PATHOLOGY OF THE IMMUNE RESPONSE 



children with this disease who have been maintained for 

 some years by appropriate therapy. 



It is a truism that the best test of a physiological concept is 

 its application to pathological conditions. An attempt must 

 therefore be made to discuss these conditions in terms of 

 a clonal selection hypothesis. I believe that this theory is 

 capable of effective application in the pathological field and 

 that the form of the clonal selection approach makes the task 

 much simpler than would be the case with any of the alter- 

 natives. This of course does not prove that the clonal selection 

 hypothesis is true, any more than the convenience of the 

 Pauling-Haurowitz theory for immunological chemists proves 

 its universal validity. 



I . Some general considerations 



If the clonal selection hypothesis is correct, antibody- 

 producing clones must, from their nature, be subject to a high 

 level of random somatic mutation in regard to the pattern 

 of gamma globulin produced. Some of the mutant patterns 

 are bound to be what by analogy with spectroscopy might 

 be called ' forbidden ' patterns, that is, capable of reaction 

 with self-components. We feel certain therefore that the 

 normal healthy individual must possess some means by which 

 minor somatic mutations giving rise to forbidden pattern, 

 either in cell surface or free globulin, are rendered ineffective. 

 There are a number of ways in which such a homeostatic 

 mechanism could be envisaged but no experimental evidence 

 whatever on the point. There are, however, some clinical 

 observations which in addition to strengthening our belief 

 that there is such a protective mechanism, offer some indirect 

 suggestions about its nature. These will be referred to in relation 

 to the disease conditions with which they are associated. 



If we omit the allergic diseases associated with exposure to 

 extrinsic agents, all the conditions to be considered are inter- 

 pretable as being based on immunological interaction of 

 cell-borne or soluble antibody with components of the body 



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