I038 ORIGIN OF ANTIBODIES 



new means of approach to the problem of antibody formation. They demonstrated 

 that tissue living outside of the organism reacts against an antigen by the production 

 of a specific antibody. They cultivated guinea pig bone marrow and lymph nodes in 

 guinea pig plasma and then added goat's erythrocytes; after five days an extract of 

 the tissue culture, plus the goat erythrocytes, was demonstrated to contain a hemol- 

 ysin for goat's corpuscles. In 1913 Przygode' produced a specific typhoid agglutinin 

 by inoculating cultures of rabbit spleen with typhoid bacilli, and in 1914 he^ obtained 

 a precipitin against the horse serum antigen that he had previously added to cultures 

 of rabbit spleen. These results indicate that bone marrow, lymph node, and spleen 

 may take part in antibody production. Kuczynski, Tenenbaum, and Werthemann,^ 

 on the other hand, could detect no hemolysin after inoculating spleen culture with 

 sheep cells. Bloom^ could not demonstrate hemolysin production in rabbit lung cul- 

 tures inoculated with pigeon's erythrocytes. His experiments showed that, while lung 

 cultures from normal rabbits did not phagocytize pigeon erythrocytes, a dilute im- 

 mune serum added to the culture induced rapid phagocytosis of the erythrocytes. 

 Tissue culture from rabbits immunized against pigeon erythrocytes actively phag- 

 ocytized introduced pigeon erythrocytes. Fischer^ immunized a pure culture of fibro- 

 blasts against foreign protein (ascitic fluid, dog serum) and found that there was a 

 relation between the amount of antigen, the time of appearance of antibodies (four to 

 five days), and their persistence. Carrel and Ebeling'' have found that a foreign pro- 

 tein inoculated into cultures of leukocytes brings about an immediate and non- 

 specific antibody response, and after four days a specific antibody response. Foot,^ 

 Hadda and Rosenthal,^ and Lambert and Hanes,' among others have demonstrated 

 that tissue cultures were inhibited in growth when plasma from animals immunized 

 against these particular tissues were used instead of normal plasma. 



In vitro tissue culture has indicated a possible solution to the origin of antibody; 

 hemolysin, precipitin, agglutinin, and phagocytosis can be induced in tissue culture. 

 Tissue culture growth can be inhibited by using an immune plasma against the specific 

 tissue in place of normal plasma. 



PHYSICAL AND CHEMICAL FACTORS ATFECTING ANTIBODY PRODUCTION 



Various physical and chemical means have been employed to promote antibody 

 production, Hektoen"' and many others have observed that after massive bleeding 



' Przygode, P.: Wien. Win. Wchnschr., 26, 841. 1913. 

 ' Przygode, P.: ibid., 27, 201. 1914. 



3 Kuczynski, M., Tenenbaum, E., and Werthemann, A.: VircJiow's Arch. f. path. Anal., 258, 

 687. 1925. 



^ Bloom, W.: Arch. Path. 6^ Lab. Med., 3, 608. 1927. 

 5 Fischer, A.: J. Exper. Med., 36, 535. 1922. 



* Carrel, A., and Ebeling, A. H. : ibid., p. 645. 1922. 



'Foot, N. C: Centralbl.f. allg. Path. u. path. Anat., 23, 577. 1912. 



* Hadda, S., and Rosenthal, F.: Ztschr. f. rmmitnitdtsforsch. tt. c.xpcr. Thcrap., Orig., 16, 524. 



1913- 



'Lambert, R. A., and Hanes, F. M.: /. Exper. Med., 13, 495. 191 1. 



"Hektoen, L.: Tr. Cong. Am. Physicians &• Surgeons, 8, i. 1910. 



