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 MODERN THE0Ri&QFt BACTERIAL 
 
 H^ltOLfe^ C;; ER^^, M.D. 
 
 
 _ :,, / BOSTO^iSfj;' ;■' :■;■•-;■ 
 
 ;;PUBl,l;CATI0i!l OFFICE QE, ■ J" 
 
 THE" TOURNfti.^ OF MEDICAL RESEARCH -, 
 
 * f88 B-OTI.STON Stbiet ,:':,; 
 
MODERN THEORIES OF BACTERIAL 
 IMMUNITY 
 
MODERN THEORIES OF BACTERIAL 
 
 IMMUNITY 
 
 
 '■f»d 
 
 .•<-^ 
 
 A*- 
 
 HAROLD C. ERNST, M.D. 
 
 BOSTON 
 
 PUBLICATION OFFICE OF 
 
 THE JOURNAL OF MEDICAL RESEARCH 
 
 688 BoYLSTON Street 
 
 1903 
 
 ;d 
 
Modern Theories of Bacterial 
 Immunity, 
 
 Immunity in the bacterial infectious processes 
 is divided into: 
 
 Natural Immunity. — By this term is meant 
 the abihty to resist the invasion of infectious 
 agencies, which is often found under natural 
 conditions, e.g., the I'esistance of many races of 
 animals to infection with typhoid fever, or the 
 resistance of the human race to hog cholera; 
 and 
 
 Acquired Immunity. — This form of immu- 
 nity is said to occur when the condition of re- 
 sistance appears, following an attack of and 
 recovery from an infectious agent. It is mani- 
 fest in persons or animals that have recovered 
 from many forms of such invasion, or it may 
 appear as the result of measures purposely 
 taken in order to favor its development. In 
 
THEORIES OF IMMUNITY. 
 
 this case it may be spoken of as an artificial 
 immunity, and such artificial immunity has been 
 obtained in a number of diflferent ways. 
 
 Acquired immunity, as seen following the 
 action of bacterial infectious agents, is again 
 divided into the forms of Active and Passive 
 Immunity, and the distinction between these 
 two is of great importance in understanding 
 many of the problems arising in connection 
 with the study of immunity in general. 
 
 Active acquired immunity occurs in the course 
 of recovery from an infection, or may be pro- 
 duced artificially. In the latter case it is the 
 result of the injection of gradually increasing 
 doses (amounts) of the toxic products of micro- 
 organisms, beginning with quantities much less 
 than the minimal lethal dose, and increasing until 
 there is reached a condition of resistance without 
 reaction to many times such minimal lethal dose. 
 Such a condition may be obtained by the injec- 
 tion of the bodies of bacteria killed by the appli- ' 
 cation of heat; of the bodies of bacteria in the 
 living condition, but whose virulence has been 
 diminished in various ways; or by the use of 
 
INTEODUCTIOI^. 
 
 The following pages are an abstract of a short 
 series of lectures delivered by request to the 
 class of 1905 in the Harvard Medical School, 
 in January, 1903. The method of illustrating 
 Ehrlich's theories is given in an attempt to 
 make this obscure subject somewhat more clear, 
 and the glossary of terms may prove useful to 
 beginners. 
 
THEORIES OF IMMUNITY. 
 
 danger and practically no discomfort, but is 
 limited in duration and disappears very rapidly. 
 An animal protected against a dose of diphtheria 
 toxine by the injection of antitoxine (of diph- 
 theria) is protected only against that dose of 
 toxine, and is susceptible to a second dose in a 
 very short time. 
 
 Attempts to produce a condition of artificial 
 immunity to infections of various kinds have been 
 made for a very long time, and there exist ac- 
 counts of such attempts among savage tribes — 
 the beginning appears to have been in the 
 direction of protection against the bites of ven- 
 omous serpents. 
 
 The most well-known efforts to secure arti- 
 ficial immunity, and before the present knowl- 
 edge of the bacteria was developed, were the 
 inoculations against small-pox — a knowledge of 
 the beneficial effects of which existed in Asia 
 certainly for generations before its introduction 
 into England by Lady Montague. These inocu- 
 lations consisted in the use of contents of the 
 pustules in mild cases of small-pox, which were 
 introduced through scarifications of the skin or 
 
THEORIES OF IMMUNITY. 
 
 mucous membranes of well persons, in the hope of 
 producing a mild case, and thus protecting the 
 individual from an attack of a more malignant 
 form of the disease. 
 
 Jenner's application of his observation in 
 Gloucestershire, vrhere he w^as born, that dairy- 
 maids handling cows sick with cow-pox ap- 
 peared to be protected against small-pox was 
 the beginning of the stamping out of this great 
 plague in all parts of the civilized world. 
 
 The discovery of the possibility of the attenu- 
 ation of the virulence of a culture on the one 
 hand, and of the possibility of securing an arti- 
 ficial immunity with such attenuated cultures on 
 the other, were more or less the result of chance, 
 Pasteur, with Chamberland and Roux, had been 
 studying the bacillus of chicken-cholera, and 
 interrupted their work during the vacation sea- 
 son of 1879. Upon attempting to resume it 
 they found that their cultures, kept over during 
 the summer, still retained their vitality, but had 
 lost their virulence, either wholly or in great 
 part. (Yalery-Eadot. La vie de Pasteur, p. 
 427.) Testing the effects of such cultures led 
 
THEORIES OF IMMUNITY. 
 
 filtered culture fluids in which bacteria have 
 grown and produced soluble poisonous products. 
 Examples of the first method are the proced- 
 ures in securing immunity against typhoid fever, 
 cholera, and plague; of the second, the first and 
 second " vaccines " of anthrax ; of the third, the 
 use of the soluble toxines of tetanus and diph- 
 theria. 
 
 Passive acquired immunity. — It has been 
 found that in certain cases of active immunity 
 produced as above, there appears coincidently 
 with the complete resistance to the injection of 
 the toxic material a substance, existing in the 
 blood-serum of the animals so treated, that has 
 an antagonistic action to the toxic material, both 
 in the test-tube and in the living animal tissues. 
 This substance is spoken of as " antitoxine," and 
 with the serum containing it is used for the pro- 
 tection of tissues invaded by the toxine-producing 
 bacteria; as in the therapeutic use of diphtheria 
 antitoxine. 
 
 Such antitoxines occur in the blood-serum of 
 animals attacked by, or immunized with the toxic 
 products of tetanus and diphtheria — the cause 
 
THEORIES OF IMMUNITY. 
 
 of both of these diseases being bacteria that pro- 
 duce extra-cellular or soluble toxines. 
 
 Thej do not occur, or only to a very limited 
 extent, in animals attacked by or immunized 
 with the toxic products (bacteria) of typhoid 
 fever, cholera, or plague; the cause of these dis- 
 eases being bacteria that produce intracellular 
 or non-soluble toxines. 
 
 When they do occur and are used for pro- 
 tective purposes, the condition following their 
 use is spoken of as Passive Immunity. 
 
 The diflFerences between these two forms of 
 immunity are very marked. 
 
 Active immunity is slow in appearing, is more 
 or less dangerous to secure, is always attended 
 with at least some discomfort, but is very lasting 
 when once attained. A horse brought to a high 
 degree of immunity to diphtheria toxine will 
 show a marked degree of such immunity for a 
 very long time — extending over months and 
 even years. 
 
 Passive immunity, on the other hand, is very 
 rapid in its appearance, is attended with no 
 
THEORIES OF IMMUNITY. 
 
 Pasteur to the steps resulting in the practical 
 application of the laboratory results in such pro- 
 cedures as the protective inoculations against 
 anthrax and rabies. (See C. Eendus de 
 I'Academie des Sciences, 1880, T. XC, pp. 936, 
 952, 1030; T. XCL, pp. 571, 673.) 
 
 The statement of the general principles was at 
 first met with much opposition and incredulity, 
 but was so overwhelmingly confirmed by other 
 observers that such incredulity soon disappeared. 
 
 The first theory that was advanced to explain 
 the phenomena seen was that of Pasteur himself, 
 and was known as The Exhaustion Theory. In 
 accordance with this, the condition of immunity 
 following the injection of attenuated cultures of 
 a bacterium may be supposed to be due to the 
 exhaustion of certain elements in the tissues used 
 by the bacteria during their growth. These ele- 
 ments are not resupplied for some time by the 
 tissues, and during that time fresh bacteria en- 
 tering the tissues, finding the absence of some- 
 thing necessary for their groAvth, cannot grow, 
 and therefore no infection can take place.A Such 
 a condition of things apparently exists in the test 
 
THEORIES OF IMMUNITY. 
 
 tube; for if a fluid in which a micro-organism 
 has grown be filtered and planted with a fresh 
 culture, no growth will occur. This certainly 
 might be due to the exhaustion of the nutrient 
 medium, and that it is so seems to be shown by 
 the fact that an addition of a very small amount 
 of fresh medium is followed by a profuse growth 
 of the bacterium in question. The same thing 
 was supposed to occur in the living tissues. 
 
 Such a theory, however, would not account for 
 the facts seen in J^atural Immunity, in which no 
 previous growth of the bacteria could be sup- 
 posed to occur. Nor would it explain the results 
 seen in Algerian sheep. These animals are not 
 susceptible to inoculation with anthrax bacilli 
 sufficient to kill ordinary French sheep, but will 
 succumb to very large doses of such bacilli. If, 
 then, the first resistance was due to the absence 
 of nutrition for a comparatively small number 
 of bacilli, how could a much larger number find 
 enough to live upon? 
 
 In view of such objections as these, Chauveau 
 brought forward his Eetention Theory to explain 
 the phenomena seen. In accordance with this, 
 
THEORIES OF IMMUNITY. 
 
 the bacteria may be supposed to elaborate a ma- 
 terial that is hurtful to themselves, and this sub- 
 stance is retained in the tissue cells or fluids for 
 some varying length of time, during which time 
 a fresh invasion of bacteria would be followed by 
 no results. To explain such cases as those of 
 the Algerian sheep by this theory — in which 
 the sheep are not susceptible to attack by small 
 doses of anthrax bacilli, but are susceptible to 
 overwhelming doses — it would be necessary to 
 suppose the existence of a fixed amount of the 
 opposing substance which would be more than 
 neutralized by the excessive doses of the anthrax 
 bacilli, after which infection occurred. Although 
 Chauveau objected to the exhaustion theory, that 
 it did not explain natural immunity, his own 
 supposition did not do so any better. Nor did 
 it serve to explain more than a very small part of 
 the experimental facts observed. Pasteur him- 
 self furnished one instance — that of chickens 
 that are not susceptible to anthrax at their 
 normal temperature, but become so when this 
 temperature is lowered. His comment upon 
 this fact and its bearing upon Chauveau's 
 theory was that it could not be supposed that a 
 
THEORIES OF IMMUNITY. 
 
 preventive substance existed that would dis- 
 appear under the influence of cold. 
 
 Buchner brought forward a theory to explain 
 the fact of obtaining immunity in the infectious 
 processes. It was based upon the then ac- 
 cepted belief (1877-1883) that a bacterium pro- 
 duced its effects in a localized fashion (that the 
 pneumococcus, for example, could produce effects 
 only in the lung), and also that the inflammatory 
 reaction occurring at the site of growth of 
 the bacteria represented a reenforcement of the 
 local tissues, by the general system. So soon 
 as evidence accumulated that the action of very 
 few bacteria is limited in the way suggested, it 
 became clear that this theory was not sufficient 
 to explain even a small part of the facts observed. 
 
 Various other partial explanations were 
 offered, each lasting only so long as the rapidly 
 growing results of experimentation needed to 
 show their limitations. 
 
 The only ones that have withstood the test of 
 time are those of Metchnikoff, representing the 
 cellular theory, and of Ehrlich, representing the 
 humoral theory. 
 
 10 
 
THEORIES OF IMMUNITY. 
 
 II. 
 
 MetchnikoflPs work is of the most remarkable 
 kind; painstaking and laborious to an extreme 
 degree, he has for more than twenty years put 
 forth a se'ries of papers that are unsurpassed 
 for the closeness of reasoning and fertility of 
 device used to demonstrate his points. I^o ac- 
 count can be so satisfactory as his own, and the 
 present summary of his theory of the phagocytic 
 action of the tissue cells in securing immunity 
 is largely paraphrased from his own words. 
 (Metchnikoff. L'Immunite. Paris, 1901, pp. 
 541 et seq.) 
 
 He began his studies on the germinative lay- 
 ers, and was able to explain satisfactorily to 
 himself the part played by the ectoderm and 
 the entoderm. While working in this direction 
 his attention was attracted to the intracellular 
 digestion occurring in many of the lower ani- 
 mals, and he was led to consider this property 
 as one common to the stock from which are 
 
 derived all present known types of the animal 
 
 11 
 
THEORIES OF IMMUNITY. 
 
 kingdom (except protozoa). Considering the 
 ectoderm as the source of the covering of all 
 primitive polycellular animals, and the entoderm 
 as the source of the organs of digestion, the 
 part of the mesoderm remained a mystery until 
 certain of his studies on sponges led him to 
 think that perhaps this layer might have acted 
 
 » 
 
 in the hypothetical primitive animals as a mass 
 of digestive cells, in every respect like those of 
 the entoderm. Such a theory necessarily at- 
 tracted his attention to the property that these 
 mesodermic cells have of seizing upon foreign 
 bodies. 
 
 The fact had been known for a long time, both 
 in respect to the power of the white corpuscles 
 of the vertebrates to seize upon foreign bodies 
 and of the ameboid cells to seize upon particles 
 of coloring matter. But no one had looked 
 upon this property as one of digestion, and it 
 had even been considered as simply a passive 
 action. Metchnikoff's studies upon sponges and 
 some of the simpler forms of sea animalculse 
 convinced him that the presence of foreign 
 bodies in the ameboid cells of the mesoderm 
 should be interpreted as an active englobement, 
 
 12 
 
THEORIES OF IMMUNITY. 
 
 and that in all its aspects it resembled very 
 closely the phenomena of intracellular digestion 
 going on in the epithelial cells lining the digest- 
 ive tract of very many of the inferior animals. 
 At Messina, in 1882-1883, he set himself to 
 secure definite evidence of this fact, and did so 
 by proving that these cells (of the mesoderm) 
 seize upon foreign bodies of very varying nature 
 by their living prolongations, and that some of 
 these foreign substances undergo a true diges- 
 tion in the interior of these ameboid cells. 
 
 Then the idea suggested itself to him that this 
 digestive function, evidently fixed in the meso- 
 dermic cells, might also play a part in many of 
 the vital processes of the animal. Working 
 from this point of view, he was able to demon- 
 strate that during the complicated metamorpho- 
 sis of echinoderms, such as the synaptera, the 
 mesodermic ameboid cells played a part in the 
 atrophy of many embryonic organs. 
 
 He had never studied medicine, but he was 
 struck at one time by an exposition by Cohnheim 
 of the facts of the latter's theory of inflammation. 
 The facts as presented impressed him strongly, 
 
 13 
 
THEORIES OF IMMUNITY. 
 
 especially that of the emigration of the leuco- 
 cytes, but the theory made to fit the facts did 
 not appeal to him, and he saw at once that study 
 of inflammation among lower animals of the 
 simplest type and organization would certainly 
 throw light on this process in the vertebrates, 
 as well as in the frog — the animal upon which 
 Cohnheim's experiments had been made. 
 
 Since, in the atrophy of the larval orga,ns of 
 the synaptera, the essential part is played by 
 the ameboid cells of the mesoderm which col- 
 lects in masses there, possibly the inflammatory 
 exudates manifest some especially important 
 function by their richness in white corpuscles. 
 So that it suggested itself to him to introduce 
 splinters through wounds under the skin of 
 transparent marine animals; if the supposition 
 was correct there should appear a collection of 
 ameboid cells at the point of irritation. Choos- 
 ing " bipinnaires," — the large embryonic forms 
 of star-fish, — he stuck rose thorns in them, and 
 these were seen to be at once surrounded by 
 masses of ameboid cells, exactly as in man after 
 the introduction of a splinter or other irritant 
 
 substance. In other words, the first point was 
 
 11 
 
THEORIES OF IMMUNITY. 
 
 determined, that an inflammatory exudate must 
 be considered as a reaction against all sorts of 
 lesions, and that exudation is a primitive phe- 
 nomenon, older than the nervous system or the 
 blood-vessels. 
 
