240 THE PRINCIPLES OF IMMUNOLOGY 



Theories of the Tuberculin Reaction. Koch is of the opinion that 

 the amount of tuberculin introduced when added to that already present 

 in the body provides a sufficient amount of toxic substance to produce 

 a definite general reaction. Koehler and Westphal thought that a 

 toxic body is formed in the tuberculous focus by the union of tuberculin 

 and the products of the tubercle bacillus. Marmorek suggested that 

 the tuberculin excited the tubercle bacilli to produce in excess those toxic 

 bodies which lead to fever. Von Pirquet and Schick were the first to 

 suggest that this is a phenomenon related to hypersusceptibility. This 

 conception fits very well the view of the relation of anaphylaxis and 

 immunity which we have indicated above (page 226). Individuals who 

 have markedly active tuberculosis are not likely to react, whereas those 

 who have quiescent or cicatrized lesions almost always react. If the 

 presence of tuberculosis leads to the formation of a sensitizing sub- 

 stance, this can well be absorbed by the cells and be responsible for the 

 local and general reactions. The tuberculin, upon local application, 

 may react with a sensitizing substance in the situation concerned, or 

 upon entrance into the circulation may similarly react with the sensitiz- 

 ing substance in more widely distributed cells, thus producing a general 

 reaction similar in principle to anaphylactic shock. If, on the other 

 hand, the tuberculous process is so active that immune bodies can be 

 found in the circulating blood, combination may be effected in that situ- 

 ation and the cells protected. The study of complement fixation in 

 tuberculosis indicates that this latter assumption is true, namely, that 

 those who have active tuberculosis are more likely to react positively 

 by the complement-fixation test, thereby indicating the presence of cir- 

 culating antibodies in the active stages of the disease. 



Krause has studied this problem extensively, particularly in experi- 

 mental animals and finds no reason for associating skin hypersensitive- 

 ness and anaphylaxis. The anaphylactic state may be induced in 

 animals by parenteral injection of tuberculo-protein, but they do not 

 acquire cutaneous hypersensitiveness. Only by establishing a focus 

 of infection, is it possible to demonstrate a skin reaction. Although 

 during the period of anaphylactic shock an animal may appear to be 

 somewhat less resistant to infection, the state of anaphylaxis produces 

 no alteration in its resistance. Krause is of the opinion that tissue and 

 cutaneous hypersensitiveness and immunity to infection occur under 

 the same conditions, and that one may probably be a function of the 

 other. In the experimental animal the degree of cutaneous hyper- 

 susceptibility and immunity parallel each other. He suggests that the 

 local reaction may also appear in the neighborhood of foci of infection 

 and thus aid in walling off the infecting agent. Krause's opinion, 

 based on much admirable work, is worthy of the highest consideration, 

 but in so far as we can determine, it is not in accord with studies of 

 immunity and cutaneous reactions in many other conditions, as pointed 

 out in our discussion of cutaneous hypersusceptibility in general. Peter- 

 sen considers the tuberculin reaction as a two-phase phenomenon. The 

 primary alteration of the ferment-antiferment balance brings about a 



