SENSITIZING ANTIBODIES 287 



duction of microorganisms subcutaneously, intravenously, or intra- 

 peritoneally. The intravenous method seems to give the most 

 abundant and speedy results. 25 The formation of agglutinins is a 

 reaction to the body substances of the bacteria themselves, rather than 

 to their toxic products. Thus agglutinins are produced in response 

 to the introduction of dead bacteria and soluble extracts of cultures. 

 Pathogenicity 26 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 a virulent 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 cap- 

 sulated organisms such as the pneumococcus mucosum and the Fried- 

 lander bacillus, since the capsule seems to insulate such bacteria 

 against reactions witli serum. It is possible to agglutinate such 

 capsulated bacteria often only by the method of Forges, the pre- 

 liminary 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 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. 27 



The Reaction between Agglutinin and Agglutinin-Stimulating 

 Substances (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 combination between the agglutinin and the agglutinin-stimulating 

 substance (agglutinogen). It is likely that this combination is of 

 a chemical nature, since, as we have mentioned, agglutinins result 

 from the injection of bacterial extracts as well as from the intro- 

 duction of living bacteria. The probability that the process follows 

 chemical laws of combination is furthermore strengthened by the 

 work of Joos 28 and others, who have demonstrated that definite 



23 Hoffmann, Hyg. Eundschau, 1903. 

 "Nicolle, Ann. de 1'inst. Pasteur, 1898. 



27 Jorgensen and Madsen, Festschrift, Kopenhagen, 1902. 



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



