ANAPHYLAXIS IN ITS RELATION TO DISEASE 159 



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., endotoxins) 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 development of the serum sickness 

 where 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 

 shown 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 

 is also 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 



