ADJUSTMENT TO INFECTIOUS DISEASE 421 



had best consult the thorough and critical discussions of 

 this subject by Wells in his "Chemical Aspects of Immunity." 

 The chemical facts which we have outlined make it quite 

 plain that in stimulating the cellular responses the so-called 

 antigenic substances unite primarily, because of their 

 non-diffusibihty, with the cell surfaces; but it is rendered 

 hkely by a number of experiments that the antigenic sub- 

 stance may secondarily be incorporated in the cell sub- 

 stance. Since, as we have seen, a relatively small part of 

 the protein molecule is associated with the specificity, 

 it may well be that the union with the cell is something 

 like an orientation of the foreign protein molecule in the 

 cell membrane, reacting through the group which carries 

 its specific affinity for the cell substance. What happens 

 after this is entirely mysterious. That the cell should be 

 capable of responding by an individually different reaction 

 product to almost any number of foreign proteins and, in 

 addition to this, to a large variety of chemically altered 

 products of each of these proteins is an easily demonstrable 

 fact for which no theory is at present adequate. The only 

 explanation of this state of affairs which has ever been 

 ventured is the side chain theory of Ehrlich, which is actually 

 nothing more than a restatement, in theoretical language, 

 of the fundamental observations. It states, in substance, that 

 after the antigen has united with the cells, the particular 

 radicles of the protoplasm which possessed the specific 

 affinity for the antigen are thrown out of action and must be 

 reproduced by the cell for its functional purposes. It is 

 assumed that continuous stimulation of the cell in this 

 manner, by repeated saturation of the particular cell con- 

 stitutents involved, leads to an overproduction of these 

 substances, which finally takes place to such a degree that 

 they are discharged into the circulation. These so-called 

 "cell receptors" become the circulating antibodies. Since 

 they possess a specific affinity for the antigen, they now 

 unite with it in the circulating blood. The theory is spoken 

 of as the "side chain theory" because, by analogy with 

 organic chemistry, Ehrlich conceived the cell receptors as 

 "side chains" of the protoplasm which could cover many 

 specificities because of the great complexity of this material. 



