THE COURSE OF INFECTIOUS DISEASE 



on the character of the infecting streptococcus. The pre- 

 dominance of Type 12 Streptococci in causing acute nephritis 

 presumably demands that in addition to providing the con- 

 ditions for weakening control the streptococcus produces 

 locally in one way or another antigenic determinants which 

 are common to the vulnerable glomerular component and 

 which are different from those concerned in the pathogenesis 

 of rheumatic fever. 



From our present point of view the main problem pre- 

 senting itself is to find why only a relatively small though still 

 substantial proportion of people who suffer streptococcal 

 pharyngitis develop rheumatic fever or nephritis. Standard 

 epidemiological approaches indicate some genetic pre- 

 disposition with a higher incidence in cold than in warm 

 countries and amongst groups of lower economic status. 

 None of these provides any specific clue at the immunological 

 level, but the genetic aspect may be worth a little speculation. 

 On a clonal selection theory of immunity one would expect 

 that genetic factors might determine to some extent at least 

 the composition of the range of primary patterns carried by 

 mesenchymal clones at the time of birth. This could be 

 reflected either in occasional failure to develop antibody 

 against some significant group of antigenic determinants or 

 more frequent appearance of one or other type of forbidden 

 mutation. It is, of course, equally possible that the homeo- 

 static mechanism varies in effectiveness for genetic reasons. 

 Obviously no answer will be possible until the nature of the 

 antigenic determinants with which the forbidden patterns 

 react has been established. Does in fact the clonal selection 

 theory offer any new leads to the experimental or clinical 

 investigation of rheumatic fever? 



If one disregards all questions of ethics, humanity and 

 practicability, what investigations on rheumatic fever patients 

 could establish or refute the present hypothesis? The assump- 

 tion basically is that just before the onset of the acute phase 

 lymphoid tissue (tonsils and cervical lymph nodes) contain 



158 