 At the time these researches were going on 
 (1882), the general theory in regard to inflam- 
 mation was that it was, at least in most part if 
 not wholly, the result of bacterial action. As a 
 result of this belief, the conclusion was reached 
 that diapedesis and the gathering of the white 
 corpuscles in inflammatory disease was to be 
 looked upon as a means of defence of the tissues 
 against the bacteria, and that the leucocytes 
 served to englobe and destroy them. Upon 
 such a hypothesis, the explanation of inflamma- 
 tion becomes at once most clear and simple, and 
 it was such an explanation that Metchnikoflf set 
 himself to prove, if possible. 
 
 The general belief of the pathologists at 
 that time was that the bacteria found a 
 favorable location in the leucocytes and were 
 carried about by them instead of being de- 
 stroyed. So that to secure recognition for his 
 theories he was obliged to overcome the then 
 
 15 
 
THEORIES OF IMMUNITY. 
 
 belief of all but a few of the specialists in that 
 branch of medicine. 
 
 His eifort was to develop the idea that cel- 
 lular digestion in unicellular organisms had 
 been transmitted by heredity to the superior 
 animals, and is preserved in the mesodermic 
 ameboid cells. These cells being able to en- 
 globe and digest all sorts of histological ele- 
 ments may well be able to apply the same 
 power to the digestion of the bacteria — and 
 that they are able to do this he demonstrated 
 in many cases by introducing bacteria into 
 lower animals and watching their englobing 
 and destruction by the ameboid elements. It 
 was evident that the simple demonstration of 
 this occurrence was not sufficient for the devel- 
 opment of the general theory, and he went on 
 to find diseases in the lower animals that were 
 illustrative of the same thing. This he suc- 
 ceeded in doing in the case of the daphnia, — 
 small Crustacea common in fresh water, — and in 
 them followed out and watched an actual 
 struggle between their leucocytes and the spores 
 of a blastomycete ; on the one hand it often 
 happened that the cells were successful in 
 
 16 
 
THEORIES OF IMMUNITY. 
 
 protecting the body against the attacks of the 
 spores, and on the other the spores overcame 
 the action of the leucocytes and overwhelmed 
 the tissues. (Yirch. Arch., 1884, T. XCYL, p. 
 177.) Some time after this he published his 
 work on anthrax (Ibid., 1884, T. XCVI., p. 
 502), in which he demonstrated in the case of 
 the vertebrates, also, that the bacteria penetrated 
 the cells and set up a definite reaction between 
 themselves and these cells. 
 
 As a result of these investigations, Metch- 
 nikoff elaborated his theory of phagocytosis 
 against bacterial invasion — based upon the 
 power of the ameboid cells to seize upon and de- 
 stroy bacterial cells, thus preventing them from 
 developing and injuring the tissues. 
 
 He goes on to say {I. c.) that he had sup- 
 posed that the facts of absorption and in regard 
 to the leucocytes already accumulated would 
 lead the pathologists to look favorably upon the 
 theory that these leucocytes were active de- 
 fenders of the system against the attacks of the 
 bacteria. This, however, was far from being the 
 
 17 
 
THEORIES OF IMMUNITY. 
 
 case, and the most active opponents of the 
 theory were those he had supposed would find 
 reason to support it. 
 
 Baumgarten was the first of these and perhaps 
 the most important, his most forcible theoretical 
 objection being that just when the danger is the 
 greatest the leucocytes are conspicuous by their 
 absence, and that this is a fatal objection to any 
 assumption that they can play an active oppos- 
 ing part to the growth of bacteria in the tissues. 
 Metchnikofi" devoted several years (Virch. 
 Arch., 1888, T. CXIY., p. 465; Ann. de I'ln- 
 stitut Pasteur, 1890, lY., p. 35) to taking up, 
 point by point, the objections raised by Baum- 
 garten and his students, and according to his 
 thought succeeded in answering them. In the 
 latter communication he makes the remark (p. 
 84) that he has often been accused of claiming 
 for phagocytosis the entire influence in the pro- 
 duction of immunity, denying any other as as- 
 sisting the organism to disembarrass itself of the 
 bacteria. He repeats again that the part of the 
 phagocytes is a very important one in the pro- 
 duction of immunity in general (and of anthrax 
 in pigeons especially), but this does not in any 
 
 18 
 
THEORIES OF IMMUNITY. 
 
 wise prove that some other influence will not 
 some day be found assisting the phagocytes in 
 their action — an influence that has as yet 
 escaped our observation. 
 
 Ziegler also, from whose text-boot Metchni- 
 koff had received his first stimulation, took up 
 a strong position against the theory, considering 
 that the intervention of these cells was purely 
 fortuitous, and that the part played by them in 
 infectious diseases was entirely accidental as 
 against the action of the bacteria. His students 
 and assistants after experimenting upon the 
 subject reached the specific conclusion that 
 phagocytosis had nothing to do with the phe- 
 nomena of immunity to be found in anthrax and 
 symptomatic anthrax, as supposed by Metchni- 
 koff; but this work was also carefully reviewed 
 by independent observers (Lubarsch, Euffer, 
 Leclainche, and Yallais) and by Metchnikoff 
 himself, and the correctness of the observations 
 was again demonstrated, by which the assertions 
 were supported that phagocytosis was an active 
 force in these diseases. 
 
 Other pathologists — notably Yirchow (Yirch.. 
 Arch., 1885, T. CI., p. 12), Eibbert (Deut. Med. 
 
 19 
 
THEORIES OF IMMUNITY. 
 
 Woch., 1890, no. 31, p. 690), and Hess (Yirch. 
 Arch., 1887, T. CIX., p. 365) were more inclined 
 to favor the theory, and Ribbert noted especially 
 that in the reactions produced by the staphylo- 
 cocci there was a modification of the phagocytic 
 action manifested by the collection of the leuco- 
 cytes about the bacteria — this collection acting 
 as a hurtful surrounding to the bacterium; 
 although MetchnikoflP considers this preliminary 
 gathering as simply a first stage to the following 
 englobing and digestion of the bacterial cells by 
 the leucocytes. 
 
 Some theories in opposition to the suggestions 
 of Metchnikofi" were offered by the bacteriologists 
 interested in the subject, and according to 
 Metchnikoff the starting point of these theories 
 was the observation made by Fodor (Deut. Med. 
 Woch., 1886, p. 617; Arch. f. Hyg., 1886, T. lY., 
 p. 129) that the defibrinated blood of the rabbit 
 was able to destroy a large number of anthrax 
 bacilli. This was the first announcement of the 
 bactericidal property of the blood, and it was at 
 once concluded from it that the body-fluids con- 
 tained a substance capable of destroying bacteria, 
 and that this property was quite sufficiently 
 
 20 
 
THEORIES OF IMMUNITY. 
 
 powerful to explain the facts seen in the occur- 
 rence of immunity, l^uttall's work (Zeit. f. 
 Hyg., 1888, T. lY., p. 353, in which he refers to 
 Fodor's work as full of errors) was in the same 
 direction and of the first importance. It was 
 based upon observations on the warm stage with 
 the defibrinated blood of various animals, in 
 which it was shown that this same bactericidal 
 property was present — existing, of course, out- 
 side of the leucocytes, and that it could be de- 
 stroyed by subjecting, it to fifty-five degrees 
 Centigrade. 
 
 Such observations as these formed the first 
 foundation for the humoral theory of immunity, 
 and served as the starting point for innumerable 
 experiments, all of which were intended to show 
 that the theory of phagocytosis had absolutely 
 no foundation in fact. 
 
 Behring was one of the first to take up the 
 bactericidal property of the blood as explaining 
 immunity. He (Cent, f klin. Med,, 1888, 'Eo. 
 39) had discovered the remarkable power of the 
 blood of the white rat to destroy anthrax bacilli 
 
 21 
 
THEORIES OF IMMUNITY. 
 
 with great rapidity — and did not hesitate to 
 conclude that this bactericidal property was re- 
 sponsible for the immunity of the animal to the 
 disease. 
 
 To generalize this fact, Behring and I^issen 
 (Zeit. f. Hyg., 1890, T. YIII., p. 41) undertook 
 a long series of experiments. They showed that 
 in animals well immunized against certain bac- 
 teria (notably "V. Metchnikovii) the blood serum 
 acquired a strong specific bactericidal property, 
 but they also showed at the same time that the 
 blood of animals, even well immunized in other 
 diseases, was very frequently incapable of de- 
 stroying the bacteria. Therefore, the bactericidal 
 property did not appear to be a general charac- 
 teristic and was of limited importance ; and such 
 facts led Behring to abandon the idea that the 
 bactericidal property was an active factor of a 
 general nature, and essential in the production 
 of immunity. 
 
 Buchner confirmed Kuttall's assertion that 
 the bactericidal property disappeared at 55° C. ; 
 demonstrated the part that the salts play in 
 the exercise of the bactericidal action; and 
 
 22 
 
THEORIES OF IMMUNITY. 
 
 especially insisted upon the fact that this prop- 
 erty depended upon the presence of special sub- 
 stances of an albuminoid nature to which he 
 gave the name of alexines. He also demon- 
 strated the very important fact that the red 
 blood globules of one species of animal intro- 
 duced into the blood of another would undergo 
 destruction (a globulicidal action) similar in 
 nature to the bactericidal action already demon- 
 strated. 
 
 In France, Bouchard especially adopted the 
 humoral theory as explaining immunity (Les 
 Microbes Pathogenes, Paris, 1892), and was 
 strongly supported by Charrin and Roger, his 
 students. Most of their work was done with 
 the bacillus pyocyaneus and their results con- 
 firmed them in the belief that the condition of 
 immunity was due to the action of the body 
 fluids, and not in any case to the action of the 
 cells. They attributed both natural and ac- 
 quired immunity to a special property of the 
 body fluids, and considered that the part of the 
 phagocytes was secondary, that they were con- 
 eerned simply in carrying off" the bodies of the 
 
THEORIES OF IMMUNITY. 
 
 bacteria, either dead or rendered inoffensive by 
 the previous action of the body fluids. 
 
 " The humoral theory made many converts in 
 all parts of the world, and was and is very 
 generally accepted. It has, however, been 
 queried by a few observers whether the phe- 
 nomena seen to take place in the test-tube 
 really are the same as those that occur in the 
 living body tissues, and it has been shown that 
 similarity of action does not uniformly exist. 
 It has been shown many times that the blood of 
 animals susceptible to infection is bactericidal 
 to the specific bacteria of that infection; while 
 on the other hand, the blood of anima,ls not 
 susceptible to such infection has absolutely no 
 bactericidal properties towards the specific bac- 
 terium. Such parodoxes as this are not at all 
 uncommon in the case of infections already 
 investigated, and are so common as to form an 
 almost insurmountable obstacle to a belief in 
 the general action of the body fluids in the pro- 
 duction of immunity." (Metchnikoff, I. c.) 
 
 In reference to what has just been said, as 
 long ago as 1889 (Cent. f. Bakt., 1889, T. YL, 
 pp. 481, 529) Lubarsch carried on a long series 
 
 24 
 
THEORIES OF IMMUNITY. 
 
 of experiments, in which he showed that animals 
 may be very susceptible to a very small number 
 of bacteria, whose blood-serum is exceedingly 
 bactericidal to a much larger number of the 
 same bacteria in the test-tube. For example, 
 the defibrinated blood and the blood serum of 
 the rabbit destroys numbers of the anthrax 
 bacilli, whilst the animals themselves succumb 
 also very promptly to the injection of a small 
 number of the bacteria in the blood vessels. 
 The assertion is made that such a contradiction 
 in results is only to be explained by the fact 
 that the blood itself undergoes a profound 
 change after its removal from the body. 
 
 In 1891 the discovery by Behring and Kit- 
 asato of the existence of the antitoxines had not 
 made much impression so far as being con- 
 sidered a factor in the production of immunity 
 was concerned. It had been demonstrated as 
 occurring in the two diseases of diphtheria and 
 tetanus, and by Ehrhch for the vegetable alka- 
 loids — ricine, robine, and abrine; but it was 
 thought of as a special phenomenon peculiar to 
 these few diseases rather than as a general prin- 
 ciple capable of wide application. It was after 
 
 25 
 
THEORIES OF IMMUNITY. 
 
 the International Congress of that year that Behr- 
 ing attempted to argue that antitoxine forma- 
 tion occurred in all forms of acquired immunity, 
 and that bacteria introduced into the bodies of 
 animals containing this principle were incapable 
 of producing any hurtful results. 
 
 Taking up this point, Metchnikoff undertook 
 to investigate the acquired immunity occurring 
 in pneumo-enteritis of hogs (hog-cholera?). 
 He demonstrated (Ann. de I'Inst. Pasteur, 1892, 
 T. "VI., p. 289 ) that the resistance of the animal 
 to the bacterium in this case does not depend 
 upon the formation of an antitoxine — which is 
 entirely wanting in this form of acquired im- 
 munity. (He demonstrated this in the paper 
 spoken of, as follows : he first tested the serum of 
 animals immunized to pneumo-enteritis, and 
 found that it made a favorable medium for the 
 cultivation of the bacillus; there was, therefore, 
 no bactericidal action in the serum. He injected 
 mixtures of the serum of animals dead of pneu- 
 mo-enteritis (hog-cholera?) with the serum of 
 immune animals and with the serum of non- 
 immune animals, and in both cases found that 
 
 26 
 
THEORIES OF IMMUNITY. 
 
 these mixtures produced just as fatal results as 
 when the serum of animals dead of the disease 
 was used alone; there was therefore no antitox- 
 ine present.) In this same article he also estab- 
 lished the fact that the serum of immune rabbits 
 possessed a very active preventive power against 
 infection with the bacillus of pneumo-enteritis 
 (hog-cholera?), which he lays stress upon as 
 being the first time that an anti-infectious prop- 
 erty had been demonstrated, in addition to the 
 bactericidal and antitoxic properties of the serum, 
 this anti-infectious property being, in accord- 
 ance with his explanation, a stimulation of the 
 phagocytes in their struggles against the bac- 
 teria. The same sort of reaction has since been 
 shown to occur in typhoid fever and cholera. 
 Richet and Hericourt (0. Rend, de I'Acad. des 
 Sciences, 1888, T. CYII., pp. 690, 748) had 
 demonstrated before this an immunizing action in 
 the serum of animals resisting inoculation with 
 the staphylococci, and when Behring and Eata- 
 sato discovered the presence of the antitoxine 
 in diphtheria and tetanus, it was supposed that 
 this staphylococcus immunity was also antitoxic 
 in nature. It was shown to be of the same kind 
 
 27 
 
THEORIES OF IMMUNITY. 
 
 as that in pnenmo-enteritis, however — of the 
 anti-infectious nature, and that the serum of the 
 immune animals did not contain an antitoxine. 
 As just stated and referred to by Metchnikoff, 
 the same thing was shown to occur in the arti- 
 ficial disease produced by the injection of the 
 cholera spirilla; in PfeiflFer's results (Zeit. f. 
 Hyg., 1894, T. XYI., p. 268) in cholera he ob- 
 tained a serum from highly immunized animals 
 with no antitoxic power, but with very active 
 anti-infectious properties. 
 
 Such instances as these, together with many 
 others that may be found admirably summarized 
 in Metchnikoff 's book upon Immunity (chapter 
 YI.), together witli the demonstration of a 
 marked excitation of the phagocytic reaction, 
 served at that time to turn the scale of judg- 
 ment in favor of the cellular theory of immunity, 
 but the discovery of " Pfeiffer's phenomenon " 
 seemed at the time to upset it entirely just as it 
 was about to be " at least admitted into court." 
 Buchner in the meantime had attempted to 
 reconcile the two theories by supposing that his 
 " alexines " originated in the phagocytes, but 
 that they were present in the body fluids and 
 
THEORIES OF IMMUNITY. 
 
 performed their functions there, while the en- 
 globing and digestive action of the phagocytes 
 was a secondary process. 
 
