Studies on Tubercle Bacillus-Monocyte Relationship

Abstract

Studies of the mechanism of immunity in tuberculosis have focused attention upon a number of interesting but rather controversial issues. One of these is concerned with the relative importance of humoral and cellular factors in immunity.The role of mononudear phagocytes in the destruction of human tubercle bacilli in the natively resistant animal has been reported by Lewis and Sanderson (1). Histological and cultural studies by Lurie (2) of the fate of tubercle bacilli contained in normal and immune phagocytes cultivated in the anterior chambers of the eyes of normal rabbits have suggested a greater capacity of the mononuclear phagocytes of the tuberculous animal to inhibit multiplication of tubercle bacilli. The recent experiments by Surer (3) appear to confirm Lurie's conclusions that the mononudear cells of immune animals are peculiarly and specially endowed with the capacity for handling virulent tubercle bacilli. Investigations by Mackaness (4), on the other hand, revealed no significant differences in the behavior of normal and immune monocytes toward virulent strains of Mycobacterium tuberculosis.Although various reasons may account for these diametrically opposed findings, it seemed likely that a major contributing factor was the absence of any quantitative enumeration of the monocyte population used in the experiments. Since the conclusions are based on the numbers of intracellular bacilli per total monocyte population, it is axiomatic that either a decrease or an increase in cell population would markedly distort the final results.The present investigation is an attempt at a more precise quantitative analysis of the problem. The survival of cell populations when cultivated in vitro under various conditions in the Mackaness type of chamber is described. Data indicating a degenerative effect of virulent tubercle bacilli upon normal and immune cells cultivated in vitro and an inhibitory or delaying effect of sera of animals vaccinated with BCG upon this cell degeneration are also presented.

Studies of Tubercle Bacillus-Histiocyte Relationships

“…Detailed descriptions of procedures and materials used in these studies have been described in earlier reports (1)(2)(3)(4)(5)(6) and are therefore briefly described herein.…”

Studies on Tubercle Bacillus-Monocyte Relationship

“…Most of the materials and methods used in these experiments were described in detail in a previous report (1), and are therefore considered briefly in this paper. Complete details are given for materials and methods not previously described.…”

“…Quantitative enumeration of monocytes with variations of 5 per cent or less was made possible by a special square constructed in the eyepiece of the microscope and by calibrated stage markings which were correlated with the square in the eyepiece. Full details of this were described in a previous paper (1).…”

“…Non-specificity of Serum Action in Protection of Monocytes against Virulent Tubercle Bacilli.--A previous report (1) has shown that the serum of rabbits immunized with BCG delayed the bacilli-induced degeneration of normal monocytes and prevented its occurrence in cultures of immune monocytes. The specificity or non-specificity of the humoral components in the serum of rabbits immunized with BCG was not established in this earlier investigation.…”

“…As previously indicated (1), valid conclusions concerning the role of cells in acquired immunity against tuberculosis require analyses of bacterium-cell relationships during periods when the in dtro cell populations show no change in cell numbers. Under such conditions, it was observed that the virulent H37Rv strain of tubercle bacillus regularly induced degeneration of both normal and immune monocytes (derived from rabbits immunized with BCG) when these were cultivated in vitro in the presence of normal rabbit serum (derived from tuberculin-negative rabbits); in contrast, the serum of rabbits immunized with BCG protected immune but not normal cells against the degenerative effects of virulent tubercle bacilli.…”