AGGLUTINATION 541 



destroyed by heating, and we know of no corresponding action in 

 the case of an immune-body. The subject is one of considerable 

 complexity, but it may be said that the most important varia- 

 tions in the opsonic content observed in infections depend on 

 the specific immune-opsonins, though the presence of immune- 

 body may play a part in raising the index by leading to the 

 union of more normal-complement-opsonin. 



Further study will be necessary before the exact relationships 

 of these substances are fully understood, and other questions with 

 regard to them have jis yet scarcely been touched upon. 

 Increased phagocytic action had long been known by the work 

 .f Metelmikotf to be associated with the development of active 

 immunity, and the theory of stimulation of leucocytes was 

 supported liv 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) A<i<tliitin<itloi>. Charrin and Roger 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. Griiber 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 ayylutinins. 



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 inquire 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 may be said to be 

 observed generally in bacterial infections, though the degree of 

 the phenomenon and the facility with which it can be noted vary 

 greatly in different cases. Details will be found in the chapters 

 dealing with the individual diseases, etc. Furthermore, the 



