Studies on Tubercle Bacillus-Monocyte Relationship

The effect of antibody on the fate of Salmonella typhimurium within mononuclear phagocytes (MN) of rabbits was studied in vitro. Monocytes and bacteria were incubated either in absence or presence of antibody. After 45 minutes during which phagocytosis occurred infected cells were washed to remove extracellular bacilli and free antibody. The cells were then reincubated in a medium without addition of antibody, and the interaction between the MN and bacteria was followed, correlating bacterial viability and the morphology of the mixture. The following results were obtained. The anti-Salmonella antibody was not bactericidal even in presence of complement and did not enhance phagocytosis. Regardless of whether antibody was present or absent during phagocytosis, the bacteria appeared to multiply within the cells. When no antibody was present during phagocytosis the infected cells were severely damaged within a few hours of incubation, and extensive extracellular multiplication was dominating. When antibody was present during phagocytosis MN packed with bacteria persisted for a long time. Little or no extracellular growth occurred. It was possible to demonstrate the presence of the antibody within the infected MN, using the fluorescent antibody technique. The antibody appeared as a coat around the bacteria. Antibody entered the cells only during phagocytosis, presumably attached to the bacteria. The active factor of the immune serum was found in the gamma globulin fraction and reacted specifically with the somatic antigen of Salmonella typhimurium. The antiflagellar portion of the antiserum was not involved in the phenomenon described. It is concluded that this antibody protects monocytes against the effect of intracellularly located Salmonella.

Section: Discussionmentioning

confidence: 95%

The Effect of Antibody on Intracellular Parasitism of Salmonella Typhimurium in Mononuclear Phagocytes in Vitro

Gelzer

Suter

1959

“…events were dissociable, and production of protective serum factor was more readily achieved than development of cellular resistance (5). Consequently, if the present successful transfers depended on active induction of cellular resistance in recipients by bacilli or bacillary antigens, there should be simultaneous appearance of protective serum factor in recipients.…”

Section: Behavior Of Recipient Serum In Tests Formentioning

confidence: 99%

“…Our own investigations involving in vitro cultures of infected histiocytes have shown that peritoneal exudate cells of normal and immunized rabbits could modify virulent tubercle bacilli, thereby reducing bacillary virulence for mice and inducing changes in certain other bacterial attributes (4). Although these modifications of virulent tubercle bacilli occurred after interaction of bacilli with either normal or immune histiocytes, only immune histiocytes were able to alter virulent tubercle bacilli to the extent where they lost the ability to necrotize the histiocytes themselves (5); this latter observation may be indicative of a greater capacity of immune histiocytes to modify bacillary virulence. Additional evidence for the concept of acquired cellular resistance in tuberculosis may be found in the recent observations of Sever (6) that immune histiocytes will passively transfer resistance to tuberculosis in the whole animal.…”

mentioning

confidence: 99%

Studies on Tubercle Bacillus-Histiocyte Relationship

Fong

Chin

Elberg

1962

Self Cite

Studies of passive transfer of cellular resistance, as manifested by refractoriness to necrotization with virulent tubercle bacilli, have shown that immune histiocytes or immune lymphocytes were effective transferring agents; immune polymorphonuclear leucocytes and immune serum as well as comparable cells from normal animals lacked this capacity. Comparisons of immune histiocytes and immune lymphocytes showed that the former cells were more efficient; this was indicated by (a) the smaller numbers of immune histiocytes needed for passive transfer, (b) the longer duration of cellular resistance in recipients given histiocytes than in those given lymphocytes, (c) the greater capacity of histiocytes to effect serial passive transfer, and (d) the ability of histiocytic but not lymphocytic lysates to transfer cellular resistance. Experiments to establish the mechanism of passive transfer of cellular resistance showed that there was no active induction of resistance in recipients through transfer of bacillary antigens contained in immune histiocytes; in fact, the results of serial passive transfers with immune histiocytes suggested an active replication of the "cell resistance factor."

“…In this respect, immune-passaged bacilli (i.e., bacilli obtained from an immune system) seemed more sensitive than normal-passaged bacilli. Whether this was the result of a greater modification of bacilli by immune cells was not established in these investigations, but it is of interest to note than an earlier report (9) had demonstrated that immune-passaged bacilli, but not normal-passaged bacilli, failed to cause degeneration of normal rabbit monocytes; it is therefore a possibility that immune monocytes were more effective in modification of virulent bacilli and that the inability to demonstrate marked differences in mouse virulence between normal-passaged and immune-passaged bacilli in these studies may possibly be a reflection of the relative insensitivity of mice, as opposed to monocytes, to small differences in virulence.…”

Section: Discussionmentioning

confidence: 85%

“…An earlier paper (9) has shown that passage of virulent tubercle bacilli in an immune system (monocytes of BCG-immunized rabbits cultivated in homologous immune serum medium) resulted in decreased capacity of bacilli to induce degeneration of normal monocytes.…”

mentioning

confidence: 99%

Studies on Tubercle Bacillus-Monocyte Relationship

Fong

Chin

Elberg

1961

Self Cite

There are various observations to indicate that under appropriate conditions of in vitro cultivation, attenuation of virulent tubercle bacilli may be achieved.The BCG strain of tubercle bacillus, originally a virulent bacillus of the bovine type, provides a classical example of in v/tro attenuation after prolonged cultivation on a glycerol-potato-bile medium (1). Similar reductions of bacillary virulence have also been accomplished by cultivation of virulent forms at low hydrogen ion concentrations (2, 3) and by growth beneath the surface of fluid media (4-6).Although naturally occurring in ~/vo attenuation of virulent tubercle bacilli has been reported, particularly in association with lupus (7), it has been the general experience of investigators that experimental attenuation of virulent tubercle bacilli by in v/vo methods was unsuccessful; even prolonged growth of mammalian tubercle bacilli in the bodies of cold-blooded animals has not resulted in any significant reduction of virulence (8).As virulent tubercle bacilli which gain access into animal tissues are largely phagocytosed by mononudear cells, it seemed a reasonable assumption that if destruction of bacilli or alteration of bacillary virulence were to occur, a propitious time for this would be during growth of bacilli in these cells. An earlier paper (9) has shown that passage of virulent tubercle bacilli in an immune system (monocytes of BCG-immunized rabbits cultivated in homologous immune serum medium) resulted in decreased capacity of bacilli to induce degeneration of normal monocytes.The present paper reports the decreased capacity of tubercle bacilli to cause death of mice following passage of virulent bacilli in normal systems (normal monocytes maintained in normal serum medium) as well as in immune systems; it also describes certain other changes in the behavior of passaged bacilli. Materials and MettwdsDetailed descriptions of procedures and materials not previously used are presented below; those which were employed in earlier studies (9--11) are briefly described herein.Monocytes.--Normal adult rabbits and rabbits injected intradermaliy with viable BCG