Th Cell Polarization
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Questions and Answers

Which molecule on the APC binds to CD28 on the Th cell?

  • DAMP
  • HLA-2
  • PAMP
  • CD80/86 (correct)

    • What is the result of Ag recognition in the absence of co-stimulation?

  • T cell anergy (correct)
  • T cell proliferation
  • T cell differentiation
  • T cell activation

    • What is the function of IL-2 in T cell activation?

  • Causes T cell apoptosis
  • Activates the Th cell and causes it to enter the cell cycle (correct)
  • Inhibits T cell proliferation
  • Prevents T cell differentiation

    • What is the role of CD4+ helper T-lymphocytes (Th) in immunity?

    <p>They activate or inhibit other cells through direct contact</p> Signup and view all the answers

    What is the advantage of HLA-2 and costimulator expression increasing only when the APC recognizes a DAMP or a PAMP?

    <p>It allows for specific recognition of pathogens</p> Signup and view all the answers

    What is the result of CD28-CD80/86 binding and recognition of antigen by the TCR?

    <p>Synthesis of IL-2 and the high-affinity IL-2R</p> Signup and view all the answers

    What is the function of Bcl-2 in T cell activation?

    <p>It is an apoptosis inhibitor</p> Signup and view all the answers

    What is the fate of anergic T cells when they encounter Ag presented by APCs that express co-stimulatory molecules?

    <p>They remain anergic and cannot proliferate or differentiate</p> Signup and view all the answers

    What is the role of IL-2 in lymphocyte activation?

    <p>Inducing the differentiation of naive T-cells into effector cells</p> Signup and view all the answers

    Which of the following T-cell types is involved in the regulation of immune responses to extracellular pathogens?

    <p>Th2</p> Signup and view all the answers

    What is the function of the co-receptor CD4 in T-cell activation?

    <p>Enhancing the binding of the TCR to the MHC molecule</p> Signup and view all the answers

    What is the role of the cSMAC in T-cell activation?

    <p>Forming the central supramolecular activation cluster</p> Signup and view all the answers

    Which of the following is a characteristic of Th1 cells?

    <p>Produce IFN-γ and regulate cell-mediated immune responses</p> Signup and view all the answers

    What is the function of the CD28 molecule in T-cell activation?

    <p>Providing co-stimulatory signals to T-cells</p> Signup and view all the answers

    Which of the following T-cell types is involved in the regulation of immune responses to fungal infections?

    <p>Th17</p> Signup and view all the answers

    What is the function of the CD80 molecule in T-cell activation?

    <p>Providing co-stimulatory signals to T-cells</p> Signup and view all the answers

    What type of cells can activate or inhibit other cells through secretion of cytokines?

    <p>All of the above</p> Signup and view all the answers

    What is the process by which T-helper cells become specialized to 'help' in a specific way?

    <p>T-cell polarization</p> Signup and view all the answers

    What determines the type of T-helper cell?

    <p>The type of cytokines present in the environment</p> Signup and view all the answers

    What are PAMPs or DAMPs?

    <p>Both a and b</p> Signup and view all the answers

    What happens to dendritic cells after phagocytosing a pathogen?

    <p>They migrate to a lymph node or other secondary lymphatic organ</p> Signup and view all the answers

    What type of dendritic cell may be involved in a Th1 response?

    <p>Conventional dendritic cell, type 1 (cDC1)</p> Signup and view all the answers

    What do cytokines secreted by polarized T-helper cells mediate?

    <p>Distinct effector cell functions</p> Signup and view all the answers

    Why is it important to understand T-helper cell polarization?

    <p>All of the above</p> Signup and view all the answers

    What is the best type of immunity for a viral infection?

    <p>Production of antibodies that prevent invasion AND killing of cells that are infected by CD8+ T-cells</p> Signup and view all the answers

    What determines the type of immune response, Th1 or Th2?

    <p>The 3rd signal from the APC, usually a polarizing cytokine</p> Signup and view all the answers

    What is the function of T-regulatory cells?

    <p>To down-regulate the effector activities of other immune cells</p> Signup and view all the answers

    What is unique about the development of regulatory T-cells?

    <p>They arise in environments with anti-inflammatory cytokines</p> Signup and view all the answers

    What is the inducing/polarizing cytokine for T-regulatory cells?

    <p>TGF-β</p> Signup and view all the answers

    What happens to animals or humans that cannot produce effective Tregs?

    <p>They develop severe autoimmune disease</p> Signup and view all the answers

    What is uncommon for Th cells?

    <p>For Th1 cells to become Th2 cells</p> Signup and view all the answers

    What is the purpose of cross-regulation in Th cells?

