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:
Antigen Recognition: Detects foreign antigen using MHC-I molecules and T-cell receptors (TCR).
Clonal Selection: Proliferation of activated cytotoxic T cells.
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
Binding: Cytotoxic T cell binds to infected cell using TCR and MHC class I.
Perforin Release: Creates pores in the infected cell's membrane.
Target Cell Destruction: Enzymes enter and induce apoptosis in the infected cell.
Study Guide Questions
Which cell type primarily attacks and kills cancer cells?
A. red blood cell B. cytotoxic T cell C. platelet D. mast cell
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.
What T cell surface marker is present on T helper cells?
A. CD4; B. CD8; C. CD10; D. CD20; E. CD28.
List the Antigen-Presenting Cells.
Describe the functions of macrophage cells based on their location.
What is the function of nitric oxide?