Immunological Tolerance and Helper T Cells
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Questions and Answers

What is the main difference between natural tolerance and induced tolerance?

  • Natural tolerance is a passive response, whereas induced tolerance is an active manipulation of the immune system. (correct)
  • Natural tolerance prevents autoimmune diseases, while induced tolerance focuses solely on organ transplants.
  • Natural tolerance occurs without any immune response, unlike induced tolerance which still involves immune recognition.
  • Natural tolerance involves only self-antigens, while induced tolerance involves only external antigens.

    • Why is T cell tolerance considered more important than B cell tolerance?

  • B cells can produce antibodies without T cell assistance.
  • T cells only recognize self-antigens while B cells can recognize both self and non-self.
  • B cells fail to activate in the absence of T cell help for most antigens. (correct)
  • B cells represent a smaller population than T cells in the immune response.

    • Which type of helper T cell is primarily involved in combating intracellular pathogens?

  • Tfh
  • Th17
  • Th2
  • Th1 (correct)

    • How does Th2 assist B cells in the immune response?

    <p>By promoting the production of IgE antibodies and certain subclasses of IgG.</p> Signup and view all the answers

    What role do Tfh cells play in the immune system?

    <p>They help B cells develop into antibody-secreting plasma cells in lymphoid follicles.</p> Signup and view all the answers

    What function does Th17 primarily serve in the immune system?

    <p>They protect mucosal surfaces against extracellular bacteria.</p> Signup and view all the answers

    Which statement correctly describes immunological tolerance?

    <p>It is a complex active process that can be induced or natural.</p> Signup and view all the answers

    What can result from a failure in immunological tolerance towards self-antigens?

    <p>Autoimmune diseases due to the immune system attacking body proteins.</p> Signup and view all the answers

    What is the main reason that some antigens are not detected by the immune system?

    <p>They may appear in very low concentration.</p> Signup and view all the answers

    What occurs during clonal deletion in T cells?

    <p>Functionally immature cells undergo a programmed cell death.</p> Signup and view all the answers

    Which process leads to the inability of T cells to respond to an antigen?

    <p>Clonal anergy</p> Signup and view all the answers

    What triggers receptor editing in B cells?

    <p>Binding to soluble antigens with very low affinity.</p> Signup and view all the answers

    What is the role of anti-idiotype antibodies in the immune response?

    <p>Inhibit immune response to specific antigens.</p> Signup and view all the answers

    Which statement correctly describes suppressor T cells (Regulatory T cells)?

    <p>They produce cytokines like TGF-β and IL-10.</p> Signup and view all the answers

    What can lead to the termination of experimentally induced tolerance?

    <p>Immunization with cross-reactive antigens.</p> Signup and view all the answers

    Which characteristic is associated with regulatory T cells?

    <p>They express high levels of CD25 but not other markers of activation.</p> Signup and view all the answers

    What is the primary function of central tolerance in the immune system?

    <p>To eliminate autoreactive lymphocytes</p> Signup and view all the answers

    During which phase do T cells undergo positive selection?

    <p>In the thymic cortex</p> Signup and view all the answers

    What happens to immature B cells that strongly bind self peptides in the bone marrow?

    <p>They are signaled to apoptosis</p> Signup and view all the answers

    Which type of tolerance occurs after lymphocytes exit primary lymphoid organs?

    <p>Peripheral tolerance</p> Signup and view all the answers

    What role do transcriptional regulators AIRE and Fezf2 play in T cell tolerance?

    <p>Promoting the expression of self tissue antigens</p> Signup and view all the answers

    Which mechanism of peripheral tolerance involves the inactivation of self-reactive T cells?

    <p>Clonal anergy</p> Signup and view all the answers

    What is indicated by the term 'tolerogen'?

    <p>An antigen that induces tolerance</p> Signup and view all the answers

    What occurs during the process of receptor editing in B cells?

    <p>B cells rearrange genes to develop a new BCR</p> Signup and view all the answers

    Why is T cell tolerance generally longer lasting than B cell tolerance?

    <p>T cell tolerance is more robustly maintained</p> Signup and view all the answers

    Which statement accurately differentiates between central and peripheral tolerance?

    <p>Central tolerance primarily involves negative selection of lymphocytes.</p> Signup and view all the answers

    What is a main consequence of the clonal deletion process?

    <p>Prevention of auto-reactive T and B cells</p> Signup and view all the answers

    How does ignorance contribute to immunological tolerance?

    <p>It permits the presence of self-reactive cells without activation.</p> Signup and view all the answers

    Which process leads to the death of T cells that cannot bind to MHC complexes?

