126 Immunity 



when introduced into serum of animals infected with or 

 immunized against cultures of Bacillus pyocyaneus ceased 

 their active movements, became aggregated in clusters and 

 settled to the bottom, leaving the fluid clear. Observations 

 confirming and enlarging upon the observation were made 

 by MetschnikofT, * Issaefff and others. Gruber and DurhamJ 

 made an elaborate and now classic study of the subject, first 

 employing the term "agglutination" to the phenomenon, 

 and "agglutinins" to the substances in the serum by which 

 it might be brought about. They found that when cholera 

 or typhoid bacilli are mixed with their respective immune 

 serums, the organisms lose motility and become aggregated 

 in clusters, masses or "clumps." They further showed 

 the reaction to be specific within certain limitations, i. e., 

 typhoid immune serum agglutinated typhoid-like bacilli 

 but no others, etc., and they saw in the phenomenon a 

 practical means for the differentiation of different, closely 

 related bacteria, an application that has, indeed, become a 

 useful one. 



It remained for Widal to show that it had a much more 

 important application, in that the micro-organism being 

 known, the effect produced by a serum upon it would be an 

 indication of the past infection of the animal from which 

 the serum was secured. The first practical application was 

 made in connection with typhoid fever, and the brilliant 

 success attending it had led to the test being known as the 

 "Widal reaction" (q-v.). 



The agglutinins are stable substances that resist drying 

 and can be kept dry and active for years. Widal and Sicard 

 found that they pass with difficulty through a porcelain 

 filter and do not dialyze. They are precipitated in part by 

 1 5 per cent, of sodium chloride that throws down fibrinogen, 

 and further precipitated with magnesium sulphate, which 

 throws down globulins. They therefore think they are inti- 

 mately related to the globulins and to fibrinogen. A tem- 

 perature of 60 C. diminishes their activity, but they are not 

 destroyed below 80 C. Sunlight has no effect upon them. 



Metschnikoff looks upon agglutination as preliminary to 

 phagocytosis and to bacteriolysis, and thinks it the effect 

 of enzymes in the serum preparing and clustering the bacteria 



*"Ann. de 1'Inst. Pasteur," v, 1891. 



t"Ann. de 1'Inst. Pasteur," vn, 1893. 



t "Mtinchener med. Woch.," 1896, No. 9. 



"Societe Medicale des Hopitaux," June 26, 1896. 



