AGGLUTININS, AGGLUTINOIDS AND PROAGGLVTINOIDS 149 
typlioid bacilli if the virus is brought into contact with the tissue 
cells. As a general rule the concentration of a specific agglutinin 
is greater in the blood stream than in the tissues of the body. 
Preparation of Specific Agglutinating Sera.— Specific agglutinating 
sera for exjjeriniental purposes are best obtained from rabbits, whose 
serum normally contains no agglutinin. Several, usually three to 
five intravenous injections of 1, 2, 3 and 5 loopfuls respectively of 
killed cultures of typhoid bacilli at five- or six-day intervals, produce 
powerful agglutinating sera. The animal is bled about two weeks 
after the last injection. For large amounts of agglutinating sera 
horses or asses must be used. 
Properties of Agglutinins.— Agglutinins are of unknown chemical 
composition, but they may be separated from solution by those pre- 
cipitants which throw down globulins, and they may be removed 
from solution by absorption in animal charcoal. Toward heat they 
are moderately resistant, usually remaining active after an exposure 
of twenty minutes to 55° C, a degree of heat sufficient to inactivate 
complement. Agglutinins, therefore, appear to be quite distinct 
from bacteriolysins. The temperature at which agglutinins are 
destroyed depends somewhat upon their specificity, agglutinins for 
plague bacilli being more sensitive to moderate heating than typhoid 
agglutinins. The reaction of the medium also affects their stability. 
Alkalis, even in very dilute solution, rapidly destroy agglutinins; acids 
are somewhat less harmful. Naturally the duration of exposure to 
these various agents exercises an important influence upon their 
resistance. Agglutinins do not appear to pass through parchment 
membranes, but it is stated that agglutinogen will slowly diffuse under 
similar conditions. This would suggest that the agglutinin molecule 
is larger than the agglutinogen molecule. Preserved in a dry state, in 
a cool place away from light, agglutinins preserve their properties 
unimpaired for months. In solution, and upon standing, agglutinins 
rapidly lose their property of clumping bacteria, but they still retain 
their original ability to unite firmly with bacteria. Ehrlich designates 
agglutinins which have lost their ability to cause clumping but still 
retain their combining power for agglutinogen, agghdinoids. In his 
terminology they are side-chains of the second order which have lost 
their agglutinophore (ergophore) group. Krumwiede, Cooper and 
Provost, however, ha\'e found that the phenomena ascribed to aggluti- 
noids by Ehrlich may be reproduced by the addition of certain sub- 
stances apparently of colloidal nature, to agglutination systems. ' 
Agglutinins acting in neutral salt-free media also fail to cause clumping 
of bacteria, but in this case the addition of a small amount of NaCl or 
even some weak acid very soon brings about a typical reaction.- This 
and similar observations have attracted attention to the similarity 
between the precipitation of bacteria, to which agglutinin is anchored, 
1 Jour. Immunol., 1925, 10, 93. 
2 Bordet: Ann. Inst. Pasteur, 1899, 13, 225- 
