Anaphylaxis, Hypersensitiveness, 

 and Protein Intoxication 



WARFIELD T. LONGCOPE 



AND > 



GEORGE M. MACKENZIE 



NEW YORK 



Introduction. When the eminent French physiologist, Charles 

 Richet, observed the increased susceptibility of dogs to a second parenteral 

 injection of a glycerin extract from the tentacles of a sea-anemone, he in- 

 dicated a path for investigation which has since been brilliantly illumi- 

 nated by many experimenters. Although Richet was the first to appreciate 

 the significance and give the name of Anaphylaxis to this extraordinary 

 phenomenon, the observations of several investigators, beginning with 

 Magendie in 1839, had foreshadowed the discovery of this biological phe- 

 nomenon. 



In the 18 years since Richet's observation, the efforts of scores of work- 

 ers have added much to our information on this subject, but complete suc- 

 cess is far from being attained. The applicability of the essential fact in 

 anaphylaxis to innocuous, as well as toxic proteins, observed first by Flex- 

 ner in 1894, by Arthus in 1903 and by Theobald Smith in 1904, was am- 

 plified by Otto, Rosenau and Anderson, Gay and Southard, Friedmann, 

 Doerr, and Friedberger. With investigations, elimination of the possibility 

 of a cumulative effect in the specificity of the reaction was determined, and 

 it thus became well established that an animal, when injected subcu- 

 taneously, intraperitoneally or intravenously with a small amount of for- 

 eign protein, was rendered susceptible to a second injection of this same 

 protein made at least 914 days after the preliminary dose. While the 

 preliminary or sensitizing dose may be very small, the second or intoxicat- 

 ing dose, in order to produce symptoms, must be considerably larger, but 

 when this is properly gauged and made into the peritoneum or the vein, 

 the animal dies within five minutes to one hour, the symptoms depending 

 somewhat upon the type of animal which is employed for the experiment. 

 This phenomenon is known as active anaphylaxis. 



A second condition, known as passive anaphylaxis, described by 

 Gay and Southard, Richet, Otto, Friedmann, and Nicolle, consists in 

 the transfer of specific sensitiveness from a guinea-pig previously injected 



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