MECHANISM OF ANTIBODY FORMATION 59 



ence of soluble specific substance in the blood and urine of experi- 

 mental animals and of patients suffering from lobar pneumonia. A 

 positive reaction for soluble specific substances (Types I, II, III) in 

 the blood was found as early as 12 hours after the initial chill, and was 

 demonstrable in one instance five weeks after defervescence. A positive 

 precipitin test with urine against anti-pneumococcal serum was, in 

 certain cases of Type I pneumonia, demonstrable as late as 42 days 

 after the infection; with Type II pneumonia, after 58 days, and with 

 Type III, 30 days after the infection. Quigley (1918) studied 82 cases 

 of Types I, II, and III, pneumococcus lobar pneumonia and obtained 

 positive urine tests for soluble specific substance in 81 per cent of the 

 cases as late as the 21st day during convalescence. Similar results were 

 obtained by Blake (1918). Pepper (1934) following the excretion 

 of polysaccharide in urine by several cases of lobar pneumonia, reported 

 that two Type I cases of empyema excreted large amounts of S sub- 

 stance late in the disease, one of them until the 41st day and the other 

 until the 27th day. Urinary S substance did not appear until agglu- 

 tinins for Type I pneumococci appeared in the blood. 



In immunization experiments, Avery and Goebel (1933) found that 

 acetyl polysaccharide, corresponding to the above cited soluble specific 

 substance, persisted in the circulation of the treated rabbits for con- 

 siderable period of time, was slowly excreted by the kidney, and ap- 

 peared in the urine in its naturally acetylated form, though, for reasons 

 as yet not understood, acetyl polysaccharide does not induce any im- 

 mune response in the rahhit. However, the fact remains that the type 

 specific antigenic component of pneumococcal vaccine, acetyl poly- 

 saccharide, is excreted without being attacked by the host enzymes. On 

 the other hand, it is a well-established fact that this same substance, or 

 its slightly modified forms, produce immunity in mice and men 

 (Schiemann and Casper, 1927; Saito and Ulrich, 1928; Wadsworth 

 and Brown, 1931; Zozaya and Clark, 1932, 1933; Sevag, 1934; 

 Felton, 1935; Heidelberger et al., 1946). It is further to be noted 

 that the polysaccharides which persist in the circulation without 

 producing immune response were shown to be antigenic determinants 

 by coupling with serum globulin (Avery and Goebel, 1931). Type 

 III polysaccharide coupled with serum globulin immunized rabbits 

 against infection by virulent Type III pneumococcus, and the immune 

 serum contained type specific antibodies which precipitated Type III 



