354 IMMUNOLOGY 



In the past all attempts to employ tuberculin in antigen-anti- 

 body reactions have failed. Seibert (1935) reports that the 

 precipitin reaction between tubercle protein and its homologous 

 antiserum is inhibited by her tuberculin preparation SOTT having 

 a molecular weight of 3800. By means of tlie ultraeentrifuge and 

 electrophoresis Seibert, Pedersen and Tiselius* (1938) have studied 

 the constituents of tuberculin. They have isolated a protein with 

 a molecular weight of 32,000 from culture filtrates. This protein, 

 when injected into tuberculous guinea pigs, caused death. They 

 isolated substances of lower molecular Aveight (9,000-16,000), from 

 old tuberculin, that were active in producing skin reactions. Ac- 

 cording to Chase and Landsteiner (1939), Maschmann (1937) has 

 reported success in separating tuberculin into two fractions, one 

 (resistant to proteolytic enzymes) that gives systemic and the 

 other (destroyed by trypsin) that gives positive skin reactions. 



Specific Substances in Bacteria. — Early Discoveries.^ — In 1921 

 Zinsser obtained a specific substance from tubercle bacilli. It 

 was obtained by alkaline extraction of ground tubercle bacilli, and 

 was heat stable, alcohol-insoluble, and gave positive precipitin 

 and complement fixation tests with specific immune serum. 



A gumlike substance that reacted with serum of animals im- 

 munized with tubercle bacilli was isolated by Laidlaw and Dudley 

 (1925). Tubercle bacillus polysaccharides were isolated by Heidel- 

 berger and Menzel (1932) and Seibert, Pedersen and Tiselius 

 (1938). Heidelberger and Menzel (1938) have continued tlieir 

 studies of tubercle bacillus polysaccharides and have been able to 

 isolate two whicli are immunologically active; one is low and the 

 other is high in pentose. They "are apparently built up chiefly 

 of d-arabinose and d-mannose units in varying proportions." 



Pick (1912) had isolated similar soluble specific substances 

 from E. tjjphosa and Dochez and Avery (1917) had found in the 

 urine and blood of pneumococcus pneumonia patients a substance 

 that gave specific reactions with pneumococcus immune serum. In 

 1923, Zinsser and Parker found similar substances in pneumo- 

 cocci, staphylococci, influenza and typhoid bacilli. Heidelberger 

 and Avery have shown the soluble specific substances of pneumo- 

 cocci to be polysaccharides and type-specific. These and other im- 

 portant reacting carbohydrates and proteins isolated from a num- 

 ber of other bacteria will be discussed briefly later in this chapter. 



•Seibert, F. B., Pedersen, K. 0., and Tiselius, A.: J. Exper. Med. 68: 413, 

 1938. 



