ANAPHYLAXIS 377 



These experiments, however, as well as similar ones by other 

 workers, have shown that, once sensitized, animals may remain so 

 for very extensive periods. In the work of Rosenau and Anderson 59 

 the limit of horse serum sensitization was 245 days. A few guinea 

 pigs, sensitized with toxin-antitoxin mixtures, gave positive reac- 

 tions after 732 days; more recently they have obtained a reaction 

 after 1,096 days. 60 



In properly sensitized animals the result of a sufficient dose of 

 antigen, given at the proper time, is very often death. When the 

 time and quantity are so chosen that instead of death there is merely 

 a more or less severe anaphylactic shock, the animals are immediately 

 thereafter in a refractory condition. That is, they are no longer 

 sensitive to further injections of the antigen. This observation was 

 made by Otto and by Rosenau and Anderson in their pioneer inves- 

 tigations, was confirmed by Gay and Southard, and was subsequently 

 very thoroughly studied by Besredka and Steinhardt. 61 The last- 

 named workers named this refractory or immune condition "anti- 

 anaphylaxis." There is obviously a great deal of both practical and 

 theoretical significance in this fact, and methods were sought by 

 which such an anti-anaphylactic state might be induced in sensitized 

 animals without subjecting them to the dangers of actual shock. It 

 was found that this could be accomplished in a number of ways. 

 According to Besredka and Steinhardt the injection of moderate 

 quantities of the antigen at a time just preceding the development of 

 hypersusceptibility, in the preanaphylactic period, will render them 

 refractory to later injections. This preventive administration, how- 

 ever, must be given during the later days of the anaphylactic incu- 

 bation time. If given too soon after the first injection it does not 

 prevent eventual sensitization, though it may occasionally delay its 

 development, acting then simply as though a larger dose had been 

 given in the first place. Thus if antigen is given by a method of 

 introduction and in a quantity which would justify us in expecting 

 hypersusceptibility to be developed at the end of 12 days, we can 

 render the animal a antianaphylactic" by a second administration 

 given, say, on the 8th, 9th, or 10th day. If we give it on the 2d, 3d, 

 or 4th day after the first injection, it is very likely that sensitization 

 will proceed nevertheless. Rosenau and Anderson have also investi- 

 gated the repeated injection of antigen during the incubation time, 

 and their results would also seem to emphasize the necessity of mak- 

 ing the preventive injection close to the time at which hypersuscepti- 

 bility may be expected. If quantities of 2 c. c. were injected 10 times 



59 Rosenau and Anderson. U. S. Pub. Health and M. H. S. Hyg. Lab. 

 Bull 50, 1909. 



60 They express the belief from this that a guinea pig may remain sensi- 

 tive throughout life. 



61 Besredka and Steinhardt. Loc. cit. 



