704 ANTIGENS AND THEIR SPECIFICITY 



a small quantity of the monoamino acids which are the chief constituents of most 

 proteins, are non-antigenic. 



FUNDAMENTAL BASIS OF ANTIGENIC ACTIVITY 



As yet we do not know just what structural or chemical features of the protein 

 molecule confer the antigenic function. Probably the colloidal state, or the molecular 

 magnitude which confers non-diffusibility, is a factor, for as far as now known all 

 antigens are colloids. As soon as the protein molecule is disintegrated the antigenic 

 capacity is destroyed. The products of hydrolysis of proteins are almost if not quite 

 devoid of antigenic activity, whether injected alone or all together.' But if the cleav- 

 age products of proteins are resynthesized into larger, colloidal aggregates, the so- 

 called "plasteins," these will be found to be antigenic. 



Apparently the colloidal state of proteins is not alone responsible for their anti- 

 genic action, for it is possible to destroy the antigenic activity of a protein by race- 

 mization without destroying its colloidal character. Racemization is accomplished by 

 treating proteins with alkalies, which alter some of the amino acids so that they lose 

 their optical activity. Dakin believes that the change consists in a rearrangement 

 within the protein molecule whereby the radical 



H 



I 

 R-C-NH., 



I 

 CH3 



undergoes enolization to the form 



R = C-NH. 



CH, 



thus destroying the asymmetry of the a carbon atom, on which the optical activity 

 depends. Such racemized proteins form colloidal solutions, are soluble, coagulable by 

 heat, and give the usual protein reactions, but they are not antigenic. As they also 

 resist digestion by pepsin and trypsin and are not disintegrated when injected into 

 the body, the inference may be made that antigenic activity is in some way related 

 to digestive proteolysis. 



These and other facts have given rise to the hypothesis that antibody formation 

 is a defense reaction against foreign proteins. Under ideal normal conditions no 

 foreign protein gets by the epithelial barriers of the skin and mucous membranes. 

 Whenever these barriers are passed by foreign proteins, whether bacteria, snake 

 venoms, food proteins, or injected therapeutic sera, the body is supposed to protect 

 itself by digestive proteolysis within the tissues, just as ordinarily the foreign proteins 

 are destroyed in the alimentary canal. Zinsser has suggested pertinently that perhaps 

 the reason only colloidal substances serve to arouse the formation of demonstrable 

 antibodies may be their non-diffusible nature. Diffusible foreign substances can enter 

 the cells and be destroyed therein, but to combat non-diflfusible foreign substances the 

 cells must excrete their protective agents in order that these may accomplish destruc- 

 tion outside the cells. 



» See Fink, E. B.: /. hifecl. Dls., 25, 97. 1919. 



