ANAPHYLAXIS 377 



relation is not as definite as at first assumed. In the tables given 

 by them guinea pigs receiving 0.01 c. c. reacted severely after 14, 17, 

 and 155 days; others, receiving 1 c. c,, after 14, 17, and 155 days; 

 and, again, another series sensitized with 8 c. c. reacted severely 

 after similar intervals. All of these series reacted but mildly after 

 245 days, showing apparently that the anaphylaxis, contrary to gen- 

 eral belief, does not last so much longer after the larger than after 

 the smaller sensitizing doses. 



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 



This seems to indicate that perhaps individuals once sensitized 

 may remain so for life. And, as we shall see, a hyper susceptible 

 subject, temporarily desensitized by antigen, will again gradually^ 

 become sensitive. 



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 "anii- 

 anapliylaxis." 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 



80 Kosenau 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. 



