NATURE OF THE ACTIVE PRINCIPLES 327 



duced by the intravenous injections of tlie immune guinea pig- 

 serum six, twenty-four, forty-eiglit, and seventy-two hours foi- 

 lo^ving preparation ^vith the same immune guinea pig serum. 



As mentioned previously, fresh normal guinea pig serum injected 

 intravenously produced reactions in prepared skin sites in one- 

 third of rabbits. Similarly, the fresh anti-spleen guinea pig serum 

 produced reactions in the prepared sites. The normal and anti- 

 spleen guinea pig sera heated at 56° c. for twenty minutes 

 failed to elicit reactions. The ability of the anti-spleen serum to 

 produce purpura following subcutaneous injections remained 

 unimpaired. It seems clear, then, that the reacting potencies of 

 the normal guinea pig serum and of the anti-spleen guinea pig 

 serum must be attributed to the interaction of a heat-labile natu- 

 ral antibody Avith some of the rabbit tissue or cell antigen, but 

 not to the pinpura-producing antil)odies of the anti-spleen serum. 



Gratia and Linz claimed that the Roskam anti-platelet serum 

 ^vas able to enhance reactions produced by combined intradermal 

 and intravenous injections of bacterial filtrates. It is possible that 

 the purpura-producing effects of cytotoxic sera may be superim- 

 posed upon the hemorrhagic lesions produced by the active prin- 

 ciples of the phenomenon, similarly to the enhancement of the 

 lesions of the phenomenon by pneumococcus substances of pri- 

 mary purpurogenic properties (see Chapter i) . It seems advis- 

 able to differentiate clearly, hoAvever, the complicating and super- 

 added effects of toxic sera and bacterial substances from the lesions 

 produced by the active principles proper of the phenomenon. 



RECAPITULATION 



Physico-chemical and immunological properties of the bacterial 

 active principles of the phenomenon indicate a close resemblance 

 to true exotoxins. A number of properties considered together 

 differentiate sharply the active principles from the endotoxins, 

 namely: the extracellular nature; the regidarity of the effect upon 

 animals; consistent neutralization by immune sera in multiple 

 proportions; and high antigenicity. Lethal factors of certain bac- 

 teria possessing properties similar to those described by Zinsser 

 under the term x-substances may run parallel to the concentra- 

 tion of the active principles of the phenomenon in "agar ^vash- 

 ings" filtrates. These lethal factors differ from endotoxins since 

 their production does not depend on autolysis and since they are 

 specifically neutralized by immune sera. Addition of a small 



