Cellular Response #1
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Questions and Answers

What altered T cell is used to treat adults with certain types of large B-cell lymphoma?

  • IL-2
  • CTLA-4 Ig
  • CTLA-4 : B7
  • Chimeric antigen receptor (correct)

    • What role do dendritic cells play in the initiation of T-cell responses?

  • They capture and present protein antigens to naïve T-cells. (correct)
  • They inhibit the migration of T-cells to lymph nodes.
  • They directly kill microbes.
  • They are responsible for producing antibodies.

    • Which characteristic of dendritic cells makes them particularly effective at initiating primary T-cell responses?

  • Their production of large volumes of antibodies.
  • Their ability to replicate rapidly in lymph nodes.
  • Their strategic location at sites of microbial entry. (correct)
  • Their capability to eliminate infected tissues.

    • What is necessary for dendritic cells to activate naïve T-cells?

    <p>High levels of co-stimulatory molecules.</p> Signup and view all the answers

    How do dendritic cells respond to microbial infections?

    <p>They activate and present antigens from infected cells.</p> Signup and view all the answers

    Where do dendritic cells preferentially migrate after capturing antigens?

    <p>To T-cell-rich zones of lymph nodes.</p> Signup and view all the answers

    Dendritic cells express receptors that enable them to capture microbes and respond to microbes

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

    Dendritic cells carry antigens from _______ to _________ lymphoid organs to then present to naive T cells.

    <p>Dendritic cells carry antigens from periphery to secondary lymphoid organs to then present to naive T cells.</p> Signup and view all the answers

    What is the primary role of CD28:B7 interaction in T cell activation?

    <p>Stimulates the survival, proliferation, and differentiation of T cells</p> Signup and view all the answers

    What is the first signal required for T cell activation?

    <p>Recognition of peptide-MHC complexes</p> Signup and view all the answers

    Which T cell population is primarily activated by class II MHC molecules?

    <p>Naïve CD4+ T cells</p> Signup and view all the answers

    What process follows the antigen recognition by naïve T cells during activation?

    <p>Cytokine secretion</p> Signup and view all the answers

    Dendritic cells present peptides from protein antigens primarily to which type of T cell?

    <p>CD4+ T cells through class II MHC</p> Signup and view all the answers

    Which costimulatory interaction is essential for T cell activation after antigen recognition?

    <p>CD28 (T cell) binding to B7 (DC)</p> Signup and view all the answers

    The production of which molecule is crucial for promoting T cell survival, proliferation, and differentiation following activation?

    <p>IL-2</p> Signup and view all the answers

    What is the role of the CD40L interaction in the T cell activation?

    <p>It activates antigen presenting cells to express B7, enabling costimulation</p> Signup and view all the answers

    Which of the following is necessary for a complete T cell response to occur?

    <p>Both antigen recognition and costimulation signals, such as CD28 binding to B7</p> Signup and view all the answers

    Which receptor interaction is primarily responsible for the initial activation of naive T cells?

    <p>CD28:B7</p> Signup and view all the answers

    What is a primary outcome of T lymphocyte activation?

    <p>Cytokine secretion</p> Signup and view all the answers

    Which interaction serves to inhibit effector T cell activation in peripheral tissues?

    <p>PD:PD-Ligand</p> Signup and view all the answers

    Which interaction is critical for the development of helper T cells and subsequent antibody responses?

    <p>ICOS:ICOS-Ligand</p> Signup and view all the answers

    What is the effect of CTLA-4:B7 interaction on T cell activation?

    <p>Inhibits the initial activation of T cells</p> Signup and view all the answers

    Which condition is CTLA-4 specifically approved to treat?

    <p>Rheumatoid arthritis</p> Signup and view all the answers

    What is a therapeutic application currently being explored for inhibitors of the CD40L:CD40 pathway?

    <p>Chronic inflammatory diseases</p> Signup and view all the answers

    Which of the following therapies is currently approved for tumor immunotherapy?

    <p>Antibodies against CTLA-4</p> Signup and view all the answers

    Which disease is CTLA-4 currently in clinical trials for treatment?

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

    What is the primary purpose of CTLA-4 in therapeutic use?

    <p>Blocking costimulatory signals</p> Signup and view all the answers

    What are the 5 functional responses of T cell activation?

    <p>Increase surface expression of molecules, increase IL-2 secretion , clonal expansion of that specific T cell clone, differentiation of activated T cells and development of memory cells.</p> Signup and view all the answers

    What is the primary function of IL-2 in T cell biology?

    <p>Stimulating T cell survival and proliferation</p> Signup and view all the answers

    Which cell type is the main producer of IL-2 following antigen recognition?

    <p>CD4+ T cells</p> Signup and view all the answers

    How does IL-2 exert its effects in the immune response?

    <p>By promoting differentiation of T cells and increasing cytokine production</p> Signup and view all the answers

    Which of the following cytokines is increased in production due to the action of IL-2?