    <p>To prevent other local Th cells from being polarized into a different type</p> Signup and view all the answers

    What is the main function of Th17 cells?

    <p>To protect against infection and autoimmune disorders</p> Signup and view all the answers

    What cytokines are involved in the polarization of Th17 cells?

    <p>IL-23, IL-6, and TGF-β</p> Signup and view all the answers

    What is the transcription factor that polarizes a Th17 cell?

    <p>ROR-γt</p> Signup and view all the answers

    What is the main difference between Th1 and Th17 cells?

    <p>Th1 cells stimulate B-cells, while Th17 cells do not</p> Signup and view all the answers

    What is the role of Tfh cells?

    <p>To re-polarize to another Th type</p> Signup and view all the answers

    What is the function of IL-22 and IL-17 in Th17 cells?

    <p>To induce release of IL-6, IL-1, TNF-α, GM-CSF</p> Signup and view all the answers

    What is the purpose of Th1 and Th17 responses?

    <p>To provide a general 'Type 1 response' against infection</p> Signup and view all the answers

    What is the role of follicular Th cells?

    <p>To aid antibody production in secondary lymphoid organs</p> Signup and view all the answers

    What is the role of Th1 cells in B-cell development?

    <p>They opsonize targets</p> Signup and view all the answers

    What is the result of Tfh cells interacting with B-cells?

    <p>Induction of germinal centers</p> Signup and view all the answers

    What is the purpose of the '2 rounds' of B-cell antibody production?

    <p>To produce high-affinity antibodies</p> Signup and view all the answers

    What is unique about the development of Tfh cells?

    <p>It is a complex process involving 2 major steps</p> Signup and view all the answers

    What is the result of the first round of antibody production?

    <p>Production of low-affinity antibodies</p> Signup and view all the answers

    What is the role of Tfh cells in SLOs?

    <p>To induce the formation of germinal centers</p> Signup and view all the answers

    What is the purpose of affinity maturation?

    <p>To produce high-affinity antibodies</p> Signup and view all the answers

    What is the result of IL-2 production on Tfh development?

    <p>It inhibits Tfh development</p> Signup and view all the answers

    What is the primary function of CD80/86 on the antigen-presenting cell?

    <p>To bind to CD28 on the T helper cell</p> Signup and view all the answers

    What is the consequence of T cell activation in the absence of costimulation?

    <p>The T cell becomes anergic and cannot produce IL-2</p> Signup and view all the answers

    What is the role of IL-2 in the activation of T cells?

    <p>It induces the synthesis of the high-affinity IL-2 receptor</p> Signup and view all the answers

    What is the consequence of CD28-CD80/86 binding and antigen recognition by the TCR?

    <p>The T cell synthesizes IL-2 and the high-affinity IL-2 receptor</p> Signup and view all the answers

    What is the primary function of CD4+ helper T-lymphocytes?

    <p>To activate or inhibit other cells through direct contact or cytokine secretion</p> Signup and view all the answers

    What is the advantage of HLA-2 and costimulator expression increasing only when the APC recognizes a DAMP or a PAMP?

    <p>It ensures that T cells are only activated in response to pathogens</p> Signup and view all the answers

    What is the role of CD4 in T cell activation?

    <p>It binds to HLA-2 on the antigen-presenting cell</p> Signup and view all the answers

    What is the consequence of IL-2 binding to the high-affinity IL-2 receptor on the T helper cell?

    <p>The T cell activates and enters the cell cycle</p> Signup and view all the answers

    What is the role of IL-21 and IL-12 in humans?

    <p>Induction of Tfh cells</p> Signup and view all the answers

    What is the mechanism of killing used by cytotoxic T-cells?

    <p>Granzyme/perforin and Fas/FasL interactions</p> Signup and view all the answers

    What is required for the activation of naïve CD8+ T-cells?

    <p>Two signals from a dendritic cell</p> Signup and view all the answers

    What is the function of CD40L on Th cells?

    <p>Activation of B-cells and cytotoxic T-cells</p> Signup and view all the answers

    What is the result of a CD8+ T-cell encountering its specific antigen?

    <p>Immune attack without the need for co-stimulation</p> Signup and view all the answers

    What is the role of cross-regulation in Th cells?

    <p>Negative regulation of Th2 cells</p> Signup and view all the answers

    What is the function of dendritic cells in cytotoxic T-cell activation?

    <p>Presentation of antigen to CD8+ T-cells</p> Signup and view all the answers

    What is the role of Th1 cells in cytotoxic T-cell activation?

