100 INFECTION AND RESISTANCE 



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 conception 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 transferable 

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

 mixture of the toxin with the immune serum brings about a neutrali- 

 zation 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 

 of rabbits that had thyroid hypertrophies and were, in consequence, 

 atropin-susceptible. Other observations of a similar significance 

 have been made by Physalix and Contejean 78 on curare, but have 

 not been confirmed, and the investigations of all other workers on 

 this subject have had negative results. It seems from available evi- 

 dence that tolerance (immunity) against drugs is due to cellular 

 rather than to serum antagonism. 



THE ORIGIN OF ANTIBODIES 



The tissue cell, as the ultimate functional unit, must, of course, 

 })G looked upon as the source from which originate the various pro- 

 tective constituents of normal and immune sera ; and, though per- 

 haps unrecognizable by the coarse tests of morphological investiga- 

 tions, it is in the cells that changes must take place primarily when 



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

 zenberg, Berlin, 1911, p. 517. 



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

 Meyer and Gottlieb, loc. cit. 



78 Physalix and Contejean. Cited from Meyer and Gottlieb. 



