I 



CHAPTER L 

 ANTIGENS AND THEIR SPECIFICITY' 



H. GIDEON WELLS 



Otho S. A. Sprague Memorial Institute and the University of Chicago 



DEFINITION 



An "antigen" is a substance which incites the development of specific reactive 

 agents, "antibodies," when introduced under proper conditions into the circulation 

 or tissues of an animal. These antibodies are demonstrated by their producing 

 recognizable reactions when the serum (or tissues) of the immunized animal is brought 

 into contact with the antigen, the so-called "reactions of immunity," e.g., precipitin, 

 agglutinin, complement fixation, and anaphylaxis reactions. Because of this con- 

 ventional method of demonstrating the existence of antigens and antibodies, it has 

 sometimes been assumed that all substances giving specific reactions with antibodies 

 are antigens, but this is not always true, and so a deplorable confusion has arisen as 

 to the use of the term "antigen." This is particularly noticeable in the case of the 

 Wassermann test and related reactions used in the diagnosis of syphilis, for the so- 

 called "antigen" in these reactions is not antigenic in the sense of being able to incite 

 the formation of specific antibodies when injected into animals. The essential differ- 

 ence between true antigens and the specific immunological reactive agents which are 

 not antigenic is clearly shown by recent work on the immunological behavior of 

 separated components of pneumococci by Dochez, Avery, Heidelberger, and others. 

 It has been shown that pneumococci, and probably numerous other bacteria, contain 

 varied components with distinctly different immunological behavior. One fraction of 

 a solution of the pneumococcus substance, which seems to be related to nucleoprotein, 

 is strongly antigenic, but the antisera it engenders will react as well with the nucleo- 

 proteins of one type of pneumococci as another; i.e., the pneumococcus nucleoprotein 

 is antigenic, but the antibodies it engenders are not specific for pneumococcus types, 

 although specific for the pneumococcus species. Another fraction seems to be com- 

 posed of a complex carbohydrate, free from protein, which is not antigenic, since it 

 engenders no antibodies when injected into animals; but it does react specifically with 

 antiserum obtained by immunizing with the same type of penumococci that furnishes 

 the carbohydrate. Here is an example of a non-antigenic bacterial substance which 

 reacts with more limited specificity with an immune serum than a true antigenic 

 substance of the same bacteria.^ 



In this discussion the term "antigen" will be used to indicate only substances 

 exhibiting antigenic activity. Non-antigenic substances which react specifically with 



' Bibliography to 1924 given by H. Gideon Wells in The Chemical Aspects of ImmimUy, chaps, 

 ii and iii, Chemical Catalog Co., 1925. 



^ See Avery, O. T., and Heidelberger, M.: J . Exper. Med., 38, 81. 1923; 42, 347, 367, 701, 700, 

 727. 1925. A good discussion of this topic is also given by J. Pryde, in Recent Advances in Biochemistry. 

 Blakiston, 1926. 



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