THERAPEUTIC IMMUNIZATION IN MAN 519 



kins, McBurney and the writer 177 inoculated into the testes after 

 apparent recovery from a previous lesion. Ordinarily in rabbits, 

 as we have stated before, no generalized resistance is developed dur- 

 ing the disease, and the opposite testis can be successfully inoculated 

 before, during, and after the existence of a lesion on the other side. 

 In these rabbits it was found that testes that had apparently recov- 

 ered from a previous lesion, were not subsequently as easily infected 

 as were normal testes. It has seemed to us from this as well as from 

 a careful study of the observations of other investigators, that re- 

 sistance in syphilis was probably a matter of localized reaction. 

 Tissues which have sustained active invasion with the living virus 

 react and gain thereby a certain degree of resistance which expresses 

 itself in a failure to react to subsequent inoculation. This would 

 explain why in syphilis of the human being reinoculation is unsuc- 

 cessful and reinfection of the skin and mucosse does not occur spon- 

 taneously at a period later than the early secondary stages when the 

 virus has become systemically distributed. It would furthermore 

 explain why in this disease organ after organ may be pathologically 

 involved when skin infection is no longer possible. This point of 

 view is entirely in harmony, though perhaps from a slightly different 

 aspect, with the skin immunity suggested by Kraus and Volk, where 

 the resistance is attributed to the tissue as a whole rather than to a 

 local cell group. The cells which have once reacted to the living 

 virus no longer respond, i. e., can no longer be injured for an in- 

 definite period after recovery. However, the factors which lend 

 them this resistance, whatever they may be, are not distributed to 

 the blood stream in a way analogous to that in which antibodies are 

 mobilized in bacterial diseases, and the effect of the resistance of the 

 local area is not distributed to remote parts of the body. It is of 

 course likely that a certain amount of phagocytosis of treponemata 

 by the now resistant fixed cells may account for the absence of local 

 injury. This, however, we have not yet been able to prove suffi- 

 ciently, and further studies on this point are necessary. As far as 

 any positive evidence can be adduced at the present time, the newly 

 entering treponemata may not be entirely destroyed. It may well 

 be that the tissues do not react and are in the state which Neisser 

 calls "Anergie." The treponemata that enter during this period 

 may nevertheless remain uninjured and be as capable of subsequently 

 causing lesions in other locations as are those already present in the 

 patient. This phase is being studied by comparative histological 

 observation on the fate of treponemata which have been injected into 

 normal tissues and into tissues rendered resistant by previous in- 

 fection. 



In animals like monkeys and man where generalization is rapid 



177 Zinsser, H., Hopkins, J. G., and Gilbert, R. Jour. Exper. Med.. 1915, 

 xxi, 213. 



