ANAPHYLATOXIN 225 



within their bodies a toxic substance that does not form antibodies when liberated in 

 animals. The first injection of antigen produces bacteriolytic or cytolytic antibodies 

 possessing the power of liberating the endotoxic poisons from the proteid molecule. 

 When the second injection is given, these bacteriolytic antibodies at once cause a rapid 

 liberation of the intracellular toxic fraction, and injury to the animal results. Wolff- 

 Eisner's theory can apply only in a certain number of instances, because the essential 

 factor of cytolysis is not always present; very many bacteria, especially tubercle bacilli, 

 are not thus broken up. 



This view has, however, been the fundamental thought for the later very important 

 work of Friedemann and Friedberger. By these supporters of the humoral theory 

 the main influence is placed upon the union which takes place in vivo between the anti- 

 gen -f- amboceptor + complement. As a result, anaphylaxis may be incited in one of 

 two ways. The mere absorption of the complement may bring about the anaphylactic 

 shock. This diminution in the complement content of the serum is always demon- 

 strable. Or, as is more probable, the union of the above three elements causes a destruc- 

 tion of the antigen and a liberation of a toxic agent. This theory is strengthened by the 

 demonstration that not only in vivo but also in vitro can such a toxic substance be 

 obtained by mixing antigen -f- amboceptor + complement. 



In 1902 Weichardt immunized rabbits with a proteid derived 

 from syncytial cells. By mixing the fresh immune serum 

 with an emulsion of the syncytial cells and filtering, he derived 

 a very toxic fluid which was named syncytio toxin. In 1909 

 Friedemann and Citron simultaneously isolated in vitro toxic elements 

 which could bring about anaphylaxis. This was confirmed by Fried- 

 berger several months later. Friedemann got his poisonous agent by 

 mixing erythrocytes, inactive hemolytic serum and complement. 



Three c.cm. sheep's blood + i c.cm. inactive hemolytic serum are allowed to 

 remain at room temperature for one-half hour, then centrifugalized. The sensitized 

 erythrocytes are mixed with 4 c.cm. fresh rabbit's serum (complement) and placed 

 into the water bath at 37.5 C. for exactly five minutes; then cooled down by ice and 

 centrifugalized. The red blood cells remain almost all unhemolyzed. The superna- 

 tant fluid is only slightly reddened and when injected intravenously into a rabbit 

 (1310 gms.) causes general weakness, diarrhea and death on the following day. 



It is to be observed that the anaphylatoxic substance was formed even 

 though' no hemolysis took place. 



Citron accomplished the same end by a mixture of tuberculin, serum 

 from a tuberculous individual who spontaneously produced antituber- 

 culin amboceptors, and normal guinea-pig's serum (complement). 



o.i to 0.2 c.cm. T.+ 0.2 to 0.4 c.cm. antituberculin + 0.3 to 0.5 c.cm. comple- 

 ment are mixed and incubated for one hour. The entire quantity is injected intra- 

 peritoneally into tuberculous guinea-pigs; the animals die in four to five hours. 

 Tuberculous animals receiving o.i to 0.2 c.cm. T. alone or o.i to 0.2 c.cm. T. -f 0.2 to 

 0.4 c.cm. antituberculin, remain alive. 