 ..Pfeiffer's phenomenon seemed to show, how- 
 ever, that there was no cell action whatever 
 necessary in the production of immunity, for it 
 took place in a fluid apparently entirely free from 
 cells. It consisted (Zeit. f. Hyg., 1894, T. XYII., 
 pp. 1, 355) in the following: In working to 
 secure immunity in guinea-pigs against experi- 
 mental cholera he found that living and virulent 
 cholera spirilla injected into the peritoneal cav- 
 ity of a fresh guinea-pig together with a small 
 amount of the serum of an immunized guinea- 
 pig, and then examined at short intervals, became 
 bunched together, granular, and finally disap- 
 peared entirely. This destruction he claimed to 
 depend entirely upon the action of the body fluids, 
 and to be the result of the action of a substance 
 wholly diffierent from the alexines of Buchner; 
 the immune serum in an inactive state did not 
 contain it by itself, but as soon as it was intro- 
 duced into the tissues of a fresh animal, the bac- 
 tericidal substance undergoes some change as a 
 
 29 
 
THEORIES OF IMMUNITY. 
 
 result of " the activity of the endothelial cells," 
 changes to an active condition, and becomes 
 capable of destroying great numbers of the 
 spirilla. This activity of the endothelial cells 
 was developed into a "new fundamental law" of 
 immunity (Deut. Med. "Woch., 1896, pp. 97, 119), 
 and the discovery renewed the vitality of the 
 *' humoral theory." 
 
 As Metchnikoff {I. c.) himself goes on to say, 
 it may be easily supposed that he undertook 
 the investigation of this phenomenon of extra- 
 cellular destruction of the bacteria as soon as 
 possible, with a view of determining its real im- 
 portance in the question of immunity. He was 
 soon able to show that Pfeiffer's phenomenon 
 takes place in special circumstances only; previ- 
 ously existing phagocytes must undergo much 
 damage before the spirilla can become trans- 
 formed into granules ; such " phagolysis " is in- 
 dispensable in order that Pfeiffer's phenomenon 
 may occur in the peritoneal fluids. If it be sup- 
 pressed by preparing the phagocytes beforehand 
 — by the injection of various liquids — an in- 
 stantaneous phagocytosis is produced instead of 
 
 30 
 
THEORIES OF IMMUNITY. 
 
 PfeiflPer's phenomenon; in places where there are 
 no or almost no preexisting leucocytes, PfeiflPer's 
 phenomenon does not occur at all. The same 
 with the cholera vibrio, — the extra-cellular de- 
 struction does not exist except under special con- 
 ditions, and the vast majority of other bacteria do 
 not show this phenomenon at all under the con- 
 ditions in which the cholera vibrio manifest it. 
 
 Metchnikoflf interprets the facts as indicating 
 that this destruction of the bacteria takes place 
 in the tissues as the result of the action of the 
 soluble ferments of the phagocytic digestion. 
 These ferments are normally found in the inte- 
 rior of the phagocytes, and not outside except as 
 the result of the destruction or temporary injury 
 of these cells. 
 
 Such a conclusion was in direct contradiction 
 to Pfeiffer's belief, who laid especial stress upon 
 an action of the endothelial secretions. So that, 
 to prove that these latter had nothing to do with 
 it, the reaction should occur outside of the body. 
 This Metchnikoff easily did by adding a httle 
 lymph, full of leucocytes, to an inactive auti-in- 
 
 31 
 
THEORIES OF IMMUNITY. 
 
 fectioTis serum — when the transformation of the 
 cholera spirilla into granules promptly made its 
 apjjearance. 
 
 This result was what led Bordet (Ann. de 
 rinst. Pasteur, 1895, T. IX, p. 462, and 1896, 
 T. X., p. 760) to study the intimate nature of 
 the reaction. He was successful in producing 
 it, not only by adding a little of the peritoneal 
 fluid to the specific serum, but also by adding a 
 little of the fresh blood from the same animal 
 (from which the peritoneal fluid had come). 
 These and other results of his work brought him 
 (Bordet) to the generahzation that the destruc- 
 tion of the bacteria in immunized animals re- 
 sults from the action of two substances, — one of 
 these is the alexine of Buchner, which under 
 normal conditions is to be found in the leu- 
 cocytes. It produces bacteriolysis properly so- 
 called when it exists normally within the cells, 
 and also when it has escaped from them as 
 the result of phagolysis. There must, however, 
 be present a second substance in addition to the 
 alexine, and this is the " substance sensibilisa- 
 trice " of Bordet, which circulates in the plasma 
 
 32 
 
THEORIES OF IMMUNITY. 
 
 and carries the " specific " property that is not 
 possessed by the alexine at all. 
 
 Bordet continued his most important studies 
 (Ann. de I'Inst. Past., 1898, T. XII., p. 688; 1899, 
 T. XIII., p. 273) by attempting to determine the 
 fate of the red blood corpuscles in the animal 
 body as the result of hemolysis. He established 
 the exceedingly narrow line between the devel- 
 opment of the bacteriolytic and the hemolytic 
 properties of the serum of animals, prepared by 
 repeated injections of bacteria and of blood, and 
 his results were soon confirmed by Bhrlich and 
 Morgenroth (Berl. Khn. Woch., 1899, p. 6), who 
 added the important conception that the sensi- 
 tizing substance of Bordet (the intermediary 
 body of Ehrlich and Morgenroth) has the prop- 
 erty of fixing itself in the red corpuscles. The 
 work of these three observers during the last 
 few years has rendered it possible to get some 
 conception of the mechanism of the action of 
 the two substances on the bacteria and the cells 
 of the animal tissues, as will be more clearly 
 stated below. 
 
THEORIES OF IMMUNITY. 
 
 Metchnikoff (Z. c.) summarizes the present 
 status of affairs in substance, as follows: The 
 theory of Ehrlich is not in opposition to the 
 theory of phagocytosis. Ehrlich considers that 
 the bacteriolytic ferments as well as the cyto- 
 toxic-alexines or complements (called cytases by 
 Metchnikoff) exist in a soluble condition in the 
 circulating blood plasma, whilst Metchnikoff 
 believes that they are normally present in the 
 interior of the phagocytes. This has nothing 
 to do with the Ehrlich theory in regard to the 
 receptors or lateral chains, which considers the 
 antitoxines and certain other anti-bodies (inter- 
 mediary substances) as products detached from 
 the cells and having an affinity for the toxines 
 and bacterial products. 
 
 The theory of phagocytosis seeks to estabhsh 
 the part played by the cells in the destruction 
 of the bacteria. It premises that the vital phe- 
 nomena of the phagocytes, such as motility, 
 sensitiveness (chemiotaxis), and voracity are 
 essential conditions for relieving the tissues from 
 the bacteria, for the true bacterial ferment is 
 contained within the phagocytes except when 
 phagolysis has occurred. The destruction of 
 
 34 
 
THEORIES OF IMMUNITY. 
 
 bacteria follows the laws of the destruction of 
 formed elements in general, and this resorption 
 is, in the last analysis, the work of two soluble 
 digestive ferments, of which one (fixateur, 
 immune body) is easily excreted by the phago- 
 cyte into the plasma of the blood and exuda- 
 tions, and the other may exist there at all times. 
 
 The theory of the phagocytes attempts to es- 
 tablish these principles in as exact a fashion' as 
 possible, but it has not attempted to penetrate 
 the depths of the phenomena of intracellular di- 
 gestion, which is mixed up with the action of 
 soluble ferments in general, and this problem is 
 still far from being solved. 
 
 In spite of the numerous objections, the theory 
 of phagocytosis within the limits indicated has 
 not only not been overthrown, but appears to 
 have slowly and gradually gained strength, as is 
 shown by the marked disappearance of opposi- 
 tion that is very noticeable of recent years. 
 Such changes are shown by the instance given 
 (Metchnikoflf, I. c.) of Buchner's change of atti- 
 tude toward the theory (Muench. Med. Woch., 
 1900, p. 1133). At the International Medical 
 Congress in Paris he maintained his theory of 
 
 35 
 
THEORIES OF IMMUNITY. 
 
 the leucocjtic secretion of the alexines, but 
 he went a step further than had before been the 
 case; he admitted that phagocytic activity has a 
 decisive importance in many cases in overcom- 
 ing the infectious processes, particularly in those 
 in which the alexines secreted have been unable 
 to produce more than a passing diminution in 
 the vitality of the bacteria. In such conditions 
 the bacteria have been so modified that their 
 chemical functions have been transformed into 
 a latent condition from which they would be 
 able to revive in full vital energy if the phago- 
 cytes were not present to prevent them from 
 doing so. In any case, as Metchnikoff says, this 
 conception is far from Buchner's original theory, 
 according to which the phagocytes are to be 
 considered only as capable of englobing dead or 
 harmless bacteria. He further speaks of other 
 marked changes in opinion which have occurred, 
 and sums up the present condition of things as 
 follows: the theory of phagocytosis has been 
 strengthened by the demonstration of the follow- 
 ing facts, that the phagocytes, in cases of immu- 
 nity, englobe and destroy living and virulent 
 bacteria, without these having been previously 
 
 36 
 
THEORIES OF IMMUNITY. 
 
 deprived of their toxines- that the phagocytes 
 contain the bactericidal cytases and produce the 
 fixatives ; that the phagocytes absorb the toxic 
 substances. The great contradiction between the 
 occurrence of the bactericidal property and the 
 non-occurrence of immunity is to be explained by 
 the fact that the bactericidal substances in the 
 living tissues remain in the leucocytes and do not 
 escape except when the cells have received some 
 injury. The fact brought out by Gengou, that 
 the blood plasma has no bactericidal property, 
 has given the " coup de grace " to the bacteri- 
 cidal theory of the body fluids. 
 
 This work of Gengou (Ann. de I'Inst. Past., 
 1901, T. XY., p. 231) is one of the strongest 
 supports of Metchuikoff's theory. In it he at- 
 tempted to determine whether the properties of 
 the shed blood are actually the same as those of 
 the blood in the body. The general results 
 were of great importance in showing that in 
 blood received under conditions preventing the 
 appearance of coagulation there would appear 
 no, or almost no, bactericidal properties, while 
 
 37 
 
THEORIES OF IMMUNITY. 
 
 in the same blood after coagulation there would 
 appear marked bactericidal powers. 
 
 If further experiments serve to support these, 
 and to show that under ordinary circumstances 
 there is no bactericidal property in the circu- 
 lating blood, it can easily be seen how impor- 
 tant this would be for Metchnikoff 's theory of 
 the formation of such a property in the cells as 
 the result of vital action. 
 
 Metchnikoff goes on, in his summing up, to 
 say that; There is only one constant element in 
 immunity, — either natural or acquired, — and 
 that is the property of phagocytosis. The ex- 
 tent and importance of this factor cannot be 
 denied. It has been fully shown that the phago- 
 cytes are sensitive cells that react against mor- 
 bific agents whether they are organized or not. 
 These cells englobe the bacteria and absorb the 
 soluble substances. They seize upon bacteria 
 that are living and able to exercise their hurtful 
 properties, and subject them to the action of 
 their cellular contents which are able to kill and 
 digest the bacteria, or at least prevent their 
 
 38 
 
THEORIES OF IMMUNITY. 
 
 pathogenic action. The phagocytes act by 
 virtue of their vital properties and the power of 
 exerting a fermentative action on the morbific 
 agents. . . . 
 
 This is a brief statement of the position of 
 Metchnikoff 's theory of Immunity, by which the 
 facts seen are supposed to be due in large part 
 to the vital activity of the mesodermic cells, 
 which have retained their power of englobing 
 and digesting foreign substances. The full 
 details can of course only be obtained by a 
 study of his book upon Immunity, in which may 
 be found a most complete summary of the work 
 done, with the interpretation of the results from 
 his point of view. 
 
 39 
 
THEORIES OF IMMUNITY. 
 
 III. 
 
 We come now to a discussion of Ehrlich's 
 theories in explanation of the same phenomena, 
 which are based upon the idea that the reactions 
 seen are primarily chemical in nature, although, 
 as will appear, it is impossible to neglect the 
 vital factor even in these theories. 
 
 Dr. James Ritchie (Review of current theories 
 regarding immunity. The Journal of Hygiene, 
 1902, Yol. II., nos. 2, 3, 4) has published a 
 very elaborate and painstaking discussion of 
 these theories, the best and most complete that 
 has yet appeared in English. It is, however, 
 useful only for those who already have some 
 familiarity with the subject. 
 
 It has been attempted, therefore, in what fol- 
 lows to condense the material gathered, to the 
 end that confusing details may not enter, and 
 that merely the main facts may be brought out. 
 The method adopted for illustrating the reac- 
 tions supposed to occur is entirely original, and 
 
 40 
 
THEORIES OF IMMUNITY. 
 
 is evidently capable of indefinite expansion, as 
 well as of being applied to all the reactions at 
 present known to occur. 
 
 Bhrlich first conceived his theory, or at least 
 the beginning of it, to explain the occurrences 
 in passive immunity; specifically, those seen in 
 the application of the antitoxine treatment of 
 diphthei'ia. 
 
 For the proper understanding of the case the 
 two types of bacterial action must be borne in 
 mind. The first, of which diphtheria is an 
 example, is that in which the results seen follow 
 the action of soluble poisons; which are de- 
 veloped during the growth of the bacteria; 
 which pass away from the site in which the 
 development of the bacteria may be going on; 
 and which produce their results at a distance 
 from that site. Diphtheria and tetanus are both 
 examples of this form of bacterial action; in both 
 of these diseases the bacteria producing them 
 grow mainly in one place in the body, and pro- 
 duce poisonous substances that act at a dis- 
 tance from this place. In the cases mentioned, 
 the poisonous substances also act upon special 
 
 41 
 
THEORIES OF IMMUNITY. 
 
 groups of cells. Therefore it happens that the 
 toxic substances are brought into existence out- 
 side of the cells, or at any rate can be separated 
 from the bacterial cells with ease, and may go 
 on producing their results after the bacteria 
 themselves have disappeared. In cultures, also, 
 the filtrates are found to contain the poisonous 
 products, whose action can be studied in such 
 filtrates, whilst the residue, consisting of the 
 bodies of the bacteria, is found to have very 
 little or no poisonous action whatever. The 
 actual constitution of these poisonous products 
 is not known, in spite of all the work done upon 
 them, but they are examples of extra-cellular 
 toxines, and they have the common property of 
 being precipitated by agents that also precipitate 
 the intermediate products of ordinary digestion — 
 the albumoses, — a fact that is of interest, for it 
 is possible that these toxic bodies may not be 
 far removed in composition from those that under 
 normal conditions form the food of certain of 
 the tissue cells. 
 
 Bacteria which grow in this way more or less 
 locally and produce their effects most promi- 
 
 42 
 
THEORIES OF IMMUNITY. 
 
 nently by means of " soluble " toxiues are mem- 
 bers of the first group. 
 
 The second group of bacterial diseases, how- 
 ever, is a most important one, and in it there is 
 seen no such production of separate and soluble 
 toxines. In the bacteria concerned, the filtrates 
 of bouillon cultures have little — or absolutely no 
 — poisonous properties, and the efiects in the 
 diseases produced by them are more or less di- 
 rectly connected with the bacterial cell itself. 
 These diseases are the result of the growth of 
 bacteria, which if they act by the production of 
 toxines at all do so by what are called " intra- 
 cellular toxines." These substances are inti- 
 mately connected with the bacterial protoplasm 
 and cannot be separated from it, or if they are, 
 only with very great difficulty. Pneumonia, the 
 septicemias, typhoid fever, cholera, plague, and 
 tuberculosis (as a chronic disease) are examples of 
 this form of bacterial action. The general char- 
 acteristics of all diseases of this type are fever as 
 a general manifestation, and of infiammation as a 
 sign of the local presence of the bacteria. In 
 the bacteria producing results of this general 
 
 43 
 
THEORIES OF IMMUNITY. 
 
 character, bouillon cultures, filtered, show in the 
 filtrate very slight toxic power, and the bodies 
 of the bacteria left behind often give evidence 
 of containing much more powerful substances. 
 
 An illustration of the conditions resulting 
 from such properties is furnished by the many 
 curious facts developed in attempting to secure 
 protection against cholera and typhoid. In 
 both cases it is possible to immunize an animal 
 by the use of small and gradually increasing 
 doses of a virulent culture of the typhoid ba- 
 cillus, or cholera spirillum, but the serum of an 
 animal so immunized is found to have no power 
 of protecting another animal against injections 
 of the toxines, but only against injections of 
 the bacterium itself — representing, of course, 
 Metchnikoff 's "anti-infectious" condition. The 
 same thing is true in regard to plague. 
 
 The two groups of diseases outlined above 
 should be carefully distinguished from each 
 other, for there is a marked difference in the 
 practical results that can be obtained in each — 
 in the degree (at present), in the method, and in 
 the explanations offered, in accordance with 
 
 44 
 
THEORIES OF IMMUNITY. 
 
