TOLERANCE TO ANTIGENS 



produced. Studies with bacterial and viral antigens have 

 usually failed to demonstrate tolerance, although Buxton's 

 ( 1 954) positive findings with a Salmonella pullorum vaccine in 

 chick embryos should be mentioned. In fact, this may be 

 due to the large number of antigenic determinants involved 

 in such antigens. 



More work has been done with soluble antigens, notably 

 bovine serum albumin (BSA) in the rabbit. If large doses 

 of BSA are given from birth a prolonged suppression of 

 ability to respond to this antigen is obtained (Hanan and 

 Oyama, 1954). If a series of large inocula of the same anti- 

 gen are given to mature rabbits a similar inhibition of anti- 

 body-producing capacity can be induced, but after a rest 

 period the capacity is rapidly regained. The problem of the 

 part played by persisting antigen in these reactions has been 

 clarified by recent experiments due to Smith (1958). They 

 showed that tolerance produced by a single dose of 100 mgm. 

 of bovine serum albumin given to rabbits on the day of 

 birth could be maintained indefinitely if the rabbits were 

 challenged at approximately three-month intervals. Each 

 inoculation of antigen failed to provoke antibody, and the 

 rate of removal of the foreign protein from the circulation 

 was comparable to what would be found for homologous 

 serum albumin. If, however, challenge is deferred until 200 

 days after the tolerance-producing injection, the animal 

 develops antibody. The time over which tolerance persists is 

 a function of the dose initially given and all the results are 

 consistent with the view that at birth in the rabbit, potential 

 antibody-producing cells of the appropriate clones are in- 

 hibited from activation and from normal maturation as long 

 as antigenic determinants remain attached. Once all antigen 

 has been eliminated by normal metabolic processes the 

 inhibition is removed and the cells develop the normal re- 

 activity of a mature cell. 



This interpretation is in accord with all the experimental 

 facts available, but it does not necessarily eliminate the possi- 



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