19S IMMUNOLOGY 



arsenic in an atoxyl-azo antigen leads to an arsenic-free antibody, 

 although the arsenic acid radical determines the specificity. ' ' This 

 is further borne out by the work of Heidelberger and Kendall, 

 who found that R-salt-azobenzidineazo-egg albumin givas rise to 

 colorless antibodies although the colored part of the antigen is 

 the portion determining specificity, 



Heidelberger further calls attention to tlie failure of quantita- 

 tive studies to support Manwaring's views since he says, "As much 

 as eight mg. of circulating antibody may be produced per milli- 

 gram of antigen injected, and since this is only a portion of the to- 

 tal antibody produced, the amount seems inconsistent with the 

 idea that specific antigen fragments are present, though the evi- 

 dence is not conclusive." He then cites the work of Hooker and 

 Boj^d and also of Topley, who disagree with Manwaring. In a 

 later paper Heidell)erger, Kendall, and Soo Hoo (1933) state Hint 

 they obtained a total response for tlie rabbit of over 100 mg. of 

 circulating antibody for every milligram of antigen injected. 



Buclmer's original tlieory was soon supplanted by Elirlich's 

 side-chain theory. He conceived of antibodies as chemical food 

 receptors produced by the tissue cells in excess as a result of stimu- 

 lation resulting from injury or demand. Since his theory is only 

 of historical interest it will not be discussed. 



Heidelberger (1932) reviews the work of Breinl and Haurowitz 

 who conclude that the presence of antigen in the tissues "dis- 

 turbs the mechanism of globulin synthesis, proba1)ly in the amino- 

 acid-peptid stage, modifying tlie method of union or the spatial 

 relations of the globulin components so that a new globulin, an 

 antibody, is formed which reacts specifically with the antigen by 

 virtue of the distortion caused by the presence of the antigen at 

 the moment of synthesis, for if the antigen can only affect amino 

 acids having affinity for it, these should retain that affinity after 

 their synthesis into globulin." 



Sabin (1939) suggests that antibodies represent proteins cast 

 off by the clasmatocytes. While no one seems to know positively 

 how they are formed, there is a great deal of evidence indicating 

 they are formed by cells of the reticulo-endothelial system. 



Unitarian Theory of Antibodies. — Zinsser (1939) says that 

 this theory does not imply that only one antibody will be pro- 

 duced against a complex cellular antigen. He says, however, that 



