W1-6 Workshop on T Lymphocyte Development
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Questions and Answers

What is the primary function of the thymus?

  • Synthesis of antibodies
  • Storage of white blood cells
  • Maturation of T-cells (correct)
  • Production of red blood cells

    • What happens to the thymus with age?

  • It produces more immune cells
  • It becomes larger and more active
  • It becomes the primary site for B-cell development
  • It atrophies and fills with fibrous tissue (correct)

    • Which of the following is NOT a factor influencing T-cell development?

  • Thymotaxin
  • Thymus size
  • Spleen (correct)
  • Thymopoietins

    • What is the primary role of thymopoietins in T-cell development?

    <p>Promotion of T-cell maturation</p> Signup and view all the answers

    Which substance is primarily produced by the thymus to support T-cell development?

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

    What is the main role of thymotaxin in T-cell development?

    <p>Regulating the migration of T-cells</p> Signup and view all the answers

    What is required for major histocompatibility complex-restricted antigen presentation?

    <p>Interaction of the TCR with antigenic peptide and MHC molecule</p> Signup and view all the answers

    How does the TCR differ from the BCR in terms of antigen recognition?

    <p>TCR recognizes a linear peptide bound to MHC molecules, while BCR recognizes free antigen</p> Signup and view all the answers

    Which subset of T cells reacts to MHC-I?

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

    Which cells express MHC-II?

    <p>Professional APCs (pAPCs)</p> Signup and view all the answers

    What is the main function of CD4 T cells?

    <p>Regulate adaptive immune responses</p> Signup and view all the answers

    Where does the process of T cell development start?

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

    What is the role of T lymphocytes in immune responses?

    <p>Recognizing self and non-self</p> Signup and view all the answers

    In the context of TCRs and BCRs, what is a major difference between them?

    <p>TCRs recognize antigens through MHC-II, while BCRs recognize antigens through MHC-I</p> Signup and view all the answers

    Which cells respond to MHC-restricted antigen presentation and require CD4 coreceptors?

    <p>T-helper cells</p> Signup and view all the answers

    What is the process involved in positive selection of T lymphocytes?

    <p>Promotion of self-tolerance in developing T lymphocytes</p> Signup and view all the answers

    What is the main function of effector T lymphocyte subset TH1?

    <p>Cell-mediated immunity against intracellular pathogens</p> Signup and view all the answers

    Which antigen-presenting cells are involved in the development and activation of T-cytotoxic cells?

    <p>Dendritic cells</p> Signup and view all the answers

    What is the outcome of negative selection in T lymphocytes?

    <p>Activation of autoreactive T lymphocytes</p> Signup and view all the answers

    Which type of T lymphocytes are characterized by γ:δ TCRs?

    <p>Innate-like lymphocytes</p> Signup and view all the answers

    What is the function of TH2 effector T lymphocyte subset?

    <p>Induction of allergic responses</p> Signup and view all the answers

    What is the process that leads to central tolerance in T lymphocytes?

    <p>Elimination of autoreactive T lymphocytes</p> Signup and view all the answers

    Which cytokines are responsible for the differentiation of CTLs (cytotoxic T-lymphocytes)?

    <p>IL-12 and IFN-γ</p> Signup and view all the answers

    What is the role of peripheral tolerance in the immune system?

    <p>Suppression of immune responses against pathogens</p> Signup and view all the answers

    Where do mature T cells traffic from after exiting the thymus in search of their specific antigen?

    <p>Lymph node</p> Signup and view all the answers

    Where do lymphocyte progenitor cells arise?

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

    Where do lymphocytes develop into mature naïve T lymphocytes?

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

    At which point do T cell progenitors enter the thymus?

    <p>Corticomedullary Junction</p> Signup and view all the answers

    What type of epithelial cells produce a variety of polypeptides that influence the phenotypic maturation of progenitor cells from the bone marrow and the modulation of the functions of mature T cells?

    <p>Medullary thymic stromal cells</p> Signup and view all the answers

    Which factor is responsible for engaging thymocyte interleukin 7 receptors and stimulating thymocyte development?

    <p>IL-7</p> Signup and view all the answers

    What type of animals demonstrate the importance of the thymus in T cell development?

