Central and Peripheral Tolerance in Immunology
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Central and Peripheral Tolerance in Immunology

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Questions and Answers

What factor is primarily responsible for exacerbating autoimmune diseases through T cell activation?

  • Environmental toxins
  • Adaptive immune response
  • Commensal microbiota
  • Inadequate self-tolerance (correct)

    • Which autoimmune disease is NOT mention as a result of single-gene mutations?

  • Systemic lupus erythematosus (SLE)
  • Antiphospholipid syndrome (APS)
  • Autoimmune lymphoproliferative syndrome (ALPS)
  • Rheumatoid arthritis (correct)

    • How might infections contribute to the development of autoimmunity?

  • By inducing apoptosis in self-reactive lymphocytes
  • By promoting MHC mismatch
  • By improving lymphocyte turnover
  • By enhancing expression of costimulators (correct)

    • Which aspect is NOT a characteristic of the genetic basis of autoimmune diseases?

    <p>Autoimmunity is strictly monogenic</p> Signup and view all the answers

    What is the primary role of helper T cells in the context of autoimmune diseases?

    <p>To regulate all immune responses to proteins</p> Signup and view all the answers

    What is the primary outcome for immature T cells that recognize self antigens with high avidity during central tolerance?

    <p>They undergo deletion or develop into regulatory T cells.</p> Signup and view all the answers

    Which process is NOT a mechanism of peripheral T cell tolerance?

    <p>Positive selection</p> Signup and view all the answers

    What role does the autoimmune regulator (AIRE) play in T cell tolerance?

    <p>It facilitates expression of peripheral tissue antigens in the thymus.</p> Signup and view all the answers

    In central tolerance, what happens to B cells that encounter self antigens?

    <p>They are deleted or change their specificity.</p> Signup and view all the answers

    Which mechanism is primarily responsible for the functional unresponsiveness of self-reactive T cells?

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

    What is a key feature of central tolerance as it relates to T cells?

    <p>It occurs in generative lymphoid organs such as the thymus.</p> Signup and view all the answers

    Which statement correctly describes peripheral tolerance?

    <p>It can include suppression by regulatory T cells or deletion in peripheral tissues.</p> Signup and view all the answers

    Which of the following is NOT a factor determining immunogenicity and tolerogenicity?

    <p>The location of antigen presentation</p> Signup and view all the answers

    What is the role of TGF-β1 in T cell differentiation?

    <p>Regulates the differentiation of FoxP3+ Tregs</p> Signup and view all the answers

    How does IL-10 influence macrophage activity?

    <p>Inhibits co-stimulator expression</p> Signup and view all the answers

    What is a key characteristic of tolerogenic antigens?

    <p>They are expressed in generative lymphoid organs</p> Signup and view all the answers

    What occurs when immature B lymphocytes recognize self antigens in the bone marrow with high affinity?

    <p>They change their specificity or are deleted</p> Signup and view all the answers

    What describes central tolerance in lymphocytes?

    <p>Induced by exposure to self antigens in generative lymphoid organs</p> Signup and view all the answers

    Which of the following statements about peripheral tolerance is true?

    <p>It can occur with the absence of specific helper T cells</p> Signup and view all the answers

    What is the consequence of the failure of self-tolerance in the immune system?

    <p>Development of autoimmune diseases</p> Signup and view all the answers

    Which process does TGF-β promote following local immune reactions?

    <p>Tissue repair</p> Signup and view all the answers

    Which mechanism is primarily responsible for retaining the functionality of self-reactive T lymphocytes in peripheral tissues?

    <p>Development into FoxP3+ Tregs</p> Signup and view all the answers

    What condition occurs when B lymphocytes recognize self antigens without T cell assistance?

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

    What is a common factor that increases the likelihood of developing autoimmunity?

    <p>Genetic susceptibility</p> Signup and view all the answers

    Which of the following describes the process by which immature B cells change their specificity in response to self-antigens?

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

    What is a primary consequence of defective self-tolerance in the immune system?

    <p>Increased production of autoantibodies</p> Signup and view all the answers

    Which of the following describes an abnormal display of self antigens relevant to autoimmunity?

