Adaptive Immunity: Cell-Mediated Immunity and T Cell Function

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Adaptive Immunity: Cell-Mediated Immunity

Introduction to Adaptive Immunity

Adaptive immunity is a highly specific defense mechanism that involves the recognition and elimination of pathogens, abnormal cells, and foreign tissues. The cell-mediated arm of adaptive immunity primarily involves T cells, which are subdivided into Helper T (TH) cells (CD4+) and Cytotoxic T (TC) cells (CD8+). These cells are essential for targeting intracellular pathogens, cancer cells, and foreign cells from transplants.

Helper T (TH) cells: Activate and regulate other immune cells.
Cytotoxic T (TC) cells: Directly kill infected or abnormal cells.
CD: Stands for "cluster of differentiation," a marker used to identify cell types.

T Cell Development and Maturation

T cells originate in the bone marrow and migrate to the thymus for maturation. During this process, gene rearrangements produce a diverse population of T cells, each capable of recognizing a specific antigen. The thymus screens T cells for their ability to recognize antigens, ensuring immunocompetence and self-tolerance.

Clone: A population of T cells specific to a particular antigen.
Immunocompetence: Ability to mount a normal immune response.
Self-tolerance: Destruction of self-reactive T cells to prevent autoimmunity.
Naïve T cells: Mature T cells that have not yet encountered their specific antigen.

T cell maturation and migration from bone marrow to thymus and lymph node

Antigens and Immunogens

An antigen is any substance recognized by B or T cells, often peptides but can include carbohydrates, lipids, and metals. Only certain antigens, called immunogens, elicit an immune response. Haptens are small antigens that become immunogenic only when attached to a protein carrier.

Antigenic determinant: The specific region of an antigen recognized by a T cell receptor.
Self antigens: Antigens present on one's own cells, not immunogenic in the host.
Example: Urushiol from poison ivy acts as a hapten when it binds to skin proteins.

Major Histocompatibility Complex (MHC) Molecules

T cells recognize antigens only when they are presented by MHC molecules on cell surfaces. MHC molecules are critical for tissue compatibility and immune recognition.

Class I MHC: Found on nearly all nucleated cells; present endogenous antigens.
Class II MHC: Found only on antigen-presenting cells (APCs); present exogenous antigens.
Endogenous antigens: Originating inside the cell (e.g., viral proteins, mutated cancer antigens).
Exogenous antigens: Originating outside the cell, taken in by phagocytosis.

Antigen Processing and Presentation

Antigen processing involves breaking down antigens and displaying their fragments on MHC molecules. The process differs for endogenous and exogenous antigens:

Class I MHC: Processes and displays endogenous antigens synthesized within the cell.
Class II MHC: Processes and displays exogenous antigens taken up by phagocytosis.

Class I MHC processing and display of endogenous antigens Class II MHC processing and display of exogenous antigens

Role of MHC Molecules in T Cell Activation

The distinction between class I and class II MHC molecules is crucial for proper immune function. Helper T cells (TH) interact with class II MHC on APCs, while cytotoxic T cells (TC) interact with class I MHC on diseased cells. This prevents inappropriate destruction of healthy cells.

TH cells: Activated by APCs presenting exogenous antigens on class II MHC.
TC cells: Activated by diseased cells presenting endogenous antigens on class I MHC.

TH cell interaction with class II MHC on APC TC cell interaction with class I MHC on diseased cell

T Cell Activation, Clonal Selection, and Differentiation

T cell activation involves antigen presentation, co-stimulation, and proliferation. Dendritic cells can cross-present antigens on both MHC classes, activating both TH and TC cells. Activated T cells proliferate and differentiate into effector and memory cells.

Clonal selection: Antigen selects a specific T cell clone for activation.
Co-stimulator: Additional molecules required for full T cell activation.
Effector cells: Cause immediate immune effects.
Memory T cells: Provide rapid response upon subsequent antigen exposure.

Dendritic cell presenting antigens to T cells T cell binding co-stimulator on dendritic cell T cell proliferation and differentiation into effector and memory cells

Effects of T Cells

Helper T (TH) Cell Functions

Helper T cells coordinate immune responses by secreting cytokines that activate macrophages, cytotoxic T cells, and B cells. They are essential for both innate and adaptive immunity.

Innate immunity: TH cells secrete interleukin-3, stimulating macrophages and enhancing phagocytosis.
Feedback loop: Macrophages produce interleukin-12, which further stimulates TH cells.

TH cell effects on macrophages via interleukin-3 and interleukin-12

Activation of Cytotoxic T (TC) Cells

TH cells secrete interleukin-2 (IL-2), which is required for the activation and proliferation of cytotoxic T cells. Without IL-2, TC cells fail to activate.

IL-2: Key cytokine for TC cell activation.

IL-2 mediated activation of cytotoxic T cells

Stimulation of B Cells

TH cells directly bind to B cells and secrete interleukins, stimulating B cell proliferation and antibody production. This is crucial for adaptive antibody-mediated immunity.

Interleukins: Cytokines that promote B cell proliferation and antibody synthesis.

TH cell stimulation of B cell proliferation and antibody production TH cell effects on macrophages, TC cells, and B cells

Cytotoxic T (TC) Cell Functions

Cytotoxic T cells kill infected, cancerous, or foreign cells by recognizing antigens bound to class I MHC molecules. They release perforin and enzymes to induce cell death, and can also trigger apoptosis.

Perforin: Protein that forms pores in target cell membranes.
Apoptosis: Programmed cell death induced by TC cells.

TC cell killing target cell via perforin and apoptosis

Organ and Tissue Transplantation and Rejection

Types of Transplants (Grafts)

Transplants are classified based on the genetic relationship between donor and recipient:

Type	Description	Immune Response
Autograft	Tissue from same individual	No response
Isograft	Tissue from genetically identical individual	No response
Allograft	Tissue from nonidentical individual of same species	Possible rejection
Xenograft	Tissue from different species	High risk of rejection

Graft Rejection and Prevention

Allografts and xenografts contain foreign antigens that can trigger immune rejection, leading to necrosis and organ failure. Prevention involves matching antigens (especially MHC/HLA genes) and immunosuppressive therapy.

Necrosis: Death of transplanted tissue due to immune attack.
Immunosuppressive therapy: Medications to suppress immune response and prevent rejection.

Bone Marrow Transplantation

Bone marrow transplants, also known as hematopoietic stem cell transplants (HSCT), are commonly performed to treat various diseases and require careful matching to prevent rejection.