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In vivo and in vitro cell-mediated immunity in tuberculous meningitis
Abstract:
This study assessed in vivo and in vitro parameters of cell-mediated immunity in 45 tuberculous meningitis patients. Delayed-type hypersensitivity responses to purified protein derivative of tuberculin (PPD), Candida albicans and streptokinase-streptodornase antigens were lacking in 34 patients compared to 2 of 54 normal volunteers. Circulating T lymphocyte subpopulations (E-rosetting active and total T cells) were diminished in 41 patients studied compared to 41 normal donors (p less than 0.001). Lymphocyte blast responses to PPD (25 micrograms-500 micrograms/ml) were positive but quantitatively depressed in all 34 patients studied compared to PPD positive normal donors (p less than 0.001). Phytohemagglutinin responses were significantly depressed (p less than 0.001). Repeat studies in 20 patients 4-5 months post-therapy resulted in reversals of all parameters to control values with heightened blastogenic responses to all PPD concentrations.
Insights
Tuberculous meningitis severely impairs cell-mediated immunity, evidenced by suppressed T cell responses and delayed hypersensitivity. Treatment reverses these immune deficits, restoring normal T cell function.
Area of Science:
- Immunology
- Infectious Diseases
- Neurology
Background:
- Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting the central nervous system.
- Cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis infection.
- The immunological status of TBM patients requires thorough investigation.
Purpose of the Study:
- To evaluate in vivo and in vitro cell-mediated immunity in patients with tuberculous meningitis.
- To assess the impact of TBM on T lymphocyte subpopulations and their function.
- To determine the reversibility of immune deficits following anti-tuberculosis therapy.
Main Methods:
- Assessed delayed-type hypersensitivity (DTH) responses to microbial antigens (PPD, Candida albicans, streptokinase-streptodornase).
- Quantified circulating T lymphocyte subpopulations (total T cells, active T cells) using E-rosetting.
- Measured in vitro lymphocyte blastogenic responses to purified protein derivative (PPD) and phytohemagglutinin (PHA).
- Conducted follow-up studies post-therapy in a subset of patients.
Main Results:
- A significant proportion of TBM patients (34/45) exhibited absent DTH responses compared to healthy controls.
- Diminished levels of circulating T lymphocytes were observed in TBM patients (p < 0.001).
- Lymphocyte blastogenesis to PPD and PHA was quantitatively depressed in TBM patients (p < 0.001).
- Post-therapy, all immune parameters normalized, with enhanced blastogenic responses to PPD.
Conclusions:
- Tuberculous meningitis is associated with profound defects in cell-mediated immunity.
- These immune impairments are reversible upon successful anti-tuberculosis treatment.
- Restoration of immune function post-therapy suggests potential for improved patient outcomes.