376 INFECTION AND RESISTANCE 



suffice to sensitize, whereas 100 or more times this amount is neces- 

 sary to produce intoxication, it is easy to understand why the rectal 

 route sensitized in Lesne and Dreyfus' work, but no toxic effects 

 followed in the experiments of Besredka. Furthermore, the slow 

 absorption from the intestine in these experiments explains the de- 

 velopment of anti-anaphylaxis in Besredka's work, in that they are, 

 in this respect, analogous to later experiments of Friedberger, cited 

 below, in which it was shown that sensitized guinea pigs, which 

 could (in controls) be killed by rapid intravenous injection of 0.1 

 c. c. of antigen and less, would withstand many times this amount 

 when gradually administered by slow injections extending over 

 periods of an hour or longer. 



In referring to the quantities of antigen by which sensitization 

 may be accomplished, we have already called attention to the very 

 small amounts which have been found sufficient for this purpose. 

 There seems, indeed, to be a wide latitude in this regard, the re- 

 quired quantities ranging from as little as a millionth of a cubic 

 centimeter (Rosenau and Anderson) to as much as 10 c. c. or more. 

 On second injection, however, toxic effects are never produced by 

 quantities as minute as those which suffice for sensitization, though 

 here, too, a wide range of effectual amounts exists. An important 

 problem, moreover, is the relation which has been said to exist be- 

 tween the sensitizing dose and the interval necessary for the devel- 

 opment of the hypersusceptible state (anaphylactic incubation time). 

 In their first publications, Rosenau and Anderson, Otto, and others 

 expressed the opinion that the length of incubation time was in- 

 versely proportionate to the size of the sensitizing dose; in other 

 words, animals sensitized with small quantities (0.01 c. c. or less) 

 would become hypersusceptible and react to a second injection in 

 from 8 to 12 days, whereas animals receiving two, three, or more 

 cubic centimeters of the antigen would take weeks or months to be- 

 come anaphylactic. The same opinion was expressed by Otto, 57 and 

 is now generally found in the literature. Later experiments of 

 Rosenau and Anderson, 58 however, have seemed to show that this 

 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. 



5T Otto. Loc. cit. See also in "Kolle u. Wassermann Handbuch," Ergan- 

 zungsband II, p. 241. 



58 Rosenau and Anderson. U. S. Pub. Health and M. H. S. Hyg. Lab. 

 Bull. 45, 1908. 



