ANAPHYLAXIS 391 



taining 2 per cent. NaOH) into 2 fractions a toxic alcohol-soluble 

 and a non-toxic alcohol-insoluble one. The former fraction gave 

 protein reactions, and they regard it as a true protein while Wells, 21 

 considering the hydrolytic nature of the cleavage resorted to, con- 

 siders this fraction as possibly a soluble peptone or polypeptid (the 

 positive protein reactions being possibly due to ammo acids). The 

 non-alcohol-soluble, non-toxic fraction also gives proteid reactions. 

 Injections into guinea pigs of the toxic fraction produce symptoms 

 riot unlike anaphylaxis but do not sensitize against protein. The 

 alcohol-soluble portion is non-toxic and sensitizes against protein in 

 doses of 0.001 to 0.005 gm. Based on these results, their views of 

 mechanism of anaphylaxis are as follows : 



At the first injection a slow lysis (cleavage) of the injected pro- 

 tein gradually liberates a fraction, corresponding to the alcohol-in- 

 soluble substance and this by its antigenic action gives rise to the 

 formation, in excess, of an enzyme (lysin), which on reinjection 

 brings about the rapid cleavage of the injected protein with an ex- 

 plosive liberation of the toxic fraction and consequent symptoms. 22 



Nicolle believes that the injection of a protein into an animal induces 

 the production in the subject of antibodies. These are preeminently two 

 albuminolysins, which cause its cleavage, and albuminocoagulins or precipi- 

 tins, which coagulate and prevent the action of the lysin. At the time at 

 which an animal is hypersusceptible or anaphylactic there has been a pro- 

 duction of albuminolysins which cause cleavage of the protein, with the 

 rapid liberation of toxic substances; but the albuminocoagulins or precipi- 

 tins have not yet adequately developed. In a refractory animal the neu- 

 tralizing action of the albuminoprecipitins prevents the harm which the lytic 

 action might otherwise accomplish. The relative amounts of these two anti- 

 bodies present in the circulation of the animal at any particular time deter- 

 mine whether the animal is anaphylactic or refractory or immune. This 

 theory assumes arbitrarily the protective nature of precipitation, an idea 

 which has no foundation in experiment and, in fact, is rendered extremely 

 unlikely by more recent developments of our knowledge of the precipitating 

 antibodies. 



Given, then, a reasonable hypothesis in which anaphylaxis is 

 associated with the cleavage of protein by lysis, given, in other words, 

 an antigen-antibody conception, it is but natural that experimenters 

 should ask themselves: What is the relation of the alexin to this 

 cleavage ? For in all known lytic reactions, of course, the union of 

 antigen and antibody leads to the absorption of alexin, by means of 

 which, then, the lysis has been assumed to take place. This problem 

 suggested itself to a number of the earlier investigators who attempted 

 to approach it by determining whether or not the sera of sensitive 



21 Wells. Jour. Inf. Dis., Vol. 5, 1908. 



22 For the sake of completeness it is well also to mention Nicolle's 23 

 iheory, which, though attractive, is not borne out by recent knowledge con- 

 cerning the nature of precipitins. 



2:! Nicolle. Am. de I'Inst. Past., Vol. 22, 1998. 



