ANAPHYLAXIS 383 



was not a direct, but an indirect, one after the anaphylactic ''anti- 

 body" of the sensitive serum had become bound to the cells. It will 

 be necessary to recur to this problem when we discuss the various 

 theories of anaphylaxis. For the present it will suffice to state that 

 the problem has been greatly complicated because of subsequent 

 work which, in agreement with Weill-Halle and Lemaire, has shown 

 that an interval is not always necessary. Richet 82 brought evidence 

 of this in experiments with crepitin in 1909. It will be inter- 

 esting to note that he spoke of his experiments as "reaction anaphy- 

 lactique in vitro/' He sensitized a dog to crepitin, then bled him 

 during the hypersusceptible period, mixed the serum with a harm- 

 less dose of crepitin, and injected the mixture into a normal dog. 

 Violent anaphylaxis resulted almost immediately. 



At about the same time Friedemann 83 published his very im- 

 portant studies on the mechanism of anaphylaxis in rabbits. He 

 found that passive sensitization in these animals, in contrast to the 

 work of others upon guinea pigs, was best obtained by the simul- 

 taneous intravenous injection of antigen and anaphylactic serum. If 

 the injection of the sensitive serum preceded that of the antigen by 

 as much as 24 hours, the reaction became indistinct (undeutlich), 

 and Friedemann concluded that here, at least, there could not be 

 assumed the necessity of preliminary sensitization of the body cells 

 by the anaphylactic serum, as is the case in guinea pig anaphylaxis. 

 The anaphylactic poison, whatever it may be, Friedemann concludes,, 

 is, in rabbits at least, formed in the circulating blood. In the same 

 communication Friedemann showed that a poisonous substance^ 

 which would give rise to the symptoms of anaphylaxis, could be pro- 

 duced by allowing fresh alexin or complement to act upon sensitized 

 red blood cells. These results, of the utmost importance to our 

 knowledge of anaphylaxis, will be considered in greater detail in a 

 succeeding section. 



His observations upon rabbits, together with Weill-Halle and 

 Lemaire's work on guinea pigs, largely contradicting the views con- 

 cerning the necessity of an interval between the two injections in 

 passive anaphylaxis, left the problem in considerable confusion, and 

 work especially aimed at this point was undertaken by Biedl and 

 Kraus 84 and others. The outcome of this was to show that ap- 

 parently even in guinea pigs it was possible to produce anaphylaxis 

 in passively sensitized animals without allowing an interval between 

 injections of the two necessary factors. Biedl and Kraus found 

 that shock could ensue in guinea pigs even when the two substances, 

 sensitive serum and antigen, were mixed in vitro, and that animals 

 so treated were subsequently anti-anaphylactic. They, too, record 



82 Richet. C. R. de la Soc. Biol, Vol. 66, June, 1909. 



83 Friedemann. Zeitschr. f. Immunitatsforschung, Vol. 2, June, 1909. 



84 Biedl and Kraus. Zeitschr. f. Immunitatsforschung, Vol. 4, 1910. 



