HYPERSUSCEPTIBILITY 221 



serum of sensitized guinea-pigs and horse serum. The fact that 

 further investigation, as for example that of Wells and of Kato, has 

 failed to demonstrate a manifest difference between sensitizing and 

 intoxicating fractions of the protein, is an argument against this 

 hypothesis. Friedberger's original conception was that the primary 

 injection leads to the development of receptors in the cells but in such 

 small amounts as not to be liberated into the blood stream. These 

 " sessile " receptors are responsible for an increased affinity of the 

 cells for the antigen, the consequent disturbances resulting from the 

 rapid anchoring of the protein by the cells. If injections are repeated 

 before the anaphylactic state is developed the receptors are formed in 

 large amounts and appear in the blood stream as precipitins. This 

 hypothesis accords well with the modern conception of immunity and 

 anaphylaxis save for the assumption that the sensitizing substance and 

 precipitins are identical. This theory was followed by Friedberger's 

 anaphylatoxin theory. Somewhat more concrete is the hypothesis of 

 Vaughan and Wheeler. After a long period of study of toxic frac- 

 tions of bacterial and other proteins by Vaughan and his co-workers, 

 the following statement in regard to anaphylaxis was made. " When 

 a foreign protein is introduced into the blood or tissues it stimulates 

 certain body cells to elaborate the specific ferment which will digest 

 that specific protein. When this protein first comes in contact with 

 the body cells, the latter are unprepared to digest the former, but this 

 function is gradually acquired. The protein contained in the first 

 injection is slowly digested, and no ill effects are observable. When 

 subsequent injections of the same protein are made, the cells prepared 

 by the first injection pour out the specific ferment more promptly, and 

 the results are determined by the rapidity with which digestion takes 

 place. The poisonous group in the molecule may be set free rapidly, 

 and in amounts sufficient to produce symptoms, or to kill the animal." 

 Jobling and his co-workers, however, have reached the conclusion that 

 the development of proteases in the blood is not dependent upon anti- 

 bodies and is not specific. Vaughan replies to this objection that " we 

 have only transferred the problem of specificity from the development 

 of a specific enzyme to the specific uncovering of a non-specific 

 enzyme." Undoubtedly, the bodies studied by Vaughan are extremely 

 toxic. As an example, he found that the product of i gram of casein 

 is sufficient to kill 800 guinea-pigs. We are not ready to admit that 

 toxic substances of this sort produce clinical and pathological changes 

 that are identical with anaphylaxis. Weil has given the participation 

 of the cells most extensive study. He considered that the cells are of the 

 utmost importance in the destruction and elimination of foreign protein 

 and that in the course of this process they construct an antibody. The 

 union of antigen and antibody within the cells gives rise to the serious 

 disturbances which constitute anaphylaxis. His excellent work was 

 interrupted by his death in the service of his country, but his hypothesis 

 is one which serves equally well in the phenomenon of desensitization 

 and in anaphylaxis. In support of the assumption that the primary 



