BMS 150 Week 4: T-Cell Development and Tolerance
76 Questions
2 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What happens to a DP T-cell if it has a high affinity interaction?

  • It is allowed to survive
  • It undergoes positive selection
  • It becomes a regulatory T-cell
  • It dies (correct)

    • What is the purpose of positive selection?

  • To test TCRs for their ability to interact with HLA molecules (correct)
  • To remove T-cells that recognize self-antigens
  • To allow only CD8+ T-cells to survive
  • To eliminate T-cells with low affinity interactions

    • What happens to DP T-cells that fail to interact with TECs?

  • They die (correct)
  • They choose to express CD4 or CD8 co-receptors
  • They become regulatory T-cells
  • They undergo positive selection

    • What is the approximate percentage of developing T-cells that survive positive and negative selection?

    <p>5%</p> Signup and view all the answers

    What happens in the cortex of the thymus?

    <p>TCR recombination, testing, and positive selection</p> Signup and view all the answers

    What is central tolerance?

    <p>Tolerance achieved in primary lymphoid organs</p> Signup and view all the answers

    What is the purpose of negative selection?

    <p>To eliminate T-cells that recognize self-antigens</p> Signup and view all the answers

    What happens to a DP T-cell after it has been positively selected and has survived negative selection?

    <p>It tests whether CD8 or CD4 co-receptors interact better with medullary TECs</p> Signup and view all the answers

    What type of stem cells are involved in T-cell development?

    <p>Hematopoietic stem cells (HSC) and multi-potential progenitor cells (MPP)</p> Signup and view all the answers

    Where do T-cells undergo minimal maturation?

    <p>Bone marrow</p> Signup and view all the answers

    What is the function of medullary and cortical thymic epithelial cells?

    <p>To guide T-cell development</p> Signup and view all the answers

    What is the outcome for T-cells that recognize antigen presented via HLA?

    <p>They undergo positive selection</p> Signup and view all the answers

    What is the purpose of negative selection in the thymus?

    <p>To eliminate T-cells that recognize self-antigens</p> Signup and view all the answers

    What is the purpose of the thymus in T-cell development?

    <p>To develop functional T-cell receptors</p> Signup and view all the answers

    What is the significance of IL-7 in T-cell development?

    <p>It influences lymphoid progenitor cell division</p> Signup and view all the answers

    What is the outcome for T-cells that bind self-antigens with high affinity?

    <p>They undergo negative selection</p> Signup and view all the answers

    What is the primary function of AIRE in central tolerance?

    <p>To bind with a wide range of transcription factors and activate them to express self-antigens</p> Signup and view all the answers

    What is the result of defects in AIRE?

    <p>Autoimmune polyendocrinopathy syndrome (APS)</p> Signup and view all the answers

    What is required for CD4+ Treg cell polarization?

    <p>Interaction with an APC and presence of high circulating levels of TGF-β</p> Signup and view all the answers

    What is the characteristic of the environment in which TGF-β is expressed in higher concentrations?

    <p>Non-inflammatory</p> Signup and view all the answers

    What is the role of thymic epithelial cells in central tolerance?

    <p>To express a wide range of self-antigens on their HLA</p> Signup and view all the answers

    What is the fate of T-cells that recognize self in central tolerance?

    <p>They are deleted through negative selection</p> Signup and view all the answers

    What is the effect of CTLA-4 binding to B7 molecules on APCs?

    <p>Downregulation of APC presenting antigen</p> Signup and view all the answers

    What is the result of knocking out CTLA-4 in a mouse?

    <p>Severe autoimmune disease</p> Signup and view all the answers

    What is expressed by T-reg cells after polarization?

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

    What is the effect of a low-level of co-stimulatory molecules on an effector CD4+ cell?

    <p>Shut down of the cell</p> Signup and view all the answers

    What is produced by APCs when T-reg cells inhibit them?

    <p>Kynurenic acid</p> Signup and view all the answers

    What is expressed by T-reg cells in addition to FoxP3?

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

    What activates the binding of antibody to antigen?

