170 CHEMISTRY OF THE IMMUNITY REACTIONS 



influence their reaction; these physico-chemical factors greatly com- 

 plicate the possibility of reaction between two colloids, and to these 

 influences are added the influence of the chemical structure in deter- 

 mining subsequent chemical reactions. It would seem possible that 

 the existence of all these factors may account for specificity, it being 

 necessary for each one of a long series of both physical and chemical 

 adjustments to agree perfectly in order that reaction may take place 

 — 'just as in a combination lock one lever after another is thrown by 

 the proper manipulation of the dial, and only when all the long series 

 of levers is in just the proper position does the bolt engage and the 

 lock open.^^ 



The studies of Pick and his colleagues, amplified somewhat by other 

 investigations, have led to the following view of the chemistry of 

 specificity: There exist two sorts of specificity in each protein mole- 

 cule; one of these is easily altered by simple physical measures, e. g., 

 heat, cold, partial coagulation, etc., without essentially changing the 

 chemical composition of the protein. When so altered the antigenic 

 properties of the protein are likewise altered, in that the antibody 

 it engenders differs somewhat in the scope of its reactivity from the 

 antibody engendered by the original unaltered protein; but the altera- 

 tion does not affect the species characteristics of the antigen. Thus, 

 a heated antigen may engender precipitins that will react with this 

 heated antigen, but not with similar heated proteins from other 

 species of animals, while the antibodies engendered by the same but 

 unheated antigen will not react with the heated protein. 



The other sort of specificity is not so easily affected, only marked 

 chemical alterations of the antigen modifying it, and this concerns the 

 species characteristics of the antigen. This fundamental species speci- 

 ficity seems to be closely related to the aromatic radicals of the protein 

 antigen, for it is affected by introducing into the protein molecules 

 substances which are known to combine with the benzene ring, e. g., 

 iodin, diazo and nitro groups. Proteins thus chemically altered will 

 act as proteins foreign to animals of the species from which they are 

 derived, and the antigens they develop are devoid of species specificity, 

 although quite specific for proteins like themselves; e. g., a nitro- 

 protein made by treating rabbit serum protein with nitric acid, will, 

 if injected into even the same rabbit, cause the formation of antibodies 

 which will react with this same nitro-protcin, and also with nitro- 

 protcins derived from entirely different species or even from plants, — 

 but it reacts only with nitro-proteins. It is also possible to cause 

 chemical modifications analogous to the physical modifications previ- 

 ously mentioned, which change only the scope of specificity of the 



" The "resonance theory" of Traube assumes that the surface forces of react- 

 ing substances must harmonize, just as the vibration of one tuning fork starts 

 vibrations in another fork only when the two are in liarniony, or as electromag- 

 netic waves incite resonance plienomena (see Zeit. f. Immunitat., 1911 (9), 246 

 and 779). 



