MECHANISM OF ANTIBODY FORMATION 65 



fatal cases, there was an increasing septicemia, steady rise in the 

 amount of soluble antigen excreted in the urine, and complete failure 

 to develop either precipitins or agglutinins in the blood. Apparently 

 in fatal cases the body was unable to combat the progress of the infec- 

 tion by the production of sufficient antibodies to neutralize and over- 

 balance either the living antigenic cell or its soluble products. 



The coincidence of antigen and antibody in the blood of an im- 

 munized animal has been variously reported (for a brief review see 

 Opie, 1923). Using whole serum or egg-white, Opie found that while 

 an antigen can persist in a normal animal for a long time, it is more 

 readily removed when introduced into an immune animal. The pres- 

 ence of antigen coincident with antibody shown in precipitin tests was 

 associated with the use of complex antigenic mixtures such as whole 

 serum. Apparently, differences in the relative amounts of antibodies 

 formed to various antigens in such a mixture were responsible for 

 these observations. When a repeatedly crystallized preparation of egg 

 albumin was used as antigen its presence in the blood of a rabbit 

 immunized (titer 1:100,000) against this substance could not be 

 demonstrated. It caused temporarily the complete disappearance of 

 precipitin, and though it may have appeared in the blood, in no in- 

 stance was antigen and its precipitin simultaneously demonstrable. 

 Apparently, the introduction of an antigen into a well immunized 

 animal brings about a combination between antigen and antibody 

 whereby the latter is temporarily removed from circulation. Its sub- 

 sequent reappearance may either be due to the elimination of antigen 

 or to the synthesis of new amounts of antibody. 



These observations corroborate oft reported findings that with the 

 progress of immunization the demonstration of antigen in the circula- 

 tion becomes increasingly difficult. Wolfe and Dilks (1946) obtained 

 immune sera from seven chickens, four immunized against goat and 

 three against horse sera. Each chicken was bled 61 or 62 days after 

 the last injection and immediately reinjected with the antigen previ- 

 ously used. Large decreases in antibody concentration were noted at 

 two to five hours after the reinjection which was the earliest interval 

 tried. For example, a chicken which had produced an antigoat serum 

 precipitating at 1 : 102,400 dilution of antigen showed no precipitin in 

 the serum obtained by bleeding four hours after the reinjection of the 

 homologous antigen, and showed a titer of 200 after 22 hours. A 



