibald & Constable, London, 1909. 
Zinsser. Infection and Resistance. Macmillan, New York, 1919. 
JOURNALS PUBLISHED IN THE UNITED STATES 
Abstracts of Bacteriology. Baltimore. 
Journal of Experimental Medicine. Rockefeller Institute, New York City. 
Journal of Immunology. Baltimore. 
Journal of Infectious Diseases. Chicago. INDEX 
In this index micro-organisms are listed under the names 
usually used in conversation: typhoid, diphtheria, ameba, 
streptococcus, etc.; for their scientific names see the table of 
synonyms, p. 230. A list of the organisms illustrated in this 
text is given under the index heading Micro-organisms. Black 
type is used throughout to distinguish references to illustrations 
from subject matter. 
A 
Abrin, toxin, 88 
Acidophilus 
feeding, 26, 31-35 
intestinal content, 31 
Acne, 180 
opsonic index, 136 
vaccine, 186 
Agglutination (see also Agglu- 
tinins), 110, 114 
aid 
antiserum selection, 117, 121 
bacterial destruction, 111, 113 
diagnosis disease, 111-2, 117-9, 
121 
distinguish types of organ- 
isms, 117, 121, 122, 123 
immunity, disease, 62 
blood relationship, 125 
blood, spinal fluid, 122 
body reaction, 109, 112 
chemicals, relation, 110 
cholera, 110 
coli, 114 
complement fixation, corrobo- 
rate, 116 
curves, different vaccines, 176 
delayed, 119, 121 
dysentery, 112, 113 
glanders, 121-2, 115 
gonorrhea, 123 
hanging drop, 114 
Malta fever, 123 
meningitis, 114, 121 
paratyphoid, 111 
Agglutination 
pneumococcus, 110 
spinal fluid, 122 
strengths, 112, 113, 120, 123 
technique, difficulties of, 120 
tests, 111, 117 
hanging drop, 114 
microscopic, 114, 118 
naked eye, 114-5, 116 
respiratory diseases, 121 
types of, 118-9 
time, 115, 127 
tuberculosis, 123 
typhoid, 109-111, 121 
typhoid, 110, 114 
typhus fever, 123 
variability in, 120 
whooping cough, 123 
Agglutinins (see also Agglutina- 
tion) 
amounts present, 112, 113 
antiserum values, 75 
atypical cases, disease, 62 
blood steam, 109 
cross, 112 
foreign cells, 124 
function, 49, 109-111 
group, 111-2 
lysins, compared, 113 
non-bacterial, 124 
normal, origin, 120 
persistence, typhoid, 117 
precipitins, 115-6 
red blood cells, 124 
blood identification, 126 
transfusion, 125 
235 236 
INDEX 
Agglutinins, red blood cells, rela- 
tionship, animal groups, 125 
legal aids, 125 
types, 125 
relation 
opsonins, compared, 128-9 
other antibodies, 113-4, 115, 
124 
specific organisms, 111 
unrelated organisms, 112, 123 
Aggressins 
bacteria, virulence, 56, 150 
phagocytosis, 150 
white corpuscles, 150 
Albumose, vaccine, 177 
Allergy, 198 
Ameba, 23, 142 
cause disease, 66 
food ingestion, 141, 143 
movement, 144 
tissue destruction, 23 
Ameboid activity, 141 
Anaphylactic shock, 193 (see Ana- 
phylaxis ) 
Anaphylaxis (see Protein sensi- 
tiveness ) 
allergy, 198 
amount, protein, 191 
antibody relation, 193-4 
antiserum 
administration, 195, 201-3 
dangers, 200 
diphtheria, 191, 197, 201 
initial dose, 201-2 
bacterial immunity, 211 
causal substances, 192 
cellular theory, 194-5 
dosage 
sensitizing, 192, 195, 197, 200 
shock, 191, 195, 197, 201, 205 
enzyme theory, 194 
epidermal cells, 204 
foods (see Food sensitiveness) 
foreign protein, amount, 178 
hay fever (see Hay fever) 
historical review, 191 
infectious diseases, 192-3, 211 
local symptoms, 195 
meaning, term, 190-1 
persistence, 192 
plant proteins, 204 
precipitins, 194 
prevention 
Anaphylaxis, prevention, dosage 
divided, 196, 201 
single, 201 
trial, 201 
drugs, 201 
oil combinations, 201 
protein reduction, 201 
refractory period, 195, 199, 202 
treatment, 191, 195 
protein reaction, 192, 198 
protein sensitiveness, 198,211-12 
inherited, 197 
non-bacterial, 191, 192, 212, 
213 
relation, other types, 197, 202 
systemic, 191 
protein susceptibility, 191 
quantitative relations, 195-6 
