PHENOMENA FOLLOWING IMMUNIZATION 99 



by combining these twenty amino-acids in different groupings an 

 enormous number of isomeric but varying compounds can be formed 

 even without assuming the additional possibility of quantitative 

 variations. He reasons that 3 "Baustcine" A, B, and C could 

 form 6 different structures, A B C, A C B, B C A, B A C, C A B, 

 C B A. Similarly 4 could form 26, and finally 20 could form 2, 432, 

 902, 008, 176, 640, 000 different compounds. 75 



The analogy between the active immunization of animals with 

 the various antigens and certain chemically well-defined poisons, 

 alkaloids, etc., is so obvious that it has led to much speculation as to 

 a possible similarity in the physiological mechanisms of the two phe- 

 nomena. As a matter of fact the acquired tolerance for such sub- 

 stances as morphin, atropin, and other alkaloids is not really anal- 

 ogous to the physiological reactions which follow the treatment of an- 

 imals with bacterial and other proteins, for whatever toxic properties 

 there are in the latter are, as we shall see later, rather the results of 

 the interaction of these injected substances and the reaction products 

 supplied by the cells and fluids of the body. It is at least probable 

 in the light of our modern conceptions that such protein antigens are 

 not toxic per se, in the native state. This, however, will receive 

 detailed consideration in succeeding sections. The analogy of drug 

 tolerance, however, to the acquired immunity against true bacterial 

 toxins and vegetable poisons like ricin, crotin, and others is a strik- 

 ing one, since in both classes of poisons there is a gradually devel- 

 oped tolerance for substances toxic in the native state and often very 

 similar in physiological effects (strychnin and tetanus toxin, etc.). 

 In the case of the toxins, however, there is a development of im- 

 munity by actual neutralization of the poisonous principle brought 

 about by a specific antibody, which circulates in the blood of im- 

 munized animals and man the process following, within certain 

 limits, the law of multiple proportions. In the case of morphin 

 and other alkaloids no such neutralizing antibodies have as yet 

 been demonstrated. 76 Whereas toxin immunity is passively trans- 

 ferable from one animal to another with the blood serum, and, in 

 vitro, the mixture of the toxin with the immune serum brings about a 

 neutralization of the poison, no such phenomena have been observed, 

 as a general rule, in the case of the alkaloids. We say "as a general 

 rule" since an exception is recorded in the observations of Fleisch- 

 mann, 77 who claims to have found antagonistic action to atropin in 

 the blood of normal rabbits, this power being absent from the blood 



75 We have not repeated the arithmetical labor and take Abderhalden's 

 word for it. 



76 Hans Meyer and Gottlieb. "Exp. Pharm.," 2d Ed., Neban & Schwart- 

 zenbers-, Berlin, 1911, p. 517. 



77 Fleischmann. Archiv f. exp. Path. u. Pharm., 62, 1910, cited from 

 Meyer and Gottlieb, loc. cit. , 



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