104 AGGLUTINATION. 



that for paratyphoid in the fourth row diminishes, while the titer in the second row for 

 paratyphoid remains the same. 



c. If a mixed infection exists, the agglutination titer in the first and fourth row dimin- 

 ishes and in the second and third row remains the same. 



In this connection a few exceptions may be mentioned: 



A serum which is kept for a long time, frequently loses part 

 Agglutinoids. or even all of its agglutinating titer. Whereas it formerly 

 agglutinated in the strength of i : 1000, it may now become 

 inactive in dilutions even of i : 10. The first thought that arises in explana- 

 tion of this is that the serum has perhaps degenerated and the aggtutinins 

 destroyed. If, however, further dilutions are made, i : 100 may show mild, 

 while i : 500 strong agglutination. This, first of all, demonstrates that 

 agglutinins are still present, although diminished in amount, and second, 

 that another substance has arisen which in the stronger concentrations 

 interferes with agglutination. A simple experiment explains this. 



If the test-tube containing the serum dilution i : 10 and the non-agglutinated bacteria 

 be centrifugalized, the serum removed and the bacteria mixed with a known strongly 

 agglutinating serum, it will be found, that the bacteria have become inagglutinable. 

 Substances of certain kinds have combined with the bacteria and prevented them from 

 undergoing agglutination. These substances are strongly specific, acting only upon 

 homologous bacteria. Their origin can also be demonstrated. 



An agglutinating serum which is heated to 65 or 70 C. loses its agglutinating power 

 but the substance interfering with the subsequent agglutination has remained. Ehrlich 

 explains the situation as follows : He claims that agglutinins are built complexly ; that they 

 possess a binding (haptophore) group by means of which they unite with the bacteria 

 (agglutinogen) and a second group (ergophore or agglutinophore) by virtue of which 

 agglutination results. If serum is kept for a long period of time, or exposed to high 

 temperature, many of the ergophore groups are rendered inactive, while the haptophore 

 groups being more resistant remain with their full potentialities, and unite with bacteria. 

 Agglutinins possessing only their haptophore groups are known as agglutinoids. They 

 combine with the bacteria, and still do not agglutinate them, but at the same time prevent 

 other agglutinins from acting. If this old agglutinoid and agglutinin containing 

 serum is diluted, so few of both of these substances remain that the bacteria can 

 absorb both, allowing the relatively few agglutinins to manifest their activity. 



It is important to note in this respect, that occasionally even a fresh, highly valent 

 serum, will present a tendency towards interfering with the agglutination processes. 

 This is also explained by the existence of agglutinoids a fact as yet not definitely proven. 



Another finding, only encountered in exceptional cases, is the existence 

 of the so-called non-agglutinable strains of bacteria. These give all the 

 characteristics of the general class of bacteria to which they belong, but are 

 not agglutinated by their respective serum; as, for example, a strain of 

 typhoid bacilli, which are not agglutinated by any typhoid serum. The 

 only positive proof that they are typhoid bacilli, is the ability to produce by 

 their employment an active immunity against fully virulent typhoid bacteria. 



Non-agglutinable strains of bacteria can be isolated especially from the lower animals. 

 At times, however, they regain their agglutination property when they are grown in 



