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.' The formation of agglutinins is a reaction to the body- 

 substances 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 ^ 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. 



While agglutinins can be produced with almost all the known bac- 

 teria, there are great differences between various species in the quantity 

 and speed of production, and NicoUe and Thenel ^ have classified bac- 

 teria in three groups according to their power of stimulating the pro- 

 duction of agglutinins in immunized animals. As a rule, the agglutinins 

 appear in the blood of animals three to six days after the introduction of 

 bacteria. From the third to the sixth day they rapidly increase to a 

 maximum 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."* 



The Reaction between Agglutinin and Agglutinin-Stimulating Sub- 

 stances (Agglutinogen) . — ^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 com- 

 bination between the agglutinin and the agglutinin-stimulating sub- 

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

 nature, since, as we have mentioned, agglutinins result from the in- 

 jection 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 ^ and 

 others, who have demonstrated that definite quantitative relations ex- 

 ist between the agglutinin-stimulating substances and the agglutinins. 

 Every agglutination reaction, therefore, wiU vary in its degree of com- 



' Hoffmann, Hyg. Rundschau, 1903. 



2 NicoUe, Ann. de I'inst. Pasteur, 1898. 



a NicoUe et Thenel, Ann. de I'inst. Pasteur, 1902. 



* Jorgensen and Madsen, Festschrift, Kopenhagen, 1902. 



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