refractory period, 195, 199, 201 
respiratory membranes, 204-5 
sensitizing dose (see dosage) 
shock, 193 
dose, 191, 195, 197, 201, 205 
time interval, 191 
skin tests, 191, PI. I 
smooth muscle relation, 196-8 
specific, 192, 195 
susceptibility, persistence, 192 
symptoms 
animals, experimental, 190-1, 
195-8 
disease, Vaughan’s theory, 211 
dosage, 201 
serum sickness, 201 
man, 197, 200-203 
systemic condition, 191 
tests disease, 207-11 
gonorrhea, 210 
susceptibility serum, 196, 201 
syphilis, PI. I, IV, 210 
tuberculosis, 208-10 
typhoid, 210 
Theobald Smith phenomenon, 191 
theories, 194-5 
time interval, 191, 195 
vaccines, 191, 195, 199 
tuberculin, 200 
Anderson, anaphylaxis, 192 
Animal inoculation tests, 122 
Animal passage, effect, bacteria, 
58-9, 171, 172 
Animal relationships and agglu- 
tination, 125 INDEX 
237 
Anthrax, 45, 61 
frog, corpuscles, 148 
guinea pig, 148 
lysins, 153 
Nuttall, rabbit, 153 
rabbit, 148, 153 
Anti-bacterins, 52 
Antibodies (see also respective 
antibodies) 
balance, bacterial activity, 54 
blood steam, 52 
cell, compared 
food relations, 50-3 
chronic, 57 
classification, 49 
concentration, 71, 76 
content, 49 
increased, 56-7 (see Vaccine 
also) 
measured, 78 
curves, infection, 58, 59 
diagnosis disease, 55 (see Tests) 
elimination body, 55 
globulin character, 93-4 
normal immunes, 62 
reactions, bacteria, 48-49 
identification, 118 
relation, various kinds, 49-50 
retention body, 117 
sources, 48 
specific, 49, 56 
Antibody extracts, 71-3 
Antigens, 180 
complement fixation tests, 163-4 
non-specific, 180 
syphilis, 163-4, 180 
substitutes, 163 
tests, disease, 180 
vaccines, compared, 180 
Antiserums, (see also Antitoxin 
and Serum) 
administration, 76, 81, 96, 106, 
202-3 
agglutinin content, 124 
antibacterial, 84 
antibodies contained, 74 
antitoxic, 84 
antitoxins compared, 73, 90 
chemical sterilization, 93, 95 
collection, 80 
concentration, 96 
dosage, 75, 78, 79 
Antiserums, dysentery, 84 
elimination body, 79, 203 
factors affecting value and dos- 
age, 83, 106 
filtration, 72, 93, 95 
gas gangrene, 84 
injection methods, 81 
meningitis, 138 
mixed, 82 
modified, 71, 89-90, 93-6, 103 
non-bacterial, 75 
opsonin values, 129-30, 137-8 
pollens, 75 
polyvalent, 82 
preparation, 72, 80 
production horse, 91-2 
proteins reduced, 89-90, 93-6 
protozoan infections, 75 
scarlet fever, 84 
snake, 75 
standardization, 77-8, 123-4, 137 
sterility, 95-6 
storage, 96 
treatment, present status, 83-4 
typed, 80 
unit, 77 
Antitoxins (see diphtheria and 
tetanus) 
action, 49 
antiserum compared, 89, 106 
diagram, 57 
diphtheria 
preparation, 90 
standardization, 96-7 
unit, 77, 97 
dosage, 98 
double, 87 
enzymes, 89 
filtration, 94 
gas gangrene, 105 
non-bacterial, 88 
Shiga’s dysentery 
production, 103-4 
prevention, 104-5 
tetanus, unit, 77, 97 
venoms, snake, 88 
-\rth us, anaphylaxis 
systemic relations, 191 
time relation, 191-2 
Asthma, 197, 201, 203 
Autogenous vaccine, 176 238 
INDEX 
B 
Bacillus (see Micro-organisms) 
Bacteremia, 39 
Bacteria (see Micro-organisms) 
adaptation, body tissues, 64 
aggressins 
relation virulence, 56 
relation white corpuscles, 150 
attenuation, 171, 172 
animal passage, 58 
vaccines, 63 
blood stream, 30, 40, 41 
capsule, 148 
resistance, 149 
virulence, 149 
destruction 
ameboid, 141 
fixed cells, 32-3, 142-3 
lymphatics, 143 
lysins, 153, 155, (see also 
Lysins) 
resistance 
aggressins, 150 
capsules, 149 
spleen, 143 
white corpuscles, 142-150 
displacement by another type 
31, 32, 35, 36, 92, 131 
distribution in body, 37-40 
carried white corpuscles, 40 
effects, body, 17, 40 
absorption rate, 174 
destruction tissue, 18, 20-1, 
24-5, 33-5, 39, 43 
emboli, 29 
fever, 27 
fibrin, accumulation, 29 
limiting factors, animal body, 
31-35 
bile, 35 
HC1, 35 
lung conditions, 35 
