NATURE OF THE ACTIVE PRINCIPLES 3OI 



toxicity (toxoid formation) without any impediment of the anti- 

 toxin coml)ining po^\'er. A con\ersion of toxins into toxoids 

 ^vithout any loss of the antitoxin combining power may be ob- 

 tained through the influence of \'arious reagents of which for- 

 maldehyde is the cons])icuous example. 



If progressive titrations are made of increasing multiples of 

 toxin against correspondingly increasing multiples of antitoxin, 

 there is not the regular progression of neutralization multiple by 

 multiple ^vhich could be expected theoretically; the fact is best 

 explained by }. Bordet's colloidal adsorption theory. 



Any amoinit of toxin, ho^vever, can be neutralized provided 

 a sufficient amount of antitoxin is added to it. The latter differ- 

 entiates this neutralization from irregular inactivation which may 

 occur through adsorption of toxic substances by incidental floc- 

 ctdation of bacterial proteins with immune antisera. Also, non- 

 neutralizable split products might be thus inactivated in the 

 process of ffocculation. If increasing multiples of the non-neu- 

 tralizable substances are used, no complete inactivation takes 

 place, however, no matter how great the amount of serum may be. 



Zone phenomenon is the same as observed in other antigen -(- 

 antibody reactions. The interaction of toxin ^vith antitoxin oc- 

 curs only ^vith proper proporticnis, the excess of any of the reactive 

 bodies beyond certain limits reducing the effect. 



The neutralization of the toxin by antitoxin may l^e obtained 

 also with considerable regularity in animals passively immunized 

 by injection of antitoxin prior to the injection of the toxin. 



The inactivation of toxin by antitoxin in vivo appears to pro- 

 ceed without any demonstrable implication of phagocytic tissue 

 cells (Jugenblut) . Animals which have loeen inoculated with cul- 

 tures or diphtheria toxin subcutaneously can be saved by large 

 doses of antitoxin as little as twenty-four hours after the injec- 

 tion. However, the prevention of death becomes impossible after 

 a \er\ short interval in animals in ^vhich the toxin has been 

 introduced directly into the circulation. 



Exotoxins are highly antigenic, the antigenicity being deter- 

 mined by the presence of the haptophore group (the antibody- 

 combining fraction) . The process of immunization brings about 

 active acquired immunity and stimulates production of anti- 

 toxins in the tissues and blood stream of the animal. 



The above general characteristics of the true toxin-|-antitoxin 

 reaction were outlined for the sake of comparison with the neu- 

 tralization reaction observed with the active principles of the 



