350 IMMUNOGENETICS 



antibodies may fail to produce a visible reaction for numerous reasons other than 

 univalence, and the careless use of this term suggests an explanation for their behavior 

 which should be applied in any particular case only when this explanation has been 

 established in fact. Univalence in a proper sense can derive from several different 

 causes: some antibody maybe univalent when it is made, an originally bivalent anti- 

 body may be split into two univalent fractions, or one of the valence sites may be 

 covered by aggregation, sometimes with quite different materials such as serum 

 albumin. 



Aside from their heterogeneity in respect to visible effect produced on the antigen 

 under test, antibodies are heterogeneous in numerous other respects as well. Of 

 primary concern is their heterogeneity with regard to specificity ; some antibodies react 

 essentially only with the antigen that induced their formation, whereas others cross-react 

 with related antigens as well. The directions of these deviations in specificity vary 

 within the heterogeneous antibody population, so that within the limits imposed by the 

 general concept of serologic specificity there is a smear of subspecificities in any given 

 antiserum. Recognition of this kind of heterogeneity is important to interpretation of 

 antiserum reaction in immunogenetics. 981, 985 Perhaps a related type of antibody 

 heterogenity involves the avidity with which an antibody combines with its corre- 

 sponding antigen. Variations in avidity can be conceived as variations in the closeness 

 of fit and in the extent of mutual complementarity between the combining sites of the 

 antigen and antibody. Operationally, avidity is generally expressed in the behavior 

 of the system upon dilution. The equilibrium, 



Antigen + Antibody ^ (Antigen-antibody Complex) 



lies to the right with avid antibody, to the left with antibody of lesser avidity. Anti- 

 body is also heterogeneous on physical-chemical grounds, as measured by solubility, 

 electrophoretic behavior, chromatography, and ultracentrifugation. Changes in the 

 character of antibody, with regard to specificity, avidity, and other characteristics, 

 commonly occur during the course of an immune response. 663 



Some types of immune responses have not been shown to involve the participation 

 of classical, plasma antibody. Among these are reactions that appear to be strictly 

 cell borne and cell mediated, such as the delayed hypersensitivity reactions, 770 and at 

 least some types of tissue-transplant rejection. 861 Except for some reference to tissue- 

 transplant rejection, however, consideration here will be limited to plasma antibody 

 responses and genetic test systems based on such antibody. 



IMMUNOGENETICS OF RED BLOOD CELLS 



Procurement of antisera. — In general, it is the immune response resulting from 

 exposure to a foreign antigen that provides the most useful tools in immunogenetics. 

 In many important instances, however, antibody-like materials which react specifically 

 with the red blood cells of other individuals are normally present in the plasma of 



