216 CHEMISTRY OF THE IMMUNITY REACTIONS 



with the stroma rather than with the hemoglobin, and the result of the union is to 

 render the stroma permeable to the hemoglobin, or to separate the bonds that 

 unite the hemoglobin to the stroma, f^" There are grounds for believing that the 

 amboceptor not only binds the complement, but that it also produces changes in 

 the corpuscles (Muir). Mathes^* contends that red corpuscles cannot be dissolved 

 by hemolytic serum or by pancreatic juice until after they have been killed; as 

 heated serum does not kill them, this is presumably done by the complement. 

 Corpuscles that have been killed can then be dissolved in their own serum. Le- 

 vene^^ tried to produce hemolytic serums by immunizing with different consti- 

 tuents of corpuscles, using — (1) pure crystalline hemoglobin; (2) proteins of the 

 stroma soluble in salt solutions; (3) an extract with alcohol-ether; and (4) an extract 

 in 1.5 per cent, sodium bicarbonate. Only the last gave positive results, and the 

 serum was almost devoid of agglutinative properties. Injection with corpuscles 

 that had been digested with trypsin gave about the same results as alkaline ex- 

 tracts; corpuscles digested by pepsin gave a much weaker serum; in neither was 

 agglutination obtained. According to Bang and Forssmann*'^ and others ethereal 

 extracts of red corpuscles give rise to production of hemolysins on immunization, 

 and this "lysinogen" substance can be precipitated with acetone, is insoluble 

 in alcohol, is not destroyed by boiling, and gives rise to no agglutinin. Numerous 

 other olDservers, however, have failed to confirm these findings. Ford and Halsey^* 

 ol)tained serum with both lytic and agglutinative powers by injecting either the 

 stroma or the laked blood free of stroma. Stewart^^ obtained similar results by 

 immunizing with corpuscles laked by physical means, by serums, or by saponin. 

 Pure hemoglobin itself is not antigenic. ^^ According to Guerrini,*^^ nucleoprotein 

 obtained from dog's blood engenders specific hemolysins, and Beebe states that 

 nucleoproteins from visceral organs do not have this effect. Levene's alkaline 

 erythrocyte extracts probably also contained nucleoproteins. Vedder,^* was unable 

 to produce hemolysins when he used ether extracts of corpuscles as antigen, or with 

 globulin from stroma, but the protein extract left after removing the globulin, 

 presumably albumin, as well as lipoid-free stroma, produced hemolj-sin. The 

 henolysin itself seems to be a globulin. On the other hand, Bennett and Schmidt^' 

 obtained hemolysin by immunizing with the globulin precipitated from hemolyzed 

 erythrocytes by CO2. 



Immunization with extracts of tissues and cells of various sorts, even when 

 entirely free from blood (e. g., spermatozoa), may produce hemolytic sera. The 

 fact that various tissues from many different species of animals, when used as 

 antigen, may give rise to hemolysin for sheep corpuscles, is an interesting but so 

 far unexplained phenomenon, which is discussed under "Specificity" (Chapter 

 vii). 



The Complement. — Hemolytic complement possesses the same properties as 

 bacteriolytic complement, resembling enzymes to the extent that it is susceptible 

 to heat, causes a disintegration of cells, and is largely retained by Berkefeld 

 filters.'" The joint action of amboceptor and complement is strikingly like the 

 activation of trypsinogen by kinase. On the other hand, hemolysis by serum is 

 quite different from the effect of trypsin on corpuscles, as trj-psin completely dis- 

 organizes the hemoglobin and destroys the stroma, while in hemolysis the stroma 

 and hemoglobin seem to be merely separated from one another but not chemically 

 altered. Again, hemolysin acts quantitatively, although that may be due to a 



^" Corpuscles treated with osmic acid will unite with hemolysins of diverse 

 origin, but when used for immunizing they engender no hemolysins (Coca; also 

 V. Szily, Zeit. Immunitiit., 1909 (3), 451). Heating corpuscle stroma alters 

 greatly the reactivity (Landstciner and Frasek, ibid., 1912 (13), 403). 



" iVIiinch. med. Woch., 1902 (49), 8. 



" Jour. Med. Research, 1904 (12), 191. 



" Hofmeister's Beitr., 1906 (8) 238. 



" Jour. Med. Research., 1904 (11), 403. 



^' Amer. Jour, of Physiol., 1904 (11), 250. 



8" .Schmidt and liennctt, Jour. Infect. Dis., 1919-(25), 207. 



" Riv. crit. di clin. mod., 1903 (4), 561. 



"8 Jour. Immunol., 1919 (4), 141. 



" Jour. Immunol., 1919 (4), 29. 



'0 Muir and Browning, Jour. Path, and Bact., 1909 (13), 232. 



