IMMUNOLOGICAL TOLERANCE 



(ii) yet bacteria and bacterial products are highly potent 

 antigens producing detectable antibody in the rabbit 

 usually within four days. 

 Several workers have suggested that tolerance becomes pro- 

 gressively easier to induce the closer the foreign antigen is 

 to normal body components. Homologous living cells and 

 mammalian serum proteins have been the reagents chiefly 

 used in tolerance experiments. 



On the other hand, experimenters concerned with demon- 

 strating early production of antibody have almost always 

 used killed Gram-negative bacteria or soluble agglutinogens 

 (endotoxins) derived from them. Harris et al.'s (1956) work 

 on the production of antibody in an X-rayed recipient 

 rabbit by the transfer of normal lymph-node cells treated 

 in vitro by a soluble Shigella preparation is a typical example. 

 The serum of the recipient contains moderate amounts of 

 antibody presumably produced by donor cells within four 

 days of their injection. Under these conditions there seems 

 to be inadequate time available for the selective proliferation 

 and mutation of a small number of cells from clones with 

 appropriate predetermined patterns. 



The difficulty in regard to tolerance is relatively less 

 important and may depend only on the multiplicity of deter- 

 minants in all bacterial antigens plus their high activity in 

 mature or maturing animals. 



The relevant work on the antigenicity of bacterial products 

 has been carried out almost wholly in rabbits and any dis- 

 cussion of the speed with which bacterial agglutinins or anti- 

 toxins can be produced after a primary stimulus can legiti- 

 mately be confined to rabbit reactions. An important clue 

 seems likely to be found in the character of the cellular 

 reactions induced in rabbits by bacterial endotoxins. These 

 are closely related to, if not identical with, the polysaccharide- 

 containing somatic antigens of the Gram-negative intestinal 

 bacteria. 



Under appropriate conditions of injection or manipula- 



102 



