55 



as to stimulate the production of antibodies. This third factor 

 is very difficult to define. It is usually described by saying 

 that the antigen must be " foreign " to the animal body in 

 which an immune response is to be excited ; the difficulty is to 

 give precise expression to what is vaguely described by saying 

 that the " foreign " protein must be different from the protein 

 constituents of the animal body with which it reacts. One 

 may say that the antigen, being introduced parenterally, must 

 cause some disturbance in the general metabolism of the body, 

 and thereby stimulate the production of some new mechanism, 

 possibly an enzyme, for dealing with the altered conditions. 

 But this disturbance need not be great. No marked changes 

 in protein metabolism need result from the introduction of 

 foreign protein; and a single small dose of antigen may give 

 rise to a plentiful supply of antibody. 



It is obvious that this difference between the chemical or 

 chemico-physical structure of an antigen and the proteins of 

 the animal to be immunised must be retained long enough for 

 the antigen to act as a stimulus. Hence good antigens possess 

 molecules of large size and are not readily broken up. In 

 accordance with these observations, it is found that antigenic 

 properties are readily lost when the antigen is exposed to the 

 action of proteolytic ferments. 



It is of interest to note, however, that some antigenic 

 capacities may, in a modified form, survive this treatment. 

 For example, Obermeyer and Pick exposed bovine serum to 

 prolonged tryptic digestion and found that the digest produced 

 an immune serum which formed a precipitate with the digest 

 but failed, or almost failed, to react with the undigested material. 

 But the specificity characteristic of the animal species "was 

 retained completely ; their immune serum gave no reaction 

 with the tryptic digest of horse serum. 



This example of antigenic change resulting from a process 

 analogous to metabolism in the body should be borne in mind 

 as a possible explanation of antisera which are efficient in vivo 

 but do not react with antigen in vitro. 



Influence of Physical Conditions on Specificity. 



The most important of these conditions is the fact that the 

 reactions of antigens are inseparably associated with their 

 colloidal state. Hence it follows that reactions between antigens 

 and antibodies are conditioned by the laws which govern the 

 interaction of colloids. 



A few of the more important consequences which may follow 

 from this circumstance are worth considering. 



1. Quantitative Relationships. — One has to remember that, 

 in addition to qualitative conditions of a chemical or physico- 

 chemical nature, the quantitative relationships of the interacting 

 substances are of special importance in colloidal reactions. In 



