132 PROTEIN THERAPY 



split products the enzyme reaction will seldom be as clear cut as here 

 portrayed. 



But why the tissues react more readily the second time is a question 

 that is of such vast biological significance that we can merely surmise 

 some of the more superficial and obvious alterations that are involved. 

 Even were we to consider nothing but antibody reactions in the im- 

 munological sense recent work would indicate that this alteration 

 allergy is not necessarily specific. Bieling has demonstrated that any 

 primary sensitization leaves the body in a state of high grade hyper- 

 sensitiveness. Animals immunized to cholera, for instance, required but 

 a minute fraction of the ordinary dose of typhoid antigen to bring 

 about a high degree of immunity to typhoid. The fact that a second- 

 ary injection of a heterologous protein or other nonspecific agent will 

 mobilize the antibodies formed against a previously injected antigen 

 is of course well known and has been extensively studied by Bieling, 

 Hektoen, Johnson and others. The cell has been so altered that its 

 reactivity is increased, as though a dull instrument had been suddenly 

 shaped to razor-like keenness. To what degree this involves more or 

 less permanent alterations in the physical make-up of the cell ecto- 

 plasm, in how far the protoplasm of the cell is involved, is of course 

 purely speculative. 



We must go back for a few moments and consider the possible 

 mechanism of the suppression of the skin reactivity to which we have 

 called attention in relation to certain conditions, such as pregnancy, 

 acute infectious diseases, cachexia, etc. If in the nonspecific enzyme 

 action that goes on in the skin the proteolytic activity can be sup- 

 pressed, then intoxication and inflammation that is due to the splitting 

 of native proteins to the toxic forms should also be inhibited. Such 

 inhibition can take place when the chemical reaction of the medium 

 is not suitable or when we have an excess of antiferment present. All 

 of the states during which the skin reactions are suppressed are con- 

 ditions associated with an increase in the titer of the serum anti- 

 ferment. Stern made a careful study of the suppression of the tuber- 

 culin reaction during pregnancy, when the antiferment titer of the 

 serum is of course greatly augmented. Blb'te confirmed this work and 

 showed that this was by no means a specific phenomenon because 

 when he used an extract of jequirity in place of the tuberculin he 

 obtained a similar result. This increase in the antiferment titer which 

 oceurs after nonspecific injections of various kinds, after serum sick- 

 ness, during antianaphylaxis, is coincident with the alteration in the 

 permeability of the capillary endothelium to which Luithlen, von den 

 Velden and others ascribe the alteration in the skin reactivity and 

 which must also have a large share in the mechanism. 



Meyer has studied particularly the inhibition in the cutaneous 

 reactions to tuberculin which takes place after prophylactic typhoid 

 vaccination. Here, too, we deal with a nonspecific reaction, with an 



