376 INFECTION AND RESISTANCE 



more slowly, it being necessary to wait two days after ingestion be- 

 fore the anti-anaphylaxis had developed sufficiently to protect. Since 

 attempts by mouth were not as rapidly successful as those per rec- 

 tum, it is clear that these facts are in keeping with Lesne and Drey- 

 fus' results in showing that the antigen is probably absorbed chiefly 

 or solely from the large intestine. In Lesne and Dreyfus' experi- 

 ments the sensitizing dose was given into the intestine, the toxogenic 

 or second dose being administered intravenously, and since, as we 

 shall see, minute doses may suffice to sensitize, whereas 100 or more 

 times the sensitizing amount is necessary to produce intoxication, it 

 is easy to understand why sensitization followed in Lesne and Drey- 

 fus' work, but no toxic effects followed in the experiments of Bes- 

 redka. Furthermore, the slow absorption from the intestine in these 

 experiments explains the development of anti-anaphylaxis in Bes- 

 redka'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 

 without symptoms many times this amount when it was gradually 

 administered by slow injection covering 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. 

 rw oon nTir j ipj^tinri; however, trmc effects^are never produced by 



q-nflyit.it.ipjp as -minute as thoSft TyVnVh anffW for 



tual 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 



57 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. II. S. Hyn. Lab. 

 Bull. 45, 1908. 



