382 INFECTION AND RESISTANCE 



a definite period must elapse between the injection of the sensitive 

 blood and that of the antigen. 



Both Friedemann and Otto found that when the sensitive serum 

 was injected subcutaneously the best results were obtained by ad- 

 ministration of the antigen 24 to 48 hours after this. On intra- 

 peritoneal injection of the sensitizing serum Doerr and Russ 80 ob- 

 tained the best results by permitting an interval of 24 hours to 

 elapse, and the same investigators still further shortened this period 

 to 4 hours by injecting the sensitive serum intravenously. Beyond 

 this, the interval could not be shortened with success. Indeed, some 

 writers, notably Gay and Southard, have claimed that the maximum 

 hypersusceptibility in guinea pigs treated with sensitive serum is 

 reached only after 10 or more days, and Rosenau and Anderson, 

 Lewis, and others have obtained results which seem to point in 

 the same direction. However, as we have already indicated, the 

 testing of animals so long after the injection of sensitive serum 

 leaves us in doubt whether we are dealing with true "passive" trans- 

 ference of anaphylaxis or with active sensitization due to traces of 

 antigen carried over with the serum of the sensitive animal. For 

 the purposes of theoretical deduction, therefore, it is better to ignore 

 these cases and consider chiefly passive transference in which reac- 

 tions are obtained within 24 hours or less after the injection of the 

 anaphylactic serum an interval so short that active sensitization 

 can hardly be considered as a reasonable possibility. 



The important point, in this connection, is the fact that in most 

 of the earlier investigations it was found that between the adminis- 

 tration of sensitive serum and of antigen a definite interval, however 

 short, was invariably necessary. 81 



From these observations the natural deduction was made that the 

 anaphylactic symptoms were the result of cellular occurrences, and 

 that the antigen could act only after the sensitizing substance (how- 

 ever conceived) had become attached to certain cells, probably to 

 those of the central nervous system. It was thought that a meeting 

 of antigen and the sensitizing substance in the circulation would 

 result in no reaction; that, in other words, the effective reaction 



80 Doerr and Russ. Zeitschr. f. Immunitatsforschung, Vol. 3, p. 181, 

 1909. 



81 An exception to this, contradicting the then prevailing opinion, were 

 the researches of Weill-Halle and Lemaire (C. E. de la Soc. de Biol., Vol. 

 65, July, 1908, p. 141), who showed that, under certain conditions, guinea 

 pigs would react with typical, often fatal, anaphylaxis if injected simul- 

 taneously with the serum of sensitized rabbits and the antigen horse sorum. 

 According to them, the success of such experiments depended entirely upon 

 the condition of the sensitive serum that is, the time at which the rabbits 

 treated with horse serum were bled. These experiments, we shall see, were 

 later confirmed. We record them, though important, in a footnote, since we 

 wish at present to emphasize the reasoning which led to the assumption of a 

 cellular participation in the reaction. 



