354 INFECTION AND IMMUNITY 



tion, but not yet separated from the cells that had produced them; the cells 

 thereby becoming more vulnerable to the poison. In the same category 

 belongs the observation of Kretz, who noticed that normal guinea-pigs did 

 not show any reaction after injections of innocuous toxin-antitoxin mixtures, 

 but that marked symptoms of illness often followed such injections when 

 made into immunized guinea-pigs. Other phenomena which are now re- 

 garded, a posteriori, as probably depending upon the principles involved in 

 anaphylaxis, are the tuberculin and mallein reactions, fully described in 

 another place, and the adverse effects often following the injections of anti- 

 toxins in human beings, conditions spoken of under the heading of "serum 

 sickness." The last-named condition has been made the subject of an exhaus- 

 tive study by v. Pirquet and Schick. 5 



That the injection of diphtheria antitoxin in human beings is often 

 followed, after an incubation time of from three to ten days, by exanthematous 

 eruptions, urticaria, swelling of the lymph glands, and often albuminuria 

 and mild pulmonary inflammations, has been noticed by many clinicians, 

 who have made extensive therapeutic use of antitoxin. It was recognized 

 early that such symptoms were entirely independent of the antitoxic nature 

 of the serum, but appended upon other constituents or properties peculiar 

 to the antitoxic serum. Moreover, symptoms of this description were by 

 no means regular in patients injected for the first time, but seemed to 

 depend upon an individual predisposition, or idiosyncrasy, v. Pirquet and 

 Schick, however, noticed that in those injected a second time, after intervals 

 of weeks or months, the consequent evil effects were rapid in development, 

 severe, and occurred with greater regularity. 



The fundamental observations from which our present knowledge of 

 anaphylaxis takes its origin are those made in 1898 by Hericourt and 

 Richet, 6 who observed that repeated injections of eel serum into dogs gave 

 rise to an increased susceptibility toward this substance instead of im- 

 munizing the dogs against it. Following up the lines of thought suggested 

 by this phenomenon, Portier and Richet 7 later made an interesting observa- 

 tion while working with actino-congestin a toxic substance which they ex- 

 tracted from the tentacles of Actinia. This substance in doses of 0.042 gram 

 per kilogram produced vomiting, diarrhea, collapse, and death in dogs. If 

 doses considerably smaller than this were given in quantities sufficient to 

 cause only temporary illness, and several days allowed to elapse, a second 

 injection of a quantity less than one-quarter or one-fifth of the ordinary 

 lethal dose would cause rapid and severe symptoms and often death. Similar 



5 Pirquet and Schick, "Die Serum Krankheit," monograph, Leipzig and Wien, 

 1905. 



6 Hericourt and Ricliet, Compt. rend, de la soc. de biol., 5,3, 1898. 



7 Portier and Eichet, Compt. rend, de la soc. de biol., 1902 j Eiclict, Ann. de 

 Tinst. Pasteur, 1907 and 1908. 



