ANAPHYLAXIS 407 



is independent of complement, and more thermostable than either 

 the mechanism causing necrosis or that responsible for hemolysis. 



Kecent studies of the writer 72 on the toxic action of goat serum 

 for rabbits have shown that, contrary to Loeb, Strickler, and Tuttle, 

 hemagglutination and blood coagulation can be excluded as causes 

 of death, and that, in agreement with Fhlenhuth and Haendel, the 

 toxic action is due to a proteolytic action on the part of the serum 

 not necessarily identical with the hemolysins, but producing from 

 the protein of the recipient a poison similar to the anaphylatoxins. 

 Unlike Uhlenhuth and Haendel, however, it seemed clear that the 

 participation of alexin was definitely necessary the process being 

 probably entirely analogous to Friedemann's results with immune 

 liemolytic (cytolytic) sera. The poisonous action of dissolved hemo- 

 globin could be excluded. In principle, therefore, the toxic action 

 of normal sera would seem to depend upon a mechanism similar to 

 that of other anaphylactic phenomena. 



Toxin liy per susceptibility, which is often acquired by animals 

 in the course of immunization with diphtheria and tetanus toxin, is 

 usually classified with anaphylaxis, indeed is often cited as the 

 earliest observation of this phenomenon. However, it is by no 

 means clear that the two conditions are actually analogous, since in 

 the case of the toxins we are dealing with antigens which are not only 

 toxic in themselves, but against which neutralizing antibodies are 

 formed in the reacting animal. This last fact alone would separate 

 toxin hypersusceptibility sharply from true protein-anaphylaxis in 

 that entirely different reacting-mechanisms seem to be called into 

 play by the two varieties of antigen. It will be necessary, therefore, 

 to discuss toxin hypersusceptibility at some length. 



Probably the earliest authentically recorded observation is that 

 of von Behring, 73 who determined, both for diphtheria and tetanus 

 toxins, that animals once inoculated with these poisons were oc- 

 casionally more sensitive to them subsequently than were normal 

 animals. He spoke of "Gift Ueberempfindlichkeit" as a property 

 acquired by reason of a preceding injection, and the observation was 

 further developed by Knorr 74 in 1895, and by v. Behring himself, 

 in collaboration with Kitashima, 75 a few years later. These writers 

 showed that guinea pigs which are treated repeatedly with small 

 doses of diphtheria toxin may, under certain circumstances, not only 

 fail to show immunity, but may even develop a susceptibility in- 

 creased to such an extent that doses far too small to injure a normal 

 anhnal will cause their death. Again, in the case of diphtheria toxin 

 similar observations were made upon horses by both Salomonsen and 



72 Zinsser. Jour. Exp. Med., Vol. 14, 1911. 



73 Von Behring. Deutsche med. Woch., 1893. 



74 Knorr. Quoted from Otto, "Dissertation," Marburg, 1895. 



75 Von Behring u. Kitashima. Berl. klin. Woch., 1901. 