saliva, 32 
tears, 32 
mechanical injury, 29 
normal body activities, 27 
entrance 
body, 30-5 
preferred methods, 41-2 
extracts, vaccines, 174 
invasion 
bacteremia, 39 
Bacteria invasion, living tissue, 
21, 32 
pyemia, 39 
relation, tissue condition, 37 
septicemia, 39, 40 
unrecognized, 63 
lysins, blood cells, 19, 27 
multiplication, rates, 36 
number, relation, infection, 36, 
43-4 
oxygen needs, 37 
preparatory relations, 28-9 
reactions to, body, 48-9 
temperature needs, 37 
varieties or types, 79-81 
identified, antibodies, 118 
virulence 
adaptation host conditions, 56 
aggressins, 56 
air conditions, 57 
animal passage, 63 
capsules, 149 
host conditions, 56-7 
variations in, 56 
vaccines, modified, 63 
Bacterin, vaccine, 179 
Bacterio-lysins, 156 
Bacterium (see Micro-organisms) 
Blood (see Antiserums and also 
specific antibodies) 
immune 
transfer, 68-9 
red cells, destruction, 19, 27 
malaria, 67, 68 
trypanosome, 27 
used, disease tests, 160-164 
transfusion, 157 
agglutinin test for, 125 
complement fixation tests, 157- 
8, PI. IV 
dangers, 125 
lysin tests, 157-8, PI. IV 
types, tests 
agglutinins, 125 
chemical, 157 
legal phases, 126, 156-7 
lysins, 126, 155-158 
methods, 126 
precipitins, 126, 157 
white cells (see Phagocytosis 
and White corpuscles) 
whole 
amount foreign protein, 71 
dangers transfer, 70 INDEX 
239 
Blood, whole, infantile paralysis, 84 
scarlet fever, 84 
serum, compared, 74 
Boils (see Opsonins) 
opsonic index, 130, 132, 136, 137 
staphylococcus, 18 
vaccines, 57, 174, 183 
Bordet 
lysin, double substance, 158 
toxin-antitoxin combination, 99 
Botulism 
antitoxin, 106 
food poisoning, 89 
spores, 89 
toxin 
absorption, 19 
destruction, 89 
specific, 56 
Brilliant green dye, 117, 118 
Bulgaricus bacillus, 26, 35, 36 
Bull, agglutination, 109, 110, 113 
C 
Calmette, tuberculosis vaccine, 187 
Capsule 
bacterial resistance, 149 
virulence, 149 
Carriers 
adaptation bacteria, 56 
tolerance of, 56 
typhoid, 56 
Cell (tissue) destruction 
ameba, 23 
bacterial, 18, 20, 25, 33-4 
cancer, 43 
normal enzymes, 34 
relations 
food, 50-1, 51-7, 159 
toxins, 50-3, 56, 57 
syphilis, 166 
tuberculosis, 24, 25, 207 
typhoid, 39 
Centrifuge, 131 
Chemicals 
inhibiting, 66-7, 117-118 
Cholera 
agglutinins, 110 
intestinal lesions, 18 
lysins, effect, 153, 155, 158 
vaccine, 179, 185, 189, 200 
Colds, vaccine, 186 
Colon organism (Bacterium coli), 
112, 119 
Complement 
changes—heat, 155, 158-9 
changes—disease, 159 
combining powers, 159-164 
double substance, 159 
fixation, 160 
antiserum standardization, 167 
blood determination, 157, 159 
glanders, 166 
gonorrhea, 166-7 
meningitis, 167 
protein identification, 167 
syphilis, 161-5 
tests, 160 
tuberculosis, 167 
typhoid, 166 
values, comparative, 166-7 
whooping cough, 166 
function normal body, 158, 159 
non-specific, 159 
source, 159 
D 
Diphtheria 
anaphylactic effects, 197, 200-2 
antiserum 
modified, 71, 93-6, 201 
antitoxin (see Toxin-antitoxin 
also) 
concentration, 96 
dosage, 76, 79, 97-8 
horse production, 91-2 
mortality rates, change, 103, 
104 
preparation, 90 
present status, 84 
standardization, 96-7 
storage, 96 
treatment, 79, 97-8, 103 
unit, 77, 97 
causal organism, 90, 91 
displaced 
Hofmann’s organism, 92 
staphylococcus, 31 
effects, body, 20 
entrance, preferred method, 42 
immunity following 
antitoxin, 99, 100 
diphtheria, 55 
toxin-antitoxin, 100, 102-3 240 
INDEX 
Diphtheria, immunity, inherited, 
102 
lysins, 49 
mortality, 103, 104 
serum sickness, 103, 201 
Shick test, 100, PI. I 
pseudo-reactions, 100 
value, 101-2 
susceptibility 
age, 62, 101-2 
exposure relation, 102 
infants, 102 
test (see Shick test) 
toxins 
effects, body, 20 
extracellular, 22 
types, 87 
vaccines, 64, 98, 175, 185 
toxin-antitoxin 
combination, 99 
immunity following, 100, 102-3 
