PATHOLOGY OF THE IMMUNE RESPONSE 



these conditions. As has already been mentioned, a third 

 assumption is specially necessary to give the basic hypothesis 

 any validity — that there must exist a homeostatic mechanism 

 which prevents most of the potentially harmful mutant 

 clones that must be continually arising from becoming 

 dominant enough to produce symptoms. 



Possibly one of the commonest of forbidden antibody 

 patterns is one directed against autologous gamma globulin 

 that has been denatured by mild physical agents such as heat, 

 surface spreading or attachment to a carrier of specific anti- 

 genic determinants. Najjar et al. (1955, 1957) have studied 

 extensively the aggregation reactions which indicate that 

 an antigen-antibody complex has antigenic determinants 

 not present in either component. I have been particularly 

 interested in the potentialities of antibody against auto- 

 logous denatured gamma globulin as a possible initiator of 

 a vicious circle in persons who, for one reason or another, 

 have a weak or malfunctioning homeostatic control. If anti- 

 body is deposited for any reason on a reactive surface within 

 the body the new denatured configuration presents anti- 

 genic determinants which we can call D. This will on 

 occasion stimulate cells of clone d capable of producing anti- 

 body which will react with D. This in its turn will mean the 

 deposition of more antibody globulin on the area and more 

 production of D. One wonders whether we have here a 

 mechanism which may have much to do with the accumula- 

 tion of gamma globulin in the glomeruli of disseminated 

 lupus cases and even with the deposition of amyloid which 

 has most of the features of denatured gamma globulin in 

 cases of chronic suppuration, etc. 



Special interest attaches to those conditions in which one 

 tissue is particularly involved, for example, polymyositis or 

 lupoid hepatitis. The suggestion is strong here that the patho- 

 genic mesenchymal clones react with determinants which 

 are characteristic of, or much more frequently present on, 

 the surface of the cells in question. In a considerable pro- 



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