    <p>Providing an activating signal to cytotoxic T-cells</p> Signup and view all the answers

    What is the primary function of T-helper cells?

    <p>To activate or inhibit other cells through secretion of cytokines</p> Signup and view all the answers

    What determines the type of T-helper cell polarization?

    <p>The type of cytokines present in the immediate vicinity of the newly-activated Th</p> Signup and view all the answers

    What is the role of polarizing cytokines in T-helper cell polarization?

    <p>To activate specific transcription factors that determine the T-helper cell phenotype</p> Signup and view all the answers

    What is the outcome of T-helper cell polarization?

    <p>The secretion of a specific profile of cytokines that mediate distinct effector cell functions</p> Signup and view all the answers

    How do dendritic cells respond to pathogen encounter?

    <p>They phagocytose the pathogen and migrate to secondary lymphatic organs</p> Signup and view all the answers

    What is the role of the microenvironment in T-helper cell polarization?

    <p>It determines the type of T-helper cell polarization</p> Signup and view all the answers

    What is the difference between Th1 and Th17 cells?

    <p>Th1 cells are involved in responses to intracellular pathogens, while Th17 cells are involved in responses to extracellular pathogens</p> Signup and view all the answers

    What is the outcome of Th1 polarization?

    <p>The activation of CD8+ cytotoxic T-cells</p> Signup and view all the answers

    What is the primary function of Th17 cells in response to bacterial and fungal disorders?

    <p>To induce release of IL-6, IL-1, TNF-α, and GM-CSF</p> Signup and view all the answers

    What is the role of TGF-β in the polarization of Th17 cells?

    <p>To promote the differentiation of naive Th cells into Th17 cells</p> Signup and view all the answers

    What is the main difference between Th1 and Th17 cells in terms of antibody production?

    <p>Th1 cells stimulate B-lymphocytes to produce antibodies, while Th17 cells do not</p> Signup and view all the answers

    What is the role of ROR-γt in Th17 cell polarization?

    <p>To prevent the secretion of non-Th17 cytokines</p> Signup and view all the answers

    What is the primary function of follicular Th cells in antibody production?

    <p>To aid in the production of antibodies through optimal stimulation of B-cells</p> Signup and view all the answers

    What is the purpose of cross-regulation in Th cells?

    <p>To prevent Th cells from being polarized into different types</p> Signup and view all the answers

    What is the role of IL-23 in Th17 cell polarization?

    <p>To promote the differentiation of naive Th cells into Th17 cells</p> Signup and view all the answers

    What is the primary function of Tfh cells in antibody production?

    <p>To re-polarize into a different Th type after the antibody response is completed</p> Signup and view all the answers

    What is the role of IL-22 and IL-17 in Th17 cells?

    <p>To induce the release of pro-inflammatory cytokines and anti-microbial proteins</p> Signup and view all the answers

    What is the main difference between Th1 and Th17 responses?

    <p>Th1 responses are involved in protection against viral infections, while Th17 responses are involved in protection against bacterial and fungal infections</p> Signup and view all the answers

    Study Notes

    T-Lymphocyte Biology: Objectives

    • Recall the process of Th activation and the mechanism of T-lymphocyte class restriction
    • Compare the function and location of costimulator, co-receptor, and adhesion molecules during APC-Th interaction
    • Describe the role of IL-2 in lymphocyte activation and its mechanism of release

    T-Cell Activation

    • 2-step process: signal 1 and signal 2
    • Signal 1a: T-cell receptor interacting with HLA-2 (specificity of adaptive immunity)
    • Signal 1b: CD4 co-receptor interacting with HLA-2 (increases T-cell activation)
    • Signal 2: co-stimulatory interaction (CD28 on Th cell binding to CD80/86 on APC)
    • Costimulators (CD80/86) are key to Th activation, increasing HLA-2 and costimulator expression only when APC recognizes a DAMP or PAMP

    Interleukin 2 (IL-2) and Lymphocyte Activation

    • IL-2 is a major T-cell and B-cell growth factor
    • Proliferation and differentiation of activated naïve T cells and B cells
    • IL-2 binding to Th IL-2R acts in an autocrine fashion, activating the Th cell and causing it to enter the cell cycle
    • Synthesis of both IL-2 and the high-affinity IL-2R is induced after CD28-CD80/86 binding and recognition of antigen by the TCR

    Helper T-Cells and Immunity

    • CD4+ helper T-lymphocytes (Th) aid immunity by activating or inhibiting other cells through direct contact and secretion of cytokines
    • Th cells differentiate after activation to "help" in a specific way (T-cell polarization)