    <p>Clonal deletion</p> Signup and view all the answers

    Which method is NOT involved in inducing peripheral tolerance?

    <p>Receptor editing</p> Signup and view all the answers

    Study Notes

    Immunological Tolerance

    • Immunological tolerance is the failure to mount an immune response to an antigen. This can be natural (self-tolerance) or induced.
    • Natural/Self-tolerance: The immune system doesn't attack the body's own proteins or antigens; crucial for preventing autoimmune diseases.
    • Induced tolerance: Tolerance to external antigens, achieved through several methods:
      • Treating allergic reactions (e.g., peanuts, insect stings, pollen).
      • Allowing transplanted organs to survive.
      • Preventing inflammation against harmless or beneficial gut bacteria.
    • Tolerance is an active, specific response to an epitope (part of an antigen recognized by antibodies).
    • T cell tolerance is more important than B cell tolerance because B cells need T cell help to produce antibodies to most antigens.

    Types of Helper T Cells

    • Four types of helper T cells are identified:
      • Th1: Crucial for cell-mediated and antibody-mediated immunity, essential against intracellular pathogens (e.g., viruses, TB bacteria). Provides help to cytotoxic T lymphocytes.
      • Th2: Provides help to B cells, essential for IgE antibody production and some IgG subtypes. Crucial against extracellular pathogens.
      • Tfh (Follicular helper T cells): Provide help to B cells in lymphoid follicles, leading to antibody-secreting plasma cells. Most abundant helper T cell.
      • Th17: Protects surfaces against extracellular bacteria (e.g., skin, gut).

    Central Tolerance

    • Central tolerance (also called negative selection) eliminates self-reactive T and B lymphocytes during development.
    • This process ensures the immune system doesn't attack self-antigens.
    • Lymphocyte maturation, including central tolerance, occurs in primary lymphoid organs (bone marrow, thymus).
    • B cells mature in the bone marrow, T cells in the thymus.

    Mechanisms of Central Tolerance

    • B cell tolerance: Immature B cells that bind self-antigens undergo apoptosis (clonal deletion), receptor editing (modifying the receptor), or anergy (inactivation).

    • T cell tolerance:

      • Positive selection: T cells are tested for their ability to bind peptide-MHC complexes with appropriate affinity. Inability to bind means apoptosis. Binding results in survival and development as CD4+ or CD8+ T cells. This occurs in the thymic cortex.
      • Negative selection: T cells are checked for affinity to self-antigens. High affinity to self leads to apoptosis. This occurs in the thymic medulla. The thymus displays self-antigens for this process.

    Peripheral Tolerance

    • A backup system to prevent autoimmunity in case of escaped self-reactive cells from central tolerance.
    • Mechanisms include anergy and regulatory T cells (Tregs).

    Immune Tolerance - Mechanisms

    • Clonal deletion: Elimination of self-reactive T and B cells.
    • Clonal anergy: Inactivation of self-reactive T and B cells.
    • Peripheral suppression by T cells: Regulatory T cells suppress immune responses.

    Tolerance Induction and Termination

    • Tolerogen: An antigen that induces tolerance.
    • Tolerance is specific and can be in B or T cells (or both). T-cell tolerance lasts longer than B-cell tolerance.
    • Tolerance to cells/tissues can be induced in neonatal animals or immunocompromised animals.
    • Tolerance can be broken naturally (autoimmune disease) or artificially (drug treatment, radiation).
    • Ignorance: A passive form of tolerance where the immune system doesn't "see" self-antigens, e.g. low concentrations or sequestered locations (eye, brain, testes).

    Mechanisms of Tolerance Induction

    • Anti-idiotypic antibodies: Antibodies that bind to the receptors of other lymphocytes to regulate against the antigen response.
    • Suppressor cells (Regulatory T cells): Suppress immune responses through cytokine production, most importantly TGF-β and IL-10. CD4+ T cells that express high levels of IL-2rα chain (CD25) but not other activation markers.

    Tolerance to Antigens

    • Tolerance to soluble antigens has been observed in different experimental models., showing various factors determine whether an immune response or tolerance to an antigen may occur.
    • Induction of tolerance in T cells is easier than in B cells. Persistence of the antigen is important for maintaining tolerance.

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    Description

    This quiz covers the concepts of immunological tolerance, including both natural and induced forms. It also explores the different types of helper T cells and their roles in the immune response. Dive into the mechanisms that prevent autoimmune diseases and facilitate organ transplants.

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