 Ehrlich's theories, of the reactions by which 
 they are obtained. 
 
 In the first group — those in which soluble 
 poisons are formed — the results are secured by 
 successful efforts to protect the tissues against 
 the soluble toxines, without reference to the 
 presence or absence of the bacilli themselves. 
 In the second the actual bacterial cells them- 
 selves must be considered as well as the toxic 
 substances that are very intimately connected 
 with them and only to be separated with diffi- 
 culty. 
 
 Ehrlich's theories were first elaborated to 
 explain the conditions seen in the protection of 
 the tissues against the antitoxine of diphtheria 
 (passive immunity) , and were based upon the fun- 
 damental supposition that the action of the anti- 
 toxine upon the toxine was of a chemical nature ; 
 and this opinion was supported, among other 
 facts, by the demonstration that the two can be 
 titrated against each other " like an acid and an 
 alkali, and that it takes place more readily with 
 concentrated solutions than with weak.'' The 
 
 45 
 
THEORIES OF IMMUNITY. 
 
 experiments with porcelain filters coated with 
 gelatine were also brought forward to show 
 that the reaction is an actual chemical combina- 
 tion. In them it was found that at first, in mix- 
 tures of toxine and antitoxine, the latter would 
 not pass through, but the former would ; later, 
 however, a neutral fluid would appear, which was 
 interpreted as showing that an actual chemical 
 combination had taken place. 
 
 Subsequent observations showed that a simple 
 chemical reaction was not sufficient to explain 
 all the conditions. It was found that toxines 
 lost a considerable degree, if not all of their 
 power, if allowed to stand for some time, an ob- 
 servation that had been made by many observers ; 
 but Ehrlich also found that this weakened toxine 
 — to which he gave the name " toxoid " — re- 
 quired the same amount of antitoxine to neutral- 
 ize it as when fresh. In other words, the toxic 
 power of the toxine had diminished, whilst its 
 combining power remained the same. This being 
 true, the reaction could not be considered the 
 same as a simple chemical neutralization. 
 
 46 
 
THEORIES OF IMMUNITY. 
 
 The explanation offered by Bhrlich of this loss 
 of toxic power with no loss of combining power 
 is this : he supposes that in the ultimate toxine 
 molecule there exist two chemical affinities (sets 
 of atom-groups) , one of which has the power to 
 bind the molecule to a corresponding affinity in 
 the antitoxine molecule, and to which he gives 
 the name of " liaptophorous " affinity ; but he 
 supposes that there also exists another set of 
 atom-groups, which exert the toxic power of the 
 toxine molecule when the haptophorous group 
 has bound the molecule to another, and this he 
 calls the " toxophorous " affinity or atom-group. 
 In the case of the loss of toxicity observed in 
 toxine that has been kept for some time, he sup- 
 poses that it is this toxophorous group that has 
 been altered, whilst the haptophorous group has 
 remained unchanged. This supposition, if cor- 
 rect, would account for the condition seen — the 
 loss of toxic property, and the retention of the 
 combining property in as high a degree as it 
 existed at first. 
 
 Applying this supposition to actual facts ob- 
 served, the action of the toxines in diphtheria 
 
 47 
 
THEORIES OF IMMUNITY. 
 
 and tetanus may be explained in this way; the 
 evidence in favoi- of a chemical union between 
 the toxine and antitoxine already exists, and in 
 the same way there may be supposed to exist a 
 similar affinity between the toxine and the cells 
 of the tissues upon which it exerts its action. If 
 these affinities be satisfied — if the toxine is 
 bound to the tissue cell by the haptophorous 
 atom-group — the condition called susceptibility 
 appears, and the specific results of the toxic 
 action make their appearance; this of course 
 being the interference with the normal metabol- 
 ism of the cell by having the cell molecule dis- 
 turbed and perhaps destroyed. 
 
 So, also, an explanation of the production of 
 the an ti- toxine may be built up on this supposi- 
 tion. "It is impossible to conceive that the 
 affinities in the brain cell to which, for example, 
 the tetanus toxine becomes attached, are ordi- 
 narily of no use in the cellular metabolism. They 
 must bear a part in the latter, or else they would 
 be examples of absolutely useless mechanism in 
 the body. Now the process of immunization 
 consists in its initial stages in the administration 
 
 48 
 
THEORIES OF IMMUNITY. 
 
 of small non-fatal doses of the pathogenic agent. 
 Looking at the action of the first of these, we 
 see that the cells must be robbed of afiinities 
 needed in the ordinary metabolism, by the fact 
 of the attachment of toxine molecules to these 
 afiinities or " side-chains." (Eitchie, I. c.) The 
 use of the term " side-chain " is unfortunate, for 
 in chemistry it can only be employed in relation 
 to molecules of which the exact composition is 
 known, and this is not the case with any of the 
 toxines ; furthermore, it should be employed only 
 in connection with molecules in which the " ben- 
 zine ring " appears, and of course there is no 
 thought of its presence in these toxine molecules. 
 
 IS^ow, in accordance with general biological 
 law, that protoplasm tends to repair injuries if 
 not too great, — and furthermore, that this re- 
 pair, if it occurs, occurs in excess, — it may 
 be supposed that, when the interference with the 
 cell metabolism is not too great, the tendency 
 is to repair the loss of the haptophorous cell- 
 groups, — which if not replaced would result in 
 the death of the cell; that this replacing goes on 
 to excess, — and that when this occurs the ex- 
 
 49 
 
THEORIES OF IMMUNITY. 
 
 cess of haptophorous groups are cast off from 
 the cell molecule, and exist free in the blood 
 stream as the antitoxine, ready to combine with 
 such molecules of toxine as may come in its way. 
 When such combination occurs, the haptopho- 
 rous group of the toxine is taken up by the 
 similar atom-group in the antitoxine. This being 
 so, of course the toxine cannot combine with 
 anything else; if it cannot so combine, its tox- 
 ophorous atom-group can exert no deleterious 
 influence, and no result is produced; in other 
 words, immunity exists. 
 
 Bhrlich has demonstrated the reactions illus- 
 trating his theory by the use of figures which 
 are familiar to most persons interested in this 
 subject, but they have been found to be confus- 
 ing to the beginner. Being figures, and having 
 something the appearance of cells with pseudo- 
 podia extending out from their periphery, it has 
 been shown by experience that many students 
 have difliculty in separating the idea of a vital 
 action from the reaction which they are intended 
 to illustrate. It has, therefore, seemed best to 
 adopt some other method for illustrating the 
 
 50 
 
THEORIES OF IMMUNITY. 
 
 reaction just spoken of, and this has been found 
 as follows: 
 
 Let H represent the haptophorous atom-group, 
 T represent the toxophorous atom-group, 
 and X represent the remainder of the atom- 
 groups in the molecule. 
 
 Then the toxine molecule ^H+T+X, 
 and the antitoxine molecule ^H+X. 
 
 When two such molecules come together, the 
 haptophorus groups will combine by reason of 
 the affinity they have for each other, and the 
 result is the inability of the toxine to effect 
 further or different combination, so that its tox- 
 ophorous groups will be unable to exert any 
 hurtful influence : the combination would appear 
 thus : /H+T+X 
 
 \H+X 
 
 The production of the antitoxine may be 
 illustrated in very much the same way, except 
 that here the reaction lies between the toxine 
 molecules and those having the same haptopho- 
 rous groups in the tissue cells. 
 
 51 
 
THEORIES OF IMMUNITY. 
 
 In this case, the toxine molecule is to be rep- 
 resented as before : 
 
 The toxine molecule =H+T+X, 
 The cell molecule =H+lsr-}-X, 
 
 in which the N may be supposed to represent 
 the atom-group concerned in nutrition, and X 
 other atom-groups not necessary in the expres- 
 sion of this reaction. 
 
 Then the H groups in the two molecules com- 
 bine (the combination appearing thus: 
 
 ^H+T+X 
 
 \H+I^+X) 
 
 and a double action may be supposed to tate 
 place; on the one hand the T group will exert a 
 more or less irritant action on the cell molecule, 
 and on the other hand the H group of the tox- 
 ine molecule will take up the H group in the cell 
 molecule. ISTow, under ordinary conditions this 
 H group of the cell molecule is necessary for 
 the proper growth and metabolism of the cell, — 
 if it be taken up for something else, the cell 
 molecule will die or else its H group must be 
 replaced. This replacement occurs in the case 
 we are su.pposing, and takes place in excess; 
 
 52 
 
THEORIES OF IMMUNITY. 
 
 the excess of atom-groups is thrown out from 
 
 the cell and exists free in the blood stream as 
 
 H+X, which is the antitoxine. 
 
 This is not only the simplest way for illus- 
 trating what goes on in passive immunity (the 
 use of diphtheria and tetanus antitoxine), but 
 this passive immunity and the production of the 
 antitoxine is the simplest form of immunity that 
 workers in the subject are called upon to ex- 
 plain. In giving the formulae thus far shown, 
 it is of course to be understood that only the 
 simplest forms are used, and that the X dis- 
 played must be siipposed to contain all the other 
 atom-groups that are useful in other reactions, 
 but not in the particular one under discussion. 
 
 The believers in the physiological explana- 
 tion of the condition of immunity are not under 
 the necessity for supposing any such reaction 
 as that just illustrated; they believe that the 
 antitoxine excites the cells to resist the toxine, 
 and the evidence for this rests upon the series 
 of experiments (Buchner, Calmette with snake 
 venom, Wassermann) in which it was appar- 
 
 53 
 
THEORIES OF IMMUNITY. 
 
 ently shown that a mixture of antitoxine and 
 toxine neutral to one species of animal was not 
 neutral to another; if this was so, there could have 
 been no chemical union between the two. These 
 experiments are discredited, however, by the sup- 
 porters of the chemical theory of union, on the 
 ground that the mixture was not exactly neutral 
 in the first place. 
 
 Apparently the strongest support of the 
 theory of chemical union are the experiments 
 of Martin and Cherry (Proc. Royal Soc. of 
 London — quoted by Ritchie, I.e.), mentioned 
 above, in which they tested the behavior of 
 mixtures of toxine and antitoxine when passed 
 through a porcelain filter whose pores had been 
 filled with gelatine. The non-appearance of the 
 toxine after a time they interpret as an indica- 
 tion that a complete chemical union had taken 
 place — although the opponents of the theory 
 of chemical action say that the results may be 
 equally dependent upon an actual degeneration 
 of the toxine due to the amount of time elaps- 
 ing, such as is constantly seen when toxine is 
 allowed to stand by itself. 
 
 54 
 
THEORIES OF IMMUNITY. 
 
 Another point in favor of the chemical nature 
 of the reaction is brought forward by Bhrlich in 
 the case of the action of the red corpuscles and 
 the alkaloid ( ?) ricine. By injections of the latter 
 he was able to secure a resistance to it by the 
 red corpuscles of the animal injected, an anti- 
 ricine is formed, apparently of the same nature as 
 the antitoxine in diphtheria, and this serves to 
 protect the red corpuscles against a further 
 action of the ricine. IS^ow, he says, if the union 
 is not of the nature of a chemical reactian, a 
 new physiological function must be ascribed to 
 the red-blood corpuscles, which are not usually 
 looked upon as anything but acting as carriers 
 of oxygen. This supposition, however, goes on 
 the ground that there never will be any new 
 function ascribed to them, which is of course 
 inadmissible. 
 
 A great deal of experimental work has been 
 brought forward in support of Ehrlich's theory 
 of a purely chemical relationship between the 
 substances active in the various reactions, and 
 much also that has been interpreted as support- 
 
 55 
 
THEORIES OF IMMUNITY. 
 
 ing his views, but that is certainly open to other 
 constructions. 
 
 The most important seems to be that of 
 Madsen upon tetanus. His experiments were 
 carried on in the test-tube, avowedly to avoid 
 any chance of physiological action, and were 
 of extreme interest and importance. He found 
 that in certain cultures of the tetanus bacillus 
 he was able to demonstrate a substance which 
 he called " tetano-lysin," and which was capable 
 of destroying the red-blood corpuscles, and that 
 this might exist side by side with the ordinary 
 " tetano-spasmin." He further showed, by special 
 methods, that an anti-tetano-spasmin could be 
 produced which would act in a manner precisely 
 similar to that of diphtheria antitoxine. 
 
 A most important matter for the support of 
 Ehrlich's theory is the determination of the 
 place where the antitoxine is formed, for if it 
 be supposed that the antitoxine is produced by 
 a specific chemical reaction in the cells, it must 
 also be supposed that this reaction takes place 
 in certain tissue cells and no others. It must 
 be formed in at least some of the fixed cells, 
 
 36 
 
THEORIES OF IMMUNITY. 
 
 otherwise the experiments of Heymans (quoted 
 by Ehrlich himself) would upset the theory 
 entirely. In these he injected a minimal lethal 
 dose of tetanus toxine and immediately removed 
 all the blood of the animal, at the same time 
 replacing it by the blood of a fresh animal, yet 
 death occurred from tetanus just the same. 
 These experiments as well as many others show 
 that the toxine must act within the fixed cells as 
 well as in the free cells of the blood or body 
 fluids, but just where this reaction takes place 
 has not been definitely proven. The suggestion 
 that the antitoxine may be the result of the 
 splitting up of the toxine molecule, while con- 
 ceivable, is negatived by the facts thus far 
 observed that seem to show that the toxine 
 molecule is smaller than that of the antitoxine. 
 
 Antitoxine is formed in the body somewhere, 
 there can be no doubt of that in the minds of 
 any one who has ever had to do with the im- 
 munizing of horses with diphtheria toxine. In 
 these animals, after bleeding and the removal of 
 a considerable proportion of the antitoxine pres- 
 ent, there is a return of antitoxic strength in the 
 
 57 
 
THEORIES OF IMMUNITY. 
 
 blood after a short time, even if no more toxine 
 be injected to induce its return. This has also 
 been shown by Roux and Vaillard in the case of 
 a rabbit immunized against tetanus, in which 
 practically the whole of the blood was removed 
 during a series of days, with no sensible lessen- 
 ing of the antitoxic power; whilst a similar 
 thing was demonstrated by Salomonson in goats 
 immunized against diphtheria. (Ann. de I'Inst. 
 Past., 1893, yil., p. 65; and lUd., 1898, XII., 
 p. 763.) 
 
 All of these instances would seem to indicate 
 that the production of antitoxine is in the nature 
 of a hypertrophy of function, and how great this 
 may be is illustrated in not an extreme degree 
 by Ritchie {I. c, p. 236), in which he demon- 
 strates that an antitoxic serum may be produced 
 one hundred times stronger than the toxine 
 originally introduced; i.e., if tetanus toxine be 
 acted upon by hydrochloric acid until its tox- 
 icity be destroyed, it still retains the capacity of 
 giving rise to immunity. By acting for the 
 same time on different portions of the toxine 
 there is no doubt that on each occasion the 
 
 58 
 
THEORIES OF IMMUNITY. 
 
 state of the modified toxine would be the same. 
 Guinea-pigs were immunized by this modified 
 toxine, and instead of gradually increasing 
 doses, the amount used was always kept the 
 same. One set of animals received four doses 
 of the modified toxine, and another set eight 
 such doses. Of the serum of the first series of 
 animals 0.5 gram was required to protect against 
 a minimal lethal dose of the toxine — whilst of 
 the serum of the second series .005 gram was 
 sufficient to exert the same amount of protection. 
 In other words, twice the amount of toxine 
 gave rise to a serum of one hundred times the 
 strength. 
 
 Of course many objections have been raised 
 against Ehrlich's theory, and after all is said 
 there are many points that are still obscure. 
 These objections are nowheres brought together 
 as in the papers by Ritchie {I. c), and the first 
 is this : How is it that after an animal has been 
 brought to a very high degree of immunity, 
 consisting according to Ehrlich's theory in the 
 presence of a large number of antitoxine units 
 in the blood, free and ready for combination, 
 
 59 
 
THEORIES OF IMMUNITY. 
 
 that the toxine is not neutralized by these free 
 antitoxine units before it gets a chance to reach 
 the cells where its function will be to excite the 
 production of more antitoxine units? Even after 
 it gets to the cells, why is it not taken out of 
 them by the stronger aflinities of the haptopho- 
 rous groups existing in the blood-stream, as is 
 known to be the ease in ordinary diphtheria 
 immunity ? As a matter of fact the toxine is not 
 destroyed in this way, and upon injection it 
 does go on increasing the activity of the cells 
 in throwing off fresh haptophorous atom-groups, 
 and this is a difficulty that is not easy to explain 
 away. This objection does not arise from the 
 physiological point of view, for the first irritation 
 of the cells is a continuous one and does not 
 require the supposition of the existence of free 
 antitoxine molecules in the blood stream. 
 
