240 M. R. IRWIN 



We should avoid misunderstanding about the meaning of the terms com- 

 monly used in immunological literature. For example, the word antigen was 

 originally defined as any substance which, when introduced parenterally into 

 an animal, would invoke the production of antibodies. This definition would 

 now be extended to include any substance which will react visibly with an 

 antibody. And an antibody would be defined as a constituent of the serum 

 which reacts with an antigen in any of several ways. The circle of reasoning 

 here is obvious. However, insofar as chemical studies of various antigens have 

 contributed to an understanding of their specificities, the specificities have 

 always been associated with structural differences of the antigenic sub- 

 stances. On the other hand, the reasons underlying the specificities in re- 

 activity of the antibodies are almost completely unknown, although it is 

 known that the antibodies are intimately associated with the globulins of the 

 serum, and in fact may constitute the gamma globulins of the serum. 



CELLULAR ANTIGENS IN HUMANS 



As our first example of these antigenic substances, let us consider the well 

 known and extensively studied O, A, B, and AB antigenic characters, or 

 blood groups, of human cells. Following their discovery by Landsteiner 

 (1900, 1901), it soon became clear that these substances were gene controlled. 

 At the present time, the theory of three allelic genes, as postulated by Bern- 

 stein (1924) on statistical grounds, is generally accepted. The two other the- 

 ories proposed for their inheritance — independent and linked genes, respec- 

 tively — are fully discussed by Wiener (1943). Landsteiner noted that the 

 serum of certain individuals would agglutinate (clump) the cells of other 

 individuals, and from this observation the reciprocal relationship between the 

 presence and absence of each antigen and its specific antibody has been 

 elucidated. 



A or B Antibody 



Antigen on of the 



Group the Cells Serum 



O None Anti-A, Anti-B 



A A Anti-B 



B B Anti-A 



AB AB None 



It may readily be seen that the presence of an antigen, as A, on the cells 

 is accompanied by the presence of the antibody (anti-B) for the contrasting 

 antigen, as B, in the serum, and vice versa. If both antigenic characters are 

 found on the cells, as in AB individuals, the serum contains no antibodies. 

 While if neither A nor B is present on the cells, the serum contains both anti- 

 A and anti-B. 



These phenomena pose the question whether the genes producing the cel- 

 lular substances also have an effect on the antibodies of the serum. That is, 

 does the gene which is responsible for the O antigen (which is definitely an 

 entity but is less reactive than A and B) also effect both anti-A and anti-B 