    <p>PRR activation</p> Signup and view all the answers

    What is the role of T-independent B-cells in mice?

    <p>Important for immune response</p> Signup and view all the answers

    What drives lymph flow into lymph capillaries?

    <p>Interstitial fluid build-up on the outside of the capillaries</p> Signup and view all the answers

    What prevents backflow of lymph in larger lymphatic vessels?

    <p>One-way valves in lymphatic vessels</p> Signup and view all the answers

    What is the function of the right lymphatic duct?

    <p>Drains the right arm, thoracic region, and right head/neck</p> Signup and view all the answers

    What is the function of the thoracic duct?

    <p>Drains the rest of the body</p> Signup and view all the answers

    What is the result of interstitial fluid build-up on the outside of lymph capillaries?

    <p>Cells are pushed apart and lymph enters</p> Signup and view all the answers

    What facilitates the flow of lymph from the abdomen towards the chest during inhalation?

    <p>Pressure created through breathing</p> Signup and view all the answers

    What is the primary function of the thymus in T-cell development?

    <p>To facilitate the maturation of T-cells</p> Signup and view all the answers

    What is the outcome for T-cells that recognize antigen presented via HLA?

    <p>They are positively selected</p> Signup and view all the answers

    What is the role of medullary and cortical thymic epithelial cells?

    <p>To guide T-cell development</p> Signup and view all the answers

    What is the significance of IL-7 in T-cell development?

    <p>It facilitates the differentiation of lymphoid progenitors</p> Signup and view all the answers

    Where do T-cells undergo minimal maturation?

    <p>In the bone marrow</p> Signup and view all the answers

    What is the outcome for T-cells that bind self-antigens with high affinity?

    <p>They are negatively selected</p> Signup and view all the answers

    What is the purpose of the thymus in central tolerance?

    <p>To remove T-cells that recognize self-antigens</p> Signup and view all the answers

    What type of stem cells are involved in T-cell development?

    <p>Hematopoietic stem cells and multi-potential progenitor cells</p> Signup and view all the answers

    What is the primary function of AIRE in central tolerance?

    <p>To activate thymic epithelial cells to express a wide range of proteins on their HLA</p> Signup and view all the answers

    What is the characteristic of the environment in which TGF-β is expressed in higher concentrations?

    <p>Non-inflammatory environment</p> Signup and view all the answers

    What is the outcome of defects in AIRE?

    <p>Autoimmune polyendocrinopathy syndrome (APS)</p> Signup and view all the answers

    What is required for CD4+ Treg cell polarization?

    <p>Interaction with an APC and presence of high circulating levels of TGF-β</p> Signup and view all the answers

    What is the role of thymic epithelial cells in central tolerance?

    <p>To express a wide range of self-antigens on their HLA</p> Signup and view all the answers

    What is the fate of T-cells that recognize self in central tolerance?

    <p>They are deleted</p> Signup and view all the answers

    What is the primary reason why a DP T-cell with a high affinity for a TEC HLA bound to self antigen is eliminated during negative selection?

    <p>This is a T-cell with a TCR that recognizes self, and it should not be allowed to survive</p> Signup and view all the answers

    What is the primary function of the cortex and medulla in the thymus during T-cell development?

    <p>To conduct positive and negative selection, respectively</p> Signup and view all the answers

    What is the primary difference between central and peripheral tolerance?

    <p>Central tolerance occurs in the thymus, while peripheral tolerance occurs in secondary lymphoid organs</p> Signup and view all the answers

    What is the primary function of the TCR during positive selection?

    <p>To recognize self-antigens with low-medium affinity</p> Signup and view all the answers

    What is the primary outcome for T-cells that recognize self-antigens with low-medium affinity during positive selection?

    <p>They are allowed to survive and undergo further development</p> Signup and view all the answers

    What is the primary function of medullary TECs during T-cell development?

    <p>To facilitate the expression of CD4 or CD8 co-receptors on T-cells</p> Signup and view all the answers

    What is the primary reason why some T-cells that recognize self-antigens are allowed to survive during negative selection?

