HYPER6ENSITIVENESS 495 



2. Desensitization is satisfactorily explained by assuming that 

 the antibodies are either exhausted or neutralized during the re- 

 action, hence, after recover}^ when a second dose of antigen is 

 administered there are no antibodies available to react with 

 antigen, 



3. The specific tetanic contraction of smooth muscle does not 

 explain the prolongation of clotting time frequently, although not 

 invariably, observed in anaphylaxis. If one pastulates physical 

 changes occurring at the surface of or within the hepatic paren- 

 chyma cells or perhaps in the endothelium of the liver sinusoids, 

 one might explain the appearance of a heparin-like substance 

 which would cause the prolongation of the clotting time of the 

 blood. 



4. The inflammatory response observed in the Arthus phe- 

 nomenon might be explained as due to similar changes in the 

 skin. Not infrequently it is explained by assuming that the spe- 

 cific precipitate formed acts as a foreign body in causing inflam- 

 mation. The exact mechanism involved is not understood. 



Further Discussion of the Histamine Theory. — Certain ob- 

 jections to Lewis' theory that the reaction between antigen and 

 antibody causes an explosive liberation of histamine which acts 

 locally and perhaps always systemically have been summarized 

 and discussed by Wells and others. 



Among the objections are listed the failure of histamine to 

 desensitize animals, its inability to produce coagulation changes 

 of the blood similar to those observed in anaphylactic shock, and 

 finally its ability to produce strong contractions in desensitized 

 uterine horns. Wells calls attention to the fact that the first 

 and third objections arc not necessarily valid. Since the histamine 

 is theoretically liberated as a result of an antigen-antibody reaction, 

 the phenomenon of desensitization Avould mean an exhaustion of 

 antibody and not an acquired tolerance for histamine. If antibody 

 is exhausted during shock, then the second injection of antigen will 

 find no antibody to unite with it and therefore no histamine will 

 be liberated. A similar explanation is applicable to the third 

 objection that histamine will produce a reaction in a desensitized 

 uterine horn. If the antibodies present in the uterine horn are ex- 

 hausted, then an antigen-antibody reaction cannot occur when 

 antigen is added. Therefore no histamine will be liberated. The 