    <p>Athymic animals</p> Signup and view all the answers

    Which region of the thymus do thymocytes migrate towards upon entering?

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

    What happens to T cell progenitors upon interaction with cortical thymic stromal cells (cTECs)?

    <p>They receive signals to proliferate and commit to the T cell lineage</p> Signup and view all the answers

    Which signaling pathway stimulates Notch1 on the surface of thymocytes?

    <p>Direct signaling provided by Notch1 ligand on cTECs</p> Signup and view all the answers

    T lymphocytes play a major role in the defense against which of the following?

    <p>Viruses and intracellular protozoa</p> Signup and view all the answers

    What is the role of T cells in immune surveillance?

    <p>Recognition and killing of tumor cells</p> Signup and view all the answers

    What is the main component of the antigen receptor complexes in T lymphocytes?

    <p>Both antigen binding and signaling parts</p> Signup and view all the answers

    How many distinct specificities can each clone of T cell receptors potentially have?

    <p>~10^16 distinct specificities</p> Signup and view all the answers

    What mediates the effector functions in T cell receptors?

    <p>Constant (C) regions of secreted Ig</p> Signup and view all the answers

    What type of antigens do B cell receptors (BCRs) recognize?

    <p>Free antigens</p> Signup and view all the answers

    Apart from the antigen binding part, what triggers a signaling cascade in a B cell receptor complex?

    <p>Proteins (Igα and Igß) associated with membrane Ig</p> Signup and view all the answers

    What is the function of secreted antibodies as part of the BCR complex?

    <p>Ag specificity</p> Signup and view all the answers

    What forms of antigens are mainly recognized by antibodies (immunoglobulins)?

    <p>Macromolecules (proteins, polysaccharides, lipids, nucleic acids), small chemicals</p> Signup and view all the answers

    What is responsible for antigen specificity in the BCR complex?

    <p>Antigen binding part only</p> Signup and view all the answers

    What type of antigens do T cell receptors (TCRs) recognize?

    <p>MHC-linked antigens</p> Signup and view all the answers

    Which cytokine is key in the early development of T lymphocytes?

    <p>IL-7</p> Signup and view all the answers

    What is the primary role of the CD3 molecule in T cell development?

    <p>Assisting in signal transduction</p> Signup and view all the answers

    Which type of TCR is found on the majority of T lymphocytes?

    <p>α:β TCRs</p> Signup and view all the answers

    What is the outcome if a functional γ:δ TCR is produced before a functional β-chain?

    <p>Formation of δ:γ TCR-expressing T cells</p> Signup and view all the answers

    What signals double-negative thymocytes to stop rearrangements of the β-chain gene and undergo proliferation?

    <p>Formation of pre-TCR complex</p> Signup and view all the answers

    What is the composition of the CD8 molecule?

    <p>An α-chain and a β-chain</p> Signup and view all the answers

    What is the function of terminal deoxyribonucleotidyl transferase (TdT) in T cell development?

    <p>Promotion of gene rearrangement</p> Signup and view all the answers

    What is the role of RAG-1 and RAG-2 in T cell development?

    <p>Supporting gene rearrangement</p> Signup and view all the answers

    What happens if a functional α:β TCR is produced first during thymic development?

    <p>Continuation of gene rearrangements</p> Signup and view all the answers

    What is the lifespan of double-positive (DP) thymocytes?

    <p>3-4 days</p> Signup and view all the answers

    Which enzyme joins a D segment to a J segment during TCR rearrangement?

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

    What type of antigens do γ:δ TCR-expressing T cells recognize?

    <p>CD1:glycolipid antigens</p> Signup and view all the answers

    What is the role of the CD3 molecule in T cell development?

    <p>It provides phosphorylation sites for signal transduction</p> Signup and view all the answers

    What triggers a signaling cascade in a B cell receptor complex?

    <p>Antigen binding part</p> Signup and view all the answers

    What is the outcome if a functional γ:δ TCR is produced before a functional β-chain?

    <p>Development of γ:δ TCR-expressing T cells without undergoing any selection process</p> Signup and view all the answers

    What type of epithelial cells produce a variety of polypeptides that influence the phenotypic maturation of progenitor cells from the bone marrow and the modulation of the functions of mature T cells?

