FREDERICK P. GAY 889 



first with complete failure, owing to the resistance of this animal to the t^^^hoid 

 bacillus when administered by the mouth. The previous ingestion of ox bile rendered 

 rabbits so susceptible to both typhoid and paratyphoid bacilli that they died with 

 suggestive symptoms and lesions. These results have since been repeated in rabbits 

 by several investigators (Zingher and Soletsky/ Neri,^ Glotoff),^ and in guinea pigs 

 by Sedan and Hermann.'' That this lowered resistance, however, is dependent on 

 epithelial desquamation of the intestinal mucosa which renders the animal at all 

 analogous to the naturally susceptible human being is doubtful. Others, notably 

 Webster,^ have shown that bile in itself is very toxic, and how far this may account 

 for the lethal effect is an open question. Moreover, many who have reported on the 

 immunizing effect of bile typhoid vaccines in rabbits, Zingher and Soletsky, Neri, 

 Teale,^ and Gye,^ have failed to confirm the positive results claimed by Besredka. 



The prominence we have given to the work of Besredka in the field of local immu- 

 nization is justified by the stimulus it has given to the more profound study of the 

 possibilities of local immunization rather than from a belief in the correctness of his 

 explanation of the mechanism of local immunity. Besredka's hypothesis, however 

 unsatisfactory it may be in final explanation, has the merit of rather extensive formu- 

 lation and completeness and therefore furnishes a basis of discussion and experimen- 

 tation which cannot but carry us forward in a very important and neglected field ot 

 investigation. 



I believe, in the first place, that there is now overwhelming evidence of the 

 existence of a truly localized form of immunity confined under certain conditions, and 

 in response to certain infectious agents, to localized areas or cell groups of the body, 

 and representing not only the natural resistance enjoyed by many cells, but also the 

 exaggerated and important conditions of true active, acquired immunity. I would 

 list tentatively as representative conditions of active local immunity the marked 

 protection against smallpox and typhoid fever which follows recovery or vaccination, 

 and also in a more restricted sense localized streptococcus and staphylococcus infec- 

 tions. I believe that these conditions are due primarily to "re tuning" {Umstimmimg) 

 of particular cells or cell groups which may simply acquire new potentialities of re- 

 action that are extremely durable (typhoid, smallpox) or may be due to an increase 

 in numbers and strategic location of certain cells in the more transitory conditions, 

 as in our studies of streptococcus infections. This local or tissue immunity would not 

 be in the nature of a desensitization, but rather in the nature of a cell immunization. 

 We may revive the original conception of Knorr, that the particular cells concerned 

 in active immunity and antibody formation are the more resistant rather than the 



'Zingher, A., and Soletsky, D.: Proc. New York Path. Soc, 20, 133. 1920. 

 ^ Neri, F.: Boll. d. Instil, sieroterap. milanese, 2, 275. 1922. 



3 Glotoff, E.: Compt. rend. Soc. de biol., 89, 368. 1923. 



4 Sedan, J., and Hermann, R.: ibid., 90, 567. 1924. 



5 Webster, L. T.: /. Exper. Med., 37, ^^. 1923. 



*Teale, T. P.: "Discussion" to paper by Besredka, Tr. Roy. Soc. Trop. Med. &" Hyg., 17, 346. 

 1924. 



7 Gye, W. E.: ibid., p. 346. 1924. 



