ZINSSER AND MUELLER 729 



of various sizes are obtained. This would seem to indicate that the body can be power- 

 fully sensitized in the course of the disintegration of bacteria, either by autolysis or 

 by the enzymes active in the inflammatory tissues with which they are in contact, 

 with consequent liberation of an antigen far more active immunologically than that 

 which can be obtained by methods of chemical extraction. It seems reasonable to 

 suppose that resistant organisms like the staphylococci, the streptococci, and the 

 various types of tubercle bacilli which we have attempted to subject to autolysis in 

 vitro, so far with only partial success, may undergo lytic changes within the infected 

 body. Evidence obtained from the study of intraperitoneal injections of tubercle bacil- 

 li into tuberculous animals points in this direction, and the histological study of tuber- 

 culous lesions in many parts of the body has a similar significance. Indirect evidence 

 of this is also obtained from the Mcjunkin' experiment, in which an antigen which has 

 sensitizing properties different from and more effective than any that can be obtained 

 from the bacilli in culture or by chemical extraction seems to be liberated in the peri- 

 toneum of tuberculous animals injected with tubercle bacilli. Indeed, we are inclined 

 to believe that the secret of the mechanism of the tuberculin reaction lies in this — a 

 matter which, however, cannot be proved until a method of satisfactorily autolyzing 

 tubercle bacilli in vitro can be discovered. 



At any rate, the liberation in inflammatory foci of bacterial, autolytic substances 

 gains considerable theoretical importance from the observation that autolysates of 

 bacteria have a sensitizing potency which is wholly or partially destroyed in the ma- 

 nipulations necessary for the preparation of nucleoproteins. 



Ill 



When an animal is infected with living bacteria the processes set in motion are 

 complex and by no means completely understood; for there are responses on the part 

 of the fixed-tissue cells — such, for instance, as those described by Gay and his col- 

 laborators- in the pleural cavities of streptococcus-immune animals — which do not 

 find adequate explanation in any of the current immunological conceptions. On the 

 other hand, in so far as the bacterial-cell constituents and products are antigenic in the 

 sense referred to above, considerable understanding has been gained by the correlation 

 of biological function with chemical study. 



We are of course omitting in our discussions any reference to the problem of bac- 

 terial exotoxins, since this phase of bacterial antigen-antibody reactions involves so 

 many special factors that it must be separately dealt with.^ We are confining our- 

 selves, therefore, entirely to the biological activities of the bacterial-body substance. 



The bacterial cell consists largely of the so-called "nucleoprotein" material, prob- 

 ably in combination with the carbohydrate structures which Avery and Heidelberger 

 speak of as the "specific soluble substances." When the animal is infected with living 

 bacteria or when dead bacteria are administered without any extensive solution of the 

 bacterial cell, this "complete" antigen arouses the formation of the specific antibodies 



' Mcjunkin, F. A.: /. Exper. Med., 33, 751. 1921. 



^ Gay, F. P., and Rhodes, B.: J. Infect. Dis., 21, loi. 1923; and Gay, F. P.: /. Immunol., 8, 

 I. 1923. 



3 Cf. chaps. liv-lvi, Ixxxdii. 