    T-Cell Polarization

    • T-helper cells become polarized after activation, determined by the environment they are found in
    • Polarization: specialized Th phenotype secreting a "profile" of cytokines that mediate distinct effector cell functions
    • Key information: inducing cytokines, transcription factors, cytokines secreted, and microenvironment

    Th1, Th2, Th17, Tfh, and Treg Helper T-Cells

    • Th1: viral or intracellular bacteria infections, polarizing cytokines (IL-12, IFN-γ), transcription factor (T-bet), cytokines secreted (IFN-γ, TNF-α), microenvironment (intracellular)
    • Th2: parasitic infections, polarizing cytokines (IL-4, IL-13), transcription factor (GATA-3), cytokines secreted (IL-4, IL-5, IL-13), microenvironment (parasitic)
    • Th17: bacterial and fungal infections, polarizing cytokines (IL-6, TGF-β, IL-23), transcription factor (ROR-γt), cytokines secreted (IL-22, IL-17), microenvironment (chronically inflamed tissue)
    • Tfh: activation of B-cells, polarizing cytokines (IL-6, IL-21), transcription factor (Bcl-6), cytokines secreted (IL-21, IL-4), microenvironment (B-cell follicles)
    • Treg: down-regulation of effector activities, polarizing cytokine (TGF-β), transcription factor (FoxP3), cytokines secreted (TGF-β, IL-10), microenvironment (anti-inflammatory)

    Cross-Regulation between Th Cells

    • Signals generated by a polarized Th cell tend to prevent other local Th cells from being polarized into a different type
    • Exception: Tfh cells often "re-polarize" to another Th type after the antibody response they help is completed

    T Cell Activation

    • T cell activation is a 2-step process involving co-stimulators, which are key to Th activation
    • Major co-stimulator: CD80/86 on the APC, which binds to CD28 on the Th
    • CD80/86 expression on APCs increases only when the APC recognizes a DAMP or a PAMP

    Interleukin 2 (IL-2) and Lymphocyte Activation

    • IL-2 is a major T cell and B cell growth factor
    • IL-2 promotes proliferation and differentiation of activated naïve T cells and B cells
    • IL-2 binding to the Th IL-2R acts in an autocrine fashion, activating the Th cell and causing it to enter the cell cycle, and avoid apoptosis
    • Synthesis of IL-2 and the high-affinity IL-2R is induced after CD28-CD80/86 binding and recognition of antigen by the TCR (via HLA-2)

    Helper T-cells and Immunity

    • CD4+ helper T-lymphocytes (Th) never kill pathogens or other “foreign-looking” entities directly
    • Instead, they activate or inhibit other cells through direct contact or secretion of cytokines
    • Th cells differentiate after activation to “help” in a specific way, known as T-cell polarization

    Th Polarization

    • Th cells become polarized after activation, specializing in a specific Th phenotype
    • Polarization is determined by the environment, particularly the types of cytokines present in high concentrations
    • Key information about Th polarization includes:
      • Inducing cytokines and transcription factors
      • Cytokines secreted by the Th
      • The microenvironment and effects of the cytokines

    Th1 Polarization

    • Th1 polarization occurs in response to infection, likely viral or intracellular bacterial
    • Dendritic cells phagocytose the pathogen, activating PRRs and migrating to lymph nodes or secondary lymphatic organs
    • Th1 cells secrete IL-2, IFN-γ, and TNF-β, which activate macrophages and enhance antibody secretion

    Th17 Polarization

    • Th17 cells were discovered recently and are implicated in protection from infection and many autoimmune disorders
    • Th17 cells are polarized by IL-6, IL-23, and TGF-β, which are produced by activated dendritic cells
    • Th17 cells produce IL-22 and IL-17, which:
      • Induce release of IL-6, IL-1, TNF-α, and GM-CSF
      • Cause release of chemokines that recruit neutrophils and macrophages
      • Cause secretion of anti-microbial proteins from cells in inflamed tissue

    Follicular Th Cells and Antibody Production

    • Follicular Th cells (Tfh) are the main Th cell that aids full B-cell development in SLOs
    • Tfh cells remain in SLOs, inducing formation of germinal centers and aiding B-cell antibody production
    • Tfh cells are polarized by IL-21 and IL-12, which are different from Th1 and Th17 polarizing cytokines

    Cytotoxic T-cells

    • Cytotoxic T-cells kill cells that express abnormal intracellular antigens on HLA-1
    • Activation of cytotoxic T-cells requires two signals:
      • An activating signal from a dendritic cell that has been licensed to present antigen
      • An activating signal from a Th1 cell in the near vicinity of the cytotoxic T-cell and its activating dendritic cell

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