FITZGERALD AND FRASER 815 



1921, showed that spontaneous agglutination of some species of bacteria may be pre- 

 vented by employing 0.42-0.1 per cent saline suspensions of micro-organisms. Acid 

 agglutination suggested by Michaelis, Beniasch, and others has not been found to be 

 of any service even in the differentiation of bacterial species which are not readily 

 susceptible to serum agglutination. One of us (J. G. F.) some years ago showed that 

 acid agglutination did not aid in the differentiation of closely related species of 

 bacilli which constitute the encapsulated, gram negative group. 



Specific or immune agglutinins appear in the body fluids of man and lower animals 

 during the course of various infectious diseases. They may also be produced by the 

 injection of bacterial and other antigens. In man, vaccination against typhoid and 

 paratyphoid fever, dysentery, and cholera is marked by the appearance of agglutinins 

 which persist for varying lengths of time. Intravenous, intraperitoneal, or subcu- 

 taneous injection of emulsions of dead or attenuated bacteria, at suitable intervals, 

 usually repeated on several occasions, will give rise to potent agglutinating sera. As is 

 the case in other types of antibody response to the injection of antigens, some time 

 elapses after the completion of active immunization before the agglutinin concentra- 

 tion is high. The degree of response and the length of this period varies in different 

 animals and with different antigens. Where the injection of emulsions of one species 

 of bacteria results in the appearance of agglutinins for this and other closely related 

 species, dilution may be resorted to, when the major agglutinins will be found in much 

 higher dilutions than the minor. Castellani,' in 1902, introduced the procedure of ab- 

 sorption of agglutinins which in cases of mixed infection may be employed to remove 

 certain of them while leaving others. This depends upon the fact that, when an 

 animal is immunized against more than one species of bacteria, major and minor 

 agglutinins may be formed for each species. 



Agglutinins resist heating to 60° C, but above this temperature they are gradu- 

 ally destroyed and at 75° C. destruction is complete. They are not dialyzable and are 

 precipitated in the globulin fraction of serum. They are active in a neutral or slightly 

 acid menstruum. Agglutinins in dried serum will persist for a long time. The iso- 

 electric point of a serum globulin fraction in which the agglutinins are salted out is 

 pH 5,5. The iso-electric point of agglutinins, according to Szent-Gyorgi,^ lies between 

 pH 5.69 and 5.39. While agglutination is favored by a temperature of 37° C, it goes 

 on more slowly at lower temperatures. 



A hypothesis to explain the mechanism of practically all immune procesess was 

 formulated by Ehrlich and is known generally as the "side-chain theory." It is now 

 generally agreed that the explanation of bacterial agglutination therein outlined is 

 probably not the correct one. Further reference, therefore, to this conception of the 

 phenomenon seems unnecessary here.^ 



The agglutination of bacteria (and of red blood cells) by their homologous im- 

 mune sera is a specific antibody-antigen reaction. Bordet,-* in 1896, showed that dis- 



' Castellani, A.: Ztschr. f. Ilyg. u. Iiifektionskrankk., 40, i. 1902. 



^ Szent-Gyorgi, A.: Biochem. Ztschr., 113, 36. 1921. 



^ Cf. chap. Ixxxi, by Dr. Manwaring, in this volume. 



'' Bordet, J.: Traite de rimmunite dans ies maladies infectienses. Paris: Massons & Cie, 192c. 



