HYPERSENSITIVENESS 531 



volved in the reaction, how antigen and antibody elicit the delayed 

 response and the relationship of tuberculin allergy to immunity. 



While it is true that most of these questions cannot be answered, 

 yet it is possible to state a few experimentally derived facts that 

 seem to fit into the complex picture and which may be regarded as 

 partial answers to some of these questions. 



In regard to the nature of the sensitizing substance responsible 

 for tuberculin allergy, it seems that either the entire tubercle 

 bacillus or an antigenic tuberculin must be present in the tis- 

 sues of the body for sensitization to occur. Zinsser believes that 

 the sensitizing antigen is a nucleo-protein whose antigenic prop- 

 erty is destroyed during attempted extraction. This is apparently 

 confirmed by Seibert's work (194-1). 



Antigenic Factors Present in Acid-Fast Bacteria. — Typical skin 

 reactions are elicited by either large or exceedingly small doses of 

 tubei'culin or by large doses only of bacterial protein from other 

 members of the acid-fast group. This suggests that the tubercle 

 ))aeillus contains an antigenic fraction common to the timothy 

 bacillus and other members of the acid-fast group. 



On the other hand, Menzel and Heidelberger (1938) have isolated 

 several fractions of proteins that differed chemically and sero- 

 logically in each of the following acid-fast bacteria: human, 

 bovine and avian tubercle bacilli and the timothy-grass bacillus. 



In regard to the site of antibody formation one has what ap- 

 pears to be only a few alternatives, the tuberculous lesion itself, 

 the reticulo-endothelial and other tissues of mesenclwmal origin, 

 and the epithelial tissues. It has been generally assumed that 

 antibodies are produced by certain tissues of mesodermal origin. 



Epithelium as the Site of Antibody Production and Antigen- 

 Antibody Reaction. — ^Since Dienes (1933) has presented evidence 

 that in tuberculin skin allergy the cells of the epithelium rather 

 than the subepithelial tissues are the primary sites of the reaction, 

 and since all attempts at passive transfer of antibodies have failed, 

 one is faced with the possibilitj^ that if antibodies are involved in 

 the skin reaction, they may be produced and retained by the cells 

 of the epithelium and that the systemic reaction is due to antibodies 

 produced by other tissues of the body. This is suggested also by 

 the tissue culture work of Rich and Lewis (1927). They report 



