Immuno T cells

T Cell Activation and Cell-Mediated Immunity

Overview

  • Speaker: Dr. Rawah Faraj, DVM, MSc., Ph.D., Assistant Professor of Immunology

  • Course: VMED 809A Immunology, Spring 2026

  • Topics Covered: T cell activation, cell-mediated immunity, antigen processing and presentation.

Maturation of Lymphocytes

  • Thymus Gland: Location for T-lymphocyte maturation and education.

  • Bursa of Fabricius: Location for B-lymphocyte maturation.

  • Bone Marrow: Initial maturation and education for both T and B lymphocytes.

  • Process of Maturation:

    • In the bone marrow, immature T cells undergo mitosis.

    • In the thymus, each T cell matures by producing T cell receptors.

    • Each mature T cell has a unique T cell receptor and can differentiate into either:

    • T helper cells: assist other cells in the immune response.

    • Cytotoxic T cells: directly kill infected or cancerous cells.

Distinction Between T Lymphocytes

  • Mature T Cells:

    • Circulate throughout the body and are categorized into types based on function.

    • Each T cell expresses a unique T cell receptor (TCR).

Phagocytosis

  • Definition: The process where white blood cells such as macrophages, neutrophils, and dendritic cells engulf and digest foreign particles or pathogens.

Cytokines

  • Definition: Signaling proteins released by immune cells that regulate and modulate the immune response.

  • Etymology: Derived from Greek words "cyto" (cell) and "kinos" (movement).

  • Examples include interleukins, interferons, and tumor necrosis factors.

T Helper Cells (Th Cells)

  • Role: Activate B cells and cytotoxic T cells; crucial coordinator in immune responses.

Cytotoxic T Cells (Tc Cells)

  • Function: Recognize and kill infected cells by identifying antigens on the surface of those cells.

  • Activation Steps:

    1. Antigen Recognition: Detects foreign antigen using MHC-I molecules and T-cell receptors (TCR).

    2. Clonal Selection: Proliferation of activated cytotoxic T cells.

    3. Lethal Hit: Target cell (infected or cancerous) undergoes apoptosis.

Major Histocompatibility Complex (MHC)

  • Definition: A group of molecules displayed on cell surfaces that aid in the immune system's ability to recognize foreign molecules.

  • Types:

    • MHC Class I: Present on all nucleated cells, presenting endogenous antigens to CD8+ T cells.

    • MHC Class II: Present primarily on antigen-presenting cells (APCs) like macrophages and dendritic cells, presenting exogenous antigens to CD4+ T helper cells.

T Lymphocytes Overview

  • Definition: Essential white blood cells in the adaptive immune response characterized by their T-cell receptors (TCRs).

  • Subtypes:

    • T helper cells: Aid in the activation of B cells and other immune functions.

    • Cytotoxic or killer T cells: Directly destroy intracellular pathogens.

  • TCR Function: Recognizes small peptide fragments of antigens presented by MHC molecules on infected cells.

T Cell Antigen Receptor (TCR)

  • Structure: Composed of two polypeptide chains forming a binding site for antigenic peptides.

  • Types:

    • α/β T Cells: Majority of T cells with alpha and beta chains.

    • γ/δ T Cells: Minor population with gamma and delta chains.

  • TCR/CD3 Complex: Associated with additional polypeptide chains (CD3 complex) including γ, δ, ε chains, and a ζ (zeta) chain.

Cell-Mediated Immunity

  • Definition: An immune response that does not involve antibodies but involves the activation of phagocytes, antigen-specific cytotoxic T lymphocytes, and helper T lymphocytes.

  • Mechanism: Involves the release of various cytokines in response to antigens.

  • Examples: Immunofluorescence image showing cytotoxic T cells killing a cancer cell via lytic granules.

Antigen Presenting Cells (APCs)

  • Types of APCs: Includes dendritic cells, macrophages, and B cells.

  • Function:

    • Dendritic cells uptake virus antigens, upload bacterial antigens.

    • Macrophages engulf and process antigens and present them to T cells.

    • B cells bind microbial toxins using receptors for further immune response activation.

Macrophages

  • Role: Specialized cells that detect, phagocytize, and destroy bacteria and harmful organisms; also present antigens to T cells.

  • Cytokines Released: Includes IL-1, IL-6, and tumor necrosis factor alpha, which initiate inflammation.

  • Origin: Derive from blood monocytes that differentiate in tissues, circulating throughout the body.

  • Types and Functions:

    • Alveolar Macrophage: Located in lung alveoli; initiates immune responses to respiratory pathogens.

    • Kupffer Cells: Located in the liver; involved in immune response and tissue remodeling.

    • Microglia: In the CNS; help in the elimination of dead neurons and controlling brain immunity.

Recognition Receptors in Macrophages

  • Toll-Like Receptors (TLRs): Recognize different pathogen components (e.g., sugars, LPS) to initiate immune responses.

  • Interaction with Pathogens: Binding of bacteria to macrophage receptors leads to the release of cytokines, initiating phagocytosis and digestion of pathogens.

Antigen Processing and Presentation

  • Process: T cells do not recognize free antigens but must see them associated with MHC molecules.

    • T helper (TH) cells recognize processed antigens displayed by MHC class II molecules.

    • Cytotoxic T cells recognize endogenously synthesized antigens presented by MHC class I molecules.

Cluster of Differentiation (CD) Markers

  • Definition: CD proteins are integral for immune function, aiding in cell activation, adhesion, and response regulation.

  • Current Identified CD Proteins: Ranges from CD1 to CD371, used in research in immunology and cancer therapy.

  • Key CD Markers:

    • CD4: Present on T helper cells, assists in binding MHC class II.

    • CD8: Found on cytotoxic T cells, assists in binding MHC class I.

Table of Essential CD Markers for Immunophenotyping

  • Examples Include:

    • CD3: Found on T cells (both Human and Mouse).

    • CD4, CD8: Key markers for T lymphocyte identification.

    • More extensive lists include markers for other immune cell types (e.g., B cells, NK cells, Stem cells).

MHC Class I vs MHC Class II

  • MHC Class I:

    • Presents endogenous antigens from intracellular pathogens;

    • Found on all nucleated cells.

  • MHC Class II:

    • Presents exogenous antigens processed by APCs to CD4+ T cells.

Mechanism of Action of Cytotoxic T Cells

  1. Binding: Cytotoxic T cell binds to infected cell using TCR and MHC class I.

  2. Perforin Release: Creates pores in the infected cell's membrane.

  3. Target Cell Destruction: Enzymes enter and induce apoptosis in the infected cell.

Study Guide Questions

  1. Which cell type primarily attacks and kills cancer cells?

    • A. red blood cell B. cytotoxic T cell C. platelet D. mast cell

  2. How are antigens presented to naïve T cells?

    • A. Antigen-antibody complexes bound to a B cell; B. Infectious organisms release lipopolysaccharide; C. Macrophages display peptides with MHC molecules; D. Neutrophils release antigens from phagosomes; E. NK cells lyse infected cells.

  3. What T cell surface marker is present on T helper cells?

    • A. CD4; B. CD8; C. CD10; D. CD20; E. CD28.

  4. List the Antigen-Presenting Cells.

  5. Describe the functions of macrophage cells based on their location.

  6. What is the function of nitric oxide?