CLINICAL SIGNIFICANCE OF ANAPHYLAXIS 431 



susceptibility against horse protein may be acquired and subsequently 

 be expressed by a reaction to the first injection of antitoxin. 9 While 

 this must be considered a possibility, however, not all investigators 

 are ready to accept it and its significance is at present very uncertain. 



In the ordinary case of serum-sickness after first injection, how- 

 ever, the long incubation time elapsing between the injection of the 

 serum and the onset of symptoms, often more than 10 days, would, 

 it seems to us, tend to argue against a previous hypersusceptible 

 state of the patient. On the other hand, we have learned since 10 

 the earlier studies of Eisenberg, von Dungern, and others that for- 

 eign proteins injected into rabjbits may be excreted very slowly, and 

 that even after the formation of antibodies (precipitins) the antigen 

 may still be demonstrable in the blood serum of the rabbit. Thus 

 at periods eight to twelve days after the injection of comparatively 

 large amounts there is often present in the same individual both an- 

 tigen and its specific antibody side by side, and the essential condi- 

 tions for the production of anaphylatoxin are thus established. That 

 the two bodies do not, as a rule, unite in such serum in quantities 

 sufficient to be demonstrated by alexin fixation has been discussed 

 in another place, but this by no means excludes a gradual, slow union 

 of small amounts of antigen with antibody, consequent fixation of 

 alexin, and the liberation of anaphylatoxic products. In fact, al- 

 though there does not seem at present to be any way to bring experi- 

 mental proof to support it, it seems very likely that a slow splitting 

 of the antigen begins by virtue of the normal antibody, and as, in 

 the course of eight to ten days, the antibody appears in relatively 

 larger amounts, the toxic products of the reaction are sufficient to 

 give rise to symptoms. Such a point of view is supported only by the 

 experimental knowledge that antibody may appear in considerable 

 concentration before the antigen has disappeared from the circula- 

 tion, and upon the facts we know concerning the toxic substances 

 which arise from the union of two such reagents subjected to the in- 

 fluence of alexin. 



In fact, it seems likely that this process of antibody formation 

 may represent merely an emergency mechanism for the purpose of 

 ridding the body of foreign dissolved proteins which have penetrated 

 into the circulation, cannot diffuse unchanged through the healthy 

 excretory channels, and must remain in the blood stream until sub- 

 jected to proteolysis by the enzymes of the blood. In the course of 

 ordinary life the quantities of such substances gaining entrance into 

 the circulation are necessarily small, and would call forth but slight 

 reactions. The sudden injection of large amounts of serum, not 



9 Weichhardt, Arch. f. Hyg.,Vo\. 74, 1911, has made similar studies and 

 claims to have found toxic protein cleavage products similar to his kenotoxin 

 in exposed air. 



10 See Zinsser and Young, Jour. Exp. Med., Vol. 17, 1913. 