 The only possible explanation in accordance 
 with Ehrlich's theory is that the affinities in the 
 tissue cell are a little stronger for the toxine 
 than are the affinities in the antitoxine; so that 
 when the combination of toxine and antitoxine 
 reaches the tissue cell, as it must in circulating 
 
 60 
 
THEORIES OF IMMUNITY. 
 
 through the blood, the H group of the tissue 
 cells overcomes the attraction of the H group 
 in the antitoxine, and binds the toxine to itself, 
 so that the irritant action of the toxine may 
 occur. This, however, is no explanation, for it 
 supposes exactly the opposite of what was sup- 
 posed in the previous clause: in the present 
 instance, that the H groups of the tissue cells 
 have a stronger affinity for the H groups in the 
 toxine than have the H groups of the antitoxine, 
 while in the preceding paragraph the opposite 
 supposition is made to explain what is seen in 
 diphtheria immunity. 
 
 Another very perplexing question is brought 
 forward in the same place : What is it that pro- 
 duces the safety of the animal in the very early 
 days of the process of immunity against a toxine? 
 Active immunity? In experiments quoted by 
 Ritchie (Z. c), and upon tetanus toxine, it was 
 shown that 0.5 gram of antitoxic serum was 
 sufficient to neutralize one minimal lethal dose 
 of the tetanus toxine; as a matter of fact, the 
 animals resisted in the series spoken of an 
 average of one hundred and ten minimal lethal 
 
 61 
 
THEORIES OF IMMUNITY. 
 
 doses (if the same proportion of serum contain- 
 ing antitoxine wei'e required as just stated this 
 would need fifty-five cubic centimeters of serum, 
 and an average guinea-pig does not hold so 
 much blood); but where is it possible for the 
 extra antitoxine units to come from? The con- 
 clusion is forced upon us that resistance to a 
 toxine is not necessarily related to the possession 
 of antitoxic power in the serum, but if we are 
 forced to this conclusion, what becomes of the 
 whole theory? In the experiments spoken of 
 above (Ritchie, I. c), the animals could certainly 
 resist sixty-six minimal lethal doses without the 
 slightest symptoms of tetanus, and no part of 
 Ehrlich's theory is as yet capable of giving an 
 explanation of how the toxophorous groups of 
 this amount of toxine are prevented from acting. 
 
 Further, in the later stages of Active Immu- 
 nity — to secure a " strong antitoxine " — thou- 
 sands of minimal lethal doses are injected. In 
 accordance with Ehrlich's theory, the toxine 
 must combine with the tissue cell in order to 
 stimulate the cell to the production of fresh atom 
 groups (H groups, which shall exist in the 
 
 62 
 
THEORIES OF IMMUNITY. 
 
 blood as antitoxine). If this process goes on, 
 the T groups may produce their effects, but why 
 do not the thousands of extra T groups produce 
 some result, when it is known that in the begin- 
 ning one minimal lethal dose will do so? 
 
 Many other objections and difficulties are 
 brought forward against the theory, which of 
 course cannot be expected to explain all the 
 phenomena in such obscure reactions as these of 
 which we are speaking, but perhaps the one that, 
 whether valid or not, requires more accurate 
 terminology in those speaking upon the subject, 
 is brought out by the use of the formulae above 
 displayed. The expression is constantly heard 
 that these atom-groups (receptors, side chains, 
 radicals) are produced in the cell in excess, and 
 thrown off to exist free in the blood as the anti- 
 toxine or other antibody, as the case may be. 
 If the chemical reaction can be expressed at all 
 by such a formula as employed above, what is 
 thrown off is a radical — an incomplete sub- 
 stance — and cannot exist free in the blood as 
 would be supposed from the expressions used 
 in regard to it. It is therefore necessary to 
 
 63 
 
THEORIES OF IMMUNITY. 
 
 suppose that the radical combines at once with 
 something else — which I have represented by 
 X — so that the unfortunate conclusion may not 
 be forced upon us, that a skilled chemist has put 
 forth the supposition of , the existence of some- 
 thing in violation of the laws of all known 
 chemistry. 
 
 In considering difficulties like these one is re- 
 minded of the remark of Metchnikoif, — spoken 
 of earlier, — that he does not seek to penetrate 
 the laws governing intra-cellular digestion, which 
 has to do with processes as yet absolutely un- 
 familiar to us. 
 
 A way out of the difficulties presented has 
 been found by the suggestion that there is an 
 essential difference between the two forms of 
 immunity — active and passive; that the first 
 (active) has to do with the cell, and should be 
 called Isopathic, and that the second has to do 
 with the fluids (principally the blood) and is the 
 ordinary antitoxic immunity. 
 
 It was said in beginning to speak of the sub- 
 ject of Immunity in the case of those diseases in 
 which the results are due to the production of 
 
 64: 
 
THEORIES OF IMMUNITY. 
 
 soluble toxines, that it was the simplest part of 
 the problem. It will, however, by this time 
 appear that the term "simple" is of relative 
 significance only. 
 
 The second group of diseases produced by 
 bacteria attracted attention very soon after the 
 facts in regard to the production of passive im- 
 munity in diphtheria and tetanus were known. 
 
 It was at first supposed that similar antitox- 
 ines could be secured in these diseases also, — 
 such as typhoid fever, cholera, and plague, — but 
 it was quickly demonstrated that this was not the 
 case, except to the very slightest extent. In 
 these diseases, and others in which the bacteria 
 do not produce soluble poisons, the actual pres- 
 ence of the bacteria is necessary for the results 
 to appear, and it soon became evident that the 
 production of immunity in such processes must 
 be dependent to a great degree upon the de- 
 struction of the bacteria themselves rather than 
 to a neutralization of any poisons that they 
 might elaborate. 
 
 65 
 
THEORIES OF IMMUNITY. 
 
 Both active and passive immxinity can be 
 secured in such diseases, but the latter only to a 
 very slight degree. 
 
 The active immunity secured is obtained by 
 the injection of non-fatal or attenuated cultures 
 of the bacteria — or by the use of virulent cul- 
 tures that have been killed by heat (as in the 
 procedure of Wright and Semple against typhoid 
 fever). 
 
 The passive immunity is of the slightest de- 
 gree, and the curious fact is developed that 
 in both typhoid and cholera the serum of 
 animals treated with dead cultures of the bacteria 
 of these diseases is bacteriolytic to the living and 
 virulent bacilli, but not antitoxic to the toxine. 
 
 Bordet's publication of his results in the study 
 of hemolysis, and the light they threw upon 
 Pfeiffer's phenomenon, were the first steps tow- 
 ards the explanation of the phenomena seen in 
 the second group of bacterial infectious processes. 
 PfeitFer's phenomenon is one of a purely bac- 
 teriolytic nature (of course bactericidal also, 
 although a bactericidal serum need not be bac- 
 teriolytic), and one of the ways in which it can 
 
 66 
 
THEORIES OF IMMUNITY. 
 
 be secured is by adding the serum of an animal 
 immunized to the cholera vibrio, and that has also 
 been subjected to a temperature of 55'^ Centi- 
 grade for half an hour, to a culture of active and 
 virulent cholera vibrios, and injecting the mix- 
 ture into the peritoneal cavity of a fresh animal. 
 The bacteria are soon seen to become gathered 
 together, granular, and gradually to disappear. 
 The action is specific and limited to animals 
 immunized to the disease produced by the bac- 
 terium employed — in the case cited, of course, 
 the cholera vibrio. It was at first supposed that 
 a similar reaction could be demonstrated for 
 other bacteria, and that such a reaction could be 
 utilized for differentiating species and races of 
 bacteria from each other. 
 
 The significance of this reaction was not under- 
 stood until the publication of Bordet's results in 
 hemolysis above referred to. In these he found 
 that upon injecting the blood corpuscles of one 
 species of animal into the blood stream of an- 
 other, there resulted in this blood stream the 
 appearance of a substance that was able to de- 
 stroy the blood corpuscles of the first species of 
 
 67 
 
THEORIES OF IMMUNITY. 
 
 animal — a hemolytic or globulicidal property 
 was developed. A specific example is that of 
 using the blood corpuscles of a rabbit for injec- 
 tion into a goat; in a short time there appears in 
 the goat's blood an antibody to the rabbit's corpus- 
 cles, which will destroy those corpuscles whenever 
 it is brought in contact with them. This hemo- 
 lytic property, it was also found, would disappear 
 upon heating the serum containing it for one- 
 half an hour to fifty-five degrees Centigrade. 
 The very remarkable fact was, however, brought 
 out that it would reappear upon the addition to 
 the heated serum of a little fresh serum, although 
 this fresh serum itself possessed no hemolytic 
 property. 
 
 These are similar to the occurrences going on 
 in Pfeiffer's phenomenon (of bacteriolysis), and 
 with others formed the basis of an extension of 
 Ehrlich's theory to explain what is seen to occur 
 in immunity against infection. 
 
 In explanation of the facts seen in hemolysis, 
 Bordet, and Ehrlich as well, suppose that there 
 must be two bodies present to permit the com- 
 pletion of the reaction. One of these exists in 
 
 68 
 
THEORIES OF IMMUNITY. 
 
 normal serum, and may be destroyed by heating 
 to 55° C. for half an hour; its presence is 
 demonstrated by such an occurrence as that 
 above mentioned, in which the hemolytic power 
 returns after the addition of a little fresh serum, 
 not of itself possessing the lytic property. This 
 substance (in the fresh serum) is called " com- 
 plement " by Ehrlich (also " addiment ") , and is 
 the alexine of Bordet, MetchnikoflF, and other 
 writers; it is probably also the same as the 
 " alexine " of Buchner, although there seem to be 
 some minor differences in the thought in regard 
 to their identity. 
 
 The second substance exists in the serum of 
 an animal subjected to the process of immun- 
 ization, and can be destroyed by being subjected 
 to heat at 75° C, for one-half hour. To this 
 substance Ehrhch has given the name " immune 
 body." It corresponds as nearly as may be 
 to the " substance sensibilisatrice " of French 
 writers and supporters of the cellular theory of 
 immunity. 
 
 In order to develop his theory of chemical 
 action in explanation of the condition of immu- 
 
 69 
 
THEORIES OF IMMUNITY. 
 
 nity in this group of diseases, Ehrlich supposed 
 that in this immune body there exist two hapto- 
 phorous atom-groups of affinities — not one as 
 before — and that one of them was concerned 
 in satisfying a similar haptophorous atom-group 
 (receptor) in the blood corpuscle (of the same 
 nature as the receptor in the tissue cells in anti- 
 toxine immunity); and the second haptophorous 
 atom-group of affinities (receptor) is satisfied by 
 a similar group in the complement, which, as has 
 been seen, exists in the serum (blood stream?) 
 of fresh animals. 
 
 In the complement there is supposed to exist 
 a group of affinities analogous to the toxophor- 
 ous group of the toxines — except that now it is 
 supposed to exist normally in the blood stream 
 (or cells of the body, according to Metchnikoff), 
 and this atom-group acts as the hemolytic or 
 bacteriolytic, or, in general, the cytolytic sub- 
 stance. 
 
 The experimental evidence upon which this 
 theory rests is as follows : If a goat be treated 
 with repeated doses of sheep's blood, there devel- 
 ops in its serum the capacity of dissolving 
 
 70 
 
THEORIES OF IMMUNITY. 
 
 sheep's red-blood corpuscles. (It may be said that 
 a great number of similar hemolytic sera can be 
 obtained by treating one species of animal with 
 the blood of another species.) Bhrlich took four 
 cubic centimeters of five per cent defibrinated 
 sheep's blood in .75 per cent salt solution, 
 added one cubic centimeter of immune goat's 
 serum which had been heated half an hour to 
 55° C. (and which thus contained only immune 
 body) , and placed the mixture for fifteen minutes 
 at 40° C. The question of where the immune 
 body was, he now investigated in the following 
 way: the mixture was centrifugalized until all 
 the corpuscles were deposited at the bottom of 
 the tube; the supernatant clear fluid was de- 
 canted, and there was added to it .2 cubic cen- 
 timeter of ordinary sheep's blood (containing, 
 therefore, susceptible red-blood corpuscles) and 
 .8 cubic centimeter of " fresh " goat's serum 
 (containing, therefore, goat's complement) ; 
 the mixture was placed at 37° C. for two hours 
 without any trace of hemolysis occurring. IS'ow, 
 if the immune body had been left in the fluid 
 after centrifugalizing, the complement from the 
 fresh goat's serum ought by it to have been 
 
 71 
 
THEORIES OF IMMUNITY. 
 
 linked to the sheep's corpuscles, and hemolysis 
 of the latter ought to have occurred. The im- 
 mune body therefore was not here. The sheep's 
 corpuscles of the original mixture were, of 
 course, in the deposit separated by the centrif- 
 ugalization. This was now taken, stirred up 
 with four cubic centimeters of .75 per cent salt 
 solution and there was added .8 c. c. of fresh 
 goat's serum (containing of course complement). 
 The mixture was placed at 37° C. for two 
 hours, and at the end of this time there was 
 found to have occurred hemolysis of the cor- 
 puscles. During the fifteen minutes that the 
 original mixture was kept at 40°, therefore, the 
 immune body in the immune goat's serum had 
 united itself to the sheep's red corpuscles, as was 
 evidenced by the fact that when the latter were 
 exposed to fresh complement, hemolysis occurred. 
 As remarked above, complement cannot cause 
 hemolysis by itself. The method of the experi- 
 ment is that three factors are necessary to the 
 occurrence of a given hemolysis: the red-blood 
 cells to be acted on; a body resistant to heat, 
 occurring in the serum of the immune animal 
 (immune body) ; and a body susceptible to 
 
 72 
 
THEORIES OF IMMUNITY. 
 
 heat, occurring in the serum of an unimmunized 
 animal (complement). When the presence of 
 any one of these substances is suspected, it can 
 be traced by adding the other two, and observ- 
 ing whether hemolysis takes place. In the in- 
 vestigation, sheep's blood was taken next, fresh 
 goat's serum was added, the mixture centrifugal- 
 ized, and the fluid on the one hand and the de- 
 posit on the other investigated for complement, 
 l^one was found in the deposit, but it was found 
 in the clear fluid, so that no combination had 
 taken place between it and the blood corpuscles. 
 ISText it was found that there was a greater affin- 
 ity between the immune body and the blood 
 corpuscles than there was between it and the 
 complement. The proof was as follows: It 
 was observed that in a mixture of five cubic 
 centimeters of five per cent sheep's blood, one to 
 one and one-third cubic centimeters of heated 
 immune goat's serum, and one-half cubic centi- 
 meter of fresh goat's serum, there was just 
 enough of all the constituents to satisfy all the 
 afiinities and leave none over. If all these sub- 
 stances were mixed at 0° C, and the mixture 
 centrifugalized as before, it was found that the 
 
 73 
 
THEORIES OF IMMUNITY. 
 
 complement present was still free in the super- 
 natant fluid. Therefore the affinity of the im- 
 mune body for the corpuscles was greater than 
 its affinity for the complement. This last ex- 
 periment also shows that at 0° C. the immune 
 body and the complement must have existed 
 free, side by side. (Ritchie, I. c, p. 245.) 
 
 The reactions that are supposed to take place 
 may be expressed by the following formulae: 
 Hemolysis requires for its appearance 
 
 1. The blood cell. 
 
 2. The immune body (in the serum of 
 the immune animal). 
 
 3. The complement (in the serum of the 
 fresh animal). 
 
 These may be represented as follows : 
 
 1. The blood cell molecule=H+K+X 
 
 2. The immune body " =B.+E+X 
 
 3. Complement " ^fiH-L+X 
 
 The H group of the complement binds the 
 molecule to the inunune body by one of its H 
 groups, and the second H group in the immune 
 
 74 
 
THEORIES OF IMMUNITY. 
 
 body binds the two to the blood cells — thus al- 
 lowing the L atom group of the complement to 
 exert its destructive (lytic) action. 
 
