330 Chapter XI 



any of these substances as the result of injections, whether single or 

 repeated, of toxins. 



The natural immunity of the Invertebrata against bacterial toxins 

 cannot therefore be regarded as an example of humoral immunity. 

 It must be placed in the category of histogenic immunity, although 

 we are not in a position to define accurately the part played by the 

 cellular elements in the defence of the animal against these poisons. 

 We must, therefore, go higher up in the animal scale if we are to 

 solve the principal questions in regard to antitoxic immunity. 



The lowest Vertebrata, the fishes, are not well-suited for this kind 

 of research. The best known bacterial toxins act specially on warm- 

 blooded animals and require the co-operation of high temperatures. 

 Fishes do not live well in captivity except at relatively low tempera- 

 tures and soon die if placed in an incubator kept at 30 C. or 

 higher. It is necessary, therefore, to have recourse to the Amphibia, 

 which are much more easily acclimatised to these temperatures. The 

 Axolotl, coming from Mexico, is naturally capable of withstanding great 

 heat. These animals will live for long at a temperature of 30 37 C. 

 They possess the drawback, however, of being very susceptible to the 

 tetanus toxin, very small doses of it being fatal. The green frog 

 (Rana esculentd) is the most suitable for our purpose. It readily 

 adapts itself to optimum temperatures (30 36 C.) and exhibits at 

 least a certain degree of immunity against various bacterial toxins. 

 We have stated in a preceding chapter that the green frog is un- 

 affected by considerable quantities of diphtheria toxin. It is 

 resistant also to tetanus toxin, but this natural immunity appears to 

 be connected with special conditions. Courmont and Doyon 1 were 

 [347] the first to draw attention to the fact that beyond 20 25 C. green 

 frogs may contract tetanus. Refractory in winter they become sus- 

 ceptible in summer. These observers afterwards found that of frogs 

 inoculated with the same dose of toxin and divided into two sets, one 

 set kept at a temperature of about 10 C. remained quite well whilst 

 the other set subjected to one of 30 39 C. contracted tetanus after 

 five days' incubation. This experiment has been confirmed by several 

 observers, and indicates that the tetanus poison demands, for the 

 manifestation of its toxic action, a favourable and fairly high tempera- 

 ture. This result must however, be accepted with some reserve. 

 Undoubtedly the doses of tetanus toxin which induce fatal tetanus in 



1 Com.pt. rend. Soc. de biol., Paris, 1893, pp. 294, 618; 1898, p. 344. "Le tetanos," 

 Paris, 1899, p. 25. 