    <p>They are regulatory T-cells</p> Signup and view all the answers

    What is the primary outcome for T-cells that fail to interact with TECs during positive selection?

    <p>They undergo apoptosis due to lack of TCR interaction</p> Signup and view all the answers

    What is the primary mechanism that drives lymph flow into lymph capillaries?

    <p>Interstitial fluid build-up on the outside of the capillaries</p> Signup and view all the answers

    What prevents backflow of lymph in larger lymphatic vessels?

    <p>One-way valves</p> Signup and view all the answers

    What is the function of the right lymphatic duct?

    <p>Drains into the juncture of the right subclavian vein and right internal jugular</p> Signup and view all the answers

    What is the function of the thoracic duct?

    <p>Drains the rest of the body</p> Signup and view all the answers

    What is the result of interstitial fluid build-up on the outside of lymph capillaries?

    <p>Interstitial fluid build-up puts pressure on the capillary cells and forces them apart</p> Signup and view all the answers

    What facilitates the flow of lymph from the abdomen towards the chest during inhalation?

    <p>Pressure created through breathing</p> Signup and view all the answers

    What drives lymph circulation in larger lymphatic vessels?

    <p>Contraction of skeletal muscle surrounding the lymphatic vessels</p> Signup and view all the answers

    What activates the binding of antibody to antigen?

    <p>Antibody binds antigen and either C3d co-receptor activation or PRR activation</p> Signup and view all the answers

    What is the primary function of TGF-β in the mucosal barrier?

    <p>To promote the class-switching of B-cells to IgA</p> Signup and view all the answers

    What is the result of reduced TGF-β expression in the mucosal barrier?

    <p>Increased production of Th1 and Th2 responses</p> Signup and view all the answers

    What is the primary function of CTLA-4 in Tregs?

    <p>To bind to CD80/86 on APCs</p> Signup and view all the answers

    What is the result of defects in IL-2R-alpha?

    <p>Reduced production of Tregs</p> Signup and view all the answers

    What is the primary function of IgA in the mucosal barrier?

    <p>To reduce the invasion of microbes</p> Signup and view all the answers

    What is the result of exposure to antigen early in life?

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

    What is the primary function of the spleen in B-cell development?

    <p>To mature T1 B-cells to T2 B-cells</p> Signup and view all the answers

    What is the primary function of T cell-independent B-cells in the marginal zone?

    <p>To produce low-affinity IgM</p> Signup and view all the answers

    What is the result of defects in CTLA-4?

    <p>Reduced production of Tregs</p> Signup and view all the answers

    What is the primary function of the white pulp in the spleen?

    <p>To facilitate immune responses to antigens in the bloodstream</p> Signup and view all the answers

    Study Notes

    T-cell Development and Tolerance

    • T-cell development occurs in the bone marrow and thymus
    • Stem cells differentiate into lymphoid progenitors under the influence of IL-7
    • T-cells undergo little maturation in the bone marrow and need to travel to the thymus to develop functional T-cell receptors (TCRs)

    The Thymus

    • Located superior to the heart, anterior to the great vessels
    • Largest prior to puberty, shrinks afterwards
    • Divided into a cortex and medulla, surrounded by a thin capsule
    • Medullary and cortical thymic epithelial cells (mTEC and cTEC) guide T-cell development

    Thymic T-cell Development

    • Precursor T-lymphocytes undergo terminal differentiation to T-lymphocyte lineage
    • Rearrange TCR and learn to recognize antigen presented via HLA (HLA restriction)
    • T-cells with TCRs that bind to antigen presented via HLA survive (positive selection)
    • T-cells that bind to self-antigen with high affinity are eliminated (negative selection)
    • Selected to express either CD4 or CD8

    T-cell Development - Selection

    • Positive selection: DP T-cells that have arranged their TCR with low-medium affinity for thymic epithelial cells' HLA-bound self-antigen survive
    • Negative selection: DP T-cells that have arranged their TCR with high affinity for thymic epithelial cells' HLA-bound self-antigen are eliminated