treatment, 48, 98-9, 102 
toxon, 87 
treatment, 98-105 
curative, 97-8, 103-4 
prevention, 97-9, 102-3 
vaccines, 175, 185 
white corpuscle count, 152 
Diphtheria-like bacteria, 31, 37, 
92, 180 
Drugs 
diseases treated by, 67 
immunity through, 67 
isolation, typhoid, 118 
sensitiveness, 199 
Dysentery 
amebic, 66 
antitoxin, 107 
Shiga’s, 75, 107 
toxin, 106-7 
vaccines, 179, 185, 200 
E 
Enzymes 
anaphylaxis 
relation, 193 
antitoxins against, 89 
tissue destruction, 18 
Epidemics 
preparatory organisms 
influenza, 28-9 
Erysipelas 
white corpuscles, 151 
Evans, opsonins, relation protec- 
tion, 138 
F 
Fever, index, condition, 27 
Filters 
serum, 72 
structure, 73, 74 
Fixed cells 
bacterial destruction, 32-3, 142-3 
Flexner 
dog serum, 191 
infantile paralysis, 70, 71, 179 
Food poisoning, 89 
Food sensitiveness (see Protein 
sensitiveness) 
asthma, relation, 197 
diet, effects, 203 
enzyme (?) relations, 193 
predisposing causes, 203 
split-protein theory, 193 
tests, 205, 208 
treatment, 188, 203 
dosage, 204 
Foreign protein (see Proteins) 
Fowl cholera vaccine, 171 
Friedlander bacillus, 149 
Fungous infection, 68 
iodine, 6G 
susceptibility, 62 
G 
Gas gangrene 
antitoxin, 105 
bacillus, 105, 106 
effects, 18, 105 
toxin, 105-6 
Germicidal substances 
blood, 32 
corpuscle extracts, 148-9 
lysins (see Lysins) 
Giant cells, 25 
Glanders 
agglutinins, 121-2 
complement fixation, 166 
precipitin, 115, 123 
Gonococcus, 141, (see Gonorrhea) 
Gonorrhea 
tests 
anaphylaxis, 208, 210 
complement fixation, 166-7 
vaccine, 186 INDEX 
241 
H 
Hanging drop, 114 
Hay fever, 197 
asthma, relation, 204 
causal substances, 204, 212, 213 
inherited, 203 
respiratory membranes, 204 
sensitization, 204, 205 
split-protein theory, 193 
susceptibility, 204 
symptoms, 203 
tests, causal substances, 205, 208 
treatment, 188, 203, 206-7 
Hemolysins, (see Lysins) 
animal body, 155-8 
bacterial, 18, 19 
Hericourt 
anaphylaxis, 191 
eel serum, 191 
Hofmann’s bacillus, 92 
Hookworm, method of entrance, 41 
Hun toon, antibody extracts, 71-3 
I 
Immune 
blood (see Blood) 
serum (see Serum) 
Immunity (see Specific diseases 
also) 
acquired (see active) 
acquired, milk, 62 
active, 65, 68, 109, 169 
body reactions, 47-50 
age, 62 
anthrax, 61 
blood tests, 60 
curves 
in disease, 58, 59 
types, vaccine, 177 
drugs, 66, 67 
glanders, 61 
induced, 63 (see Vaccine also) 
inherited, 62, 102 
insects, 61 
local, 48 
malaria, 60 
natural, 60, 61, 63 
confused, acquired, 62 
diphtheria, 60 
relation, environment, 62,101-2 
supported, blood tests, 60 
yellow fever, 60 
16 
Immunity, normal blood, 69-70 
passive, 68-70 (see also respec- 
tive antiserums) 
period, 45, 54-5 
physical condition, 61 
pneumonia, 61 
poisons, 47 
ptomaines, 27 
racial, 60 
anthrax, 61 
environmental values, 60 
malaria, mosquitoes, 61 
negro, 60, 61 
pneumonia, 61 
tuberculosis, 61 
yellow fever, 60, 61 
selection of resistant, 60 
smallpox, 55 
toxins, 27 
transfer of blood, 68-70, 84 
tuberculosis, 61 
unrecognized infection, 62, 63 
yellow fever, 60, 61 
Incubation period, 54, 59-60 
Infantile paralysis 
antiserum, 84 
immune serum, 69 
organisms, 70, 71 
virus, 179 
whole blood, 84 
Infection, (see also Resistance] 
body reactions, 54, 58-9 
conditions limiting, 30-8 
Influenza, 78 
entrance, eye, 32 
vaccine, 179 
Injection 
drugs, 96 
serum, 96 
syringe, vaccine, 81, 82, 181 
Inoculation tests 
mouse, 122 
pneumonia, 122 
sputum, 122 
Intestinal flora, 26 
chronic affections, 26 
replacement, 26, 131 
J 
Jenner, smallpox vaccination, 170 
immune period, 55 
Jesty, cowpox inoculation, 170 242 
INDEX 
L 
Lactobacillus 
acidophilus, 26, 31, 34 
bulgaricus, 26, 35, 36 
Lethal doses, 44, 97 
Leucocytes 
bacterial tests, 145 
decrease, 146-7 
increase 
in disease, 146-7 
polynuclear, 145 
