Lymphocyte Development Quiz
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Questions and Answers

What is the primary function of positive selection in T cell development?

  • To stimulate thymocytes that bind weakly to self peptide–MHC (correct)
  • To ensure all T cells become CD4+ T cells
  • To promote the survival of all developing T cells
  • To eliminate all cells that recognize MHC

    • Which molecules on antigen-presenting cells (APCs) are essential for the activation of naive T cells?

  • Transcription factors
  • Cytokines
  • Antibodies
  • Costimulators (correct)

    • What role does CD40L play in T cell activation?

  • Inhibits T cell activation
  • Promotes apoptosis of T cells
  • Enhances T cell responses by activating APCs (correct)
  • Stimulates cytotoxic T cells exclusively

    • What is CTLA-4-Ig primarily used for in therapeutic settings?

    <p>Treatment of rheumatoid arthritis and transplant rejection</p> Signup and view all the answers

    What effect do antibodies blocking CTLA-4 and PD-1 have on T cell responses?

    <p>They enhance T cell activation and immune responses</p> Signup and view all the answers

    What is the initial step in lymphocyte development?

    <p>Commitment of progenitor cells to the B or T lymphoid lineage</p> Signup and view all the answers

    What happens after the Ig heavy chain gene or TCR β chain gene is successfully rearranged?

    <p>Proliferative expansion of lymphocyte precursors occurs</p> Signup and view all the answers

    Which transcription factors are crucial for B cell development?

    <p>EBF, E2A, and Pax-5</p> Signup and view all the answers

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

    <p>It is essential for the proliferation of T cell progenitors</p> Signup and view all the answers

    Which type of cell develops into CD4+ and CD8+ αβ T lymphocytes?

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

    What does the process of selection in lymphocyte development achieve?

    <p>Preserving functional antigen receptor proteins</p> Signup and view all the answers

    What is a known effect of mutations in the IL-7 gene?

    <p>X-linked severe combined immunodeficiency disease (X-SCID)</p> Signup and view all the answers

    What is the primary effect of DNA methylation in lymphocyte development?

    <p>Silencing of certain genes</p> Signup and view all the answers

    What type of modifications can affect gene activity in histone tails?

    <p>Acetylation, Methylation, Ubiquitination</p> Signup and view all the answers

    What is the role of remodeling complexes in chromatin?

    <p>To enhance or suppress gene expression</p> Signup and view all the answers

    What happens to the CD4 gene in CD8+ T cells during development?

    <p>It is silenced epigenetically.</p> Signup and view all the answers

    What is the function of Dicer in T cell development?

    <p>To generate miRNAs that regulate gene expression.</p> Signup and view all the answers

    What occurs during positive selection in T cell development?

    <p>T cells are matured that recognize self MHC molecules.</p> Signup and view all the answers

    Which receptors play a critical role in lymphocyte survival and maturation?

    <p>Antigen receptors and pre-antigen receptors</p> Signup and view all the answers

    What can occur if regulatory T cells (Treg) are lost due to Dicer deletion?

    <p>Development of an autoimmune phenotype.</p> Signup and view all the answers

    What is the first checkpoint during lymphocyte development?

    <p>Pre-antigen receptor signaling</p> Signup and view all the answers

    How does antigen receptor expression influence developing B and T cells?

    <p>It provides signals that are essential for survival and maturation.</p> Signup and view all the answers

    What is the ultimate recognition capability of mature T cells derived from positive selection?

    <p>To recognize foreign peptides presented by the same self MHC</p> Signup and view all the answers

    What is the primary purpose of positive selection in lymphocyte maturation?

    <p>To preserve receptor-expressing cells and generate different B cell subsets</p> Signup and view all the answers

    Which process leads to the elimination of lymphocytes that bind too strongly to self-antigens?

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

    In the maturation of αβ T cells, what do CD4+ T cells primarily respond to?

    <p>Class II MHC molecules</p> Signup and view all the answers

    What role does IL-7 play in T lymphocyte maturation?