    <p>IFN gamma</p> Signup and view all the answers

    In what manner does IL-2 impact T cell differentiation?

    <p>It supports the differentiation into effector T cells</p> Signup and view all the answers

    What does clonal expansion of T cells specifically increase?

    <p>The number of antigen-specific T cell clones</p> Signup and view all the answers

    Which statement accurately characterizes the daughter cells produced during clonal expansion of lymphocytes?

    <p>They share the same antigen specificity.</p> Signup and view all the answers

    How is clonal expansion defined in the context of T cells?

    <p>As the proliferation of a single cell leading to identical clones</p> Signup and view all the answers

    Which aspect of clonal expansion ensures the effectiveness of T cell responses?

    <p>Generating a homogenous pool of antigen-specific T cells</p> Signup and view all the answers

    In clonal expansion, what is the significance of all progeny sharing the same antigen specificity?

    <p>It allows for a coordinated attack against a specific antigen.</p> Signup and view all the answers

    Which type of T cell is primarily responsible for cytotoxic functions?

    <p>CD8+ T cells</p> Signup and view all the answers

    What is a key characteristic of memory T cells?

    <p>They can persist for years or a lifetime after initial activation.</p> Signup and view all the answers

    How do effector T cells differentiate into memory cells?

    <p>Along a linear pathway or through divergent differentiation.</p> Signup and view all the answers

    Which cytokines are typically secreted by CD4+ effector T cells?

    <p>Interleukin-4 (IL-4) and Interleukin-17 (IL-17)</p> Signup and view all the answers

    Which of the following statements correctly describes T cell differentiation?

    <p>Differentiation can lead to both effector and memory T cell populations.</p> Signup and view all the answers

    What are the two pathways memory cells can develop?

    <p>Linear and divergent pathways.</p> Signup and view all the answers

    Which of the following characteristics is NOT associated with memory T cells?

    <p>Ability to undergo rapid proliferation in response to antigens</p> Signup and view all the answers

    What role does IL-7 play in the context of memory T cells?

    <p>Maintaining the survival of memory cells</p> Signup and view all the answers

    Which statement about the number of memory T cells compared to naive T cells is accurate?

    <p>There are more memory T cells for an antigen than naive T cells.</p> Signup and view all the answers

    How do memory T cells respond to previously encountered antigens compared to naive T cells?

    <p>Their response is more rapid and of a higher magnitude.</p> Signup and view all the answers

    Which factor contributes to the prolonged survival of memory T cells?

    <p>Higher levels of anti-apoptotic proteins.</p> Signup and view all the answers

    What is one of the primary factors that leads to the decline of T cell responses?

    <p>Cessation of co-stimulation</p> Signup and view all the answers

    Which mechanism is NOT responsible for the decline of T cell populations?

    <p>Increased availability of antigen</p> Signup and view all the answers

    What role does BH3-only protein Bim play in the decline of T cell responses?

    <p>Triggers apoptosis of T cells</p> Signup and view all the answers

    Which statement accurately reflects the importance of T cell response decline in the immune system?

    <p>It is crucial for maintaining homeostasis in the immune system.</p> Signup and view all the answers

    Which of the following processes does NOT contribute to T cell decline following antigen elimination?

    <p>Induction of specific T cell differentiation</p> Signup and view all the answers

    Study Notes

    T-cell Response Initiation

    • T-cell responses begin in peripheral lymphoid organs.
    • Protein antigens are transported to these organs after entering the body.

    Dendritic Cell Role in T-cell Response

    • Dendritic cells (DCs) capture protein antigens in tissues and epithelia.
    • DCs transport these antigens to draining lymph nodes.

    Properties of DCs for Effective T-cell Activation

    • DCs are located in areas where microbes commonly enter the body.
    • DCs express receptors that recognize and bind to microbes.
    • DCs migrate to T-cell-rich zones in lymph nodes.
    • Mature DCs express high levels of co-stimulatory molecules necessary for naïve T-cell activation.
    • DCs can ingest infected cells and tumor cells, presenting antigens to CD8+ T cells.

    T Cell Activation

    • Naïve T cells, which circulate in secondary lymphoid organs, require activation to gain functionality.
    • Antigen recognition by T cells triggers activation, leading to:
      • Cytokine secretion: Cells release signaling molecules to communicate with other cells.
      • Proliferation: Increases in the number of T cells with specific antigen recognition.
      • Differentiation: Naïve T cells develop into effector or memory T cells.

    Signals for T Cell Activation

    • Signal 1: Antigen recognition is the primary activation signal for T cells:

      • CD4+ and CD8+ T cells recognize peptide-MHC complexes on antigen-presenting cells (APCs).
      • Multiple T cell surface proteins contribute to activation.

    • Signal 2: Costimulation is a second signal required for T cell activation:

      • Signal 2 works alongside antigen recognition (signal 1) to stimulate T cells.

    • CD28:B7 interaction: A crucial costimulatory pathway, CD28 on T cells interacts with B7 molecules on APCs, promoting survival, proliferation, and differentiation of activated T cells.

