The Production of Antibodies by Tissues Living Outside of the Organism

Carrel, Alexis; Ingebrigtsen, R

doi:10.1084/jem.15.3.287

Cited by 65 publications

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“…Those which employed embryonic tissues can be discarded (20,21) as can those using the insensitive precipitin test for assay (14,20). In 1912 Carrel and Ingebrigtsen (22) reported hemolysin formation to sheep red blood cells using guinea pig bone marrow. No titers were reported and only 4 experiments were positive out of 17 attempts.…”

Section: Discussionmentioning

confidence: 99%

Studies on Antibody Synthesis Initiated in Vitro

Stevens

McKenna

1958

The Journal of Experimental Medicine

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Ten µg. of the lipopolysaccharide endotoxin of Salmonella typhosa was given to rabbits intravenously to enhance the subsequent antibody response to an unrelated substance. The spleens were removed 24 hours later, diced, and incubated 1 hour with the antigen, bovine-γ-globulin (BGG), in a protein-free medium. After washing, the tissues either were extracted at once or planted and the fluids and tissues harvested 1 to 3 days later. Antibody was determined by a modification of the Boyden hemagglutination technique. Small amounts of antibody were synthesized as early as 1 hour after the addition of antigen. The antibody formed could be specifically inhibited with BGG, was not dialyzable, and did not sediment at 105,000 g for 2 hours. Dose-response studies revealed no antibody formation when the BGG concentration was 0.005 or 0.05 mg./ml. The best responses were obtained at concentrations of 0.5 to 5.0 mg./ml. These results were found irrespective of whether the animal had previously received BGG in vivo. Forty per cent autologous serum increased antibody formation about 9-fold over that secured with protein-free medium or with 40 per cent homologous serum. Antibody formed with this system could be detected by 50 per cent complement fixation test, although at much lower titer than found by hemagglutination. While spleens from rabbits previously given BGG did not produce more antibody than spleens from normal rabbits, they differed in that they produced antibody without the involvement of endotoxin. Under appropriate circumstances, endotoxin was effective in vitro in enabling spleen fragments to produce antibody to BGG. Cortisone acetate administered to rabbits prior to the removal of the spleen severely inhibited antibody production in vitro. Sodium prednisolone phosphate added in vitro showed a similar irreversible effect at concentrations as low as 2 x 10–5 M. Nitrogen mustard inhibited antibody formation at concentrations as low as 10–4 M.

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Section: Discussionmentioning

confidence: 99%

Studies on Antibody Synthesis Initiated in Vitro

Stevens

McKenna

1958

The Journal of Experimental Medicine

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“…We hope to be able to grow on these cultures some of the more strictly parasitic bacteria not developing on ordinary media, as other strict parasites have been grown by other workers, viz., poliomyelitis virus by Levaditi (4), vaccinia by Steinhardt, Israeli, and Lambert (5), and rabies by Moon (6). By comparative studies with various types of cells and various natural and artificial media, clearer ideas as to the exact part of cell plasma in antibody production, by elaborating on the methods of Carrel and Ingebrigtsen (7), Lfidke (8), Przygode (9), and others, should be possible.…”

Section: Discussionmentioning

confidence: 99%

The Reactions Between Bacteria and Animal Tissues Under Conditions of Artificial Cultivation

