194 CflEMlsTh'Y OF THE JilMiMrV REACTIOXS 



this same protein at least eight days previous!}'. This preliminary 

 dose, which may be extremely minute, renders the animal hypersen- 

 sitive to the same protein, so that a relatively small quantity (a few 

 milligrams in the case of the guinea-pig) of an ordinary entirely 

 harmless protein, such as egg white or milk, produces violent, often 

 fatal, symptpms when introduced into the blood of the animal. We 

 have not the space to discuss the general features of the reaction, 

 its history and its relation to biology and pathology, which are fully 

 covered in many easily accessible reviews,-' but shall limit our consid- 

 eration to the more definitely chemical aspects of the reaction.^ 



The Substances Involved (Anaphylactogens) . — So far as now 

 kno^vn. these are always proteins, and with the exception of gelatin ^^ 

 and a few others, practically any soluble protein will produce sen- 

 sitization and intoxication of susceptible animals, i. e., almost any 

 soluble protein may be an anaphylactogen. As with the other immun- 

 ity reactions, observations have been made which are interpreted as 

 indicating that non-protein substances can produce this reaction, but 

 these interpretations are not generally accepted.'"' It is possible, how- 

 ever, for non-protein substances to combine with or alter the pro- 

 teins of an animal so that they become as foreign proteins to that 

 animal, and thus cause sensitization; in this way can be explained 

 apparent anaphylactic reactions to iodin and arsenic compounds, 

 and other non-protein substances. So far as my own experiments 

 show, nothing less than an entire protein molecule will suffice," the 

 products of protein cleavage all being inactive.^ Presumably the 

 inefficiency of gelatin as an anaphylactogen depends upon its de- 

 ficiency in aromatic radicals, since these radicals have been shown 

 (Vaughan, Obermeyer and Pick) to be particularly r important in 

 immunological reactions. It is not necessary for a protein to con- 

 tain all the knowni amino-acids of proteins to be active, however, for 

 certain vegetable proteins (zein, hordein, gliadin) which lack one or 



5 Doerr, Kolle and Wassermann's Handbuch, 1913, Vol. II: and Zeit. f. Tm- 

 miinitat., 1010: (2, ref.), 49; also v. Pirquet, Aroh. Int. Med.. 1911 I 7), 2.'>9; 

 Friodmann, Jaliresbcr. Erpeb. Immunitiitfrsch., 1911 (6). 31; Schittenliehn. ibid., 

 p. 115; Hcktoen, Jour. Amer. Med. Assoc, 1912 (fiS), 1081; Zinsser, Areh. Int. 

 Med., 1915 (16), 223. Concerning anaphylaxis in man see Lonpcope. Ainer. .lour. 

 Med. Sci., 1916 (152), 625. 



6 Many of the chemical features of anaphylaxis I have covered in the foUowinj: 

 series of articles: .Tour. Inf. Dis., 190S (5). 449; 1909 (6). 506; 1911 (S), 66; 

 1911 (9), 147; 1913 (12), 341; 1914 (14), 364 and 377; 1915 (17), 259; 1916 

 (19), 183. 



6a Wells, Jour. Amer. Med. Assoc. 1908 (50), 527; Jour. Infect. Dis., 1908 (5), 

 459. 



<5b Concerning lipoids as antigens see Meyer, Zeit. Inimunitiit., 1914 (21), 654. 



7 Zunz (Zeit. Inimunitiit., 1913 (60), 580), however, claims to get typical re- 

 actions with the higher proteoses from fibrin, a tiling T have never succeeded in 

 doing with proteoses from egg albumen. 



sAbdcrhalden (Zeit. physiol. Chem., 1912 (81), 314) states that he has ob- 

 tained a positive reaction with a synthetic polypeptid containing 14 amino-acid 

 molecules, including only leucine and glycocoll. 