 For the production of the hemolytic property 
 (blood immunity it may be called), there are 
 required : 
 
 1. The blood cells that are injected. 
 
 2. The body cells in the animal into which 
 the above are injected. 
 
 3. Complement (present in fresh serum.) 
 The molecules of each of these and their re- 
 action upon each other may be shown thus; 
 
 1. The blood cell molecule=H+lNrH-X 
 
 2. The body cell " =H+^+I^+X 
 
 3. Complement, =i?-l-L+X 
 
 As in the preceding case, the ^ group of the 
 complement is bound to the body cell by the cor- 
 responding H group, the blood cell by another. 
 The H groups of the body cell are needed for its 
 ordinary metabolism, but are taken up in this 
 way; if the cell is to live they must be repro- 
 duced ; as the cell does live they are reproduced, 
 and as is usual, this reproduction goes on to ex- 
 
 76 
 
THEORIES OF IMMUNITY. 
 
 cess; then the H groups not needed are thrown 
 off into the blood stream and exist as 
 
 H+-H-f-X, or the immune body. 
 
 The i-eactions in hemolysis having been made 
 more clear by the investigations of Bhrlich 
 spoken of above, it became evident that the 
 reaction in bacteriolysis (of which Pfeiffer's 
 phenomenon was the first example) could be ex- 
 plained in the same way — and it can also be 
 shown by a formula similar to that used in the 
 demonstration of hemolysis, as follows: 
 
 The bacteriolytic reaction requires for its 
 completion 
 
 1. The bacterial cell, molecule=H+T+X 
 
 2. The immune body, " =H+S"+X 
 
 3. The complement, " =^+L+X 
 
 Then, as before, the complement and the im- 
 mune body are bound together by one set of 
 haptophorous atom groups ; these two are bound 
 to the bacterial cell by another similar set of 
 atom groups, and when this has occurred, the 
 lysin atom group (L) can set up its action and 
 the bacterial cell may be destroyed. 
 
 76 
 
THEORIES OF IMMUNITY. 
 
 So, also, the production of this bacteriolytic 
 property may be represented as follows : 
 Its production requires 
 
 1. The bacterial cell (which is 
 
 injected) . . . molecule=H+T+X 
 
 2. The tissue cells (from which 
 
 the immune body is pro- 
 duced) . . . molecule=H+lH-I^+X 
 
 3. The complement (present in 
 
 fresh blood) . . molecule=iy+L+X 
 
 In this reaction the H groups of the body cell 
 molecule are satisfied by the combination with 
 the similar sets of atom groups in the bacterial 
 cell and in the complement ; they are, however, 
 required for the ordinary metabolism of the body 
 cell molecule ; they must, therefore, be repro- 
 duced or the body cell molecule will die ; being 
 reproduced, they are in excess of the require- 
 ments of the cell — are thrown off" and exist in 
 the blood stream as " immune body," ready to 
 combine with fresh bacterial cells as they are in- 
 troduced, i.e., as 
 
 H+IT+X. 
 
 77 
 
THEORIES OF IMMUNITY. 
 
 The facts in hemolysis and bacteriolysis have 
 led to the investigation of the action of other 
 kinds of cells when introduced into fresh ani- 
 mals. A very large number of different kinds 
 of action of this nature have been studied, and 
 it is demonstrated that it is possible to secui-e 
 sera of many sorts which have a specific action 
 upon the cells originally used for the production 
 of the cytolytic power. Thus, for example, the 
 study of the results following the injection of 
 Uving spermatozoa has been the demonstration 
 of the production, in the sernm of the animal in 
 which they are injected, of a property that has 
 thg power of immobilizing fresh spermatozoa, if 
 not of absolutely dissolving them ; the same 
 thing holds true of other cells. Liver cells in- 
 jected in the same way will produce a serum 
 capable of inducing fatty degeneration of the 
 liver cells of a fresh animal. Of course the pos- 
 sible results that may come from such cytolytic 
 action as this are of the most important nature. 
 
 The reactions are explained by Ehrlich in the 
 same way as the phenomena of hemolysis and 
 
 78 
 
THEORIES OF IMMUNITY. 
 
 bacteriolysis, and they may be illustrated by 
 formulae similar to those already explained. 
 
 Thus — cytolysis requires 
 
 1. The cell to be acted upon, molecule=H+]S'+X 
 
 2. The immune body (produced by 
 
 the previous injection of the 
 
 above) molecule=H+fi-|-X 
 
 3. The complement . . " =i7+L+X 
 
 And when the H groups have produced the 
 necessary combinations, the L atom group of 
 the complement may exert its lytic action. 
 
 The production of the cytolytic property may, 
 of course, also be illustrated in the same way as 
 follows : 
 
 Its production requires 
 
 1. The foreign cell to be in- 
 
 jected .... molecule=H+]Sr+X 
 
 2. The tissue cells in which the 
 
 injection is made, molecule=H+^+!N^+X 
 
 3. The complement . molecule=^+L+X. 
 
 The same combinations are supposed to occur 
 in this as in preceding cases : the H atom-groups 
 combine together, so that those needed for proper 
 
 79 
 
THEORIES OF IMMUNITY. 
 
 metabolism of the tissue cells in which the injec- 
 tion is made are used for another purpose — 
 these are reproduced in excess, and cast ojOf into 
 the blood stream, where they exist as substances 
 capable of aiding in the cytolytic action. 
 
 Both sides, that which supports the "humoral" 
 and that supporting the " cellular " theory, agree 
 in supposing that two bodies are necessary for 
 the production of these reactions, but there 
 are two special points of dispute — first as to 
 whether the complement exists in the cells or out 
 of them; and second, whether it is single and 
 specific for the race of animals in which it occurs, 
 or whether it is multiple and specific only for 
 the reaction in which it appears active. 
 
 There is no dispute as to the complexity or 
 rather multiplicity of the immune bodies, which 
 are generally acknowledged to be very numerous 
 and capable of action only in special directions 
 — on the particular bacteria or tissue cells, as the 
 case may be. 
 
 As to the multiplicity of complement, it has 
 been shown that it is possible to reactivate a 
 serum by the addition of a little fresh serum 
 
 80 
 
THEORIES OF IMMUNITY. 
 
 from an animal of a different species. Such a 
 fact tends to show that complement is the same 
 in all species of animals, although there are other 
 experiments that indicate that this conclusion 
 may not be absolutely warranted. 
 
 Still another fact that is of importance is the 
 conclusion warranted by the evidence that com- 
 plement and immune body are not produced in 
 the same quantity, which would be expected 
 from the circumstances of the case. An illus- 
 tration is furnished by the possibility of demon- 
 strating that a given quantity of a cytolytic serum 
 may destroy a given quantity of cells. If, how- 
 ever, fresh serum be added, the same quantity of 
 the cytolytic serum will be found capable of 
 dissolving many times the number of cells it 
 could act upon in the first place. 
 
 The main point of controversy is upon the 
 multiplicity of complement, but not enough evi- 
 dence is yet before us to enable us to form a 
 definite opinion upon the matter. Metchnikoff 
 takes very strong ground in the matter, and de- 
 clares that the complement exists only in the 
 cells of the body, from whence it passes into the 
 
 81 
 
THEORIES OF IMMUNITY. 
 
 blood stream only after some destructive action 
 on the cells, and fm^thermore that it may take 
 part in the completion of the immunity occurring 
 in many infectious processes as well as in many 
 cell reactions. On the other hand, Bhrlich 
 argues forcibly for the multiplicity of comple- 
 ment, claiming that this substance is multiple 
 and specific for each reaction, as is the case with 
 immune body. 
 
 Walker (Journal of Hygiene, 1902, Vol. II., 
 p. 85) furnishes the specific evidence of the 
 identical nature of complement coming from dif- 
 ferent animals as follows: he found that the 
 anti-typhoid serum from a horse that has been 
 inactivated by the application of heat — thus de- 
 stroying its complement — may be reactivated 
 by the addition of serum from the rabbit, ox, and 
 the pig (thus adding fresh complement). This 
 may be represented graphically as follows : 
 
 Anti-typhoid serum contains 
 
 Complement, molecule ^H+L+X 
 Immune body, molecule=H+^+X 
 
 Other constituents, molecule=P(roteids)+S 
 (alts)+X. 
 
 82 
 
THEORIES OF IMMUNITY. 
 
 If this be heated to 55° C, for one-half hour, 
 the complement is destroyed, and the comple- 
 ment molecule (H+L-|-X) no longer exists. 
 The serum therefore is incapable of exercising 
 its bacteriolytic property. If now the fresh 
 serum of an ox, rabbit, or pig (containing of 
 course fresh complement (H+L+X)) be added, 
 the same constituents as at first would exist in 
 the anti-typhoid serum, and the bacteriolytic 
 power would be restored. 
 
 The various facts brought forward show that 
 one of the difiiculties that may arise in the treat- 
 ment of diseases of the second order (like ty- 
 phoid fever, cholera, and plague) is in the fact 
 that much more immune body may be formed 
 than there is complement to help make active, 
 and it is possible that this may be the explana- 
 tion of the poor results obtained with antitoxic 
 sera in the diseases just spoken of. Just how 
 this difficulty is to be met has not been shown, 
 but it is true that the apparently simple thing 
 to do, the addition of fresh sera (containing more 
 complement) does not fulfil the requirements, 
 at least so far as experiments have yet gone. 
 
THEORIES OF IMMUNITY. 
 
 The following summary of this part of the 
 subject is exceedingly good (Ritchie, I. c, p. 
 261) : It is to be observed that the methods by 
 which bactei'ia are dealt with in the body are 
 similar to those which obtain when many kinds 
 of foreign cells gain an entrance into the latter. 
 The development of artificial immunity against 
 such bacteria depends on the latter being intro- 
 duced either in a form not strong enough to 
 cause death, or, if virulent, not in sufficient 
 numbers to cause death. In either case, the 
 affected animal probably resists infection be- 
 cause it can develop in its body, or already 
 possesses a substance — immune body — which 
 attaches itself to the bacterial protoplasm, and in 
 virtue of this attachment permits another body, 
 the complement, which exists normally in the 
 animal's body, to act on the bacteria, with a 
 fatal result to the latter. In the case of a further 
 infection with bacteria, such as might occur 
 naturally, or as occurs during the process of 
 immunization, then no illness may result, but a 
 fresh formation of immune body may occur. 
 Whether a fresh formation of complement may 
 occur to any extent is a question for further 
 
 84 
 
THEORIES OF IMMUNITY. 
 
 investigation, but in an immune serum the com- 
 plement is always present to a less degree than 
 the immune body. What the nature of these 
 bodies is is unknown, but the complements are 
 less resistant to heat than the immune bodies. 
 Further, the nature of the reaction which takes 
 place between bacteria, immune body, and com- 
 plement is disputed, and lastly, while the multi- 
 plicity of immune body is undoubted it is still 
 open to question whether there is a great number 
 of complements in each animal's body, or whether 
 there is, for each species at least, only one com- 
 plement which is capable of acting in conjunc- 
 tion with a great variety of immune bodies, so as 
 to produce a solvent effect on many different 
 kinds of bacteria. 
 
 One of the greatest diflSculties standing in the 
 way of the supporters of Ehrlich's theories is 
 the existence of the bactericidal property in the 
 blood serum of animals that have not been 
 treated in any way, and at the same time are 
 susceptible to the action of the bacterium that 
 their blood serum will destroy. The well-known 
 fact that the blood serum of the rabbit has a 
 
THEORIES OF IMMUNITY. 
 
 marked bactericidal action upon the anthrax 
 bacillus, whilst the animal itself succumbs very 
 promptly to an infection by these bacilli, is an 
 illustration in point, and is not by any means the 
 only one that can be brought forward. 
 
 Whether or not this bacteriolytic action is the 
 same as that seen after the condition of immu- 
 nity has been produced has not been shown; if 
 it is the same, its production must be accounted 
 for, and the reactions may be explained in the 
 same way as has been adopted for the illustra- 
 tion of the other parts of Ehrlich's theory; if, 
 however, it is not the same, and its presence 
 seems to show that a bactericidal property of 
 the serum does not of necessity indicate a con- 
 dition of immunity, then the explanation of its 
 appearance and the method by which it acts has 
 not yet been furnished. 
 
 Somewhat the same position must be taken in 
 regard to the phenomenon of agglutination. 
 The relation of this phenomenon to immunity 
 does not appear to be any more intimate than 
 that of the possession of a bacteriolytic property 
 on the part of the blood serrnn. Agglutination, 
 
 86 
 
THEORIES OF IMMUNITY. 
 
 moreover, seems to be even less connected with 
 any action of a " specific " nature than the 
 bactericidal property spoken of just now. In 
 this connection it may be of interest to repeat 
 some conclusions reached in an investigation 
 upon this matter some time ago: 1, That the 
 agglutinating property does not lie in and is 
 in no way connected with the flagella of the bac- 
 teria concerned. 2, That agglutination is not 
 to be accepted as a specific property connected 
 with a condition of immunity, although this is a 
 difiicult idea to give up. 8, That the homolo- 
 gous nature of agglutination cannot be con- 
 sidered a positive characteristic, for how then 
 explain the clumping of typhoid bacilli by diph- 
 theria antitoxine? 4, Finally that no universally 
 applicable theory of agglutination has yet been 
 offered. That of Bordet (Ann. de I'lnst. Past., T. 
 XIII., p. 224, 1889) seems to us the most rational 
 yet suggested — that there is an agglutinating 
 agent (" agglutinine ") acting upon an agglutina- 
 ble substance ("substance agglutinee," the nature 
 of which is not yet determined), and that this 
 reaction occurs not only with bacteria, but with 
 many other elements — globules, casein, and 
 
 87 
 
THEORIES OF IMMUNITY. 
 
 precipitates of various kinds. (Ernst and Robey. 
 Trans. Triennial Congress of Physicians and 
 Surgeons, Yol. Y., p. 28, 1900.) 
 
 If one favors the idea that phagocytosis is the 
 active factor in disposing of bacteria in the oc- 
 currence of immunity from infection, the phe- 
 nomenon of chemiotaxis must be accounted for, 
 both positive and negative. Metchnikoif does 
 this by the supposition that there exist sub- 
 stances in the immune serum which stimulate the 
 chemiotactic power of the phagocytes toward 
 the invading bacteria. These " stimulines " are 
 supposed by Metchnikoflf to exist along with the 
 " cytases," or else to be these bodies themselves, 
 possessing the stimulating property along with 
 the others that have been ascribed to them. 
 