    <p>It acts as a critical lymphopoietic growth factor.</p> Signup and view all the answers

    What triggers the apoptosis of thymocytes during T cell maturation?

    <p>Failure to positively select by self MHC</p> Signup and view all the answers

    What is formed when the TCR β chain is expressed in association with pre-Tα?

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

    Where does functional differentiation occur in T lymphocyte maturation?

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

    Which cells are produced during the completion of T lymphocyte maturation?

    <p>CD4+ or CD8+ T cells</p> Signup and view all the answers

    What is the main function of chemokines in T lymphocyte maturation?

    <p>To drive the movement of cells into and through the thymus</p> Signup and view all the answers

    Which complex is formed once TCR α gene expression occurs in the double-positive stage?

    <p>Complete αβ TCR</p> Signup and view all the answers

    Study Notes

    Lymphocyte Development

    • Lymphocytes develop through a process called lymphocyte maturation or lymphocyte development.
    • Proliferation of lymphocyte precursors is at its highest after the successful rearrangement of the Ig heavy chain gene (B cell) or the TCR β chain gene (T cell)
    • Commitment of progenitor cells to the B lymphoid or T lymphoid lineage is a key stage in development.
    • Proliferation of progenitors and immature committed cells is essential to create a pool of cells that can generate functional lymphocytes.
    • Lymphocyte development involves the sequential rearrangement of antigen receptor genes and the expression of antigen receptor proteins.
    • Selection events are crucial to preserve cells with functional antigen receptors, while eliminating cells that recognize self-antigens.
    • B cells can differentiate into follicular, marginal zone, and B-1 cells.
    • T cells differentiate into CD4+ and CD8+ αβ T lymphocytes, NKT cells, MAIT cells, and γδ T cells.

    T Lymphocyte Development

    • EBF, E2A, and Pax-5 transcription factors induce the expression of genes essential for B cell development.
      • These factors regulate the expression of Rag-1 and Rag-2 proteins, pre-B cell receptor components, and downstream signaling proteins.
    • Notch 1 and GATA3 signaling proteins induce the expression of genes required for T cell development. Including Rag-1 and Rag-2 proteins.
    • IL-7 is crucial for the proliferation of T cell progenitors. Mutations in the IL-7 gene can lead to X-linked severe combined immunodeficiency disease (X-SCID).

    Epigenetic Regulation of Lymphocyte Development

    • Methylation of DNA on cytosine residues often silences genes.
    • Posttranslational modifications like acetylation, methylation, and ubiquitination of histone tails in nucleosomes can activate or inactivate genes.
    • Chromatin remodeling complexes can enhance or suppress gene expression.
      • For example, the commitment of developing T cells to the CD4 or CD8 lineage relies on epigenetic mechanisms that silence the expression of the CD4 gene in CD8+ T cells.
    • Silencing of gene expression by noncoding RNAs plays a role in T cell development.
      • Deletion of Dicer, a key enzyme in miRNA generation, in the T lineage can lead to a loss of regulatory T cells (Treg) and potentially autoimmune phenotypes.

    Selection Processes in B and T Lymphocyte Development

    • Lymphocyte development involves checkpoints during the maturation process.
    • Pre-antigen receptors and antigen receptors deliver signals to developing lymphocytes that are essential for their survival, proliferation, and continued maturation.
    • The pre-antigen receptor is the first checkpoint in lymphocyte development.
    • Cells express complete antigen receptors in the next stage of B and T cell maturation. Survival of these cells is determined by their antigen receptor recognition.
    • Cells that express useful antigen receptors are preserved, while potentially harmful cells that strongly recognize self-structures are eliminated.
    • Positive selection ensures the maturation of T cells whose receptors recognize self major histocompatibility complex (MHC) molecules.
    • The expression of the coreceptor on a T cell (CD8 or CD4) is matched to the recognition of the appropriate MHC molecule (class I MHC or class II MHC).
    • Mature T cells, whose precursors were positively selected by self MHC molecules in the thymus, can recognize foreign peptide antigens displayed by the same self MHC molecules on antigen-presenting cells in peripheral tissues.

