IMMUNOLOGICAL TOLERANCE 



immunological functioning. Sufficient survivors would exist 

 to damage the foreign cells and prevent their effective 

 establishment. 



2. Tolerance to antigens not associated with implantation 

 of genetically foreign cells 



It has not proved easy to demonstrate immunological 

 tolerance to antigens other than those associated with living 

 cells distinct from, but related to, those of the host. 



We may first outline the facts which have been established 

 by the use of red cells as antigen. In view of the fact that 

 Woodruff and Simpson (1955) have shown that tolerance 

 to skin graft can be established in rats up to 14 days after 

 birth, this species has been extensively used. Bauer, Peck- 

 ham and Osier (1956) showed no development of tolerance 

 if a single dose of sheep cells were given either prenatally or 

 immediately after birth and were inclined to doubt the 

 existence of any tolerance phenomena with such antigens. 

 Nossal (1958) in my laboratory has studied this system 

 extensively, and finds that with CgH mouse cells as antigen, 

 lasting tolerance can be produced by a series of injections 

 beginning immediately after birth and continuing twice 

 weekly for eight weeks. A three weeks course shows distinct 

 evidence of partial tolerance but much less than with the 

 longer course. There is no evidence to suggest that continuing 

 tolerance depends on the presence of antigen in the body 

 ' mopping up ' antibody as it is produced. Passive administra- 

 tion of antiserum to tolerant and normal rats shows a dis- 

 appearance of antibody at the same rate in each group and 

 results in no subsequent modification of response. Older rats 

 given massive doses of antigen showed no evidence what- 

 ever of any inhibition of the immune response. The fact that 

 in one series rats were still fully tolerant eight months after 

 birth, and more than three months after the last injection of 

 antigen, in itself speaks strongly against any suggestion that 

 sufficient residual antigen is present to absorb any antibody 



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