226 INFECTION AND RESISTANCE 



ers, although the fundamental principles underlying such changes 

 are not at all clear. 



Joos 25 was the first to study agglutination with particular refer- 

 ence to the effects upon the reaction of heating both the antigen and 

 the antibody. On the basis of extensive and complicated experiments 

 upon the agglutinin produced in horses by immunization with heated 

 and unheated typhoid bacilli, he drew the conclusion that agglu- 

 tinogen (agglutinin-inducing substance) in bacteria was not a single 

 element but consisted of at least two definite parts of which he speaks 

 as a and j3-agglutinogen. a-agglutinogen is a constituent of the 

 living bacteria, and is easily destroyed. at 60 to 62 C. The /?-agglu- 

 tinogen is also present in normal bacilli, but is more heat-resistant 

 and will withstand 60 to 62 C. for several hours. The injection 

 of living unheated bacilli then induces the formation of both a 

 and /?-agglutinin, which have respectively a particular affinity for 

 a and /?-agglutinogens. The injection of heated bacilli, on the 

 other hand, induces the formation only of ^-agglutinin and not a 

 trace of a-agglutinin. The a-agglutinin is considerably heat- 

 resistant, resisting 60 to 62 C., whereas the /3-agglutinin loses its 

 agglutinating property when heated to 60 C. The a-agglutinin 

 is entirely incapable of uniting with /?-agglutinogen. However, 

 /?-agglutinogen can combine or react with both the a and (3 con- 

 stituents of the bacilli. For this reason Paltauf has spoken of agglu- 

 tinin produced with the heated bacteria as "umfanglicher." This 

 is a point of great interest, and if Joos is right is, of course, of con- 

 siderable practical importance. 



However one may look upon these experiments, as well as the 

 similar ones of other workers, it seems established that heating bac- 

 teria leaves them still capable of inciting agglutinins powerfully 

 and rapidly, perhaps of an "umfanglicher 7 ' nature than those pro- 

 duced with the native cells. 



Heating bacteria may also alter their agglutinability. Thus, ac- 

 cording to Eisenberg and Yolk, 26 heated above 65 C. the bacteria 

 no longer agglutinate in the presence of specific immune serum, but 

 still absorb agglutinin. Eisenberg and Volk, therefore, distinguish 

 between a heat-sensitive constituent of the antigen, which is 

 particularly associated with the clumping, whereas the thermo- 

 stable substance represents the haptophore or combining portion. 

 It seems simpler, in this case also, to assume a change in the 

 colloidal stability of the bacteria by heating than to seek it in a 

 differentiation into combining and agglutinable parts of the same 

 antigen. 



The points raised by Joos' work have been followed up particu- 



25 Joos. CentraM. f. Bakt., Vol. 33, 1903. 



20 Eisenberg- and Volk. Zeitschr. f. Hyg., Vol. 40, 1902. 