    <p>Thymic epithelial cells</p> Signup and view all the answers

    Which type of T cell reacts to MHC-I?

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

    What happens to thymocytes that express a functional β-chain first?

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

    Which molecule is expressed by double-negative (DN) thymocytes at an early stage of their development?

    <p>CD2</p> Signup and view all the answers

    What is the key cytokine in the early development of T lymphocytes?

    <p>IL-7</p> Signup and view all the answers

    Which type of TCR is found on the majority of T lymphocytes?

    <p>α:β TCRs</p> Signup and view all the answers

    What type of antigens does the γ:δ TCR recognize?

    <p>CD1:glycolipid antigens</p> Signup and view all the answers

    Which genes are only expressed by thymocytes during the rearrangement of the T cell receptor genes?

    <p>RAG-1 and RAG-2</p> Signup and view all the answers

    What do six subunits, collectively referred to as CD3, provide for the TCR?

    <p>Assistance in signal transduction</p> Signup and view all the answers

    What does the expression of the pre-TCR signal double-negative thymocytes to do?

    <p>Start rearrangement of the β-chain genes</p> Signup and view all the answers

    What happens if a functional γ:δ receptor is produced before a functional β-chain in thymocytes?

    <p>The cell commits to the γ:δ lineage</p> Signup and view all the answers

    What happens if a functional α:β TCR is produced first in thymocytes?

    <p>The cell commits to the α:β lineage and continues thymic development</p> Signup and view all the answers

    Which enzyme is involved in the rearrangement of the TCR?

    <p>Recombination-activating genes 1 &amp; 2 (RAG1/RAG2)</p> Signup and view all the answers

    Which co-receptor molecule becomes part of the TCR complex?

    <p>CD8</p> Signup and view all the answers

    What is the primary tyrosine kinase responsible for the phosphorylation of CD3 ζ-chains?

    <p>Lymphocyte-specific protein tyrosine kinase</p> Signup and view all the answers

    Where does positive selection of thymocytes occur?

    <p>Thymic cortex</p> Signup and view all the answers

    Which antigen-presenting cells are involved in the process of positive selection?

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

    What is the outcome of positive selection in terms of cell lineage commitment?

    <p>CD4+ or CD8+ cell lineage commitment</p> Signup and view all the answers

    Where do thymocytes that have been positively selected move on to?

    <p>Thymic medulla</p> Signup and view all the answers

    Which cells present tissue-restricted peptides in the context of both MHC class I and MHC class II?

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

    What is the function of mTECs in thymocyte development?

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

    What is the primary role of CD4 co-receptor molecules in TCR interaction?

    <p>Signal TCR to bind self-MHC:self-peptide with moderate affinity</p> Signup and view all the answers

    What happens to thymocytes that remain CD4+CD8+?

    <p>Undergo negative selection and die if the TCR fails to interact with either MHC class I or MHC class II.</p> Signup and view all the answers

    What is the role of signal 3 in T lymphocyte activation?

    <p>Differentiation into T lymphocyte subsets</p> Signup and view all the answers

    Which part of the TCR complex transduces antigen recognition into an intracellular messaging response?

    <p>CD3</p> Signup and view all the answers

    What is the T lymphocyte receptor for costimulatory molecules?

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

    What type of immune responses are TH1 cells involved in?

    <p>Adaptive immune responses to intracellular pathogens</p> Signup and view all the answers

    In the presence of which cytokines are TH2 cells generated?

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

    What is the consequence of T lymphocytes failing to receive co-stimulation during antigen presentation?

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

    What is the primary outcome of incomplete T lymphocyte activation in secondary lymphoid tissue?

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

    Which molecules deliver the survival signal to T cells in the form of surface co-stimulatory molecules?

    <p>CD80 and/or CD86 (B7.1 and B7.2)</p> Signup and view all the answers

    Where does activation of mature T lymphocytes also require differentiation signals in the form of cytokines?

    <p>Secondary lymphoid tissue</p> Signup and view all the answers

    What is the main driving force behind the development of central tolerance in the immune system?

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

    What is the function of thymic regulatory T lymphocytes (tTreg) in the periphery?

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

    What process leads to the maturation and exit of mature, naïve T lymphocytes from the thymus?