Lipo-vaccines, 181 
Lockjaw (see Tetanus) 
Luetin test, PL I 
Lymphocytes 
in protozoan infections, 146 
role, 145 
Lysins, (see also Specific diseases 
action, 49, 153-4 
blood identification, 156-7 
Bordet’s contributions, 158 
cholera, 155, 158 
complement 
affected heat, 158 
combined, 159 
fixation, (see Complement fix- 
ation ) 
non-specific, 159 
replaced, normal blood, 153-4 
source, 159 
tests, (see Complement fixa- 
tion) 
diagnosis disease, 157, 159, (see 
Complement fixation) 
double substance, 158 
function, normal body, 158, 159 
heat effects, 155, 158-9 
immune 
blood, 153 
body (part), 158-60 
factor, 158 
legal phases, 156-7 
non-specific factor, 159 
normal blood, 153, 155 
Nuttall, contributions, 153 
opsonins compared, 129 
rate, bacterial destruction, 153 
red corpuscles, 155, PI. Ill, 156 
relation, other antibodies, 49, 129 
role, normal blood, 159 
source, 154-5 
specific, 156 
factor, 158-9 
Lysins, tests, based on 
animal groups, 156 
complement fixation, (see Com- 
plement fixation) 
disease, (see Complement fix- 
ation ) 
microscopic, 153, 155, 157 
plate (growth) tests, 153-4, 
158 
red cell changes, 155-6, 160-4 
PI. Ill 
transfusion, blood, 157 
white corpuscles, differ, 153, 154, 
155 
M 
Magendie, albumen experiments, 
191-2 
Malaria 
drugs, 66 
organisms, 67-8 
red blood cells, 66, 67-8 
Malignant oedema 
antitoxin, 106 
organism, 107 
Massage, vaccine, 137 
Measles 
Faroe Islands, 189 
white corpuscle counts, 151 
Meningitis, 76, 77, 79 
carriers, 121 
opsonins, 129 
tests, agglutinins, 121 
corpuscle counts, 151 
complement fixation tests, 166-7 
vaccines, 186 
Metclinikoff, white corpuscle action, 
128, 140 
Micro-organisms, (see p. 230-233 ; 
also, respective organisms) 
acidolphilus bacillus, 26, 31-4 
. acne, 180 
aineba, 23, 142 
anthrax, 45, 61 
botulinus, 89 
bulgaricus bacillus, 26, 35-6 
catarrh, 77 
cholera, 155 
eoli, 112, 119 
diphtheria, 31, 90, 91 
diphtheria-like, 37, 92, 180 
dysentery, Shiga’s, 75 
gas gangrene, 106 INDEX 
243 
o 
Opsonic index, 131-133 
diagnosis, aid, 134-5, 137 
difficulties, 132-3, 133-4, 137, 138 
pipette, 133 
prescription, aid, 134, 135, 137 
variation 
disease, types, 135 
massage, 136-7 
physical condition, 134 
treatment, vaccines, 137 
Opsonins, (see Specific Organisms, 
also) 
acne, 136 
action, 49, 128-9, 135 
agglutinins, compared, 128-9 
antiserum content, 129, 138 
bacterial count, 131 
bacterial destruction, 128, 135 
boils, 130, 132, 136-7 
curves 
death, 135 
recovery, 134 
definition, 128 
determination, 130-1 
Evans, relation, protection, 138 
gonorrhea, 136 
increased, 136-7 
joint infections, 134 
lysins, compared, 129 
meningitis, 129 
Metchnikoff, serum value, 128 
normal and immune, 128, 129, 
132 
presence, immune blood, proof, 
128 
relation to other antibodies, 128, 
130 
specific, 128, 137 
staphylococcus, 129, 136, 137 
streptococcus, 129, 134, 135 
tests for, 129-31 
tuberculosis, 129, 130-131 
white corpuscles, action, 128, 135 
Wright, technique, 132 
P 
Parasitic bacteria, 38 
Paratyphoid, 111 
agglutinins, 111 
cross agglutinins, 112 
ptomaines, 24 
Micro-organisms, gonococcus, 141 
Hofmann’s bacillus, 92 
infantile paralysis, 70, 71 
influenza, 78 
malaria, 67, 68 
malignant oedema, 107 
meningitis, 76, 77, 79 
molds, spores, 68 
paratyphoid, 111 
plague, 188 
pneumococcus, 40, 41, 121, 147 
proteus, 131 
rabies, 175-176 
sporotrichium, 68 
staphylococcus, 138, 183 
streptococcus, 18, 42, 44, 70, 148 
syphilis, 165, 166 
tetanus, 87 
tuberculosis 
avian, 38 
bovine, 38 
human, 38 
typhoid, 64, 110, 114, 117 
“vibrion septique,” 106 
Vincent's angina, 20-21 
Welch’s bacillus, 106 
xerosis bacillus, 31, 37 
yellow fever, 189 
Milk, sour, diets, 26, 31, 32 
Minimum lethal doses, 97 
Mithridatic antidote, 47 
Molds 
iodine treatment, 66 
spore production, 68 