 Xot enough attention has been paid to the 
 condition of phagocytosis in the phagocyte pro- 
 ducing tissues, after the acute stage has passed 
 away, and on this point there is much to be 
 said. Recently the condition of these tissues 
 has been studied by Roger (Les Maladies Infec- 
 tieuses, Paris, 1902, p. 680 et'seq.), and Muir 
 (Journal of Pathology, Yol. YII., p. 161, quoted 
 
THEORIES OF IMMUNITY. 
 
 and summarized by Ritchie, I. c, p. 28B et seq.). 
 " The fact has long been known that in many in- 
 fectious conditions the number of leucocytes in 
 the circulating blood is increased, but these 
 observers were the ones to demonstrate the 
 pronounced germinative activity which occurs in 
 any infection, in the precursors of these cells. 
 With regard to the leucocytic phagocytosis, 
 Muir has shown both experimentally on animals 
 and by observations on man, that in infections 
 where there is a polymorphonuclear leucocytosis, 
 not only is there evidence of an active division of 
 the parent cell in the bone marrow, but so active 
 is this process that the red marrow increases in 
 amount and encroaches on the yellow. In a 
 case of pneumonia, for instance, a few days after 
 the commencement of the disease the red mar- 
 row may have increased so as to occupy a 
 seventh part of the whole medullary cavity of 
 the femur. jS'ot only, however, does prolifera- 
 tion occur in the site of formation of such an 
 important class of cells as the polymorphonu- 
 clear leucocytes, but Muir has also shown that 
 proliferation occnrs during some infections in 
 such fixed cells as those lining the sinuses of 
 
 89 
 
THEORIES OF IMMUNITY. 
 
 lymphatic glands and also in the hyaline cells 
 lying free in the lymph sinuses, which later may 
 be connected with some at least of the large 
 mononucleate hyaline cells of the blood. He 
 further points out that similar hyaline cells — en- 
 dothelial cells, connective cells — proliferate dur- 
 ing infection, as can be shown by mitotic figures 
 being found. It is no doubt the case that in 
 different infections different groups of cells thus 
 proliferate: in typhoid fever, for instance, there 
 is no polymorphonuclear reaction, but here the 
 proliferation of endothelial cells and hyaline 
 cells in lymphatic glands has been observed. 
 Thus while Metchnikofi" has insisted with justice 
 on the importance of the local reaction and of 
 the wandering cells of the body in infections, 
 and has noted the occtu-rence of phagocytosis 
 in other cells (his fixed ameboid cells), he has 
 missed the fact of the great proliferative changes 
 in various parts of the body which may be de- 
 scribed as the reaction of the body generally 
 against infection. It must be insisted upon that 
 there are not only local chemiotactie effects, but 
 in the case of the wandering cells there is the 
 general chemiotactie effect which draws the 
 
 90 
 
THEORIES OF IMMUNITY. 
 
 polymorphonuclear leucocytes from the marrow, 
 and in all cases of severe infection there is the 
 further stimulative effect which leads cells in 
 various parts to divide. Either this stimulation 
 is part of a reparative process, or it is to be 
 looked on as the result of injury due, say, to cir- 
 culating poisons. The fact that in relation to 
 one aspect of the process, namely, the polymor- 
 phonucleate reaction, the effect is often to in- 
 crease at a given point the available number of 
 cells capable of playing the part of phagocytes 
 leads one to think that all these tissue changes 
 may be of the nature of an exaggeration of nor- 
 mal functions, the general effect of which ex- 
 aggeration is to have a beneficial effect. It is to 
 be noted as a very important point in this pro- 
 cess that most of the distant effects must be due, 
 even in the case of bacteria which in vitro do 
 not produce soluble poisons, to the circulation of 
 soluble toxines, unless — which is possible — we 
 consider bacteria capable of exerting purely 
 physical influences. Connected with these is 
 the other very important fact that embryonic 
 activity may be dissociated from any actual 
 phagocytosis on the part of the proliferating 
 
 91 
 
THEORIES OF IMMUNITY. 
 
 cells, and this taken along with such facts as 
 the proliferation in certain infections of the non- 
 phagocytic eosinophilic leucocytes raises anew 
 the question of the possible secretion of chemical 
 substances into the serum which may be con- 
 cerned in the complicated process by which bac- 
 teria are destroyed in the animal body. It may 
 also be noted here that Muir has observed an 
 increase in the size and distinctness of the gran- 
 ules in the young polymorphs which occur in the 
 marrow during a severe infection. This might 
 indicate the preparation of material to be secreted. 
 So that from what has just been said it is thus 
 possible that on the fixed cells of the body and 
 the fixed precursors of the wandering cells are 
 impressed qualities which perpetuate immunity 
 in an animal which has survived an infection." 
 (Ritchie, I. c, p. 283.) ' 
 
 Such a conclusion as that just drawn is at 
 least in part in direct accord with Metchnikoff's 
 assertion that there is an inheritance of a ten- 
 dency towards phagocytosis by the descendants 
 of cells upon which the property has been 
 impressed. 
 
 92 
 
THEORIES OF IMMUNITY. 
 
 In concluding his review, Ritchie brings for- 
 ward (p. 452, et seq.) the further considerations 
 that follow, and says in regard to them, in 
 substance, that in the first place it is diflBcult 
 to see how, granted that two substances are 
 necessary for the production of immunity (the 
 immune body and the complement), these sub- 
 stances are to meet the bacterial cell in the first 
 instance except in the body cell. Unless all 
 immune bodies are existent in the serum as " go- 
 betweens " (amboceptors) — substances of an 
 identical nature except that they are utilized for 
 the normal metabolism of the cell until needed 
 for the reactions occurring in immunity — how 
 can the bacterium when it first enters the body 
 come in contact with the immune body for which 
 it has an affinity? The receptor is in the cell 
 (as represented in the formula used to illustrate 
 the reaction) and the bacterial cell receptor must 
 also get into the tissue cell — except it be sup- 
 posed that they exist under normal conditions 
 in the blood stream. It is undoubtedly possible 
 that the immune body may exist in the blood 
 stream as the result of normal metabolism, but 
 this is the only supposition which would explain 
 
 93 
 
THEORIES OF IMMUNITY. 
 
 how it gets there; if it does not so exist, then 
 the bacterium must be conceded to enter the 
 tissue cell at the first in order to start the exci- 
 tation resulting in the production of the immune 
 bodies; if this be the explanation, then Metch- 
 nikoff's contention that phagocytosis — at least 
 cellular action — takes place in the very first 
 instance must be adopted. 
 
 In the second place the query arises as to 
 why, if the bacteria must meet both complement 
 and immune body in the cell, why is the latter 
 produced so much in excess and not the former? 
 On the basis of the supposition that the comple- 
 ment exists normally, and that the immune 
 body is the result of an excess of cell activity 
 set in motion by the taking up of the hapto- 
 phorous atom-groups needed in the ordinary 
 metabolism by the bacterial atom-groups of the 
 same nature, this is easily understood, because 
 this new vital activity goes on in excess and may 
 be supposed to result in the production of a 
 great excess of the atom-groups representing the 
 immune body. 
 
 It is most probably the case that the reactions 
 
 94 
 
THEORIES OF IMMUNITY. 
 
 occurring in the production of immunity are 
 closely related to those that go on under the 
 ordinary conditions of tissue metabolism, and the 
 only way in which this can be settled is by the 
 determination, in the first place, of what the nor- 
 mal functions of the cells are ; and in the 
 second, whether substances similar to the anti- 
 bodies exist under normal conditions in the body. 
 
 Inquiry in the first direction has as yet left 
 much obscurity to be cleared away, and the exact 
 functions of the leucocytes, or of the cells from 
 which they are derived, are not clearly understood. 
 As to the second point, so many investigations 
 have seemed to show the facts that it can hardly 
 be doubted that substances closely allied to if not 
 identical with both complement and immune body 
 do exist in the sera of normal animals — it is, 
 however, disputed as to whether they exist free 
 in the normal blood stream. 
 
 If they do so exist they must have some 
 normal function, for it is not to be supposed 
 that they exist for the sole purpose of taking 
 part in the specific reactions of immunity when 
 such necessity may arise. They must take some 
 part in normal tissue metabolism; and in attempt- 
 
 95 
 
THEORIES OF IMMUNITY. 
 
 ing to determine what these functions were 
 Bordet firgt called attention to the occurrence of 
 the so-called " precipitiiies." (Ann. de 1' Inst. 
 Past., 1899, T. XIIL, p. 225.) He found that in 
 treating rabbits with chicken's blood, a hemolytic 
 serum could be obtained; but also, that when 
 this hemolytic rabbit's serum was added to 
 chicken's blood a precipitate made its appear- 
 ance. 
 
 Many such precipitates have been obtained 
 with many kinds of blood, and also with many 
 kinds of bacteria as well. Their nature is not 
 well understood, but the reactions seem to be 
 specific and most exact, and these reactions are 
 of great medico-legal value in the determination 
 of the presence of human blood in suspected 
 stains. 
 
 The general reaction may be shown by the 
 same formulae as were used for the purpose of 
 illustrating the forms of immunity as follows : 
 
 The production of the precipitate requii"es : 
 
 1. The blood globule, molecule=H-(-N'+X 
 
 2. The immune body, " = H+JT+X 
 
 3. The complement, " = ^-|-P-|-X 
 
 96 
 
THEORIES OF IMMUNITY. 
 
 The complement and the immune body are 
 bound to the blood corpuscle molecule, and the 
 P atom-group acts in such a way as to produce 
 the precipitate. 
 
 The production of the precipitine power re- 
 quires : 
 
 1. Blood serum, molecule=H+NH-X 
 
 2. The body cell, molecule=H+J/-|-N"+X 
 
 3. The complement, molecule=jS-|-P+X 
 
 The complement and the blood serum mole- 
 cule are bound to the tissue cell by the H atom- 
 groups; these latter in the tissue cell molecule 
 are reproduced in excess and are thrown off 
 after this reproduction occurs and exist free as 
 H+^+X=the immune body, ready for the pro- 
 duction of the precipitine reaction when the need 
 arises. 
 
 Any specific reaction — as that resulting from 
 the addition of rabbit's blood to the goat — may 
 be represented by the addition of the sub-letters 
 desired. 
 
 The belief that the affinities existing in the 
 body cells are very numerous is forced upon the 
 
 97 
 
THEORIES OF IMMUNITY. 
 
 supporters of Ehrlich's explanation of the reac- 
 tions that occur, and this is especially emphasized 
 by the formulae presented in illustration. It is 
 to be supposed that these affinities are con- 
 cerned under normal circumstances in helping 
 on the normal food metabolism of the tissue 
 cells, and possibly other reactions. Ehrlich has 
 given the name of "haptine" to the whole 
 group, and that the number is great may be 
 seen by those already known — lysins, aggluti- 
 nines, precipitines, complements, ferments, anti- 
 complements, ferments, etc. 
 
 The production of an anti-complement, for ex- 
 ample, may be represented as follows : it may 
 be obtained by injecting serum containing com- 
 plement from one animal {e.g., a guinea-pig) 
 into another {e.g., rabbit) : 
 
 The injected serum, molecule=H+L+X 
 The receiving blood cell, molecule=H+(H4-H 
 
 +H+H+H)+1^+X 
 
 The two are bound together, the special H 
 group is reproduced in excess, is thrown off, and 
 exists as H+X^the anti-complement. 
 
 98 
 
THEORIES OF IMMUNITY. 
 
 The action of this anti-complement may be 
 very simply represented : 
 
 The anti-complement raolecule=H+X 
 The complement molecule =H+L+X 
 
 But the two are bound together, and therefore 
 the L atom-group cannot be bound to anything 
 else, and therefore cannot do any harm or assist 
 in the ordinary action of the complement with 
 the immune body. 
 
 99 
 
THEORIES OF IMMUNITY. 
 
 IV. 
 
 SUMMAKT. 
 
 A study of the present position of the two 
 main theories explanatory of immunity shows 
 that they are not so far apart as is generally 
 supposed. 
 
 Both sides agree that the phenomena seen in 
 active immunity require two substances (immune 
 body or substance sensibilisatrice, and comple- 
 ment or alexine). 
 
 One side, however, insists that these sub- 
 stances remain in the cells (phagocytes). The 
 other maintains that they exist in the blood 
 stream (although, as has been seen, cell activity 
 is necessary for the production of the immune 
 body, at least). This latter fact of itself pro- 
 hibits the belief in a piirely humoral explanation 
 of immunity. 
 
 Both sides agree that " immune body " (sub- 
 stance sensibilisatrice) varies, is multiple and 
 
 100 
 
THEORIES OF IMMUNITY. 
 
 specific for each reaction in which it occurs; one 
 for typhoid, one for diphtheria, and so on. 
 
 They do not yet agree, however, that " com- 
 plement " (alexine) is multiple. One side main- 
 tains that it is the same for all reactions, the 
 other that it differs and is specific for each. 
 
 The point that has been insisted upon by 
 Metchnikoff from the beginning is maintained: 
 that in all reactions the cell activity must inter- 
 vene at some stage of its production. 
 
 101 
 
THEORIES OF IMMUNITY. 
 
 Y. 
 
 SUMMABY OF METHOD OP ILLUSTKATING 
 REACTION. 
 
 Let H represent the haptophorous atom-group 
 
 in the molecule. 
 T represent the toxophorous atom-group 
 
 in the molecule. 
 ]N^ represent the nutrient atom-group in 
 
 the molecule. 
 L represent the lysin atom-group in the 
 
 molecule. 
 X represent the remainder of the molecule. 
 
 It is not necessary to separate the I^ atom- 
 group; it is done, however, to make clearer the 
 fact that there is some vital action going on. 
 
 Then to represent the interaction of toxine 
 and antitoxine the following may be used: 
 
 Toxine molecule contains . . . H+T+X 
 
 Antitoxine molecule contains . . H+X 
 
 102 
 
THEORIES OF IMMUNITY. 
 
 The two H groups are bound together, thus: 
 /H+T+X 
 
 \h+x 
 
 therefore the T group in tbe toxine cannot be 
 bound to anything else, and the substance exists 
 as a harmless material in the blood stream. 
 
 The production of the antitoxine by the injec- 
 tion of the toxine may be represented as follows : 
 Tissue cell molecule contains . . H+N+X 
 Toxine cell molecule contains . . H+T+X 
 The H groups bind the two together; but 
 the H group of the tissue cell molecule is nec- 
 essary for the metabolism of the cell ; it must be 
 reproduced if the cell is to live; being so repro- 
 duced the reproduction occurs in excess, and 
 then the H groups are thrown oflf and exist free 
 in the blood stream as 
 
 H+X, which is the antitoxine. 
 
 Bordet's work on Hemolysis, and Ehrlich's 
 later work, showed that two substances were 
 necessaiy for other reactions, and necessitated 
 the supposition of the existence of two hapto- 
 phorous atom-groups. In accordance with this 
 
 103 
 
THEORIES OF IMMUNITY. 
 
 idea the reaction in hemolysis may be shown 
 thus: 
 
 It requires the cell to be destroyed, the im- 
 mune body, and the complement. 
 The cell molecule contains .... H+!N+X 
 The immune body molecule con- 
 tains H+^+X 
 
 The complement molecule con- 
 tains ^+L+X 
 
 The complement is bound to the immune body 
 by one H group, the two to the blood cell by 
 the other H group in the immune body, and 
 then the L group in the complement may act. 
 In cases where two H groups occur, the diffei'ent 
 affinities are indicated by capital and italics. 
 
 The production of the immune body requires 
 blood cells injected, the cells of the body in 
 which the injection is made, and the complement. 
 The reaction is shown thus : 
 
 The blood cell molecule con- 
 tains H-FN+X 
 
 The body cell molecule con- 
 tains H+^+N"+X 
 
 104 
 
THEORIES OF IMMUNITY. 
 
 The complement molecule con- 
 tains If+L+X 
 
 The two H groups in the tissue cell molecule 
 are used up, but must be reproduced; being re- 
 produced, this occurs in excess; they are thrown 
 off and exist free in the blood stream as 
 
 H+//+X, which is the immune body. 
 
 So with Bacteriolysis: the formulae are the 
 same, except in this instance the cell to be acted 
 upon is the bacterial cell, and not the blood cell : 
 
 The bacterial cell, molecule con- 
 tains H+T+X 
 
 The immune body, molecule con- 
 tains H+fi4-X 
 
 The complement, molecule con- 
 tains ^+L+X 
 
 As before the H groups in the complement 
 and the immune body combine, and then these 
 two are joined to the bacterial cell molecule by 
 the remaining H groups, and thus the L group 
 in the complement may exert its destructive 
 action upon the bacterium. 
 
 105 
 
THEORIES OF IMMUNITY. 
 
 The production of the bacteriolytic power re- 
 quires the bacterial cell to be injected, the tissue 
 cell from which the immune body is to be 
 produced, and the complement existing in the 
 fresh blood stream. The reaction is as follows : 
 The bacterial cell molecule con- 
 tains H+T+X 
 
 The tissue cell molecule contains H+i?-|-]SI"+X 
 The complement molecule con- 
 tains ..... -S-l-L+X 
 The H atom-groups in the tissue cell molecule 
 being taken up, are reproduced, cast off, and 
 exist free in the blood stream as 
 
 H+-Er+X, the immune body. 
 
 Cytolytic action may also be shown : 
 The cell molecule to be acted upon 
 
 contains ..... H+N+X 
 The immune body molecule contains H+^H-fX 
 The complement molecule contains . .H-fL+X 
 
 The H groups are joined together, and the L 
 group of the complement may then act. 
 
 The production of the cytolytic property is 
 secured thus: 
 
 106 
 
THEORIES OF IMMUNITY. 
 
 The foreign cell molecule in- 
 jected contains . . . H+l^+X 
 
 The tissue cell molecule, in the 
 body in which injection is 
 made, contains . . . H+.S-|-ISr+X 
 
 The complement molecule con- 
 tains H+Jj+H 
 
 The H groups in the tissue cells are repro- 
 duced in excess, and exist free as 
 H+^+X the immune body active in cytolysis. 
 
