884 LOCAL AND TISSUE IMMUNITY 



This outline of the trend of investigation bearing on antibody formation, sche- 

 matic as it is, will serve as a necessary preliminary to the statement that in my opinion 

 the outstanding problems of immunity in general are: first, a further understanding 

 of the method of antibody formation; and, second, an appreciation of the importance 

 of fixed-tissue cells in direct defense against micro-organisms through phagocytosis. 

 I believe further that both these problems are being attacked in a new and more 

 effective manner through the recent studies in so-called "local" immunity. 



Local immunity rests on the demonstration that a given area of the body may be 

 protected by the topical application of a given antigen without involving a more 

 generalized inununity. The earlier experiments of Wassermann and Citron^ and of 

 Roemer^ which awakened the conception of local immunity rested on the unnecessary 

 assumption that such restricted protected areas are dependent on the local production 

 of antibodies. Even admitting that such local protection might be due to localized 

 antibodies, the evidence hitherto adduced would seem to point to the local mobiliza- 

 tion of antibodies from the general circulation rather than their strictly local forma- 

 tion. We have elsewhere defined local immunity as "due to a locally superior mecha- 

 nism for the disposal of a particular micro-organism.^ Local immunity may be proved 

 by the local presence of antibodies before their appearance elsewhere in the body, or 

 by their local presence in greater concentration — or again local immunity may be 

 demonstrated, and this we believe most conclusively, by the demonstration of a 

 superior method of direct disposal of bacteria in the particular area in question." I 

 do not believe that the local formation of antibodies has as yet been proved and am 

 now inclined to believe that local immunity is due primarily to an intensified response 

 of cells in the treated area — a true Umstimmung, to revive in a more understandable 

 sense the term proposed by Wassermann and Citron. 



THE RECENT HYPOTHESIS OF BESREDKA 



Widespread interest in the phenomena of local immunity has been awakened 

 through the recent work of Besredka.'' This author begins his explanation of the 

 mechanism of active immunity with an assumption that we have already expressed, 

 namely, that it cannot be accounted for entirely on the basis of antibodies. This 

 assumption is based on the lack of parallelism between the antibody content of 

 serum and protection ; on the fact that in some instances, e.g. , anthrax, chicken cholera, 

 swine erysipelas, the known antibodies may be removed by specific absorption and 

 the protective power of the serum remain. "The known antibodies should be without 

 hesitation stripped of their importance; their function in immunity is in reality 

 entirely secondary, or negative in certain cases."4 Active immunity, then, is in es- 

 sence a cellular phenomenon and depends on rendering insensitive the cells that are 

 sensitive to a particular virus or micro-organism. Besredka believes that the free 

 phagocytes in their process of phagocytosis liberate from bacteria an "antivirus," the 

 precise nature of which is not clear, but which is essentially a non-antigenic toxic 



' Wassermann, A., and Citron, J.: Ztschr. Hyg. u. Infektionskrankh., 50, 331. 1905. 



^Roemer, P.: Arch. f. Ophth., 54, gg. 1902. 



3 Gay, F. P.: Physiol. Rev., 4, 191. 1924. 



4 Besredka, A.: Local Immunisation, Specific Dressings (Amer. ed.). Baltimore: Williams & 

 Wilkins, 1927. (Contains reference to numerous articles of its author.) 