susceptibility 
ringworm, 62 
thrush, 62 
Monkeys, blood agglutinin tests 
125 
virulence, rabies, 58 
Montague, smallpox inoculation, 
170 
N 
Noguchi 
infantile paralysis, 70, 71 
Wasserman modification, 163 
yellow fever, 60, 61, 83, 189 
Nuttall, lysins, anthrax, 153 244 
INDEX 
Paratyphoid, types, 79 
vaccine, 185 
Park 
bacteria, entrance, 42 
body response, 54 
body response, vaccines, 187 
diphtheria antitoxin, 103, 197 
Pasteur 
fowl cholera, 171 
Institutes, 173 
rabies, 172 
vaccines, 171-3 
“vibrion septique,” 106 
Peyer’s patches, 39 
Phagocytes, (seeWhite Corpuscles 
Phagocytosis) 
cells, types, 141-2 
invasion tissue, 145 
Phagocytosis, 141, 147 
agglutinins, 143 
aggressins, 143 
antibodies, aid, 143 
capsulated bacteria, 149 
factors, 143 
bacteria, 143, 149 
serums, 143, 145 
white corpuscles, 143, 145-149 
fixed cells, 142 
fixed cells and opsonic index, 142 
opsonins, 143 
pneumococcus, guinea-pig, 142 
primitive activity, 142 
relation, virulence, 149 
streptococcus, rabbit, 142 
Plague, 188 
vaccine, 185 
Pneumococcus, 40, 41, 79, 121, 147 
agglutination, 110 
types, identified, 117 
Pneumonia, (see also Pneumococ- 
cus) 
causal organisms, 79 
mouse tests, 122 
serum administration, 81 
tests 
agglutinins, 110, 121-2 
animal inoculation, 122 
precipitins, 122 
white corpuscles, 151-2 
types, 79-80 
vaccines, 186 
Precipitins 
specific, 115-6 
tests, blood, 124, 126 
Precipitins, bacteria, 117-8 
foods, 126 
glanders, 115, 123 
legal aids, 126 
milk, 116 
pneumonia, 118, 122 
proteins, 115-6, 126 
reliability, 126 
unformed proteins, 116, 126 
Preparatory organisms 
influenza, 28 
pneumonia, 28, 29 
streptococcus infections, 29 
Protein identification 
anaphylactic response, 192, 203-4 
animal inoculation, 196 
complement fixation tests, 167 
precipitin tests, (see Precipi- 
tins) 
specific reactions, 192 
Protein sensitiveness, 126 (see 
Anaphylaxis) 
anaphylaxis, 191, 198, 211-2 
antibody relation, 198-9 
cross sensitiveness, 202 
foods, (see Food-sensitiveness) 
hay fever, (see Hay fever) 
horse cells, PI. I 
inherited, 202 
man, effects, initial dose, 201-2 
natural, 202 
utilized tests, 205 
pseudo-reactions, 100 
vaccine treatment, 191, 195, 199 
203-4, 206-7 
Proteins 
effect, injection,white corpuscles, 
146 
foreign 
absorption, 193, 203 
effects, 103 
in blood stream, 193 
variation, penetrability, 203, 
204 
disintegration, 28, 29, 192-3 
poisonous core, 30, 192-3, 209-211 
poisonous split, 20-1, 192-3 
pseudo-reactions, 100 
skin reactions, 100 
Proteus vulgaris, 112, 113 
Protozoa 
ameboid activity, 140, 144 
disease, causes, 66, 233 
tissue destruction, 23 INDEX 
245 
Ptomaines 
bacterial activity, 23 
chemical structure, 26 
compared toxins, 26 
intestinal disturbances, 26 
non-poisonous, 23 
poisonous, 24 
protein origin, 23 
Pyemia, 39 
R 
Pabies, 175, 176 
early experiments, dogs, 172 
Pasteur treatment, 172-3, 182 
vaccine, 172-3 
dosage, 182 
Reactions to bacteria increased, 
56-7 
Receptor theory, 52 
Red blood cells, (see Blood) 
Resident flora, normal tissues, 32 
Resistance 
initial dose, 43 
invasion, bacteria, 33-5, 58, 59 
living tissue, 38 
minimum dose, 43-4 
relation, virulence organisms, 44 
Richet, protein susceptibility, 191 
Ricin, 88 
Ringworm, susceptibility, 62 
Rosenau, anaphylaxis, 192 
S 
Saprophytic bacteria, 38 
Scarlet fever, immune blood, 84 
Sensitized vaccines, 175-6, 177 
Septicemia, 39, 40 
Sero-vaccines, 71-3, 175-6, 177 
Serum, (see also Antiserum) 
compared whole blood, 71, 89, 96 
heated 
effect, antibodies, 158 
reactivated, normal serum, 
158-9 
immune 
antibodies in, 74 
bacterial increase, 145 
modified, 71, 89-90, 93, 96 
phagocytosis, relation, 143 
reactions 
avoided 
dosage, modification, 201 
drugs, 201 
Serum, immune, reactions, human, 
200-2 
inherited, 201 
