SOME GENERAL CONSIDERATIONS 



tissues. We may, for convenience, use the term auto-antibody 

 to cover reactive globulin, either soluble or incorporated in 

 a mesenchymal cell surface, which has a specific power to 

 interact with an antigenic determinant carried by some 

 body component. As in all such situations, there are two 

 possible types of explanation not necessarily mutually ex- 

 clusive. Either there is an abnormality on the side of the 

 antigenic determinants or there is malfunctioning of the anti- 

 body-producing cells. If we look at these two alternatives 

 more closely we can see that both may function in different 

 ways and in fact there have been five basic interpretations 

 that have been put forward to cover one or other type of 

 auto-immune disease. 



(i) There are some body components which during the 

 period of development are either not present or are inacces- 

 sible to mesenchymal cells and in later life are not in potential 

 contact with any of the mesenchymal cells. If as a result of 

 pathological changes such a component becomes accessible 

 it can act as a stimulus to antibody production. This appears 

 to be the nature of Hashimoto's disease. 



(ii) Gear and others have suggested that a body com- 

 ponent may develop antigenic determinants as a result of 

 chemical modifications following micro-organismal infection 

 or chemical action. If an antibody is developed against this 

 modified component, it is assumed that it will also be active 

 against the corresponding normal component. 



(iii) The other possibilities all involve the antibody-pro- 

 ducing cells primarily and can be grouped under three 

 headings. 



A. Mesenchymal cells may be modified by persisting in- 

 fection with a low-grade virus, the change disappearing 

 with recovery. This is introduced to cover the findings 

 in infectious mononucleosis and atypical pneumonia. 

 Other examples may well be found. 



B. On the clonal selection hypothesis, random somatic 

 mutation in mesenchymal cells must continually allow 



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