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Scientific Proceedings (54). 



tion, only if minute doses were employed. " The preliminary 

 injection of more than .02 cubic centimeter is attended by an 

 uncertain result." Similar statements abound in the literature. 

 The great majority of the experiments on which these conclusions 

 are founded have employed either the intracerebral or the intra- 

 peritoneal route for the intoxicating injections. If, however, the 

 second injection is made intravenously, the results are entirely 

 different. With this method, it can be shown that a preliminary 

 mjection of as much as five cubic centimeters of horse, or other 

 serum, is invariably followed by a typical anaphylactic state, in 

 which death is produced by the second injection of an amount of 

 the same serum, which, for normal animals, is absolutely in- 

 nocuous. If guinea pigs are given repeated large injections, e. g., 

 3 c.c. of horse serum, on three or four successive days, the total 

 amounting to nine or twelve cubic centimeters, exactly the same 

 result follows. Finally, if spaced injections are employed, as in 

 the procedure followed for purposes of immunization, again the 

 animals become typically anaphylactic. There are, however, 

 certain differences in the behavior of animals sensitized, on the one 

 hand, by means of minute, and, on the other, by very massive 

 injections of serum. In the former, the minimal lethal dose is 

 often no greater than .005 cubic centimeter of horse serum. In 

 the latter, it is often one hundred times this amount. Again, 

 after a small injection, anaphylaxis frequently does not develop 

 for three weeks; after massive injections, it may generally be 

 demonstrated in ten or twelve days. These differences are trace- 

 able simply to the effects exercised upon antibody production by 

 small, as compared with large doses of antigen. With the former, 

 the antibodies are produced slowly and in small number; with 

 the latter, rapidly and in large number. Thus, in the case of 

 guinea pigs sensitized by small doses, it is generally necessary to 

 use the entire amount of blood obtainable by exsanguination in 

 order to sensitize another normal pig. After large injections, 

 however, one tenth of the total blood may suffice for this result. 

 It is probably on account of the larger amount of circulating 

 antibody that guinea pigs sensitized by large doses require a 

 larger toxic injection. 