protein sensitiveness, 201 
sickness, 190, 200 
syringe, 81, 82 
Shick test, (see Diphtheria also) 
100, PI. I 
pseudo-reactions, 100 
school tests, 101 
value, 101-2 
Side-chain theory, 51 
Skin reactions, (see Tests) 
protective covering, 50 
Smallpox 
control 
early methods, 169-170 
inoculation, 169-170 
vaccination, 170-1 
vaccine 
Jenner, 170-1 
preparation, 183-6, 185, 186 
test, potency, 183 
value, 55, 200 
virus, 179 
Smith, Theobald, phenomenon, 
191- 
Split-proteins 
. antibody response, 49 
contrast toxins, 22, 48 
experimental isolation, 22 
molecular relation, 28 29 30 
192- 200-1, 209-11 
relation endotoxins, 22 
selective effect, tissues, 21, 211 
tolerance, 23 
Sporothrichosis, 66, 68 
Staphylococci, 138, 183 
boils, 18 
diphtheria, replaced, 131 
osteomyelitis, 186 
tests, white corpuscle counts, 151 
opsonins, 130, 132, 137 
vaccine, 174, 182, 186, 200 
Stimulins, 128 
Streptococcus, 18, 42, 44, 70, 148 
capsule, 149 
hemolysins, 19 
tests, white corpuscle counts, 151 
types, 79 
vaccines, 176, 179, 200 
Syphilis 
organisms, 155, 166 
tests, 160-164, PI. I, IV 
factors affecting, 164-5 246 
INDEX 
Tetanus, soil infections, 105 
toxin 
absorption, 104 
strength, 48 
treatment, 104-5 
Theobald Smith phenomenon, 191-2 
Thrush, susceptibility, 62 
Tolerance and immunity, 22, 199 
207 
Tonsils 
entrance, disease, 41 
Vincent’s angina, 20, 21 
Tooth abscess, 42 
Toxins, (see also Specific Diseases) 
absorption, 19 
antibody response, 48, 88-9 
bacterial filtrate, 175 
cell food relations, 50-53 
characteristics, 22-3 
chemical structure, 26 
compared split-proteins, 22, 48 
definition, 88 
diagram, 22, 53, 88 
effects, 19-20 
extracellular, 22 
heat effects, 89 
non-bacterial, 88 
prevention disease, 98 
production 
animal body, 89 
foods, 89 
soluble, 19 
strength, 48, 104 
vaccines, 64, 174, 185 
Toxin-antitoxin, (see also Diph- 
theria ) 
Bordet, theory, union, 99 
dosage, effects, 102 
immunity, 103 
infants, 102 
inoculation, horse, 91 
iodine, starch parallel, 99 
reaction, 48 
results, contrasted antitoxin, 99 
treatment, 98-9, 102 
vaccine, 98, 175-6 
Toxoids, 87-88 
relation to immunity production, 
88 
Toxons, 87 
Tropins, 128, 129 
Trypanosomes, 26, 27 
Tuberculin 
temperature curve, 208 
Syphilis, luetin, PI. I 
reliability, 164-5 
spinal fluids, 165 
Wasserman test, 160-4, PI. IV 
Syringe, vaccines, 81, 82, 181 
T 
Tests, (see also Specific diseases) 
agglutinins 
against known organisms, 118 
blood, patient, 118 
corroboration, 120, 122 
negative results, 119, 121 
reliability, 120 
animal inoculation, 122 
bacteria (patient) against 
known antibodies, 118 
blood tests, 155-9 (see Blood) 
complement fixation, 160-8 
effect, other diseases, 164, 210 
isolating organisms 
feces, 118 
nose, 117 
typhoid, 118, 121 
opsonins, 120, 129, 130-2 
Schick test, 100-2 
skin tests, 209-10 
anaphylaxis reactions, 196, 209 
foods, 205, 208 
hay fever, 205, 208 
gonorrhea, 208, 210 
syphilis, 210, PI. I 
tuberculosis, 208-9 
antibodies present, 100-2 
sputum examination 
pneumococcus, 122 
tuberculous, 210 
whooping cough, 123 
susceptibility to diphtheria, 100 
1, PI. I 
technique difficulties, opsoninSj 
120 
toxin, diphtheria, 100-2 
white corpuscle counts, 151-2 
Tetanus, 87 
antitoxin 
administration, 103-4 
production, 93, 103-4 
treatment, 104-5 
unit, 77, 97 
wounds, 105 
dosage, 105 
organism, 87 
recent war, 105 INDEX 
247 
Tuberculin test, tuberculosis, 208- 
210 
treatment, (see Vaccine) 
types, 208 
vaccine, 187, 200 
Tuberculosis 
avian, 38 
bovine, 38 
giant cells, 25 
human, 38 
lesions, 24, 207 
opsonins, 129, 130-131 
sputum examination, 210 
tests 
agglutinins, 123 
anaphylactic relations, 200, 
207-8 
complement fixation, 167 
corpuscle counts, 151 
effect, other diseases, 210 
reliability, 209-210 
tuberculin, (see Tuberculin) 
