cell-mediated immunity

Cell-mediated immunity (CMI) is orchestrated primarily by T lymphocytes and is essential for defense against intracellular pathogens (e.g., viruses, Listeria, Mycobacteria, fungi, Pneumocystis) and for immune surveillance against tumors. Antigen-presenting cells (dendritic cells, macrophages, B cells) process and present antigen via MHC class II to CD4+ helper T cells, which differentiate into subsets (Th1, Th2, Th17, Tfh, Treg) based on cytokine milieu. Th1 cells secrete IFN-γ and IL-2, activating macrophages and promoting cytotoxic T cell responses—key in granuloma formation (e.g., TB). CD8+ cytotoxic T lymphocytes recognize antigen via MHC class I (present on all nucleated cells) and kill infected or malignant cells through perforin/granzyme-mediated apoptosis or Fas-FasL interactions. Natural killer (NK) cells, part of innate immunity but functionally linked, kill cells lacking MHC I expression (missing-self recognition) and are augmented by IL-12 and IFN-α/β. Macrophages, activated by IFN-γ, enhance phagocytic and microbicidal activity, forming the basis of granulomatous inflammation. Clinically, CMI defects manifest as susceptibility to intracellular organisms, viral infections (CMV, EBV, disseminated VZV), fungal infections (Candida, Pneumocystis jirovecii), and atypical mycobacterial disease. Classic examples include DiGeorge syndrome (thymic aplasia, absent T cells), HIV/AIDS (progressive CD4+ T cell depletion), and use of immunosuppressants like cyclosporine or tacrolimus (inhibit T cell activation via calcineurin pathway). The tuberculin skin test (PPD) exemplifies a delayed-type hypersensitivity (Type IV) reaction, a classic in vivo assay of cell-mediated immunity, mediated by memory Th1 cells recruiting macrophages 48–72 hours after antigen exposure. This contrasts with humoral immunity, which relies on B cells and antibodies to combat extracellular pathogens and toxins.