HYPERSENSITIVENESS 489 



Site of Reaction. — Tlie socoiid important point concerning the 

 nature of anaphylaxis is that the site of the antigen-antibody 

 reaction which leads to shock is in or on the tissue cells and not 

 in the blood stream. This is supported by the following ob- 

 servations : 



1. The introduction of sensitizing antil)odies into the blood 

 stream of a normal guinea pig docs not render it immediately 

 sensitive to antigen such as would be the case if the site of the 

 reaction were in the blood.* Instead there must elapse four or 

 more hours after the antibodies are introduced before the animal 

 becomes sensitive to antigen. This is best explained by assuming 

 that this time is required for the tissues to take up antibody. 



2. Manwaring has shown that the blood of a sensitized dog 

 may be replaced by the blood of a normal dog without impairing 

 the sensitiveness of the former. 



3. Doerr and others have shown that during passive sensitiza- 

 tion, the animal becomes progressively more sensitive as the anti- 

 bodies disappear from the blood. 



4. Weil has shown that the injection of large amounts of anti- 

 body into a sensitive guinea pig interferes with the reaction. 

 The reason is presumably that the circulating antibodies meet and 

 react with the antigen before the latter can react with antibodies 

 in the tissues. 



5. Finally both Schultz and Dale have shown that segments of 

 small intestine and also the uterine horns of sensitized guinea 

 pigs perfused free of l)lood, removed from the body and properly 

 suspended in Locke's or Ringer's solution, will give a specific 

 anaphylactic response when a nontoxic dose of antigen is added 

 to the bath. Likewise Friedberger and Mita and also Goodner 

 have siiown that the excised sensitized frog heart gives a specific 

 reaction when brought in contact with antigen. 



It should be stated, however-, that there are a number of in- 

 vestigators who have observed symptoms of anaphylaxis immedi- 

 ately after antigen and sensitizing serum were injected separately, 

 but simultaneously, or mixed immediately before injection. Zins- 

 ser and also Wells do not regard these observations as invalidat- 

 ing the conclusion that in anaphylaxis the reaction occurs in or 

 on the tissue cells. The}^ suggest that the symptoms might be 

 either anaphylactoid or toxic phenomena of undetermined cause. 



•According to Bronfennbrenner iniinetUate .sensitization occurs if homologous 

 instead of heterologous antiserum is used for passive sensitization. 



