ANAPHYLAXIS IN ITS RELATION TO DISEASE 165 



diseases may originate. In the past we have looked upon the "period 

 of incubation" as representing a period of time during which the 

 infecting organisms multiply in the body of the infected individual 

 to that point at which they would be sufficiently numerous to give 

 rise to symptoms of disease, either through their toxins (sc., endo- 

 toxins) or through interference with the metabolism of the macro- 

 organism in other ways. This explanation, however, is manifestly 

 out of the question in accounting for the "period of incubation" 

 which precedes the developement of the serum sickness w r here no 

 infecting organisms are at work. But v. Pirquet has pointed out 

 that the phenomenon is readily accounted for, if we bear in mind 

 that during this period antibody formation is taking place, and that 

 an antibody-antigen reaction will occur, as soon as the former has 

 progressed to a certain point. 



This point we may well term the threshold of anaphylactic or, more 

 generally speaking, of allergic reaction. If at this time the antigen 

 in the present instance the albumins of the horse serum has 

 disappeared from the circulation, no symptoms will, of course, 

 result; if, however, some of the material is still present, a reaction 

 occurs, during which, as we now know, poisonous substances (ana- 

 phylatoxins, apotoxins) are produced, and to these in turn we may 

 logically attribute the symptoms which then develop. The occur- 

 rences just described may be diagrammatically represented, as 

 show r n in Fig. 2. 



If, following the first injection of horse serum, a certain interval 

 be allowed to elapse, and a second injection be then given, the 

 result will differ from the first not only in point of time of reaction, 

 but also qualitatively and quantitatively, so far as the symptoms 

 are concerned. If the second injection be given at a time when 

 antibodies are still present in the circulation in considerable amount, 

 a reaction will occur either immediately or within the first twenty- 

 four hours; this may be quite violent in its intensity, though its 

 duration is shorter than in the first instance. This immediate reaction 

 also is diagrammatically represented in Fig. 2. 



If, on the other hand, the second injection be given after several 

 years, i. e., at a time when the antibodies called forth by the first 

 injection have disappeared, a certain interval of time will elapse 

 before symptoms of serum sickness develop, as in the case of the 

 first injection. But whereas this interval in the first instance is 



