200 CHEMISTRY OF THE IMMUNITY REACTIONS 



even if it is not the essential phenomenon of the anaphylactic intoxica- 

 tion. So readily is blood serum made toxic in vitro that it seems 

 highly probable that a similar development of toxicity may take place 

 in the body. Jobling^^ has found that intoxication from anaphyla- 

 toxin formation seems to occur when kaolin is injected intravenouslj' 

 into animals, and hence it is quite- possible that the presence in the 

 blood of abnormal, finely divided bodies, such as precipitated proteins, 

 cellular fragments, even bacteria, may mechanically cause anaphjda- 

 toxin formation in vivo just as they do in vitro. It is necessary to 

 distinguish, however, between the symptoms that result from capil- 

 lary embolism and true anaphylaxis, failure to do this undoubtedly 

 having caused many erroneous conclusions.^^" 

 ( Recentlj^ it has been suggested that a process similar to anaphy- 

 ' lactic intoxication is responsible for traumatic shock, disintegration 

 of traumatized tissue proteins being the source of the toxic agent. 

 (Quenu and Delbet, Cannon).^* 



The mechanism of anaphylatoxin formation is not yet under- 

 stood but there is no lack of theories. The original explanation was that 

 anaphylatoxin formation by specific antisera is the result of digestion 

 of antigen in vitro by the action of complement united to the antigen 

 by the immune antibody. For the formation of anaphylatoxin by 

 inert finely divided particles the explanation advanced was that the 

 highly developed surfaces of these particles either activated comple-. 

 ment, or united it to the serum proteins so that it digested them. 

 Jobling" has advanced the hypothesis that normal serum antifer- 

 ments, which are believed by him to be lipoidal in nature, are bound 

 by the particles or by specific precipitates, so that the complement is 

 free to attack the serum proteins. In any case, it is now generallj'' 

 agreed that the poisonous substance is derived chiefly, if not ertirely 

 from the serum of the intoxicated animal, and not from the antigen, even 

 in the case of anaphylatoxin formation by specific antigen-antibody- 

 complement reactions. ^^ This fact would seem to explain why the 

 poison seems to be the same, as far as we can analyze it by phar- 

 macological methods, no matter what protein is used as antigen, or 

 whether produced by immune or by nonspecific reactions, or by 

 chemical means, such as that of Vaughan. 



Jobling, who holds to the importance of anaphylatoxin formation as the cause 

 of anaphylactic intoxication, presents the following conception of anaphj'laxis: 

 During the course of sensitization there occurs the mobilization of a nonspecific 

 protease, which is greatly increased during acute anaphj'lactic shock; at this time 



" Jobling, Petersen and Eggstein, Jour. Exp. Med., 1915 (22), 590. 



''"See Hanzlik and Karsner, Jour. Pharmacol., 1920 (14), 379. 



" C. R. Soc. Biol., 191S (71), 850; Rev. d. Chir., 1919 (3S) 309. 



" Zcit. Immunitat., 1911 (23), 71; Jour. Exp. Med., 1915 (22), 401. 



** That the antigen must be digestible, however, is suggested by the observa- 

 tion of Ten Broeck (Jour. Biol. Chem., 1914 (17), 309) that proteins racemized 

 by Dakin's method, which cannot be digested by proteolytic enzymes, arc unable 

 to cause anaphylaxis. 



