PATHOLOGY OF THE IMMUNE RESPONSE 



(i) Variable extent of mutation, including the minor 

 changes which are regarded as always occurring and 

 providing the raw material for modification of anti- 

 body character. 

 (ii) Variable liberation by a variety of pathological 

 processes of cell components not normally present 

 in the body fluids, some of which will carry deter- 

 minants not represented in normally accessible body 

 components. 

 (iii) Selective proliferation or inhibition of mutant clones 

 as determined by the nature of the mutation, the ac- 

 cessible concentration and duration of reactive deter- 

 minants and the bearing of these on the type of response 

 (activation, proliferation or inhibition) enforced on 

 cells of the clones concerned. 

 (iv) A homeostatic mechanism must be postulated to 

 allow, under favourable conditions, the extinction of 

 mutant clones reacting with normal constituents of 

 the internal environment. Presumably this consists of 

 inhibition by excessive stimulation. It would be in 

 accord with other pathological processes if the gross 

 forms of these diseases only result when the homeo- 

 static mechanism is for one reason or another rendered 

 inoperative or grossly inefficient. 

 It is a legitimate objection to the hypothesis of somatic 

 mutation wherever it is used that it makes it too easy to 

 explain anything. Any quality required ad hoc to account for 

 some phenomenon can be said to have resulted from somatic 

 mutation. This should not, however, inhibit us from using 

 the concept where it is needed. The only criteria which must 

 be satisfied are {a) that the quality appears to be distributed 

 at random and {b) that the cells responsible for the new 

 quality can give rise to a clone of cells which can be dis- 

 tinguished from the parental clone when both are grown 

 under the same conditions. The second of these cannot yet 

 be applied in human medicine but the random character of 



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