CITRON'S THEORY FOR THE TUBERCULIN REACTION 161 



appears almost concentrated at this point. Occasionally the sessile recep- 

 tors are* relatively scarce and the first injection excites no reaction. By 

 the time of the second or third inoculation these sessile amboceptors have 

 so increased that a positive reaction is apparent when the same or even a 

 smaller dose is injected. This phenomenon of increased sessile receptors 

 explains the reappearance of subsided subcutaneous, cutaneous, or oph- 

 thalmo reactions after renewed injections of tuberculin. 



To recapitulate the biological phenomena associated with a positive 

 tuberculin reaction, it may be said that the tubercle bacilli, or portions of 

 their body substances existing in the infected focus, stimulate the adjacent 

 cells to produce a great number of sessile receptors. When the tuberculin 

 is injected for the first time, these sessile receptors at once take up the 

 tuberculin and as a result, the production of an ti tuberculin in the focus is 

 further stimulated. 



A part of the tuberculin has already been attracted by the receptors of 

 the cutis or subcutis cells (intracutaneous reaction) or the cells of the mu- 

 cous membrane (ophthalmo reaction) and here too has stimulated the 

 production of antibodies (an ti tuber culm). It is only a quantitative differ- 

 ence in the number of receptors which actually differentiates a normal from 

 a tuberculous individual. Thus is explained that even in non-tuberculous 

 individuals a local reaction may be obtained if the dose of tuberculin in- 

 jected is large enough; a focal reaction, however, will be given only by a 

 tuberculous subject. The greater the number of sessile antituberculin 

 receptors that have been formed in the tuberculous focus, the greater 

 becomes the affinity of these cells toward the tuberculin; so that with the 

 second, third, and subsequent tuberculin injections, focal reactions (i.e., 

 antituberculin productions) are more easily stimulated. 



As for the origin of the fever, it is probable that a pyrotoxic substance 

 is formed by the union between tuberculin, antituberculin and comple- 

 ment. This poison first isolated in vitro by Citron will again be referred 

 to and belongs to the class of anaphylotoxins (Friedberger) or toxopeptids 

 (M. Wassermann and Keyser). 



Finally the antituberculin receptors become so numerous that they 

 are detached from the cells and become free receptors. This period, how- 

 ever, is only transitory, as is corroborated by the difficulty connected with 

 the demonstration of these antibodies in the focus. This free antituber- 

 culin combines with the tuberculin (spontaneously formed or injected) 

 and attracts the complement, or the complement producing phagocytes. 

 Uncombined complement has no effect on the tissues. It is different, how- 

 ever, with the phagocytes. These can without any additional help act 

 directly upon the infected focus. If the tuberculin treatment is continued, 



* A sessile receptor is one which is still attached to its cell and not yet free in the blood. 