    <p>Structural changes to self antigens due to injury</p> Signup and view all the answers

    Which of the following best characterizes autoimmune diseases?

    <p>Chronic, progressive, and self-perpetuating</p> Signup and view all the answers

    What critical role do regulatory T lymphocytes have in maintaining immune homeostasis?

    <p>Controlling responses to self antigens</p> Signup and view all the answers

    Which statement best describes the role of CTLA-4 in T cell regulation?

    <p>CTLA-4 prevents activation by competing with CD28 for B7 ligands.</p> Signup and view all the answers

    What is a consequence of TCR-induced signal transduction blockage in anergic T cells?

    <p>Failure to respond to both self and foreign antigens.</p> Signup and view all the answers

    How do regulatory T cells (Tregs) primarily suppress immune responses?

    <p>By producing immunosuppressive cytokines like IL-10 and TGF-β.</p> Signup and view all the answers

    What role does interleukin-2 (IL-2) play in the function of regulatory T cells?

    <p>IL-2 is consumed by Tregs, limiting expansion of effector T cells.</p> Signup and view all the answers

    Which mechanism is directly involved in the degradation of TCR-associated proteins in anergic T cells?

    <p>Activation of cellular ubiquitin ligases.</p> Signup and view all the answers

    Which of the following accurately describes the engagement of inhibitory receptors in T cell tolerance?

    <p>They terminate T cell responses to prevent autoimmunity.</p> Signup and view all the answers

    What is the primary function of TGF-β1 produced by regulatory T cells?

    <p>To inhibit T cell proliferation and macrophage activation.</p> Signup and view all the answers

    Which feature distinguishes CTLA-4 from CD28 in T cell regulation?

    <p>CTLA-4 competes for the same ligands as CD28 but functions as an inhibitor.</p> Signup and view all the answers

    Study Notes

    Central and Peripheral Tolerance

    • Tolerance to self antigens is a fundamental property of the immune system
    • Central tolerance occurs in the generative lymphoid organs (thymus and bone marrow) when immature lymphocytes encounter self antigens
    • Peripheral tolerance occurs when mature lymphocytes recognize self antigens in peripheral tissues under particular conditions
    • Immature lymphocytes specific for self antigens may encounter these antigens in the generative lymphoid organs (central organs) and are deleted, change their specificity (B cells only), or (CD4+ T cells) develop into regulatory lymphocytes (Tregs)
    • Some self-reactive lymphocytes may mature and enter peripheral tissues and may be inactivated or deleted by an encounter with self antigens or are suppressed by Tregs

    Central T Cell Tolerance

    • Many immature T cells that recognize antigens with high avidity die (negative selection)
    • Some surviving cells in the CD4+ lineage develop into Tregs
    • The thymus expresses numerous protein antigens that are limited to certain peripheral tissues so that immature T cells specific for these antigens can be deleted

    AIRE in T Cell Deletion

    • The autoimmune regulator (AIRE) protein controls expression of peripheral tissue antigens in medullary thymic epithelial cells (MTECs)

    Mechanisms of Peripheral T Cell Tolerance

    • Peripheral tolerance mechanisms include anergy, suppression by Tregs, and deletion
    • These mechanisms may be responsible for T cell tolerance to tissue-specific self antigens and foreign antigens presented under tolerogenic conditions

    Mechanisms of T Cell Anergy

    • TCR-induced signal transduction is blocked in anergic cells
    • Self-antigen recognition without costimulation may activate ubiquitin ligases which target TCR-associated proteins for degradation
    • When T cells recognize self antigens without innate immune responses they may engage inhibitory receptors of the CD28 family, which terminate T cell responses

    Actions of CTLA-4

    • CTLA-4 is expressed on Tregs and recently activated T cells
    • CTLA-4 is a competitive inhibitor of CD28 and reduces the availability of B7 for CD28
    • CTLA-4 prevents activation of responding T cells
    • CTLA-4 on one T cell (a Treg) can inhibit responses of other T cells
    • CTLA-4 and CD28 recognize the same ligands: B7-1 (CD80) and B7-2 (CD86)