 Precipitine reactions may also be shown : 
 The blood globulin molecule contains H+I^+X 
 The immune body molecule contains H+^+X 
 The complement molecule contains . ^+P+X 
 
 The H groups being bound together, the L 
 atom-group may act, in this instance producing 
 the precipitate, and therefore it may be more 
 clearly represented as P. 
 
 The production of the precipitine power occurs 
 
 as in all the others : 
 
 Blood injected, the molecule con- 
 tains H+K+X 
 
 107 
 
THEORIES OF IMMUNITY. 
 
 The cell (of the body in which the 
 injection is made) the molecule 
 contains H+lfflSr+X 
 
 The complement (molecule con- 
 tains) fi4-P+X 
 
 The H groups are reproduced in excess as 
 before, and exist free as 
 
 H+//+X, the immune body necessary for this 
 reaction. 
 
 Anti-complement reaction is shown : 
 The complement molecule contains . H+L+X 
 The anti-complement molecule con- 
 tains ...... H+L 
 
 The two H groups combine, and the comple- 
 ment is rendered harmless by this combination. 
 
 The production of the anti-complement is 
 shown thus: 
 The injected serum (containing complement) 
 
 molecule contains H+N+X 
 The receiving blood molecule contains H+(H 
 
 +H+H+ H+etc. ) +I^+X. 
 
 The two H atom-groups combine, the one in 
 
 108 
 
THEORIES OF IMMUNITY. 
 
 the receiving blood is renewed in excess, is 
 thrown off and exists free as 
 
 H+X, the anti-complement. 
 
 It is of course to be understood that the let- 
 ters and formulae given above ai-e representative 
 of the general reaction only, in each case. If it 
 be desired to express a specific reaction — as for 
 instance that of the diphtheria antitoxine — it 
 may be done by placing a sub-letter " d " in each 
 place where its need is felt; for example, Hj,+X, 
 with the sub-letter at IT, represents the special 
 reaction used for illustration in diphtheria; any 
 other reaction may be shown in its specific nature 
 by the same means. 
 
 The molecule must also be supposed to con- 
 tain, in the. letter X, all the other atom-groups 
 not needed for the expression of the special reac- 
 tion under consideration. 
 
 [Note. — The use of H and H to indicate the binding of the com- 
 plement and the immune body, and of these two to the cell, was sug- 
 gested almost simultaneously by Prof. Neisser, of Frankfurt, and Dr. 
 Griinbaum, of Liverpool, and had been adopted when their letters 
 came.] 
 
 109 
 
THEORIES OF IMMUNITY. 
 
 VI. 
 
 GLOSSARY. 
 
 Active immunity : more or less permanent im- 
 munity, the result of the use of gradually 
 increasing doses of the toxines of a bac- 
 terium. 
 
 Addiment : another term, used by Ehrlich, for 
 complement. 
 
 Agglutinines ; substances found in the blood (and 
 possibly elsewhere) during and after the 
 progress of an infectious disease, capable of 
 clumping the bacteria producing the infec- 
 tions; non-specific; not dependent upon a 
 condition of immunity. 
 
 Alexines : substances existing in the serum of 
 both immune and non-immune animals (per- 
 haps of different nature in each) possessing 
 bactericidal properties. May be free in the 
 blood stream, or always, except by accident, 
 in the leucocytes. 
 
 110 
 
THEORIES OF IMMUNITY. 
 
 Alexines : (Bordet) bodies recognized by Bordet 
 as existing in the cells and possessed of bac- 
 tericidal properties; because of the fact 
 that they may be destroyed by heat {55° 
 C), and thus resembling Buchner's bodies of 
 the same name, Bordet called them alexines; 
 probably the same as the complement of 
 others. 
 
 Amboceptors: receptors of the third group, 
 capable of becoming normal factors in meta- 
 bolism; (Zwischen-korper, go-betweens;) 
 immune bodies. 
 
 Anti-complement : a substance produced in the 
 blood of an animal, injected with senim 
 containing only complement (no immune 
 body); it acts against the complement, and 
 prevents the latter from acting with the 
 immune body. 
 
 Anti-immune body: a substance that may be 
 supposed to exist in the blood of an animal 
 treated with immune serum in which only 
 "immune body'' exists — the complement 
 having been destroyed. 
 
 Anti-infectious: term used by Metchnikoff to 
 
 111 
 
THEORIES OF IMMUNITY. 
 
 denote the condition of resistance to further 
 injections of the infections agent. 
 
 Anti-sera: the sera of animals which have been 
 treated in such a way as to produce in them 
 substances antagonistic to various bodies ; 
 e.g., bacteria, toxines, blood-corpuscles, etc. 
 Most commonly used to denote antitoxic 
 sera. 
 
 Antitoxic immunity : passive immunity. 
 
 Antitoxine unit: the amount of immune serum 
 necessary to exactly neutralize one hundred 
 minimal lethal doses of toxine, after being 
 mixed one-half hour. 
 
 Atom-groups : atoms of the molecule supposed 
 to have special affinities ; become recep- 
 tors. 
 
 Autolysin: a substance in serum capable of dis- 
 solving the animal's own blood ; existence 
 not demonstrated. 
 
 Bacteriolysis : the breaking up of bacteria by 
 substances present in certain sera ; differ- 
 ing from proteolysis in that the bacteria 
 may not be dead. 
 
 112 
 
THEORIES OF IMMUNITY. 
 
 Chemiotaxis : the property of certain cells of 
 being attracted towards (positive) or re- 
 pelled from (negative) foreign bodies, such 
 as bacteria, or irritant substances. 
 
 Complement: first conceived by Ehrlich, in an 
 extension of his antitoxine theory, to ac- 
 count for the facts in immunity against 
 infection. Exists normally in serum and is 
 • destroyed after an exposure of one-half 
 hour to 55° C Must act Avith the immune 
 body to produce hemolysis, bacteriolysis, 
 etc. Contains two atom-groups of afl^i- 
 ties, one binding it to the immune body, 
 the other exerting the active lysin action 
 (hemolysis, bacteriolysis, etc.) ; this cor- 
 responds to the toxophorous atom-group in 
 the toxines. Perhaps the same as alexines 
 of Bordet. 
 
 Cytase : MetchnikoflF's term for the substance 
 existing in the phagocytes, which acting 
 through, or with the immune body, destroys 
 the bacteria. It is single of its kind ; cor- 
 responds to the complement of Ehrlich, 
 except that the latter is said to be of many 
 kinds and to exist in the blood stream. 
 
 U3 
 
THEORIES OF IMMUNITY. 
 
 Enzymes: non-organized ferments, capable of 
 causing splitting or decomposition of other 
 substances without entering into combina- 
 tion with them or their products. 
 
 Fermentation : the process in which a body may 
 originate changes in other bodies, whilst 
 remaining unchanged itself. 
 
 Fresh animal : fresh sera, etc. ; not treated in 
 any way to produce any form of immunity. 
 
 Globulins : albuminous bodies, insoluble in 
 water, but soluble in dilute neutral salt 
 solutions ; possibly the active principle of 
 the antitoxines. 
 
 Go-ietweens : see Zwischen-korper. 
 
 Haptines : Bhrlich's name for all the groups of 
 
 receptors. 
 Haptophorous {binding) : applied to groups of 
 
 affinities in body and bacterial cells, as well 
 
 as in toxines and immune bodies in general ; 
 
 satisfied by corresponding affinities in other 
 
 bodies; receptors. 
 
 114 
 
THEORIES OF IMMUNITY. 
 
 Hemolysis : breaking up of red corpuscles, see 
 lysins. Three factors are necessary for the 
 production of the phenomenon : 1, red-blood 
 corpuscles to be acted upon ; 2, a body oc- 
 curring in the serum of immune animals 
 and resisting heat up to 65° C, i.e., the im- 
 mune body ; 3, a body not resisting heat 
 above 55° C, and occurring in the blood 
 of a fresh animal, i.e., the complement. ' 
 
 ^^ Horror autotoadcus''' : Bhrhch's expression for 
 the fact that the tissues seldom, if ever, pro- 
 duce antibodies to receptors already exist- 
 ing in them. 
 
 Immune body : exists in the sei'um of an immu- 
 nized animal; resists one-half hour at 75° 
 C. ; has two haptophorous atom-groups, one 
 satisfied by a receptor in the cell binding 
 them together, the other satisfied by a 
 receptor in the complement binding these 
 two together. 
 
 Immunity: I^atural, exists in many animals to 
 many infectious diseases. 
 Acquired, may be the result of an 
 attack of a disease, or the result 
 
 115 
 
THEORIES OF IMMUNITY. 
 
 of aitifieial procedures. If the 
 latter, it may be 
 Active: the result of the use of 
 
 toxines, or 
 Passive: the result of the use of 
 antitoxines. 
 Immunity unit : see antitoxine unit. 
 Inactivated: used especially to denote the de- 
 struction of the complement in an immune 
 serum by exposure to heat (55"^ C), thus 
 making the immune body inactive. 
 Infection : often applied to the action of the bac- 
 teria, as distinct from that of their toxines. 
 Intermediary body : see Immune body. 
 Intoxication : applied to the results of the action 
 of bacterial poisons as distinguished from 
 that of the bacteria themselves. 
 Isolysin: a substance produced artificially in 
 serum, capable of destroying the blood cor- 
 puscles of animals of the same species. 
 Isopathic immunity : term suggested by Behring 
 to indicate the immunity of the individual 
 cell (the condition he thinks probably ob- 
 tains in active immunity) • immunity secured 
 by the use of toxines. 
 
 116 
 
THEORIES OF IMMUNITY. 
 
 Leucopenia : absence or disappearance from a 
 part of all phagocytes or wandering cells; 
 occurs temporarily in intraperitoneal injec- 
 tions. (Metchnikoff.) 
 
 Lysine : see Spermatolysin. 
 
 Macrocytase : cytase derived from the macropha- 
 gocytes, and active in 'the destruction of 
 blood corpuscles (hemolysis). (Metchni- 
 koff.) 
 
 Macrophagocytes : large mononuclear leucocytes 
 of the blood and of the endothelium, and 
 also, according to Metchnikoff, from the 
 large cells lining the sinuses of the lymph 
 glands and the sinuses of the spleen. 
 
 Microcytase : cytase derived from the micropha- 
 gocytes, and concerned in the destruction of 
 bacteria. (Metchnikoff.) 
 
 Microphagocytes : polymorphonuclear leucocytes. 
 
 Minimal lethal dose {M.L.D.): the amount of 
 any toxine necessary to kill a two hundred 
 and fifty gram guinea-pig in four days, after 
 subcutaneous injection. 
 
 Passive immunity : more or less temporary im- 
 munity, the result of the use of the serum of 
 
 117 
 
THEORIES OF IMMUNITY. 
 
 an animal already subjected to active immu- 
 nity (antitoxine immunity). 
 
 Peritoneum, : the French conception is " of a great 
 opened-out gland (un ganglion lymphatic 
 etale), whose cells have proliferative and 
 protective powers, and whose removal 
 renders an animal more susceptible to bac- 
 terial infection than usual/' (Ritchie.) 
 
 Pfeiffers reactidn (or Phenomenon) : the disinte- 
 gration of bacteria resulting when these, 
 together with immune serum, are injected 
 into the peritoneal cavity of a fresh animal. 
 The starting point of all the recent work on 
 bacteriolysis, hemolysis, etc. 
 
 Phagocytosis : the property possessed by certain 
 fixed and free ameboid cells of englobing 
 and digesting bacteria and other bodies. 
 Supposed by MetchnikofF to be derived from 
 the cells of the mesoderm. 
 
 Phagolysis : partial or complete destruction of 
 phagocytes, used especially in connection 
 with intraperitoneal injections in Pfeiflfer's 
 phenomenon. (Metchnikojff.) 
 
 Precipitines : substances found in the blood of 
 
 an animal, after injection with blood of an- 
 us 
 
THEORIES OF IMMUNITY. 
 
 other species of animal, capable of producing 
 a precipitate in the blood of the same species 
 of animal from which the injections were 
 made. The precipitate found is soluble (in 
 some cases at least) in two per cent solu- 
 tion of sodium chloride, and is therefore not 
 a coagulation. 
 Proteolysis : the breaking up of proteid bodies 
 as seen in ordinary digestion in connection 
 with the intestinal glands; takes place in 
 dead material. 
 
 deactivated : used to denote the supplying of 
 fresh complement to an immune serum, pre- 
 viously made inactive by heat (55° C), thus 
 making the immune body active. (See Inac- 
 tivated.) 
 
 Receptors: chemical affinities conceived by 
 Bhrlich as existing in the blood corpuscles, 
 other tissue cells, etc.; satisfied by corre- 
 sponding affinities in other substances (im- 
 mune bodies, toxines, etc.) . 
 
 Receptors of the first iips^der : affinities in the cell 
 concerned with fixing relatively simple ma- 
 
 119 
 
THEORIES OF IMMUNITY. 
 
 terials, i.e., toxines, ferments and other cell- 
 ular secretions. 
 
 Receiptors of the second order : affinities in the 
 cell, fixing the molecule by one arm and 
 breaking it up with another of a ferment- 
 like capacity; more complicated and for ab- 
 sorbing molecules of large size. 
 
 Receptors of the third order : affinities fixed in 
 the cell, and also containing two hapto- 
 phorous atom-groups, one fixing the food 
 particles, the other fixing the ferment-like 
 body (complement), whose action is neces- 
 sary for breaking up the particle fixed; the 
 most important of the three groups. 
 
 Sensitizing substance {substance sensibilisatrice) : 
 see Immune body; it is the same, except 
 that it is supposed to exist in the cell rather 
 than in the blood stream. 
 
 Side-chains : see Receptors. The term " side- 
 chains " should be used only of a molecule 
 whose composition is known. 
 
 Spermatolysin {and othemiysins) : refer to ex- 
 periments made with certain cells, after in- 
 jecting which sera can be obtained contain- 
 
 120 
 
THEORIES OF IMMUNITY. 
 
 ing substances capable of destroying these 
 cells. 
 Stimulines : Metchnitoff 's term to denote bodies 
 existing in immune sera, which stimulate 
 the phagocytes to move in a special direc- 
 tion, englobe, and digest invading bac- 
 teria. 
 
 Tetanus sine tetano : used by Donitz to describe 
 the condition of a rabbit dying after injec- 
 tions of tetanus toxine and antitoxine not 
 quite balanced; death from marasmus, but 
 no tetanus. 
 
 Tetano-lysin : a substance existing in some 
 bouillon cultures of the tetanus bacillus, 
 capable of destroying red-blood corpuscles 
 of certain animals; destroyed by heat at 
 50° C. (Madsen.) 
 
 Tetano-spasmin : what is usually considered the 
 tetanus toxine; with no hemolytic power; 
 very slightly affected by twenty minutes at 
 50° C. (Madsen.) 
 
 Toxine immunity ■• active immunity. 
 
 Toxophorous {poison carrier) : the group of 
 chemical affinities in the toxine molecule 
 
 121 
 
THEORIES OF IMMUNITY. 
 
 (and in the bacterial cell molecule in certain 
 cases) that exerts the poisonous action on 
 the cell, or is neutralized by the antitoxine. 
 
 Toxines : the powerful poisonous substances 
 elaborated during the growth of many bac- 
 teria; the soluble toxines are those remain- 
 ing in the filtrate of fluid cultures of some 
 bacteria. 
 
 Toxoids: the less poisonous substances remain- 
 ing in a filtered culture when this has been 
 kept for some time, and after the soluble 
 toxines have disappeared. 
 
 Toxones : supposed by Ehrlich to exist along with 
 toxines and toxoids and possessing hapto- 
 phorous atom-groups having a less strong 
 afiinity for similar groups in antitoxine 
 or cell than toxine; capable, however, of 
 combining with antitoxine, and of pro- 
 ducing very slow poisonous results {e.g., 
 diphtheria paralyses). 
 
 Vital nucleus: Ehrlich's term for his conception 
 of a centre of vital activity existing in the 
 protoplasm of the cell, with which are asso- 
 ciated the special cell capacities. 
 
 122 
 
THEORIES OF IMMUNITY. 
 
 Zwischen-lcorper : bodies in normal sera capable 
 of linking the hemolysin (or other lysins) 
 to the cell; corresponding to the immune 
 bodies in immune sera. 
 
 [Note. — This glossary contains terms found in general reading, as 
 well as those in the text.] 
 
 123 
 
S, M 
 
 Jj 
 
 
 .^/4