RELATION OF SKIN TO NONSPECIFIC RESISTANCE 131 



more promptly to outside stimuli whether specific, as with tuberculin, 

 or nonspecifically as when other proteins are injected in and about an 

 area previously injected with tuberculin, or finally when substances 

 nonprotein in character such as sugar or starch are used. (Stokes.) 

 Even those investigators who have heretofore been the most ardent 

 advocates of the specific character of the tuberculin reaction, such as 

 Wolff-Eisner, have been compelled to accept the inevitable conclusion 

 that in the tuberculous individual the skin (and the body as a whole) 

 is hypersensitive not only to tuberculin but to proteins in general. 



In a paper published with Sexsmith we have pointed out a possible 

 basis on which some of the clinical experiences as well as the conflicting 

 experimental data might be more readily understandable. 



Enzymes in Skin Reactions. Considering both the phylogenetic 

 and ontogenetic development of the skin and its function it is apparent 

 that its power to secrete enzymes is one that is more or less inherent 

 in the epithelial cell ultimately highly specialized and differentiated 

 in some of its developed organs, rudimentary and potential perhaps in 

 the structures that serve later primarily for protection rather than in 

 the active metabolic processes. As a protective structure its efficacy 

 will depend to a large extent on its ability to react both very rapidly 

 and very strongly against either invasion or intoxication. When one 

 examines the enzymes of the skin one observes apparently a decided 

 difference in the enzymes of the infant or young skin as contrasted 

 with the adult. The young skin contains more ereptase (erepsin or 

 peptidase) and little lytic protease; the adult skin on the other hand 

 little ereptase and more protease. Neither type of skin contains much 

 antienzyme. 



Let us suppose that we inject peptone into the young skin. The 

 ereptase could immediately detoxicate the material injected and there 

 would be no necessity for an inflammatory reaction. If we inject a 

 native protein which only becomes toxic when it is split, the infant 

 skin (containing less protease than the adult) is not able to split the 

 protein, no toxic products are formed and there is no reaction. Indeed 

 the action of whatever protease is present in the young skin seems 

 decidedly synthetic rather than lytic. 



If now we examine the picture in the adult we find the exact 

 reverse. If a peptone is injected there is little ereptase present to 

 detoxicate it and the material is present in the tissues long enough to 

 set up an inflammatory reaction. If on the other hand we use the 

 native protein the presence of sufficient protease in the skin will permit 

 the same to be broken up with the formation of protein split products 

 toxic to the cells and an inflammation will be the result. The relative 

 paucity of ereptase will here delay the detoxication. 



Inasmuch as our ordinary agents that we use in eliciting skin 

 reactions are usually mixtures rather than pure protein or protein 