    Regulatory T Cells

    • Tregs are a subset of CD4+ T cells that suppress immune responses
    • Tregs express the transcription factor FoxP3
    • Tregs play a crucial role in maintaining immune homeostasis and preventing autoimmunity

    IL-2 in Maintaining Tregs

    • Tregs consume IL-2, which is essential for their survival and function
    • Tregs suppress immune responses by multiple mechanisms

    Inhibitory Cytokines Produced by Tregs

    • TGF-β1 produced by CD4+ Tregs inhibits T cell proliferation and function
    • TGF-β1 stimulates production of IgA
    • TGF-β1 promotes tissue repair
    • IL-10 is an inhibitor of activated macrophages and dendritic cells
    • IL-10 inhibits IL-12 production and co-stimulator expression
    • IL-10 inhibits T cell activation and terminates cell-mediated immune reactions

    Factors Determining Immunogenicity and Tolerogenicity of Protein Antigens

    • Tolerogenic antigens are expressed in generative lymphoid organs
    • The nature of the dendritic cell displaying antigens to T lymphocytes is an important determinant of the subsequent response

    Central Tolerance in B Cells

    • Immature B cells that recognize self antigens in the bone marrow change their specificity or are deleted
    • Mature B cells that recognize self antigens in peripheral tissues without helper T cells may become unresponsive or die by apoptosis

    Summary of Tolerance Mechanisms

    • Immunologic tolerance is unresponsiveness to an antigen
    • Central tolerance is induced in the generative lymphoid organs when immature lymphocytes encounter self antigens
    • Peripheral tolerance occurs when mature lymphocytes recognize self antigens in peripheral tissues
    • Some immature T cells that encounter self antigens in the thymus die by negative selection
    • Anergy is induced by antigen recognition without adequate costimulation
    • Central tolerance in B cells is induced when immature B cells recognize self antigens in the bone marrow resulting in receptor editing or apoptotic death
    • Mature B cells that recognize self antigens in the periphery without T cell help may be rendered anergic or become functionally unresponsive

    Postulated Mechanisms of Autoimmunity

    • Factors that contribute to autoimmunity include genetic susceptibility and environmental triggers
    • Autoimmune diseases may be systemic or organ specific

    Effector Mechanisms of Autoimmunity

    • Effector mechanisms of autoimmunity include immune complexes, circulating autoantibodies, and autoreactive T lymphocytes

    Immunologic Abnormalities Leading to Autoimmunity

    • Autoimmune diseases result from inadequate self-tolerance or regulation of lymphocytes
    • Defects in deletion of T or B cells
    • Defective numbers or functions of regulatory T lymphocytes
    • Defective apoptosis of mature lymphocytes
    • Inadequate function of inhibitory receptors
    • Abnormal display of self antigens
    • Inflammation or an initial innate immune response may contribute to autoimmunity

    Genetic Basis of Autoimmunity

    • Most autoimmune diseases are polygenic
    • The greatest genetic contribution is from MHC genes

    Examples of Single-Gene Mutations That Cause Autoimmunity

    • Antiphospholipid syndrome (APS)
    • Systemic lupus erythematosus (SLE)
    • Autoimmune lymphoproliferative syndrome (ALPS)
    • Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome

    Role of Infections in Autoimmunity

    • Infections may enhance expression of costimulators in tissues
    • Infections may trigger cross reactions between microbial antigens and self antigens

    Summary of Autoimmunity

    • Autoimmunity results from inadequate self-tolerance or regulation of lymphocytes
    • Autoimmune reactions may be triggered by environmental stimuli in genetically susceptible individuals
    • Most autoimmune diseases are polygenic
    • Additional genes are believed to influence the selection or regulation of self-reactive lymphocytes
    • Infections may predispose to autoimmunity
    • Some infections may protect individuals from autoimmunity

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    Immunologic Tolerance and Autoimmunity Lecture PDF

    Description

    Explore the concepts of central and peripheral tolerance within the immune system. This quiz covers how immature and mature lymphocytes interact with self antigens and the implications of these processes for immune regulation. Learn about the mechanisms that prevent autoimmunity through central and peripheral tolerance.

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