30 INTRODUCTION TO IMMUNOCHEMICAL SPECIFICITY 



natural preformed receptors of the body cell for various chemical 

 groupings. When the number of such chemical groupings coming in 

 contact with the cell is increased (antigenic stimulus), an excess of 

 such receptors is formed. Some are cast off into the circulation and 

 constitute circulating antibody. This theory was given up when it 

 was found that antibodies could be formed against artificial groupings 

 with which the organism had never come in contact in the course 

 of its evolution and for which it could hardly be expected to possess 

 preformed receptors. 



(b) According to Haurowitz (1953), a template, which (as the 

 result of the presence of a molecule of antigen) reflects in reverse 

 the significant portions of the structure of the antigen held in the 

 expanded configuration by polar forces of a molecule of nucleic acid, 

 attracts to itself molecules of amino acids from which a duplicate of 

 itself is built up and cast off into the circulation. This theory seems to 

 require the persistence of small amounts of antigen throughout anti- 

 body formation, although this might not strictly be a necessary part 

 of the theory. 



(c) Pauling's theory (1940) is a modification of that of Hauro- 

 witz and differs mainly in Pauling's supposition that preformed 

 normal globulin, becoming unfolded ("denatured") at the ends of the 

 polypeptide chain (he assumes that they have accessible to them a 

 number of about equally stable folded configurations), fold up (are 

 "renatured") on contact with a molecule of antigen and thus become 

 specific antibody. This theory definitely presupposes the persistence 

 of antigen. 



(d) Burnet and Fenner (1949) suggested that enzymes involved 

 in the destruction of normal body constituents become adapted to 

 acting on similar molecules of foreign substances, are self-reproducing, 

 and continue to multiply after the elimination of the antigen. Anti- 

 bodies are supposed to be enzymatically inactive partial replicas of 

 these adapted enzymes. Burnet has apparently more recently changed 

 his views (Burnet, 1957, 1959). 



(e) Jerne (1955) suggested that globulin molecules of a very 

 wide variety of configurations and therefore of specific reactivities are 

 continually being produced by the body. Some of these molecules 

 happen to have configurations complementary to surface groups of 

 some antigens ; these are the "natural antibodies." When an antigen 



