226 THE PRINCIPLES OF IMMUNOLOGY 



particular manifestations observed. The sensitizing fraction of the 

 protein, if there be any such fraction, has not been isolated nor has 

 the intoxicating substance. If the second dose be given in mass, ana- 

 phylactic shock results. If, on the other hand, divided small doses are 

 given the state of the organism is so changed that severe anaphylactic 

 shock does not appear. In agreement with Besredka, we believe that 

 desensitization produces a series of minor shocks but believe that the 

 explanation lies rather in the work of Weil than in the hypothesis of 

 Besredka. In other words, there is a partial saturation of the sensi- 

 tizing substance within the cells, so that any subsequent union cannot 

 produce the intensity of reaction that would have been produced by a 

 massive injection. The time that must elapse for the production of 

 passive anaphylaxis, as well as the other experiments offered in evi- 

 dence, support the conception that some change must occur in the cells 

 in order to produce sensitization. The nature of the combination 

 between the specific protein and the substance within the cells or the 

 influence of the protein upon the cells is not definitely known, but the 

 data offered in review appear to rule out the probability that definite 

 toxic bodies are formed. Similarly the nature of the primary changes 

 in the cells upon second injection cannot be identified; as to whether 

 there is a liberation of energy of some sort or a disturbance of colloidal 

 relations must still be the subject of investigation. The specificity of 

 the reaction is similar to that of other biological reactions and is subject 

 to similar limitations of the group phenomenon. Nevertheless, we find 

 in anaphylaxis a most specific phenomenon, which is approached 

 in delicacy only by the reactions of precipitation and of com- 

 plement fixation. 



The Relation of Anaphylaxis to Immunity. If desensitization of 

 an anaphylactic animal is carried on for only a short time the period of 

 desensitization is relatively brief, but, on the other hand, if the vac- 

 cination be continued the animal may be rendered resistant. This indi- 

 cates a close relationship between the two phenomena. We do not 

 propose to discuss this at length because of the intricacy of the subject. 

 Weil pointed out in his earlier experiments by saturation of the animal 

 with proteins that although the animal may become immune in so far 

 as his body fluids are concerned he may remain hypersensitized in so 

 far as his cells are concerned. Manwaring and Kusama found that 

 the lungs of guinea-pigs immunized to a certain protein, when washed 

 free of blood, were still sensitive to perfusion with the protein in 

 question. We, therefore, revert to the conception of Weil that im- 

 munity is in large part exhibited in protective power of the blood and 

 body fluids. In the state of anaphylaxis this immunity has not been 

 established in the fluids and therefore the cells can be directly operated 

 upon by the antigen. If, on the other hand, the animal is immune his 

 blood and fluids combine with the antigen so as to protect the cells. 

 The direct bearing of this upon diseases in man is a matter of specula- 

 tion. It seems possible, however, that during the period of incubation 

 of an infectious disease the animal, as suggested by Danysz, likewise 



