AGGLUTINATION 485 



immunity and the theory of stimulation of leucocytes was 

 supported by many. The work on opsonins has caused a swing 

 of the pendulum in the other direction, and points to the 

 development of anti-substances in the serum as the all-important 

 factor. It remains to be determined to what extent the opsonic 

 and directly bactericidal properties taken together will explain 

 the phenomena of natural and acquired immunity. 



(c) Agglutination. Charrin and Koger in 1889 observed 

 that when the bacillus pyocyaneus was grown in the serum of 

 an animal immunised against this organism, the growth formed 

 a deposit at the foot of the vessel ; whereas a growth in normal 

 serum produced a uniform turbidity. Gruber and Durham, in 

 investigating Pfeiffer's reaction, found that when a small quantity 

 of an anti-serum is added to an emulsion of the corresponding 

 bacterium, the organisms become agglutinated into clumps, 

 this phenomenon depending upon the presence of definite bodies 

 in the serum called agglutinins. 



It had been already found that the serum of convalescents 

 from typhoid fever could protect animals to a certain extent 

 against typhoid fever, and, in view of the facts experimentally 

 established, it appeared a natural proceeding to enquire whether 

 such serum possessed an agglutinative action and at what stage 

 of the disease it appeared. The result, obtained independ- 

 ently by Griinbaum and Widal, but first published by the latter, 

 was to show that the serum possessed this specific action shortly 

 after infection had taken place; in other words, the develop- 

 ment of this variety of anti- substance can be demonstrated at 

 an early stage of the disease. Agglutination is also observed in 

 the case of cholera, Malta fever, bacterial dysentery, glanders, 

 plague, infection by Gartner's bacillus, b. coli, etc. Furthermore 

 the phenomenon is not peculiar to bacteria ; it is seen, for 

 example, when an animal is injected with the red corpuscles of 

 another species, haemagglutinins appearing in the serum, which 

 have a corresponding specificity. 



The physical changes on which agglutination depends cannot 

 as yet be said to be fully understood. Gruber and Durham 

 considered that the agglutinin produced a change in the envelope 

 of the bacterium, causing it to swell up and become viscous, and 

 the facts first established appeared to be in favour of this view. 

 On the other hand, this is not the full explanation, as it has 

 been shown by Nicolle and by Kruse that if an old bacterial 

 culture be filtered through porcelain, the addition of some of 

 the corresponding anti-serum produces a sort of granular 

 precipitate in it, and that when, as in the agglutination of bacteria, 



