732 PRINCIPLES OF GENERAL PHYSIOLOGY 



been desensitised. Mere contact for some hours with not too dilute a serum of a 

 sensitised animal was sufficient. Perfusion of a normal uterus with diluted serum 

 from sensitive animals also conferred a decided sensitisation. It is evident, then, 

 that interaction with other organs is not necessary for the reaction in the guinea- 

 pig, and it was found that the bronchial spasm could be produced even when the 

 liver and intestines were removed. In the dog, the reaction in the liver produces 

 some secondary reactions, by which toxic substances are sent into the blood, 

 causing exaggeration of the symptoms. 



Certain theories have been suggested in explanation of the phenomenon. That 

 there is some sort of interaction between the antigen and some constituents of the 

 serum is indicated by the results of Anderson and Frost (1910), who found that 

 serum from, a sensitised animal, after digestion with antigen, produced symptoms 

 resembling anaphylactic shock when injected into normal animals. Experiments 

 of this kind led to the theory of a kind of proteolytic digestion, but Doerr (1912, 

 p. 337) has shown that similar effects can be obtained from serum that has been 

 digested with kaolin or kieselguhr. Further, Doerr and Moldovan (1912) find 

 that many of the symptoms of anaphylactic shock can be obtained by intravenous 

 injection of some inorganic colloids, such as silica. 



According to Dale, these latter experiments indicate the direction in which to 

 look for a more satisfactory explanation than the protein digestion theory. In 

 addition to the facts mentioned, the absence of any perceptible latent period, the 

 sudden onset, and the gradual decline are quite unlike any enzyme action. The 

 effect, in fact, is like that of a powerful stimulating drug, such as /2-iminazolyl- 

 ethylamine. 



The action of inorganic colloids is usually to give rise to mutual precipitation 

 or aggregation, when mixed with protein solutions. Dale's experiments, as he 

 points out, show that the colloidal interaction must take place on the muscle 

 fibres themselves and need not actually go so far as precipitation. In the 

 light of the work of Lillie and others (page 398), on the increase of permeability 

 in the state of excitation, it seems highly probable that the contraction resulting 

 from the interaction of the sensitised muscle fibre with the antigen is a . 

 consequence of increased permeability of the cell membrane. This view is 

 supported by the fact that the presence of calcium salts tends to oppose the 

 reaction, as would be expected from their relation to colloidal processes. As 

 Dale says (p. 221), "The action of the antigen in extreme dilutions, the 

 saturation of the antibody (desensitisation), the cessation of the effect when the 

 union of the antibody and antigen may be supposed to be complete, all find their 

 reasonable explanation." 



I have spent some time in the description of these experiments because they 

 apply not only to anaphylaxis, but to immunity in general. In connection with 

 them, the fundamental paper by Wooldridge on "Chemical Protection" (1888) 

 should be referred to. The main result of this work was to show that a solution 

 of a " tissue-fibrinogen " could confer specific immunity. The solution was pre- 

 pared from the thymus of normal rabbits ; it was partly coagulated by boiling 

 and pressed through fine linen, so as to obtain a very fine suspension. When 

 injected, this suspension was found to confer immunity against anthrax. Thus, 

 it was shown " that immunity can be obtained, not, as had previously been 

 supposed, only by the inoculation of attenuated micro-organisms or their products, 

 but by the administration or introduction into the system of a chemical substance 

 which had never come into relation with or was in no sense a product of the life 

 of a micro-organism " (Introduction to " Collected Papers," p. 28). 



PHAGOCYTOSIS AND " OPSONINS " 



Certain specific substances have been described which are supposed to increase 

 the taking up of micro organisms by leucocytes. This is said to be done by 

 an action of the micro-organisms of such a nature as to make them attractive to 

 their devourers. The work of Ledingham (1912), already referred to (page 3), 

 has shown that mere agglutination is sufficient for the purpose. Further evidence 



