HYPERSENSITIVENESS, PROTEIN INTOXICATION 205 



day and increases up to the 12th day. To the same end, Dale showed 

 that, when the washed sensitized guinea-pig's lung is perfused with a fluid 

 containing the specific protein to which the animal has been sensitized, 

 contraction of the bronchial musculature occurs and gives rise to the acute 

 distention of the lungs, which typifies the anaphylactic shock reaction in 

 the living guinea-pig. Still further amplifications of these experiments 

 have been made by Weil and by \V. H. Manwaring, Y. Kusame and H. E. 

 Crow. Weil, moreover, has shown that this specific reaction may be ob- 

 tained in the smooth muscle of the Fallopian tube from the human being 

 who has been sensitized artificially to horse serum, thus demonstrating that 

 the same mechanism pertains to this reaction *both for the experimental 

 animal and for man. 



Etiology. The etiology and place of formation of the poisonous 

 substance which brings about the anaphylactic shock has received much 

 discussion, has been extensively investigated and still remains in many 

 essential regards unsatisfactorily explained. Even with the knowledge 

 afforded by numerous experiments, the place of formation of the poison- 

 ous substance which brings about the symptoms of anaphylactic shock 

 is still under considerable discussion. 



The two theories which have been most ardently adhered to are the 

 cellular and humoral theories. The adherents of the first theory, repre- 

 sented especially by Dale, Laidlaw, Schulz, Weil and others, have brought 

 forward not only the evidence mentioned in the preceding paragraphs to 

 uphold the view that the reaction in anaphylactic shock and the formation 

 of poisonous substances takes place within the cells of the body, but have 

 emphasized other factors which are important links in the argument. It 

 is known, and has been demonstrated and emphasized by Weil and others, 

 that, in order to obtain passive sensitization in the guinea-pig, an ap- 

 preciable time must elapse between the injection of the foreign protein 

 and the development of passive sensitization of the animal. The injection 

 of a normal guinea-pig simultaneously with serum from , a sensitized 

 guinea-pig and with the specific protein has not, except in extremely rare 

 instances, brought about anaphylactic shock. It is necessary, as has been 

 repeatedly shown, that a period of 4 to 6 hours at least elapse before the 

 condition of sensitiveness in the guinea-pig appears and that during the 

 next 12 to 24 hours, the degree of sensitiveness increases. Once having 

 been established, it persists in the guinea-pig for several days, although 

 tBe period of passive sensitiveness in the rabbit, according to Friedemann, 

 lasts not longer than 24 hours. The assumption is that there must be an 

 interval between the injections of the serum from the actively sensitized 

 animal and the injection of the specific protein into the passively sensitized 

 guinea-pig, in order that the anaphylactic antibody may unite with the 

 cells of the body and render them sensitive to the subsequent injection of 

 the specific protein. 



