282 president's address— section l. 



Another important feature of anaphylaxis is that, just as an 

 animal can be immunized against the various antibodies with the 

 consequent production of '' anti-antibodieiS," so a state of (viti- 

 fiiiapht/hixis may be brought about by various means. For 

 example, if an animal shows signs of shock after a second injection 

 of antigen, but recovers, it is then refractory, or, in other words, 

 immune to a further injection of the antigen. The same result 

 may be brought about by making the second injection of the 

 antigen in the 'pre-a7inphi/Iacfic period. Or, again, if the second 

 injection is given per rectum, the antigen will be absorbed so 

 ^Qcwly as to proteict. Even given by the mouth, the small amoiint 

 of the antigen abscrbed may be sufficient tO' give protection. This 

 " de-s'ensitization " is evidently merely a saturation of the anti- 

 bodies contained in the blood or. tissues of the sensitive animal 

 with the appropriate antigen in such a way as to avoid a violent 

 shock. Passive anaphylaxis can be neutralized in a similar way 

 by the proper dose of antigen, and may then be restored by a new 

 injection of immune serum (Weil and Coca, 1913). 



Thus the occurrence of the sensitive state apparently coincides 

 with the appearance of ordinary immune antibodies, such as pre- 

 cipitins, and the anaphylactic shock apparently results in sqme 

 way from a siuh/c/i antigen-antibody reaction. Further, it must 

 be noted that the reaction is specific: it is the same antigen as was 

 useid for the first injection which must be used to promote the 

 shock. 



Much difference of opinion has existed, and still exists, as toi the 

 place where the hypothetical poison " anaphylatoxin " is produced, 

 whether in the blood stream or in some of the tissue cells. The 

 incubation period necessary after the injection of a sensitized 

 serum before passive anaphylaxis occurs suggests a cellular partici- 

 pation, and Dale's experiments strongly support this view. Dale 

 (1912-1916) submitted the isolated uteri of young guinea pigs to 

 the action of various sera. The uterus was first perfused with 

 Ringer's solution through its vessels to remove all blood, then 

 suspended in 250 c.c. of Ringer's solution at 38° C. In the case 

 of a normal guinea pig, the addition of 1 c.c. of a foreign serum 

 to the fluid had no effect, and provoked no muscular contractions 

 of the uterus. In the case cf a guinea pig previously sensitized to 

 a particular serum, the addition of a mere trace of this serum to 

 the solution caused strong uterine contractions. 



Moreover, if a uterus had been stimulated to contract once by 

 its specific antigenic serum it was found thereafter desensitized. 



As we shall see later, there are experimental evidences for a 

 blood reaction, but it is limited as compared with the tissue 

 reaction. 



An obvious question arises here, since anaphylaxis is an antigen- 

 antibody reaction, what part, if any, does complement play in the 

 reaction ? 



