Studies on Tubercle Bacillus-Monocyte Relationship

Abstract

Despite intensive research on tuberculosis and the tubercle bacillus, the important and basic problems of virulence and resistance remain a challenge.Studies of acquired immunity have revolved around the relative importance of humoral and cellular factors. 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. The first of these observations posed a possible relationship between virulence and the factor in tubercle bacilli which promoted degeneration of cells cultivated in vitro. The protection of immune monocytes by the serum of rabbits immunized with BCG suggested an hitherto unexplored role for serum components in resistance against tuberculosis.The present paper represents an investigation along the lines suggested by these earlier observations. It describes the different abilities of virulent, attenuated, and avirulent strains of tubercle bacilli to induce degeneration of monocytes cultivated in vitro. It also describes the activity of bacterial culture filtrates in promoting cell degeneration and compares this activity of bacterial filtrates with those of purified protein derivative and old tuberculin. Finally, it presents data which indicate that an element of specificity is involved in the resistance of monocytes against virulent tubercle bacilli and further, that such resistance is mediated by serum components which are seemingly non-specific in nature.

Studies of Tubercle Bacillus-Histiocyte Relationships

“…When considered in itself, this observation would appear to indicate that the cellular resistance induced in rabbits by immunization with BCG was non-specific in nature. At the same time, however, there seemed to be some element of specificity in this type of resistance (2), for the histiocytes of BCG-immunized animals failed to resist necrotization by other facultative intracellular parasites such as salmonellae. Since our earlier investigations (3) have shown that Brucdla-immune histiocytes (from rabbits immunized with Brucdla mditcnsis) also exhibited resistance against both Br~dla and myco-bacteria, it seemed reasonable to analyze more closely the question of specificity of cellular resistance by comparing the behavior of Brucelta-immune histiocytes with that of BCG-immune histiocytes.…”

“…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

“…While there is no definitive information on the mechanism of resistance to tuberculosis, certain observations (6,7,11,12) have suggested that it may be partially dependent upon cellular and humoral factors. At the "tissue culture level" it was found that immune monocytes from BCG-immunized animals could be protected against the necrot/zing action of virulent tubercle bacilli by introduction of immune sera derived from animals immunized with either tubercle bacilli or agents totally unrelated to Mycobacteriura (7).…”

“…At the "tissue culture level" it was found that immune monocytes from BCG-immunized animals could be protected against the necrot/zing action of virulent tubercle bacilli by introduction of immune sera derived from animals immunized with either tubercle bacilli or agents totally unrelated to Mycobacteriura (7). As reported herein, the seemingly non-specific activity of immune sera was further substantiated by the observations that globulin derived from immune sera failed to protect immune monocytes against virulent bacilli and absorption of immune sera with homologous or closely related antigens did not remove the protective serum factor.…”

“…One of the deterrninants in protection of these monocytes was immune serum; since it was subsequently observed (7,8) that either homologous (serum of animals immunized with the BCG strain of tubercle bacillus) or heterologous (sera of animals immunlzed with Salmonella, Brucella, egg albumin) immune sera could be used for this purpose, it was suggested that the action of serum factor was entirely non-specific. This problem has been pursued further and the results obtained with absorbed sera and the globulin fraction of immune serum are described in this and the next section of the present report.…”