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

    Which signaling molecules are required for T lymphocyte activation per se?

    <p>CD3 molecules</p> Signup and view all the answers

    What happens to mature, naïve, resting T lymphocytes in the absence of antigen stimulation?

    <p>They may live for years</p> Signup and view all the answers

    Which process eliminates T lymphocytes encountering large, constant amounts of antigen shortly after exiting the thymus and in specific locations?

    <p>Activation-induced cell death</p> Signup and view all the answers

    What is responsible for the elimination or rendering of T lymphocytes unresponsive to 'ubiquitous' antigens in the periphery?

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

    What is the ability of thymocytes specific for selfMHC: self-peptide complexes that receive co-stimulation in the thymic medulla?

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

    What happens to thymocytes that have escaped negative selection?

    <p>They become mature, naïve T lymphocytes and leave the thymus</p> Signup and view all the answers

    What is crucial for antigen presentation with co-stimulation to yield activation, clonal expansion, and differentiation instead of death?

    <p>Co-stimulation (CD28 engagement)</p> Signup and view all the answers

    Which cytokines are involved in yielding TH17 cells during antigen presentation?

    <p>IL-6 and TGF-ß</p> Signup and view all the answers

    What are the two forms of TCRs that T lymphocytes can express?

    <p>α:β and γ:δ</p> Signup and view all the answers

    Which cells are specialized in the killing of infected host cells and transformed cells?

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

    In the presence of which cytokines do TH17 cells yield inflammatory TH17 cells or regTH17 cells?

    <p>IL-6 and TGF-ß</p> Signup and view all the answers

    Which type of TCR-expressing T cells comprise a small population of the T cell pool?

    <p>γ:δ TCR-expressing T cells</p> Signup and view all the answers

    In which stage of the T cell's life cycle does antigen presentation serve the purpose of reactivation of memory T lymphocytes?

    <p>Response to infection</p> Signup and view all the answers

    Which type of effector and memory cells are yielded from the activation of CD4+ T lymphocytes?

    <p>TH1 and TH2 cells</p> Signup and view all the answers

    What is the main outcome of the activation of CD8+ T lymphocytes?

    <p>Activation into cytotoxic T lymphocytes (CTLs)</p> Signup and view all the answers

    What is the role of IL-23 in antigen presentation for yielding TH17 cells?

    <p>Yielding pathological TH17 cells</p> Signup and view all the answers

    Study Notes

    • T lymphocytes are crucial for adaptive immune responses, including B lymphocyte activation and antibody production.
    • This session focuses on T lymphocyte development, early life cycle, and self/non-self discrimination.
    • Knowledge gained here is essential for understanding immunodeficiencies and immunopathologies.
    • T lymphocytes recognize antigens through T cell receptors (TCRs) and major histocompatibility complexes (MHCs).
    • TCRs are complex-restricted and engage MHCs for successful interaction.
    • MHC-I and MHC-II molecules are present on different antigen-presenting cells.
    • T cells can be CD4 or CD8, with distinct functions, requirements, and cells involved in their development and activation.
    • α:β and γ:δ TCRs differ in development and functions of the cells bearing them.
    • Bone marrow, thymus, and secondary lymphoid tissue contribute to the life cycle of α:β T lymphocytes.
    • Positive and negative selection processes shape the immune response, leading to central and peripheral tolerance.
    • Antigen presentation and T cell activation occur through specific mechanisms.
    • Incomplete T lymphocyte stimulation results in peripheral tolerance and the development of effector T lymphocyte subsets (TH1, TH2, TH17, CTLs, TFH, and Treg) with unique functions.
    • Innate-like lymphocytes (ILLs) such as NK cells, NKT cells, and IELs also play important roles in the immune system.
    • The topics covered include T lymphocyte development, structure and function of various immune cells, antigen processing and presentation, and host defense mechanisms.
    • Multiple resources, such as books and online content, are available to supplement learning.
    • The session aims to help students understand the complex immune system, its components, interactions, and functions.

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    Description

    This workshop focuses on the major histocompatibility complex-restricted antigen presentation and the interactions of the T cell receptor with antigenic peptide and MHC molecule. Learn about the composition and function of the T cell receptor complex.

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