Croonian Lecture.—The biological significance of anaphylaxis

Anaphylaxis was regarded by Richet, 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 suscepti­bility 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 possi­bility of its transfer by serum from a treated animal, it shows a very suggestive correspondence with the type of immunity associated with “pre­cipitin” 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 quality 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 develop­ment. 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.