IMMUNOLOGICAL RELATIONSHIPS ^51 



Whatever the mechanism ol this akerecl susceptibility or reac- 

 tivity may be, it must be emphasized that it offers the ()j)portunity 

 of recognizing a mechanism by means of Avhich certain l)acterial 

 acti\'e principles are capable ot rendering the tissues susceptible 

 to injury. For reasons unknown as yet, the injury can ])e inflicted 

 upon the reacti\'e cells only j^roxided the proxocative factors are 

 present in the general circulation. Thus, the reactive tissues be- 

 come a reagent for a detection of apparently widely separated 

 groups of principles producing injury by way of the blood 

 stream.^ These principles are: Neutralizable and antigenic bacte- 

 rial sidjstances: reacting factors resulting from intraxenous injec- 

 tion of agar; and finally, reacting factors resulting from in vivo 

 and ill vitro interaction of bacterial and non-bacterial antigens 

 with antibodies. Of these, agar and reacting factors residting from 

 antigen-[-antibody combinations consistently fail to induce the 

 state of reactivity of this phenomenon. An assumption is then 

 made necessary that the principles capable of eliciting the state 

 of reactivity may be different from the provocative principles 

 even ^vhen found in the same bacterial filtrate. A suggestion of 

 the sort is offered by quantitative titrations of skin-preparatory 

 and provocative factors of bacterial filtrates in which a high titer 

 of preparatory factors does not necessarily indicate a high titer 

 of provocative factors, and vice versa, high titers of provocative 

 factors may be found in bacterial filtrates with a low titer of 

 preparatory factors. Additional investigations are necessary for 

 studies on these relationships. 



Thus, it is obvious that the phenomenon of local tissue reac- 

 tivity displays a mechanism ^vhcreby injury may be produced in 

 animal tissues by bacteria or through the concerted effect of bac- 

 teria and non-related anaphylactic processes. The nature of the 

 j^henomenon can be defined at present only by the properties of 

 the sid3stances responsible for it and by the conditions necessary 

 for its elicitation. There has been a tendency in the literature 

 to classify the phenomenon as allergic. No objections can possibly 



Mt is not intended to ini|jlv h\ this hypothesis (as it appeared to C.ratia and 

 Linz) that the phenomenon is due to the ciunulative effect of two doses of toxin 

 primarily hemorrhagic. It is suggested that the reaction of this phenomenon 

 resnlts from the synergistic action of factors responsible for it when thev are 

 introduced through suitable routes at proper intervals of time. The term synergism 

 is meant to imply the cooperative, concerted effect of the preparatory and provoca- 

 tive factors, each one possibly playing a role independent from the other, the 

 result of the concerted effect being entirely different from the elfect ot eacli of 

 these factors sejiarately. 



