198 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



with some protein such as horse serum to a normal guinea-pig. When the 

 serum of the sensitized guinea-pig is injected into the normal animal, this 

 animal shows, after a period of 15-18 hours following the inoculation, 

 sensitiveness to an injection of horse serum and, with the appropriate dose, 

 dies in the same manner as the actively sensitized guinea-pig. The con- 

 dition has been studied particularly in this country by Weil, who, among 

 others, has emphasized the importance of the latent period following the 

 injection of the serum from the sensitized guinea-pig which is necessary 

 before anaphylactic shock can be produced by the subsequent inoculation 

 of horse serum. 



There is theoretical importance also to the further observation of 

 Gay and Southard showing that it is possible to sensitize a fresh animal 

 passively not only with the blood of a sensitized animal, but also with the 

 blood of an animal which is in the anti-anaphylactic state. 



A third condition which was described first in the pioneer studies 

 of Otto and in those of Rosenau and Anderson, and was made the subject 

 of investigation by Besredka and Steinhardt, is that of anti-anaphylaxis or 

 desensitization, in which, for a short period following the anaphylactic 

 shock, the actively sensitized animal becomes insensible to subsequent injec- 

 tions of horse serum. This period of anti-anaphylaxis is a temporary one, 

 and with its disappearance the animal becomes sensitive to the specific 

 protein and remains so for months or years. 



Efforts have been made to determine the quantitative relations between 

 sensitizing dose, length of incubation period, minimal anaphylactic dose 

 and minimal desensitizing dose. The results of Weil, although not in 

 complete agreement with those of other investigators, are as trustworthy 

 as any available observations on these points. Weil found that with a 

 small sensitizing dose, the incubation period is longer and the minimal 

 anaphylactic and minimal desensitizing doses are smaller than when 

 larger amounts are used for the sensitizing dose. 



Finally it was shown by Rosenau and Anderson that the repeated in- 

 jections of horse sercm, at intervals of 2-3 days, produce what has been 

 termed a refractory condition towards subsequent injections of the specific 

 protein, so that for a long period of time, animals no longer react to 

 an injection of the protein with anaphylactic symptoms. If, however, in- 

 jections of serum are stopped the refractory period finally gives way to 

 sensitiveness, and eventually the animal again becomes susceptible. Dur- 

 ing this refractory period the serum of the guinea-pig is particularly well- 

 adapted to produce the state of passive anaphylaxis in the normal guinea- 



The Pathological Physiology of Experimental Anaphylaxis. The 



symptoms occurring during anaphylactic shock vary somewhat according 

 to the animal which is used for the experiment. The vast majority of 

 observations have been made upon the guinea-pig, but the anaphylactic 