Von Pirquet, 208 
tubercles in, 205, 206 
vaccine, 187, 200 
Typhoid 
agglutination, 110, 114 
anaphylaxis, vaccine, 199 
brilliant green, isolation, 118 
carriers, agglutination tests, 117 
colonies, 117 
drugs, inhibiting, 117, 118 
entrance, 41 
isolation, feces, 118-9 
organism, 64 
Peyer’s patches, 39 
rates 
army, 187 
civil life, 187 
tests 
agglutinin, 115, 117, 118, 121 
complement fixation, 166 
tissue disintegration, 39 
vaccine, 174, 200 
killed organisms, 173-4 
non-specific, 177-8 
tetra, 179 
triple, 179 
white corpuscles, 151 
U 
Unformed proteins, 116, 126 
V 
Vaccine, (see also Specific diseases) 
active immunity induced, 63-5 
administration methods, 187-S 
anaphylaxis, 176, 188, 199, 200 
antibody increase, 91, 98, 102, 
110, 137, 181 
autogenous, 176, 178 
bacterial content, 183-4 
extracts, 174 
filtrates, 64 
boils, 57, 132, 13 
bottles, smallpox, 185 
chronic infections, 176 
colds, 179, 186 
cowpox, (see Smallpox) 
curative, 181 
dangers, live organism, 64 
diphtheria, 175, 185 
disinfectants used, 181 
disintegration products, 174 
dosage, 175, 181-183 
dysentery, 185 
emergency use, 185 
food sensitives, 188 
fowl cholera, 171 
gonorrhea, 186 
hay fever, 188 
historical review, 169 
keeping qualities, 181 
killed organisms, 64, 173-4, 181 
lipo-vaccines, 181 
live organisms, 173 
massage, 136-7 
meaning, 171, 179-80 
mixed, 178-79 
multiple, 178 
non-specific, 177-8 
objections discussed, 179, 187-8, 
195, 199-200 
opsonin changes, 132, 137, 181 
polyvalent, 178-9 
preparation, 175-9, 180-1, 183-6 
present status, various diseases, 
185-7, 189, 200 
pressure, focus, 136-7 
rabies, 172-3 
respiratory infections, 185 
sensitized, 175-6, 177 
similar organisms, 63 
smallpox, 169-171, 200 
standardization, 183-4 
stock, 176 
syringes, 82, 181 INDEX 
248 
Vaccine, tetra-vaccine, 179 
theory, 173, 178 
toxins, 64, 174-5, 185 
treatment 
recent war, 179-80, 181, 187, 
212 
simultaneous, 179 
time, reduced, 179 
triple vaccine, 179 
tuberculosis, 187, 200 
tubes, smallpox, 185, 186 
turbidity standards, 184 
types, 64, 175 
typhoid, 187 
values, 185-7, 189, 200 
virulence of organisms, 63 
weakened organisms, 63, 171-3 
Vaughan 
absorption, bacterial extracts, 
174 
disease symptoms, 211 
peptone, anaphylaxis, 205 
split-proteins, 22-3, 192, 193 
Vincent’s angina, 20, 21 
Virulence 
aggressins, 56 
animal passage, 58-9, 63 
capsule relation, 149 
incubation period, 59-60 
reduction of, 63-4 
vaccines, 63 
variations, 56-7, 59 
Virus 
definition, 179 
filterable, 83 
infantile paralysis, 179 
yellow fever, 83, 189 
Von Pirquet 
allergy, 198 
tuberculin test, 208-10 
W 
Wasserman test, 160-164, PI. IV 
modifications, 163-4 
Welch’s bacillus, 105, 106, (see 
Gas gangrene) 
White corpuscles, (see Phagocytes 
and specific disease) 
carriers, infection, 147 
changes, 146 
counts, 151-2 
disease, 150-2 
White corpuscles, interpretation, 
152 
normal, 147 
tests, based on, 150-2 
variations, disease, 147, 148, 
151-2 
decrease, 151 
influenza, 147 
early theories, 140 
enzymes, 148 
extracts, 148-9 
immune serum, relation, 140 
increase, 151-2 
Metchnikoff, theory, 140 
opsonic relation, 131, 151 
phagocytic activity, 140, 143 
145 
bacterial resistance, 149-50 
variation in, 148-9 
separation for tests, 132 
temporary destructive agents, 
142 
tests, (see Counts) 
types, 145, 146 
variations, number, (see Counts) 
Whole blood 
dangers transfer, 70 
scarlet fever, 84 
serum compared, 74 
Whooping cough 
agglutinins, 123 
causal organism, 160 
complement fixation, 166 
sputum diagnosis, 123 
vaccine, 185 
Widal test, 118 
Wound infection, treatment, 66, 
105-6 
Y 
Yellow fever, 83 
immunity, 60, 61 
Leptospira icteroides, 189 
Z 
Zingher, diphtheria immunization, 
103 
Zinsser 
capsule, virulence, 149 
diagrams, 158-160 
opsonic index, 137