176 CHEMISTRY OF THE IMMUNITY REACTIONS 



cipitated and isolated. ^^ These are fibrinogen, euglohulin (true glob- 

 ulin), and -pseudo-globulin (soluble in water). Pick^" found that 

 the precipitate obtained by 36 per cent, volume saturation with am- 

 monium sulphate contained no antitoxin; the antitoxin came down 

 in the precipitate obtained on raising the strength from above 38 

 per cent, to 46 per cent." According to Pick, in horse serum the anti- 

 toxin is associated with the pseudo-globulin, ^^ and Gibson and Banzhaf 

 found that the blood of horses immunized to either diphtheria or tetanus 

 toxin shows a marked increase (40 to 114 per cent.) in serum globulin, 

 varying somewhat according to the antitoxin content, the more solu- 

 ble globulins being most increased. At the same time the serum al- 

 bumin and euglobulin content decreases in proportion, while the 

 fibrinogen shows no characteristic alterations.^^ Mej^er^"* and his 

 colleagues, however, find in their study of the blood proteins during 

 immunization, that the proportion of globulins increases according to 

 the severity of the intoxication, and not in any definite relation to the 

 degree of immunity or antitoxin production. The average antitoxic 

 horse serum contains 12 per cent, albumin, 78 per cent, of soluble glob- 

 ulin containing antitoxin, 10 per cent, euglobulin. By heating 12 

 hours at 57° a considerable part of the soluble globulin becomes 

 insoluble, without a corresponding loss of antitoxin (Banzhaf) . 



The relation of antitoxins to proteins has also been investigated 

 by permitting digestive enzymes to act on antitoxic serum. Pick di- 

 gested the antitoxin-containing globulin of horse serum for several 

 days with trypsin; after five days, when part of the protein was still 

 not digested, the antitoxin was but little impaired in strength; after 

 nine days, when most of the protein was digested, the antitoxin had 

 lost two-thirds of its strength. This indicates a considerable resist- 

 ance of antitoxin to trypsin, but also shows that it is affected in much 

 the same way as the globulin (which is itself very resistant to trypsin) 

 and therefore is presumably of similar nature. Antitoxin seemed to 

 be much more rapidly destroyed by pepsin-HCl digestion than by 

 trypsin, in which respect it again resembles the serum globulin. ^^ 



*^ See rcsum6 by Gibson, Jour. Biol. Chem., 1905 (1), 161; Gibson and Banzhaf, 

 Jour. Exper. Med., 1910 (12), 411. 



90 Hofmeister's Beitr., 1901 (1), 351. 



91 Gibson and Collins (Jour. Biol. Chem., 1907 (3), 233) question the reliabil- 

 ity of some of Pick's results, and repudiate the salt fractionation method of clas- 

 sifying proteins. 



92 Miss Homer found tetanus and diphtheria antitoxin associated with the 

 pseudoKlobulins, but the antibodies in antidj^sentcry and antimeningococcus 

 serum were chiefly in the euglobulin fraction (Jour. Physiol., 1918 (52), xxxiii). 



93 During immunization the antitryplic power of the horse serum increases 

 with the antitoxin increase (Krause and Klug. Berl. klin. Woch., 190S (45), 1454.) 



9' Jour. Exp. Med., 1916 (24), 515; 1917 (25), 231; Jour. Infect. Dis., 1918 (22), 1. 



9'' P,erg and Kclser (Jour. Agric. Ri-s., 1918 (13), 471) found that trypsin and 

 pepsin destroy tlie antitoxin and scrum proteins at about the same rate, and their 

 failure to observn; "significant cliemical ciuinges" in the proteins of serum acted 

 upon by weak acid or alkali that slowly inactivates antitoxin, does not seem to 

 warrant tlieir deduction that antitoxin is non-protein. See also Crawford and 

 Andrus, Amer. Jour. Pharm., 1917 (89), 158. 