    Checkpoints in Lymphocyte Maturation

    • Positive selection preserves receptor-expressing cells and contributes to the generation of different B cell subsets.
    • Negative selection eliminates developing lymphocytes whose antigen receptors bind strongly to self-antigens in the generative lymphoid organs.

    Stages of T Lymphocyte Maturation

    • αβ T cells mature into CD4+ class II MHC–restricted or CD8+ class I MHC–restricted T cells.

    TCR Protein Domains

    • The TCR protein has variable domains and constant domains.
    • Complementary determining regions (CDRs) in the variable domains play a critical role in antigen recognition.

    Germline Organization of Human TCR

    • The human TCR genes are located on chromosomes 7, 14, and 15. Each TCR gene is comprised of variable (V), diversity (D), joining (J), and constant (C) gene segments.
    • The TCR beta chain gene is assembled first.

    Human TCR Repertoire

    • The TCR repertoire encompasses a vast diversity of TCRs, enabling recognition of a wide range of antigens.

    TCR Gene Recombination and Expression

    • Rearrangement of TCR genes during T cell development leads to the generation of unique TCRs.

    T Lymphocyte Maturation in the Thymus

    • Thymic stromal cells secrete IL-7, a critical lymphopoietic growth factor.
    • Chemokines drive the movement of cells into and through the thymus.
    • Cortex: CCR9:CCL25
    • Medulla: CCR7:CCL19/21
    • Cell death during thymocyte development can happen due to:
      • Failure to productively rearrange the TCR β chain gene and fail the pre-TCR/β checkpoint
      • Failure to be positively selected by self-MHC molecules in the thymus
      • Self antigen–induced negative selection

    Pre-T Cell Receptor

    • The TCR β chain is expressed on the cell surface in association with an invariant protein called pre-Tα, along with CD3 and ζ proteins to form the pre-TCR complex.
    • TCR α gene expression in the double-positive stage leads to the formation of the complete αβ TCR.
    • Double-positive cells that successfully undergo selection processes mature into CD4+ or CD8+ T cells.

    T Lymphocyte Subset in the Thymus

    • Functional and phenotypic differentiation into CD4+CD8− or CD8+CD4− single-positive (SP) T cells occurs in the medulla of the thymus. Mature T cells are then released into circulation.
    • Some double-positive cells differentiate into CD4+CD8− regulatory T cells (Treg CD4+).

    T Cell Selection

    • The selection of developing T cells relies on the recognition of antigen (peptide–MHC complexes) in the thymus. This process ensures the preservation of useful cells and the elimination of potentially harmful ones.
    • Positive selection occurs when thymocytes whose TCRs bind with low avidity (weakly) to self peptide–self MHC complexes are stimulated to survive and differentiate into CD4+ T cells or CD8+ T cells.

    Role of Co-stimulation in T Cell Activation

    • The proliferation and differentiation of naive T cells require signals provided by molecules on APCs, called costimulators, in addition to antigen-induced signals.

    Costimulatory Pathways

    • The interaction of CD40L on T cells with CD40 on APCs enhances T cell responses by activating APCs.

    Mechanisms of T Cell Costimulation by CD28

    • CD28 provides an important costimulatory signal for T cell activation.

    Costimulatory Molecules of the CD28 Family

    • The CD28 family includes costimulatory receptors that play a role in T cell activation and regulation.

    Therapeutic Costimulatory Blockade

    • CTLA-4-Ig is an approved therapy for rheumatoid arthritis and transplant rejection.
    • Inhibitors of the CD40L:CD40 pathway are in clinical trials for transplant rejection and autoimmune diseases.
    • Antibodies that block the CTLA-4 and PD-1 inhibitory receptors are approved for the immunotherapy of tumors. Blocking these pathways enhances T cell activation and can improve antitumor immune responses.

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    Lymphocyte Development PDF

    Description

    Test your knowledge on the process of lymphocyte development, including the stages of maturation and differentiation of B and T cells. This quiz covers key concepts such as gene rearrangement, selection events, and the various types of lymphocytes. Dive in to see how well you understand this vital aspect of immunology!

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