THE HUMORAL THEORIES OF ANAPHYLAXIS 593 



assumes that, on the first injection, the protein finds but few groups of 

 cellular receptors with which it can combine, and for this reason it is 

 not poisonous. During the period of incubation the animal cells develop 

 receptors specific for the homologous protein; with a single small dose 

 of protein most of these receptors remain attached to the cell (sessile) ; 

 on repeated injections, the newly formed receptors are in large part cast 

 off into the blood, and constitute the precipitins. In this manner an 

 animal relatively insusceptible to a foreign protein is rendered highly 

 susceptible, and on the second injection the protein is anchored firmly 

 to the cell, just as the cells of an animal may anchor diphtheria toxin. 

 One of the essential features of this theory is that it assumes that, ordi- 

 narily, the receptors are not preformed in sufficient numbers to anchor 

 enough protein to injure the animal with the first injection, regardless 

 of the size of the dose. On the other hand, tetanus and diphtheria 

 toxins find large numbers of sessile or cellular receptors, and are highly 

 toxic on the first injection. As originally evolved, the theory did not 

 explain the nature of the toxic agent responsible for the lesions and symp- 

 toms of anaphylaxis, and made no mention of the protein poison. Never- 

 theless it affords the best explanation we have on the formation of the 

 " ferment" or protein sensitizer (amboceptor). At one time Fried- 

 berger believed that anaphylaxis could be explained on the basis of a 

 precipitin reaction. Anti-anaphylaxis was explained on the assumption 

 that the protein of the reinjection uses up the sessile receptors already 

 developed, and, accordingly, not enough are present at the end of the 

 period of incubation to produce anaphylactic shock. Passive anaphy- 

 laxis was explained on the ground that the free receptors in the blood 

 of a sensitized animal become, on injection into a fresh animal, anchored 

 to the cells, thus forming fixed or sessile receptors that anchor the pro- 

 tein on reinjection and lead to anaphylaxis. 



Nolf 1 has proposed a theory of anaphylaxis that has come to be 

 known as the ''physical theory." It assumes that the active constituent 

 of proteins is a thromboplastic substance that disturbs the colloidal 

 equilibrium of the blood and leads to the deposition, on the surface of 

 the leukocytes and the endothelial cells of capillaries, of a delicate film 

 of fibrin. Thus stimulated, the cells pour out an unusual amount of 

 antithrombin. On account of the consumption of a part of the fibrino- 

 gen and the increased formation of antithrombin the blood fails to coagu- 

 late after anaphylactic shock or peptone poisoning. Owing to the 

 coagulation deposits on the endothelial cells, the viscidity is increased 



1 Quoted by Vaughan, "Protein Split Products," 1913, 340. 



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