THE CHEMICAL NATURE OF DIFFERENTIALS 569 



cerns the possibility of synthesizing antigens by combining a substance, which 

 alone is unable to produce antibody formation, with a foreign, heterogenous 

 protein or serum and thus to obtain a complete antigenic substance. The 

 serum in this case acts as "carrier" for the specific substance, the hapten, 

 which latter does not need to be a protein. Landsteiner first synthesized in 

 this way a hapten and a protein carrier in the case of the Forssman antigen 

 by combining the alcohol extract from heterogenetic organs with hog serum. 

 As in Obermayer's and Pick's observations, the protein in the original 

 antigen and in the substance with which the antibody is tested do not need 

 to be identical, and if they are very different, then the specificity may be 

 limited to the hapten. The hapten alone may be able to react with the anti- 

 body, provided it possesses a sufficiently large molecule, and especially if 

 this molecule has colloidal properties. Landsteiner succeeded by these means 

 in separating the ability of an antigenic substance to elicit the production 

 of an immune substance from its ability to react with such an immune 

 substance, and he furthermore recognized as a distinct property of an antigen, 

 or of a part of an antigen, the power to inhibit in a specific manner the 

 reaction between antigen and immune substance. While as stated, the first of 

 these functions requires as a rule a combination of a hapten, which may be a 

 non-protein substance, and a carrier of a protein nature, the latter two func- 

 tions may be exerted by the hapten alone. 



In studying antibodies against azoproteins, Landsteiner found that the 

 action of an antibody, which developed against a well defined chemical 

 substance, was not confined to the antigenic substance, but it included sub- 

 stances chemically similar to the homologous antigen. Landsteiner concluded 

 that the serological cross-reactions of the proteins of related animals are due 

 to similarities in the chemical structure of these substances. This constitutes 

 at least one of the possibilities of such cross-reactions. 



As to the inhibiting effect of haptens, Landsteiner extended an early 

 observation of Halban and thus found that even in cases in which the hapten 

 does not undergo a visible reaction with the antibody, its presence may be 

 recognized by its specific inhibiting effect on precipitation, complement fixa- 

 tion, and hemolysis, which would otherwise occur if the full antigen were 

 brought into contact with the antibody. It could furthermore be shown that 

 the reaction between hapten and antibody was the more specific the more 

 complex the structure of the hapten. If more simple substances served as 

 haptens, the reaction did not need to be specific. Again, it was especially the 

 aromatic groups which tended to determine the specificities in the antigen- 

 antibody reaction. By means of this reaction Wormall showed that if iodine 

 enters in combination with the tyrosin group of the protein, it calls forth a 

 new specificity, and that 3.5 iodotyrosin can specifically inhibit the reaction 

 between iodoprotein and its antiserum. 



We have mentioned already that the carrier protein, as a rule, should be 

 of a heterogenous nature, but in certain cases a homoiogenous, and, perhaps, 

 even an autogenous serum may exert a similar effect. Thus, as mentioned, 

 Klopstock and Selters believe that in the guinea pig a combination of 



