IMMUNOLOGICAL TOLERANCE 



bility that with very early or very prolonged exposure to 

 the foreign antigen the reactive clones may be completely 

 destroyed. In general, however, tolerance production is 

 a relatively inefficient process. 



In considering these phenomena, the logical point to start 

 the discussion is the question why young animals are such 

 poor producers of antibody. To a large extent this is as- 

 sociated with their inability to produce gamma globulin, and 

 this in its turn may represent an inability of modified 

 lymphocytes to take on the plasma cell (antibody-producing) 

 phase. Dixon and Weigle's (1957) finding that Harris' (1954) 

 experiment fails in new-born rabbit recipients and that this 

 is associated with failure of the transferred lymphocytes to 

 be converted, in part at least, to plasma cells, is highly 

 relevant here. This is just one indication of the part the 

 physiological environment must play in determining what 

 type of response a cell will make to an immunological 

 stimulus. 



The problem of tolerance and partial tolerance can only be 

 analysed in terms of the conditions modifying the response of the 

 cells concerned to the corresponding antigenic determinants. 



It would be quite unrealistic to believe that any mechanism 

 of antibody production can be expressed as a series of simple 

 deterministic reactions. Experiment and observation suggest 

 {a) that there are several types of response of a cell to specific 

 stimulation by an antigenic determinant and (b) that the 

 extent and type of response will be modified by a number of 

 intrinsic and environmental factors. 



A. The types of response which are called for to allow 

 a clonal selection hypothesis to account for the facts may be 

 divided into two groups according to whether the effect 

 concerns only the cell in question, or whether the effect is 

 essentially relevant to the behaviour of the cell's descendants. 



(i) Responses limited to the cell itself 



(a) Lethal damage eliminating the possibility of 

 descendants. 



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