1 26 Immunity 



immunized against it, the bacilli ceased their active movements, 

 became aggregated in clusters and settled to the bottom of the tube, 

 leaving the supernatant fluid clear. Observations confirming and 

 enlarging upon the subject were made by Metchnikoff,* Issaefff 

 and others. Gruber and Durhamf made an elaborate and now 

 classic study of the subject, first employing the term "agglutina- 

 tion" 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 aggre- 

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

 reaction to be specific within certain limitations, i.e., typhoid im- 

 mune serum agglutinated t}^hoid-hke baciUi but no others, etc., 

 and they saw in. the phenomenon a practical means for the dif- 

 ferentiation 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 impor- 

 tant application, in that the micro-organism being known, the effect 

 produced by a serum upon it would be an indication of the infec- 

 tion of the animal from which the serum was secured. The first 

 practical application was made in connection with the diagnosis of 

 t5^hoid fever, and the brilliant success attending it has led to the 

 test being known as the "Widal reaction." 



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 15 per cent, of sodium chlorid that 

 throws down fibrinogen and further precipitated with magnesium 

 sulphate, which throws down globulins. They therefore thought 

 them to be intimately related to the globulins and to fibrinogen. A 

 temperature of 6o°C. diminishes their activity, but they are not 

 destroyed below 8o°C. Sunlight has no effect upon them. 



Metchnikoff looks upon agglutination as preliminary to phagocy- 

 tosis and to bacteriolysis, and thinks it the effect of enzymes in the 

 serum preparing and clustering the bacteria to be taken up by the 

 phagocytes. Ehrhch|| finds in the agglutinins nothing more than 

 receptors of what he denominates the II order, each of which possesses 

 a zymophore and an agglutinophore group. 



Malvoz** found that the addition of chemical substances, such as 

 safranin, vesuvin, and corrosive subHmate, to cultures of the t3T)hoid 

 bacilli would cause their agglutination. Typhoid bacilli retained 

 on the Chamberland filter and washed for a long time, could no 



* "Compte rendu de la Soc. de Biol.," 1899, p. 667. 

 t Ibid., 1893, vn. 



X "Miinchener raed. Woch.," 1896, No. 9. 

 § "Soci6t6 M6dicales des Hopitaux," June 26, 1896. 

 II See Nothnagel's "Specielle Pathologie und Therapie," 1901, vm. 

 **"Ann.del'Inst, Pasteur," 1897, No. 6. ^' ^ ' 



