Discuss cell-mediated immunity.

Components of Cell-Mediated Immunity

Cell-mediated immunity is orchestrated by several types of T lymphocytes, each with a specialized role:

• Cytotoxic T Lymphocytes (CTLs or CD8+ T cells): These cells directly kill infected cells, tumor cells, and foreign graft cells.
• Helper T Lymphocytes (Th cells or CD4+ T cells): These cells do not directly kill infected cells but play a crucial role in activating other immune cells, including B cells, macrophages, and CTLs, by releasing cytokines. Different subsets of Th cells (Th1, Th2, Th17, etc.) mediate different types of immune responses.
• Regulatory T Lymphocytes (Tregs): These cells suppress the immune response, preventing autoimmunity and maintaining immune homeostasis.
• Memory T cells: These long-lived cells provide immunological memory, allowing for a faster and more robust response upon re-exposure to the same antigen.

Antigen Presentation

T cells cannot recognize antigens directly. They require antigen presentation by antigen-presenting cells (APCs). The major APCs include:

• Dendritic Cells: The most potent APCs, initiating primary immune responses.
• Macrophages: Phagocytose pathogens and present antigens, also contributing to inflammation.
• B Cells: Present antigens to helper T cells, facilitating antibody production.

APCs process antigens into peptides and present them on their surface bound to Major Histocompatibility Complex (MHC) molecules. There are two classes of MHC molecules:

• MHC Class I: Present on all nucleated cells; present peptides derived from intracellular pathogens to CD8+ T cells.
• MHC Class II: Present on APCs; present peptides derived from extracellular pathogens to CD4+ T cells.

T Cell Activation

T cell activation is a two-step process:

1. Signal 1: Antigen Recognition: The T cell receptor (TCR) on the T cell binds to the peptide-MHC complex on the APC.
2. Signal 2: Co-stimulation: Co-stimulatory molecules on the APC (e.g., B7) bind to receptors on the T cell (e.g., CD28). This provides a second signal necessary for full T cell activation.

Once activated, T cells undergo clonal expansion, proliferating and differentiating into effector cells and memory cells.

Effector Functions of Cell-Mediated Immunity

The effector functions of CMI depend on the type of T cell activated:

• CTLs: Kill infected cells by releasing cytotoxic granules containing perforin and granzymes. Perforin creates pores in the target cell membrane, allowing granzymes to enter and induce apoptosis.
• Th1 cells: Activate macrophages to enhance their phagocytic and killing abilities. They also promote inflammation and recruit other immune cells.
• Th17 cells: Involved in defense against extracellular bacteria and fungi, promoting inflammation and neutrophil recruitment.
• Tregs: Suppress the immune response by releasing immunosuppressive cytokines (e.g., IL-10, TGF-β) and inhibiting the activation of other immune cells.

Regulation of Cell-Mediated Immunity

CMI is tightly regulated to prevent excessive inflammation and autoimmunity. Mechanisms of regulation include:

• Treg cells: As mentioned above, Tregs play a critical role in suppressing the immune response.
• CTLA-4: A co-inhibitory molecule expressed on T cells that binds to B7 on APCs, inhibiting T cell activation.
• PD-1: Another co-inhibitory molecule expressed on T cells that binds to PD-L1 on target cells, dampening the immune response.

Clinical Significance

Defects in cell-mediated immunity can lead to increased susceptibility to infections, particularly intracellular pathogens. Examples include:

• Severe Combined Immunodeficiency (SCID): A genetic disorder characterized by a deficiency in both T and B cells.
• HIV/AIDS: The human immunodeficiency virus (HIV) infects and destroys CD4+ T cells, leading to a progressive decline in cell-mediated immunity.
• Organ Transplantation: CMI plays a role in graft rejection, where T cells recognize the transplanted organ as foreign and attack it.