CHAPTER LXXVIII 

 THE ISOLATION OF SUBSTANCES WITH IMMUNE PROPERTIES 



ARTHUR LOCKE' and EDWIN F. HIRSCH 

 St. Luke's Hospital, Chicago 



The first intensive studies of experimental immunization, marked by the decade 

 of 1880-90, suggested that the phenomena of the immunity state might be asso- 

 ciated with a production and accumulation, in the tissues of immunized animals, of 

 chemically individual, specific "immune substances," The capacity of the blood 

 serum of an animal experimentally immunized against cholera spirilla, to agglutinate 

 suspensions of that organism appeared, for example, to be referable to a content of 

 specific cholera agglutinin. Concepts of lysins, precipitins, antitoxins, etc., arose and 

 became crystallized to such an extent that Emmerich, in 1887, made the following 

 comment: "It should be an important task for investigators to seek out these sub- 

 stances which are associated with the immunity state and to ascertain in what 

 chemical grouping they belong."^ 



Chemical examinations of the tissues and tissue fluids of immune and non-im- 

 mune animals were made,^ and the results indicated (i) that immune substances do 

 exist as definite entities; (2) that they are neither dialyzable nor extractable by fat 

 solvents; (3) that they are readily destroyed by agents which denature or hydrolyze 

 proteins; and (4) that they are associated in the serum with some protein fraction, 

 usually the pseudoglobulin or a closely bordering euglobulin fraction. 



However, this purely analytical method of approach revealed little as regards the 

 true nature of the immune substances. It was apparent that an adsorption of immune 

 substance upon serum globulin might resist dialysis and fat extraction regardless of 

 its nature, and that its inactivation by heat and enzymic digestion might be due 

 simply to changes induced in the protein adsorbent. The protein fractions, upon 

 whose behavior the conclusions as to the nature of the immune substances had been 

 based, probably contained less than 0.2 per cent of the pure immune principle. 



Contemporary studies of the physico-chemical relations of antigen and antibody,'' 

 undertaken by Landsteiner and by Morgenroth and later by Bordet, were more pro- 

 ductive. They demonstrated the existence of a property which completely differ- 

 entiates the immune principle of an immune serum from the associated serum pro- 



' Seymour Coman Fellow in Medical Chemistry, Kent Chemical Laboratory, University of Chicago. 



2 Emmerich, R., and Tsuboi, J.: VerJiandl. d. XI. Kojig.f. inn. Med., p. 202. i8q2. 



sTizzoni, G., and Cattani, G.: Centralbl.f. Bakteriol., 9, 685. 1891; Pfeiffer, R., and Proskauer, 

 B.: ibid., 19, 191. 1896; Brodie, T. G.: /. Path, b' Bad., 4, 460. 1897; Pick, E. P.: Beilr. s. cheni. 

 Phys. u. Path., i, 351. 1902. 



4 Landsteiner, K.: Miinchen. med. Wchnschr., 49,1905. 1902; 50, 764. 1903; Morgenroth, J.: 

 ibid., p. 61. 1903; Bordet, J. (trans, by Gay, F. P.): Studies in Immunity. Wiley & Sons, 1909. 



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