302 LOCAL TLSSUE REACTIVITY 



jilicnonienoii. It is l)ey()ncl the scope of this inonot;raj)h to t^ixe 

 a detailed description ot the toxiii+antitoxin reaction, thor- 

 oughly presented by J. Bordet, Wells, Zinsser, Pick and Silberstein, 

 Walbom, Gay and his associates (1935), and others. It is easily 

 observed, however, that the active principles of the phenomenon 

 are closely related to the true toxins just described inasmuch as 

 the interaction of the neutralizing antibodies with these active 

 principles follows very closely the principles governing the diph- 

 theria toxin -)-antitoxin reaction. 



There exists unquestionable proof that the skin-pre])aratory 

 factors can be specifically neutralized by addition of immune sera. 

 It is likely, hoAvever, that there occurs a partial dissociation of 

 a certain amoinit of preparatory factors from their combination 

 with the neiUralizing antibodies in the tissue injected. WHien this 

 dissociation takes place in rabbits of high susceptibility, the 

 amount of preparatory factors may, then, prove sufficient to elicit 

 the necessary state of reactivity to the phenomenon. After con- 

 trolling the variability in the response by the use of large groups 

 of animals, the neutralizability of the skin-preparatory factors is 

 clearly brought out. 



The reacting factors can f)e neutralized specifically by imminie 

 sera. The neutralizing" potency of the sera may ])e quantitatively 

 measured. In these experiments a constant amoiuit of serum is 

 titrated against increasing quantities of reacting units. The 

 method allowing the use in certain instances {B. typJwsus react- 

 ing factors) of several hundred minimal phenomenon-producing 

 doses obviates the confusion Avhich may arise from individual 

 fluctuations in the susceptibility of rabl^its to the phenomenon, 

 and proves, unquestionably, the neutralizability of the reacting 

 factors. Althougli small amounts of natinal antibodies may be 

 foimd in normal animals, the high titer of neiuralizing sera ob- 

 tained after prolonged immtniization demonstrates clearly the 

 antigenicity of the active principles and the specificity of neu- 

 tralization. The active principles of the phenomenon treated ^vith 

 formalin can be modified similarly to diphtheria toxin. The anti- 

 genicity and the antibody-comfjining capacity are essentially un- 

 impaired. Furthermore, no comparable loss of antibody-combin- 

 ing capacity is associated ^vith the decrease in toxicity occinring 

 on standing. The incidental precipitation occinring in mixtmes 

 of potent filtrates ^vith immiuie seriun by itself does not bring 

 about inactivation of acti\'e principles. If a seriun possessing no 



