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Croonian Lecture. — The Biological Significance of Anaphylaxis. 



By Dr. H. H. Dale, F.E.S. 

 (Lecture delivered May 29, 1919.) 

 (Abstract.) 



Anaphylaxis was regarded by Eichet, who first clearly recognised the 

 phenomenon, as the opposite of immunity or " phylaxis." At an interval of 

 some weeks, after a first dose of any one of a group of poisonous proteins, the 

 animal was found to be apparently much more susceptible to the action of 

 the poison in question. Further investigation has shown that this suscepti- 

 bility is not connected with the naturally poisonous properties of the substance 

 used, but can be developed in relation to perfectly harmless protein substances, 

 provided they are obtained from a different species and introduced into the 

 system without hydrolytic cleavage. The sensitiveness is highly specific. It 

 discriminates between corresponding substances from different species, 

 between materials from different organs from the same species, and between 

 individual proteins from the same organ. It can be transferred to a normal 

 animal by blood or serum from an anaphylactic animal. In the nature of 

 the substances producing it, in the limits of its specificity, and in the possi- 

 bility of its transfer by serum from a treated animal, it shows a very 

 suggestive correspondence with the type of immunity associated with " pre- 

 cipitin " formation. A highly precipitating serum from an immunised animal 

 confers anaphylaxis on a normal animal more readily, i.e., in smaller dose, 

 than serum from an animal itself anaphylactic. Nevertheless, the serum 

 from an anaphylactic animal forms no visible precipitate with the antigen, 

 and an animal whose serum has this obvious precipitating quahty is not 

 anaphylactic, but immune. Anaphylaxis is not so much the direct opposite 

 of immunity as an anomalous concomitant of a certain phase in its develop- 

 ment. An animal rendered anaphylactic to a naturally poisonous protein is 

 immune to the natural poisonous action, but has acquired a new sensitiveness 

 to it as a protein. 



The symptoms following injection of the sensitising antigen into an ana- 

 phylactic animal are characteristic, not of the substance but of the species 

 exhibiting the reaction. In the guinea-pig the most conspicuous feature is 

 an intense tonus of the plain muscle, which by causing a valve-like closure of 

 the bronchioles produces rapid asphyxiation. In the dog the central feature 

 is a poisoning of the endothelial wall of the capillary blood vessels, especially 

 in the liver, causing a shock -like collapse of the blood-pressure and h£emor- 

 xhages into mucous membranes. In the rabbit the heart muscle seems to be 



