194 CHEMISTRY OF THE IMMUNITY REACTIONS 



will become sensitized so that it will react to a subsequent injection 

 of the lens from the other eye.^^ In general, tissue proteins are less 

 active antigens than the proteins of the blood, lymph, and secretions, 

 but even keratins maj^ produce anaphylaxis when dissolved^^ and 

 positive results have been obtained with proteins from mummies. ^^ 



The Poisonous Agent (Anaphylatoxin). — The sj^mptomatology of 

 the intoxication which follows injection of the protein into an animal 

 sensitized with the same protein, is such as to indicate that a poison is 

 responsible, although as yet the poison has not been isolated. As the 

 symptom complex is practically the same no matter what sort of protein 

 is being used, it would seem that the poison must always be the same 

 or similar — no matter how varied the nature of the proteins capable of 

 inciting anaphylactic intoxication. Probably the poison is a product of 

 cleavage of protein by tissue or blood enzymes, which act only in the 

 presence of the specific antibodies which unite the protein to the 

 enzyme (or complement). Vaughan and his collaborators showed that 

 proteins boiled with an alcoholic NaOH solution might be split into 

 two fractions, one toxic and alcohol-soluble, the other non-toxic and 

 insoluble in alcohol. The toxic fraction gives all the protein reactions 

 (except that of Molisch for carbohydrates) and in doses of 8 to 100 mg. 

 kills guinea-pigs with symptoms practically identical with those of 

 anaphylactic intoxication. The uniformity of the toxic effects with 

 preparations from different sorts of proteins suggests the existence in 

 every protein molecule of some fundamental toxic group, common to 

 all proteins, the specificity residing in other non-toxic attached groups. 

 This and other observations led him to the hypothesis that specific 

 enzymes are developed in response to the presence of foreign pro- 

 teins in the blood stream, and that upon injection of a second dose 

 of the same protein these enzymes at once disintegrate it, and some 

 of the cleavage products being toxic the anaphylactic intoxication 

 results. Many of the later developments in this field, especially 

 Abderhalden's studies on "protective ferments,'' have added support 

 to this hypothesis, so that in its fundamental conceptions it is now the 

 most generally favored explanation of the processes involved in ana- 

 phylaxis. ^^ 



Friedberger carried the matter a step farther by showing that if 

 serum from a sensitized animal is incubated for a short time with the 

 same protein, and in the presence of enough complement,a poison 

 is developed which produces the typical symptoms of anaphylactic 

 intoxication when injected into guinea-pigs. This poison resists heat- 

 ing at 56°, but not at 65°, and is not a true toxin, for it will not jiroduce 



»' Uhlenhutli and IliioiRld, Zoit. f. Iiuinunitat., 1910 (4), 7l)l. 



'8Krusiii«, Arch. f. Aiifr<'nlioilk., Sup])!., 11)10 (47), 47; Clough, Arb. kais; 

 Gesundlitsamic, 1911 Oil), 131. 



'» llil.'iihulli, Zcil. f. Imiininitat., 1910 (4), 774. 



" See VauglKUi, Aiiier. Jour. xMed. Sei., 19i;{ (145), 101; Zeit. Imiiuinitat., 1911 

 (9), 458. ALso a full review in his "Protein Split Products," Philadeii)hia, 1913. 



