3l8 LOCAL TISSUE REACTIVITY 



The above lethal factors may be endotoxic and exotoxic in nature. 

 The authors who found a parallelism between the lethal effect 

 of the endotoxins and the active principles did not study the im- 

 munological behavior of their stibstances and, therefore, no con- 

 clusions may be made concerning their relationship to the active 

 principles of the phenomenon. On the contrary, the exotoxic 

 filterable lethal factors, which may be related to the active princi- 

 ples of the phenomenon, are clearly shown to be neutralizable, 

 their neutralization occurring rouglily in "multiple proportions" 

 in vitro and i)i vivo. 



In attempting to define the nature of the active principles of the 

 phenomenon there may indeed arise a considerable handicap for 

 futtne investigations if these principles Avere labeled as endo- 

 toxins or exotoxins since it is generally conceded, on the basis 

 of recent investigations, that the division into these t^vo grotips 

 is only an arbitrary one. The purpose of the discussion presented 

 was to define the nature of the actixe principles by their physico- 

 chemical and immtniological behavior thus far investigated and 

 place emphasis on the outstanding feature, namely, on their anti- 

 genicity and specific neiUralizability by immtuie sera. This alone, 

 then, in the present conception of toxins, is sufficient to ally 

 the active principles to true bacterial exotoxins and to differ- 

 entiate them sharply from non-neutralizable endotoxins. In spite 

 of the fact that the "solubility" and extracellidar nature of the 

 active principles is beyond any dotd^t, and is considerably greater 

 than in the classical endotoxins, no special consideration is given 

 to this fact. Indeed, the localization of the toxins in the cell, on 

 its surface or otitside of it may be only an insignificant feature 

 incidental to processes entirely unrelated to the nature of the 

 toxins. 



As emphasized by Wells (1929) , and Pick and Silberstein 

 (1929) , the possibility is not excluded that true toxins represent 

 haptene-like substances linked to a protein, the antigenicity being 

 determined by the protein. It is conceivable, therefore, that the 

 active principles of the phenomenon being in the nattne of this 

 type of haptene may be found attached either to the intracellular 

 or extracellular bacterial proteins or even to the constituents of 

 the meditun itself, as suggested by Walbum (1929) in the case 

 of diphtheria toxin. The nattne of the haptene being the same 

 irrespective of the protein with which it is coupled the active 

 principles may then be endoAved xvith the same injury-producing 



