402 INFECTION AND RESISTANCE 



explain the anti-anaphylaxis which Biedl and Kraus 52 have noticed 

 after the injection of mixtures of antigen and antibody, nor the non- 

 specific antianaphylaxis which the same workers have observed after 

 peptone injections. It is clear that the nature of anti-anaphylaxis 

 remains for the present obscure, and, in view of the recent attempts 

 to account for certain phases of infectious disease by the anaphy- 

 lactic phenomena, is one of the most important problems of im- 

 munity. 



Bearing upon this condition of anti-anaphylaxis is the tolerance 

 to the anaphylactic poison which has been observed to develop in 

 animals once or twice injected. Vaughan 53 has noticed this in ani- 

 mals injected with his toxic split products, produced by alkaline- 

 alcohol splitting of colon bacilli. By repeated injection of the guinea 

 pigs he showed that a tolerance was developed which protected the 

 animal from about double the fatal dose, but the animal is not pro- 

 tected against larger multiples, and the condition is not an immunity 

 in the sense in which we have used the term. Similar observations 

 have been made by Bessau. 54 Bessau passively sensitized guinea pigs 

 with 1 c. c. of anti-horse serum intraperitoneally, and on the follow- 

 ing day injected them intravenously with 1 c. c. of horse serum. He 

 gauged his dose so that the animals should suffer severe shock but 

 survive. One or two days later he injected the amount of typhoid 

 anaphylatoxin which was fatal for normal pigs, and found that those 

 which had been treated as described were now able to withstand the 

 anaphylatoxin. These experiments of Bessau would indicate that 

 anti-anaphylaxis was to a certain extent due to tolerance of the 

 poison, and that it was non-specific. Friedberger, together with 

 Szymanowski, Kumagai, Odaira and Lura, later studied this problem 

 and came to the conclusion that anti-anaphylaxis is strictly specific, 

 depending, as Friedberger had suggested, upon the diminution of 

 specific antibodies rather than upon tolerance to the poison. They 

 claimed that animals that had been sensitized and then had survived 

 the "shock" dose of homologous protein showed no tolerance for 

 anaphylatoxin, and that animals that had been treated with the 

 sublethal dose of anaphylatoxin were, after 24 hours, as sensitive to 

 anaphylatoxin, however prepared, as were normal animals. Recent 

 studies along the same lines by Zinsser and Dwyer 55 have yielded 

 results differing from these conclusions. Working with typhoid 

 anaphylatoxin they found that guinea pigs treated with a sublethal 

 dose of anaphylatoxin developed a tolerance which enabled them to 



52 Biedl and Kraus. Zeitschr. f. Imm., Vol. 4, 1910. 



53 Vaughan. "Protein Split Products, etc.," Lea and Febiger, Philadel- 

 phia, 1913, p. 139. 



54 Bessau. Centralbl f. Bakt., Vol. 60, 1911. 



65 Zinsser and Dwyer. Reported at the meeting of Am. Ass. of Path, and 

 Bact., Toronto, April, 1914. 



