Paper I
Question
Describe the mechanism of cell mediated immune response. Add a note on its applications, detection methods, and name the immunodeficiency diseases associated with defect in cell mediated immunity. (7+2+3+3)
Answer
Mechanism of cell-mediated immune response Cell-mediated immunity (CMI) is orchestrated by T lymphocytes and does not depend primarily on antibody. Antigen-presenting cells (dendritic cells, macrophages, B cells) process and present antigenic peptides on MHC class II to naive CD4+ T-helper cells in secondary lymphoid tissue, activating them (with co-stimulation, e.g., B7-CD28) to proliferate and differentiate into effector subsets:
- Th1 cells — secrete IFN-γ, activating macrophages (enhancing phagocytosis, respiratory burst, nitric oxide production), central to defence against intracellular pathogens (M. tuberculosis, Leishmania).
- Th2 cells — secrete IL-4, IL-5, IL-13, supporting antibody responses (particularly IgE) and eosinophil activation, important against helminths.
- Th17 cells — secrete IL-17, recruiting neutrophils, important against extracellular bacteria/fungi. Endogenously synthesized antigens (e.g., viral proteins) are presented on MHC class I to naive CD8+ T cells, which differentiate into cytotoxic T lymphocytes (CTLs), directly killing infected/abnormal cells via perforin/granzyme-mediated apoptosis or Fas-FasL interaction. Memory T cells persist after the response, providing faster/stronger secondary responses on re-exposure. Delayed-type hypersensitivity (Type IV) is a related manifestation, where sensitized Th1 cells re-encountering antigen drive a mononuclear inflammatory infiltrate over 24–72 hours.
Applications:
- Vaccination — live attenuated vaccines rely heavily on inducing robust CMI for durable protection against intracellular pathogens.
- Tumour immunology/immunotherapy — CTL-mediated tumour cell killing is exploited in cancer immunotherapy (e.g., checkpoint inhibitors, CAR-T cell therapy).
Detection methods:
- Tuberculin (Mantoux) skin test — in-vivo delayed hypersensitivity reaction, indicates prior sensitization to M. tuberculosis.
- Interferon-Gamma Release Assays (IGRAs) — in-vitro measurement of IFN-γ release by sensitized T cells on antigen exposure, more specific than TST.
- Lymphocyte transformation/proliferation assay — measures T-cell proliferative response to a specific antigen/mitogen in vitro.
- Flow cytometry — enumerates and characterizes T-cell subsets (e.g., CD4 count in HIV).
Immunodeficiency diseases with defective cell-mediated immunity:
- DiGeorge syndrome — thymic aplasia/hypoplasia (22q11 deletion), impaired T-cell development.
- Severe Combined Immunodeficiency (SCID) — combined T- and B-cell defect, profound CMI failure.
- HIV/AIDS — progressive CD4+ T-cell depletion, acquired severe CMI defect.