W. H. MANWARING 1083 



their dissociation products might conceivably act as specific portal defenses to the 

 fixed tissues. Others might conceivably increase specific susceptibility. Still others 

 might cause non-specific variations in resistance. Many of the conjugates, of course, 

 might be physiologically inert. 



PHYSIOLOGICAL DATA IN HARMONY WITH THE ENZYME THEORY 



During the last two years we have obtained additional physiological data difficult 

 to explain with the specific receptor hypothesis, but readily explained on the enzyme 

 theory. The following are typical findings: 



a) If a massive dose of horse serum is injected intravenously into a normal dog, 

 and from one to six hours later a quantitative blood transfusion is made from this dog 

 as donor into a partially exsanguinated hypersensitive recipient, the recipient is 

 thrown into typical anaphylactic shock. The shock, in the transfused recipient, how- 

 ever, is invariably more severe than the shock in a control hypersensitive dog injected 

 intravenously with the calculated amount of horse protein contained in the trans- 

 ferred blood sample.' Since the donor's blood has no recognizable toxicity on a con- 

 trol transfusion into a normal dog, this increased shock is presumably due to an in- 

 creased anaphylactic potency of the horse protein contained in the donor's blood. An 

 increased specific toxicity is readily explained under the enzyme theory as a result of 

 the assumed hydrolytic cleavage of the horse protein, with the formation of a larger 

 number of specific protein molecules. 



b) If, however, instead of making the transfusion at the end of one to six hours, the 

 transfusion is delayed until the end of four days, the donor's blood is invariably 

 found to be non-toxic for the hypersensitive recipient.' Specific titration of the donor's 

 blood with rabbit precipitin shows that within the limits of the experimental error 

 there is little or no demonstrable decrease in the amount of horse protein in the donor's 

 blood by the end of four days. This anaphylactic detoxication of the horse protein is 

 readily explained under the enzyme theory as a result of the assumed normal intra- 

 venous denaturing of the horse protein, as a result of conjugation with normal serum 

 proteins. 



c) If the urinary bladder of a normal dog is transplanted by blood-vessel anastomo- 

 sis into a horse-serum hypersensitive recipient and the recipient is now thrown into 

 anaphylactic shock, the transplanted normal bladder is thrown into a typical anaphy- 

 lactic contraction. Physiological analyses have shown that this contraction is due to 

 substances having a histamine-like action on smooth muscle structures, explosively 

 formed or liberated by the hypersensitive liver.^ The bladder of an immune dog sim- 

 ilarly transplanted is wholly insusceptible to this histamine-like hepatic product.^ 

 Moreover, this acquired histamine-like insusceptibility is apparently specific, since 

 a goat-serum immune bladder transplanted into a horse -serum hypersensitive dog 

 shows no suggestion of an acquired insusceptibility to the histamine-like hepatic 

 products formed or Hberated during horse-serum anaphylactic shock.^ This finding 

 is readily explained under the enzyme theory by the assumption that the histamine- 

 like hepatic product is a secondary specific antigen, formed or liberated during the 

 process of active immunization. 



' J . Immunol., 13,357. 1927- ^ Ibid., 13, 6$. 1927. 



^ J. Immunol., 10, 57$. 1925. '* J. Immunol., 13,319. 1927. 