Smyth

1915

Journal of Experimental Medicine

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This report gives an outline of the results of observations on over 1,100 tissue cultures made during the fall, winter, and spring of 1913 to 1914. The work has been resumed in the fall of 1914 and will be continued along the same and allied lines, confirming the above results with other strains of the same organisms and with other bacteria and bacterial products. Tests should be made with tissue and plasma from other animals, and the known pathogenicity of the organism for the animal and tissue used should always be borne in mind. We hope to be able to grow on these cultures some of the more strictly parasitic bacteria not developing on ordinary media, as other strict parasites have been grown by other workers, viz., poliomyelitis virus by Levaditi (4), vaccinia by Steinhardt, Israeli, and Lambert (5), and rabies by Moon (6). By comparative studies with various types of cells and various natural and artificial media, clearer ideas as to the exact part of cell plasma in antibody production, by elaborating on the methods of Carrel and Ingebrigtsen (7), Lüdke (8), Przygode (9), and others, should be possible. After this work was begun a reference was found to the use of some pathogenic bacteria in tissue cultures by Pheiler and Lentz (10), but no publication of the results of these observations has been observed. The results here reported may be summarized as follows: Bactericidal Action of Chicken Plasma.—On Bacillus typhosus, very strong—never grows in plasma alone; on Bacillus prodigiosus, very strong—never grows in plasma alone; on Bacterium pseudodiphtheriticum, strong—slight growth in cover-glass preparations; on Bacterium diphtheriticum, moderately strong; on Bacillus coli verus, slight; on Micrococcus aureus, very slight or none. A few pseudodiphtheria bacilli and more diphtheria bacilli survived in plasma stored in the cold for four days. The presence of growing tissue overcomes the bactericidal influence of plasma on diphtheria bacilli and in some instances on pseudodiphtheria bacilli. Bacterium diphtheriticum grows in plasma without tissue only if inoculations are very heavy; and very heavy inoculations of all organisms will probably overcome the bactericidal action of plasma, as it is undoubtedly a quantitative reaction. The bactericidal influence of plasma is overcome by exposure to incubator temperature for twenty-four to forty-eight hours. Bacterium diphtheriticum in light or moderate inoculations grows in tissue cultures only in clusters around the tissue fragments, and never in plasma away from tissue. The growth of this organism has a decided inhibitory influence on tissue activity and growth, especially marked with nervous tissue, but this action may be overcome by the addition of antitoxin to the plasma. Cultures inhibited by diphtheria growth have a tendency to resume growth later, probably due to antitoxin production. Bacterium pseudodiphtheriticum is distinctly less active in tissue cultures than is Bacterium diphtheriticum and never develops in plasma without tissue. The presence of diphtheria toxin in tissue cultures causes this organism to behave as does Bacterium diphtheriticum. Without toxin it has little or no direct influence on tissue growth except in massive doses. Bacillus prodigiosus fails to develop, as a rule, in tissue cultures except where inoculated from hypertonic media, and then it has no decided influence on tissue growth. Micrococcus aureus grows freely in these cultures with or without tissue, and inhibits tissue growth markedly, except as noted with splenic tissue. Bacillus coli verus always grows freely with or without tissue fragments and is uninfluenced by splenic tissue growth. In heavy inoculations it lessens tissue growth. Bacillus typhosus, except with extremely heavy inoculations, fails absolutely to grow in these cultures with or without plasma, unless the bactericidal action of the plasma has been destroyed by incubation. When this is the case it develops freely with especial affinity for the tissue cells either for support or nourishment. It appears to have no toxic action on the tissue cells. Note the sharp differentiation between typhoid and coli verus organisms. Diphtheria toxin has a quantitatively inhibiting action on all tissue growth and on heart tissue pulsations, the action being greatest on nervous tissue and least on heart tissue growth. Tissues affected by toxin tend to recovery if not killed. Antitoxin counteracts the action of toxin. Splenic tissue has little or no effect on the growth of Bacillus coli verus, but has a decided bactericidal action on Bacterium diphtheriticum and Micrococcus aureus, probably due to lymphatic cells and cell products, as seen by the area of cell migration coinciding with the bacteria-free area, by the similar action of splenic extract on cultures, and by the failure of such action in cultures of very early splenic tissue showing no lymphatic cells.

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“…26 He co-authored 24 articles in three languages with Burrows between 1910 and 1912, and later around 42 with other colleagues, including AH Ebeling, LE Baker, andRagnvald Ingebrigtsen (1882-1975). 27 These articles and over a hundred papers as the sole author challenge the aspersions on his scientific reputation and productivity made by many critics after World War II.…”

Section: Alexis Carrel (1873-1944)mentioning

confidence: 97%

An amended history of tissue culture: Concerning Harrison, Burrows, Mall, and Carrel

Ambrose

2017

J Med Biogr

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The origin of tissue culture is commonly dated to 1907 and credited to Ross Harrison at Hopkins Medical School. But an unpublished letter from the 1942 offers a different interpretation and gives priority to Montrose Burrows with important contributions for the development of cell culture by Franklin Mall at Hopkins and Alexis Carrel at the Rockefeller Institute in New York City. The early development of tissue culture is reviewed and its applications in modern biology and medicine are briefly outlined.

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The Production of Antibodies by Tissues Living Outside of the Organism

Abstract: Since guinea pig bone marrow and lymph gland cultivated for five days with goat blood generate substances that are hemolytic for goat red blood corpuscles, it can be concluded that tissues living outside of the organism react against an antigen by the production of an antibody.

Cited by 65 publications

References 0 publications

Studies on Antibody Synthesis Initiated in Vitro

Studies on Antibody Synthesis Initiated in Vitro

The Reactions Between Bacteria and Animal Tissues Under Conditions of Artificial Cultivation

An amended history of tissue culture: Concerning Harrison, Burrows, Mall, and Carrel

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