66 CLINICAL BACTERIOLOGY. 



microscope. When excessive dilutions are employed, the 

 reaction may escape macroscopic observation ; whereas, 

 under the microscope, after a time (from one minute to two 

 hours), agglutination may yet be observed. 



In addition to typhoid-cultures, cholera-cultures, and 

 coli-cultures, the reaction of Gruber has been demonstrated 

 with numerous other, and also nonpathogenic, bacteria. 

 The agglutinating property of the serum is, further, not 

 present immediately after introduction of the bacteria into 

 the animal body ; at least three and a half, and generally 

 even five, days must elapse before this appears. Besides the 

 blood-serum, the reaction of Gruber may be obtained in an 

 intense degree with the serous contents of blisters induced 

 by vesication, in lesser degree with milk, and in still less 

 degree with urine, dropsical fluid, exudates, bile, tears, and 

 aqueous humor of the respective animals and human beings. 



Gruber considered the phenomenon of agglutination as 

 a reaction of immunity, and attempted to base upon it a new 

 theory of immunity, to which we shall later refer. A not 

 inconsiderable advance was made in this connection when 

 Widal showed that agglutination, at least in human beings, 

 represents a reaction of the period of infection. Widal dem- 

 onstrated that the serum of typhoid-fever patients at the 

 end of the first or at the beginning of the second week of 

 the disease most distinctly yields the agglutination-phe- 

 nomenon with typhoid-bacilli (Widal-Gruber reaction). 

 This fact is of the greatest importance from a practical 

 point of view. It renders possible the diagnosis of typhoid 

 fever with the aid of the serum of a suspected patient. The 

 same appears to be true for Asiatic cholera and other dis- 

 eases. We shall fully discuss the so-called serum-diagnosis 

 in the special section. (See Typhoid Fever.) 



The nature of the agglutinating substance has not yet 

 been determined despite numerous investigations, especially 

 on the part of Widal. It appears to be quite resistant, as 

 exposure of the serum to a temperature of 60 C. (140 F.) 

 for an hour fails to abolish the agglutinating phenomenon ; 

 this result is obtained only after exposure to a temperature 

 of 80 C. (176 F.). The reaction of Gruber may be 

 obtained also with dead bacilli. The bacteria are best de- 

 stroyed with formol, and they can then be kept for weeks 

 without losing in the slightest degree their sensitiveness to 

 the action of the serum. From this Widal arrives at the 



