LYSINS, AGGLUTININS, PRECIPITINS, ETC. 233 



Agglutinins may be produced in the sera of animals by the intro- 

 duction of microorganisms subcutaneously, intravenously, or intraperi- 

 toneally. The intravenous method seems to give the most abundant and 

 speedy results. 1 The formation of agglutinins is a reaction to the body- 

 stances of the bacteria themselves, rather than to their toxic prod- 

 ucts. Thus agglutinins are produced in response to the introduction 

 of dead bacteria and soluble extracts of cultures. Pathogenicity 2 does 

 not influence agglutinin formation to any great extent, non-pathogenic 

 as well as pathogenic giving rise to these substances in serum. As a 

 rule, however, agglutinins are more easily produced against avirulent 

 than against fully virulent strains of bacteria of the same species. 



Agglutinins can be produced with all the known bacteria, but great 

 difficulty may be experienced in producing them with capsulated or- 

 ganisms such as the pneumococcus mucosum and the Friedlander bac- 

 illus, since the capsule seems to insulate such bacteria against reactions 

 with serum. It is possible to agglutinate such capsulated bacteria 

 often only by the method of Forges, the preliminary destruction of 

 the capsule with weak acid and heat. As a rule, the agglutinins appear 

 in the blood of animals three to six days after the introduction of bac- 

 teria. From the third to the sixth day they rapidly increase to a max- 

 imum at the seventh to thirteenth day. They then fall off rapidly 

 until they reach a level at which they remain for a long period without 

 very considerable change. Curves to illustrate these phases have been 

 constructed by Jorgensen and Madsen. 3 



The Reaction between Agglutinin and Agglutinin-Stimulating Sub- 

 stances (Agglutinogeri) . The fact that agglutinin can be removed from, 

 or absorbed out of, serum by the specific bacilli which have led to its 

 formation indicates that there is in the act of agglutination a combi- 

 nation between the agglutinin and the agglutinin-stimulating substance 

 (agglutinogen). It is likely that this combination is of a chemical na- 

 ture, since, as we have mentioned, agglutinins result from the injection 

 of bacterial extracts as well as from the introduction of living bacteria. 

 The probability that the process follows chemical laws of combination 

 is furthermore strengthened by the work of Joos 4 and others, who 

 have demonstrated that definite quantitative relations exist between 

 the agglutinin-stimulating substances and the agglutinins. Every 

 agglutination reaction, therefore, will vary in its degree of com- 



1 Hoffmann, Hyg. Rundschau, 1903. 2 Nicolle, Ann. de 1'inst. Pasteur, 1898. 



3 Jorgensen and Madsen, Festschrift, Kopenhagen, 1902. 



4 Joos, Zeits. f . Hyg., xxxvi, 1901. 



