196 CHEMISTRY OF THE IMMUNITY REACTIONS 



bacteria) through digestion. Normally this is accomplished in the 

 alimentary tract, and complete disintegration past the toxic stage is 

 made certain by the presence of erepsin in the intestinal wall; but 

 if intact foreign protein molecules reach the blood in any wa}-, this same 

 digestive destruction is performed by the enzymes of the blood or 

 tissues. So abnormal is the "parenteral" introduction of foreign 

 proteins that, once it has happened, the protective mechanism is 

 stimulated to the production of large amounts of proteolj^tic sub- 

 stances, and on this account if another quantity of the same protein 

 is again parenterally introduced the breaking down of the protein is 

 extremely rapid. Certain of the disintegration products are toxic, but 

 with the normal rate of disintegration the amount present at any one 

 time is inadequate to cause poisoning; when the proteolysis is accele- 

 rated, as in the sensitized animal, a poisonous dose may be produced, 

 with the resulting anaphylactic intoxication. ^^ Whether this proteo- 

 lysis takes place both in the blood and tissues is not known. It has 

 been found that the specific proteolytic power of the blood is increased 

 in sensitized animals, but on the other hand, there is evidence that 

 without the intervention of the livfer (at least in dogs) anaphylactic 

 intoxication cannot take place (Manwaring and others),^* During 

 the reaction, in any event, products of protein In'drolysis appear in 

 the blood (Abderhalden),^'^ but there is no demonstrable destruction 

 or binding of the injected foreign protein. ^^ 



Among possible cleavage products of proteins which may be the 

 toxic agent in anaphylaxis, is |3-imidazolylethylamine ("histamine"), 

 which is derivable from histidine, and which produces effects resembling 

 acute anaphylactic intoxication. 2'' Not only does histamine cause 

 marked fall in blood pressure, bronchial spasm in guinea-pigs and 

 obstruction to the pulmonary circulation in rabbits, but also when 

 applied locally it causes marked urticaria resembling closely that of 

 anaphylaxis. Methylguanidine is said to produce somewhat similar 

 but slighter symptoms, 2** and to protect sensitized animals from 

 toxic doses of the antigenic protein. ^^ Other amines possibly may 

 be involved. (See Chapter iv, Ptomains; Chapter xxi. Pressor 

 Bases.) 



The relation of the normal toxicity of certain foreign sera to ana- 

 phylactic intoxication has not been determined, but there seem to be 



^'' Hcilner (Zeit. Biol., 1912 (58), 333) believes that tlie anaphylactic poisons 

 are substances which normally are destroyed by proteolysis, but that in the sensi- 

 tized animals there is a depressed catabolism which prevents tlieir destruction. 



2^ Falls found that a larger intoxicating dose must be injected into the portal 

 system to produce the same cfTects than by peripheral injection. (Jour. Infect, 

 Dis., 1918 (22), 83.) 



"Zeit. phy.siol. C^hem., 1912 (82), 109. 



"Sec Barger, '"i'he Simpler Nalural liases," London, 1914, ]h 30.' 



28 lleydc, Cent. f. Bhysiol., 1911 (2.5), 441; 1912 (20), 401. 



29 Burns, Jour. Bhysiol., 1918 (52), .\.\.\ix. 