    Dendritic Cell Role in Activation

    • Dendritic cells activate naïve T cells:
      • They present peptides from endocytosed protein antigens in association with MHC class II molecules to CD4+ T cells.
      • They present peptides from cytosolic and nuclear proteins displayed by MHC class I molecules to CD8+ T cells.

    T Cell Activation & CD28 Family Receptors

    • T cell activation is influenced by activating and inhibiting signals from the CD28 family receptors
    • Activating interactions:
      • CD28:B7 (key for activating naive T cells)
      • ICOS:ICOS-Ligand (critical for helper T cell development and antibody responses )
    • Inhibitory interactions:
      • CTLA-4:B7 (inhibits initial T cell activation in secondary lymphoid organs)
      • PD:PD-Ligand (inhibits the activation of effector cells in peripheral tissues)
    • Outcomes of T Cell Activation:
      • Cytokine secretion
      • T cell proliferation (increase in number of cells)
      • Differentiation (naive T cells become effector or memory cells)

    Therapeutic Costimulatory Blockade

    • CTLA-4-Ig is an approved therapy for rheumatoid arthritis and transplant rejection.
    • CTLA-4-Ig is currently in clinical trials for the treatment of psoriasis and Crohn’s disease.
    • Inhibitors of the CD40L:CD40 pathway are also in clinical trials for transplant rejection and chronic inflammatory diseases.
    • Antibodies against CTLA-4 and PD-1 are approved or are in clinical trials for the immunotherapy of tumors.

    Therapeutic Costimulatory Blockade

    • CTLA-4 is an approved therapy for rheumatoid arthritis and transplant rejection.
    • CTLA-4 is currently in clinical trials for the treatment of psoriasis and Crohn’s disease.

    Inhibitors of the CD40L:CD40 Pathway

    • Inhibitors of the CD40L:CD40 pathway are also in clinical trials for transplant rejection and chronic inflammatory diseases.

    Immunotherapy of Tumors

    • Antibodies against CTLA-4 and PD-1 are approved or are in clinical trials for the immunotherapy of tumors.

    IL-2 Secretion and IL-2Rα Expression

    • IL-2 is a crucial cytokine that promotes T cell growth, survival, and differentiation.
    • IL-2 is primarily produced by CD4+ T cells shortly after encountering an antigen and receiving co-stimulatory signals.
    • IL-2 has an autocrine function, meaning it acts on the very cells that produce it, and a paracrine function, meaning it can influence neighboring cells.
    • IL-2's key roles include:
      • Stimulating T cell survival and proliferation.
      • Promoting T cell differentiation into various subtypes.
      • Enhancing the production of IFN-gamma and IL-4 by T cells.
      • Playing a critical role in the survival of certain T cell populations.

    Clonal Expansion of T Cells

    • Proliferation of T cells results in an increase in the number of antigen-specific clones.
    • Clonal expansion is the production of daughter cells from a single cell.
    • In clonal expansion of lymphocytes, all progeny cells (daughter cells) share the same antigen specificity.

    Activated T Cell Differentiation

    • CD4+ T cells differentiate into effector cells that express specific surface molecules and secrete cytokines.
    • CD8+ T cells differentiate into cytotoxic T cells.

    Memory Cell Development

    • Memory cells develop for specific antigens and can persist for years or a lifetime.
    • Memory cell development can occur via a linear pathway from effector cells or from divergent differentiation of effector populations.

    Properties of Memory T Cells

    • Memory T cells express higher levels of anti-apoptotic proteins, allowing them to survive for longer periods.
    • They respond quicker to known antigens compared to naive T cells.
    • The body maintains a larger pool of memory cells specific to a particular antigen than naive T cells for the same antigen.
    • Memory T cells can migrate to peripheral tissues, enabling them to respond to infection at various sites.
    • In the absence of antigens, memory T cells undergo slow proliferation, which contributes to their long-term persistence.
    • The maintenance of memory T cells relies on the cytokine interleukin-7 (IL-7).

    Memory T Cells - Properties

    • Increased anti-apoptotic protein expression - leads to enhanced survival, allowing for long-term immune memory.
    • Faster response to antigens - allows for quicker and more efficient immune response upon re-exposure to the same pathogen.
    • Higher abundance - compared to naive T cells specific for the same antigen.
    • Migration to peripheral tissues - facilitates rapid immune response at the site of infection.
    • Slow proliferation - in the absence of antigen, ensuring the long-term maintenance of the memory cell pool.
    • IL-7 dependence - for survival and maintenance of memory T cell population.

    T Cell Response Decline

    • T cell response contraction is necessary for maintaining immune homeostasis.
    • The decline is triggered by the elimination of the antigen.
    • Cessation of co-stimulation and growth factor production (IL-2) contributes to the decline.
    • Activation of cellular stress sensors, specifically the BH3-only protein Bim, initiates apoptosis in T cells during contraction.

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    Activation of T Lymphocytes

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