THE COURSE OF INFECTIOUS DISEASE 



in which the local lesion spreads progressively, usually with 

 the appearance of distant foci as well. ( i ) Some of these are 

 found to possess no gamma globulin and, unlike the agamma- 

 globulinaemic children who respond normally, these fail to 

 develop any skin sensitivity. The course appears to be un- 

 influenced by administration of immune globulin and in 

 Kempe's experience always terminates fatally. In these 

 children it seems that there is some additional functional 

 weakness not yet clearly formulated that reduces the effec- 

 tiveness of the complex cellular functions of which skin 

 sensitivity is one index. 



(2) There are some cases which have normal levels of 

 globulin but nevertheless show progressive infection. One 

 subgroup (2 a) show a good clinical response to the admini- 

 stration of moderately large doses of immune gamma 

 globulin, although they show little evidence of capacity for 

 skin sensitization. Here it seems possible that we are dealing 

 with individuals whose complement of available clones is in- 

 adequate to allow an effective early response, and the excess 

 of antigen eventually paralyses immunological activity. The 

 situation can be righted by provision of antibody produced 

 by another individual. 



(2 b) Other cases do not respond even to very large doses 

 of immune gamma globulin. In one patient shown me by 

 Dr Kempe, recovery had followed heroic treatment involving 

 surgical excision of the whole infected region and administra- 

 tion of leucocyte suspensions and lymph node cells from 

 recently vaccinated donors. This is the only successful result 

 so far obtained in this group of cases. 



It may be of some interest to discuss the lines of investiga- 

 tion which could be suggested on the basis of the clonal 

 selection theory of immunity for these cases of progressive 

 vaccinia in infants. The possible functional disabilities are: 



(i) Congenital agammaglobulinaemia. 

 (ii) Physiological delay in the normal development of gamma 

 globulin production around 2 to 3 months of age. 



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