298 INFECTION AND IMMUNITY 



of new facts. They showed conclusively that the action of the horse 

 serum had no relationship to its toxin or to its antitoxin constituents, 

 that the "sensitization" of the guinea-pigs by the first injection became 

 most marked after a definite incubation time of about ten days. Sen- 

 sitization was accomplished by extremely small doses (one one-millionth 

 in one case, usual doses ?ST to 1 c.c.). Rosenau and Anderson, further- 

 more, excluded hemolysin or precipitin action as explanations of the 

 phenomena, and proved that hypersusceptibility was transmissible from 

 mother to offspring, and that it was specific animals sensitized with 

 horse serum not being sensitive to subsequent injections of other pro- 

 teids. These authors, Vaughan 1 and Wheeler, Nicolle, 2 and others, 

 furthermore, showed that the reaction was by no means limited to animal 

 sera, but was elicited by proteins in general, pepton, egg albumin, milk, 

 the extract of peas, and bacterial extracts. 



The typical anaphylactic reaction, then, is obtained when animals, 

 preferably guinea-pigs, are injected with a small quantity of a given 

 protein, and ten or fifteen days subsequently given a second injection 

 of the same substance employed for the first or sensitizing inoculation. 

 The quantity used for the second injection should be considerably 

 larger than that used for sensitization when the injection is made 

 intraperitoneally or subcutaneously. When given intravenously, intra- 

 cranially, or intracardially, amounts as small as 0.25 to 0.008 c.c. may 

 suffice. The time at which a second injection gives rise to the most 

 violent symptoms, moreover, is to a large extent dependent upon the 

 size of the sensitizing dose. 3 After extremely small initial quantities 

 (0.005-0.002 c.c.), the anaphylactic state is usually well developed, ac- 

 cording to Rosenau and Anderson, 4 after twelve or fourteen days. After 

 larger doses 5 the time required for the development of anaphylaxis is 

 usually longer extending often over weeks, or even months. 



While the sensitizing or first dose may be given subcutaneously, 

 intravenously, intraperitoneally, or intracardially with equal success, 

 Besredka and Steinhardt maintain that no anaphylaxis results if the 

 first dose is given intracranially. This statement, however, has found 

 contradiction in the work of Rosenau and Anderson. The time required 

 for full sensitization, furthermore, depends, according to the last-named 

 authors, also upon the mode of injection of the first dose; on this point, 

 however, no conclusions are, at present, justified. 



1 Vaughan, Assn. Am. Phys., May, 1907. 3 Besredka, Ann. de 1'inst. Pasteur, 1907. 



2 Nicolle, Ann. de 1' Inst. Pasteur, 2, 1903. 4 Rosenau and Anderson, loc. cit 

 6 Otto, Munch, med. Woch., 1907. 



