HYPERSENSITIVENESS 493 



ported by certain experimental studies of Dale postulates the 

 existence of an histamine-like substance (H-substance) in loose 

 combination with the tissue cells. According to this theory the 

 H-substance is released as a result of the antigen-antibody reac- 

 tion. The symptoms of anai^liylaxis are due to the H-substance 

 thus liberated. 



There are a number of observations whicli support tlie physical 

 theoiy just mentioned. These may be summarized as follows: 



1. It is definitely established by experiment that changes in the 

 colloidal dispersion of both antigenic substance and antibody 

 globulin accompany antigen-antibody reactions in vitro. 



2. Specific agglutination and precipitation phenomena have 

 been observed within animal tissues. 



3. The results of Bronfenbrenner's (1914, 1915) investigations 

 of the Abderhalden reaction suggest that the union of antigen 

 and antibody is accom])anied l)y physicochemical change which 

 lowers tlie antitryptic index. Tliis leads to the liberation of toxic 

 l)i'oducts by the action of proteolytic enzymes. 



4. Wells has called attention to experiments wliich show that 

 slight changes in colloidal disjiei-sion of phisma proteins may 

 render them exceedingly toxic. 



It would appear that such a theory might explain the smooth 

 muscle reaction of Schultz and Dale as well as the clinical symp- 

 toms of shock. 



One can also offer strong evidence in support of the histamine 

 theory of Lewis or some modification of his theory which does not 

 restrict tlie toxic sul)stance to histamine. The evidence which has 

 been offered in support of Lewis' theory may be summarized 

 as follows : 



1. The symptoms of histamine shock in the guinea pig, rabbit, 

 dog, and cat are very similar to those of an;T])hylactic shock in 

 tlie respective animals. 



2. Histamine will produce a contraction of the intestinal loop 

 or uterine horn which gives a kymograph tracing identical in ap- 

 pearance with the specific anaphylactic response. 



3. It is generally agreed that histamine and histamine-like sub- 

 stances are widel}" distributed throughout the tissues of the body. 



Dale has shown that histamine is present in apparently loose 

 combination with various fresh normal tissues (1939) and Drag- 



