HYPERSUSCEPTIBILITY 211 



ficulty in the work with lipoids lies in the fact that it is practically 

 impossible to obtain the lipoids in pure form ; an extremely small amount 

 of adsorbed protein may produce the reaction. 



The method of sensitization is by parenteral routes, although 

 Rosenau and Anderson in their original communication state that they 

 had been able to sensitize guinea-pigs by feeding horse serum. Bes- 

 redka was unable to confirm this, but in a few dogs we have obtained 

 results which have been highly suggestive. A question of fundamen- 

 tal importance in this connection is whether or not proteins may be 

 absorbed through an intact intestinal mucosa without digestion. Ac- 

 cording to the work of Van Alstyne and Grant, such absorption may 

 occur. Absorption of the whole protein through the intestinal mucosa 

 or the mucosa of other surfaces might well serve to sensitize animals 

 or man, but as yet the problem is not conclusively settled. If 

 the inoculation be by parenteral routes there is apparently little 

 difference in outcome whether administered subcutaneously, intra- 

 venously or intraperitoneally. 



The amount of protein necessary for sensitization is extremely 

 small. In their original work, Rosenau and Anderson found that in 

 guinea-pigs 0.000,001 c.c. horse serum suffices. Wells succeeded in 

 sensitizing guinea-pigs with 0.000,000,05 gram crystallized egg albumin. 

 Larger sensitizing doses are necessary in order to produce subsequent 

 death from anaphylactic shock. Such minute doses are not applicable 

 in the case of rabbits, dogs and monkeys, in which it may be necessary 

 to inject the material on two or three successive days in order to 

 sensitize. The minimal sensitizing dose in man is not known. In 

 experimental animals there is an optimal sensitizing dose which bears 

 a certain relation to the subsequent intoxicating dose, as has been shown 

 by White and Avery. In a general way, the smaller the sensitizing 

 dose, the larger the minimum intoxicating dose and vice versa, but a 

 sensitizing dose may be too large for satisfactory sensitization. Accord- 

 ing to Besredka the larger doses also require a longer time for sensi- 

 tization to appear. 



Period of Incubation. For a period of eight to twelve days after 

 the sensitizing dose, subsequent injections of the same material produce 

 no evidence of hypersusceptibility. Gay and Adler reported that if the 

 euglobulins of serum are employed for sensitizing, the period of incu- 

 bation may be shortened to four or five days. If during this period 

 a second injection be given the animal is more likely to become immune 

 than hypersusceptible. Rosenau and Anderson found that the state 

 of hypersusceptibility increases until the twenty-first day, after which 

 it very gradually diminishes but persists in modified form probably 

 throughout the life of the animal. 



Intoxicating Injection. The French term, injection dechainante, 

 is highly descriptive of this part of the process, as it indicates the 

 explosive character of the manifestations that are likely to occur. This 

 injection may be intravenous, intrameningeal, intraperitoneal or sub- 

 cutaneous. The rapidity of reaction and severity of symptoms are most 



