92 THE PRINCIPLES OF IMMUNOLOGY 



serve also to produce agglutinins upon injection. Thus it would 

 appear that agglutinogens are bodies of small molecular size capable 

 of slow diffusion and almost certainly protein, although Stuber 

 maintains that they are of fatty nature. The influence of heat on 

 agglutinogens has been carefully studied by Joos, who concluded 

 that the agglutinogen consists of relatively thermolabile and ther- 

 mostable constituents (the dividing line being 60 to 62 C.) which 

 induce the formation of separate agglutinins. The thermostable 

 fraction resists heat up to 165 C., is soluble in alcohol, and does 

 not give protein reactions, whilst the thermolabile fraction gives all 

 the protein reactions. This work is more fully discussed subsequently. 



Alterations of Agglutinability. Of considerable interest in con- 

 nection with agglutinogens is the alteration of agglutinability of the 

 cell. This probably is more closely associated with the cell as such 

 than with the agglutinogen. If bacteria are heated above 65 C. 

 they are not agglutinable by specific immune sera, but can absorb 

 agglutinin from the sera. Organisms freshly isolated from cases of 

 infectious disease often show similar reductions of agglutinability, 

 but recover it after prolonged growth on artificial media. This is 

 likely to be true in the case of " carriers," and Welch has referred to 

 it as a quasi-immunity which the bacteria themselves have acquired 

 by acting against the immune bodies of the host, an immunity, how- 

 ever, which the organisms lose on living in the environment of the 

 artificial culture media. Such inagglutinability may be produced 

 artificially by growing the bacteria on media containing a specific 

 immune serum, heated to destroy any bacteriolytic influence. In a 

 personal communication to us M. Cooper has stated that the pres- 

 ence of capsules about bacteria serves to establish a quasi-immunity 

 for the organisms against antibodies, and that such capsules appear 

 after cultivation in immune sera. This peculiar phenomenon is ex- 

 plained on the Ehrlich theory by assuming that the bacteria are 

 practically exhausted of receptors. Nevertheless, such inagglu- 

 tinable bacteria upon injection into animals lead to the production 

 of agglutinins for agglutinable strains, but not for inagglutinable 

 strains. It has also been assumed that they are saturated with 

 agglutinoid, but in America, at least, the Welch theory has been 

 given wide acceptance as an important philosophical conception. 

 Not only may agglutinability be altered, but different strains of an 

 organism show natural differences in agglutinability. For example, 

 Cole has shown that against a specific agglutinating serum five 

 strains of pneumococcus showed titers of 1-4000, 1-4500 (2), 1-7000, 

 and 1-8000. These are not " types " of a species but strains, and show 

 no specific agglutinability for sera produced by the strain in question. 



The Nature of Agglutinins. The chemical study of the agglu- 

 tinins shows that, like antitoxins, they are precipitated out of the 

 serum in the globulin fraction, and so far they have not been fur- 

 ther purified. They pass through filters less readily than their 

 antigens, and therefore have a larger molecular structure. Pepsin 



