PATHOLOGY OF THE IMMUNE RESPONSE 



the nature of the antigenic determinant involved before 

 making any more detailed suggestions. 



Such a formulation of homeostatic mechanism is con- 

 sistent both with the primary postulates of the clonal selection 

 theory and with the available facts. It is by no means the 

 only possible mechanism but the hypothesis presented seems 

 readily susceptible to an experimental approach, notably by 

 an elaboration of Askonas and White's findings in regard to 

 the greater activity of distant lymph nodes than of those 

 nearest an antigen deposit. 



8. Summary 



From the point of view taken in this chapter, Hashimoto's 

 disease and perhaps sympathetic ophthalmia are the only 

 true auto-immune diseases in the sense that they are pro- 

 duced as a result of the interaction of ' inaccessible ' body 

 components with a normal antibody-producing mechanism. 

 The other conditions discussed, including haemolytic 

 anaemias and the collagen diseases proper, are all regarded 

 as being associated with abnormal functioning of clones of 

 globulin-producing cells. These have taken on a new heritable 

 character and are therefore said to have undergone somatic 

 mutation. It must remain open whether such mutation is 

 wholly random in its initiation or sometimes enforced — for 

 example, by a chronic virus infection or some product of 

 streptococcal growth. Until positive evidence to the contrary 

 is available, we prefer to believe that the directive effect of 

 infective or hormonal agents is due to selective factors acting 

 on mutations occurring at random. 



One might conclude that the evidence from (what might 

 be called) the pathological aspects of antibody production 

 is not inconsistent with, and in fact fits naturally into the 

 framework of the clonal selection hypothesis. The direct 

 template hypothesis appears to have no relevance to the 

 phenomena. The indirect template theory, in which body 

 components do not provoke antibody because of the presence 



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