Chapter 8: T Cell-Mediated Immunity

8.1 Overview of T Cell-Mediated Immunity

• Activation of Naïve T Cells: Triggered upon encounter with specific antigens, leading to differentiation into effector T cells.

• Effector T Cells Properties: Distinct functions and interactions with APCs (Antigen-Presenting Cells).

8.2 T-Cell Activation Process

• T-Cell Activation: The first stage in a primary adaptive immune response.

• Types of Effector T Cells:

  • Cytotoxic CD8 T Cells: Kill infected cells.

  • CD4 T Cells: Secrete cytokines to activate other immune cells, categorized into:

    • TH1

    • Treg (Regulatory)

    • TH2

    • TH17

    • TFH (T Follicular Helper)

8.3 Nature of T-Cell Activation

• Initial Encounter: Recruitment of naïve T cells to secondary lymphoid tissues via lymph.

• Professional APCs (P-APCs): Dendritic cells play a crucial role in presenting antigens for T cell activation.

• Non-P-APCs: Engage naïve T cells, leading to inactivation instead of activation.

8.4 Role of Dendritic Cells

• Antigen Capture and Migration: Dendritic cells capture antigens from infection sites and migrate to lymphoid tissues.

• Mature Dendritic Cells: Upon activation, they present antigens to naïve T cells in lymph nodes; become phagocytic and express MHC I and II molecules.

8.5 T Cell Recirculation and Activation

• Naïve T Cell Movement: Enters lymph nodes via blood or afferent lymph; binds to high endothelial venules (HEVs).

• Antigen Recognition: TCR examines peptide:MHC complexes on dendritic cells; specific interactions lead to T cell retention and activation.

8.6 Adhesion Molecules and Homing

• Cell Adhesion Molecules: Determine T cell migration patterns; specific adhesion molecules facilitate passage through HEVs into lymph nodes.

• Chemokines: Draw naïve T cells to secondary lymphoid organs, expressing receptors like CCR7 to bind CCL21 and CCL19.

• Selectins and Integrins: Different classes play roles in T cell adhesion and movement.

8.7 Co-Stimulatory Signals

• Requirement for Activation: Binding of TCR to peptide:MHC is not sufficient; a second signal from co-stimulatory molecules (B7/CD28) is necessary.

• B7 Molecules: Two forms (B7.1 and B7.2) are crucial for T cell activation, primarily expressed during infections.

8.8 Activation Mechanisms

• Signaling Pathways: Intracellular signaling changes gene expression in activated T cells.

• IL-2 Production: Key for T cell proliferation and differentiation; requires both TCR and co-stimulation signals.

8.9 Effector T Cell Function

• Differentiated Effector T Cells: Circulate to sites of infection; express different surface molecules indicating activation (e.g., LFA-1).

• Cytokine Secretion: Different effector T cells (e.g., TH1, TH2) produce unique cytokines impacting various immune functions.

8.10 Cytotoxic CD8 T Cells

• Mechanism of Action: Recognize infected cells via TCR binding to peptide:MHC I and induce apoptosis through cytotoxic granules.

• Granule Contents: Contain perforin and granzymes pivotal for target cell lysis.

8.11 TH1 and TH2 Functions

• TH1 Cells: Activate macrophages and enhance responses against intracellular pathogens.

• TH2 Cells: Promote responses to extracellular parasites and modulate antibody production.

8.12 Regulatory T Cells (Treg)

• Suppressive Function: Regulate and limit immune responses through inhibitory cytokines (IL-10, TGF-b).

• Importance: Maintain immune homeostasis and prevent autoimmunity.

8.13 Summary of Key Mechanisms

• Dendritic Cells: Leadership role as P-APCs to prime naive T cells.

• Co-Stimulation: Essential for effective activation of T cells.

• Cytokines: Influence differentiation and effector function of T cells providing immunity against infection.