    Peripheral vs. Central Tolerance

    • Central tolerance: occurs in primary lymphoid organs with negative selection
    • Peripheral tolerance: occurs in secondary lymphoid organs or peripheral tissue

    Central Tolerance

    • AIRE gene plays a central role in central tolerance
    • AIRE activates transcription factors, causing thymic epithelial cells to express a wide range of proteins on their HLA
    • Defects in AIRE result in autoimmune polyendocrinopathy syndrome (APS)

    Peripheral Tolerance

    • CD4+ Treg cells: polarized by interaction with APC and high circulating levels of TGF-β
    • CTLA-4: expressed by helper T-cells, binds to B7 with higher affinity than CD28, and can cause anergy or Treg polarization
    • T-reg cells often express CTLA-4, shutting down CD80/86 expression on APCs

    Lymphatic System

    • Lymphatic capillaries: driven by interstitial fluid build-up on the outside of capillaries, which puts pressure on the capillary cells and forces them apart
    • Lymphatic flow in larger channels: driven by contraction of skeletal muscle surrounding lymphatic vessels and pressure created through breathing

    Lymphatic Anatomy

    • Lymph vessels combine to form trunks, which combine to form one of two lymphatic ducts that drain into the blood system
    • Right lymphatic duct drains the right arm, thoracic region, and right head/neck into the juncture of the right subclavian vein and right internal jugular
    • Thoracic duct drains the rest of the body into the juncture of the left subclavian vein and left internal jugular

    Here are the study notes:

    Lymphocyte Development and Immune Tolerance

    • Lymphocyte development occurs in the bone marrow, where stem cells differentiate into lymphoid progenitors under the influence of IL-7.
    • T-cells, unlike B-cells, undergo little maturation in the bone marrow and need to travel to the thymus to develop functional T-cell receptors (TCRs).

    The Thymus

    • The thymus is a key organ in T-lymphocyte development, where precursor T-lymphocytes:
      • Become terminally differentiated to the T-lymphocyte lineage
      • Rearrange the TCR
      • "Learn" to recognize antigen presented via HLA (HLA restriction)
      • "Learn" to ignore self-antigens presented via HLA
      • Are selected to express either CD4 or CD8

    T-cell Development

    • Positive selection: DP T-cells with low-medium affinity for thymic epithelial cell HLA bound to self-antigen are allowed to survive.
    • Negative selection: DP T-cells with high affinity for thymic epithelial cell HLA bound to self-antigen are killed.

    Central Tolerance

    • Central tolerance occurs in primary lymphoid organs, such as the thymus, and involves negative selection to eliminate self-reactive T-cells.

    Peripheral Tolerance

    • Peripheral tolerance involves the generation of regulatory T-cells (Tregs) that suppress autoreactive T-cells.
    • Tregs are polarized by interaction with an APC and high circulating levels of TGF-β.

    Barrier Tolerance

    • Barrier tolerance occurs in mucosal surfaces, where secreted IgA reduces invasion of microbes and TGF-β promotes class-switching to IgA by B-cells.

    Genes Implicated in Decreased Tolerance and Autoimmunity

    • IL-2R-alpha and CTLA4 are key genes implicated in decreased tolerance and autoimmunity.

    Central Tolerance in B-cells

    • Central tolerance in B-cells involves the elimination of self-reactive B-cells through receptor editing and clonal deletion.

    The Spleen

    • The spleen is a secondary lymphoid organ where immature B-cells mature and undergo negative selection.
    • The spleen has a key role in immune responses to antigens in the bloodstream.
    • The spleen is composed of white pulp (surrounds arterioles) and red pulp (peripheral to the white pulp).

    Lymphatic System

    • The lymphatic system provides the driving force for lymph to enter lymph capillaries through interstitial fluid build-up on the outside of the capillaries.
    • Contraction of skeletal muscle surrounding the lymphatic vessels and pressure created through breathing facilitate lymph circulation in larger lymphatic vessels.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    BMS 150 Immunology - T-Cell Development & Tolerance

    Description

    This quiz covers T-cell development, lymphocyte development, and tolerance in the context of immunology, as part of BMS 150 course.

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser