γδ T Cells Overview
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γδ T Cells Overview

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Questions and Answers

What is the primary developmental pathway NKT cells follow before diverging during the DP stage?

  • B cell pathway
  • αβ T cell pathway (correct)
  • γδ T cell pathway
  • Macrophage pathway

    • Which receptor engagement can enhance the activation of NKT cells in addition to TCR engagement?

  • MHC Class II molecules
  • IL-12 or IL-18 receptors (correct)
  • CD1d molecules
  • CD4 and CD8 receptors

    • What is a key effector function of activated NKT cells?

  • Production of antibodies
  • Secretion of cytokines and chemokines (correct)
  • Phagocytosis of pathogens
  • Direct cytolytic activity

    • What type of molecules do NKT cell TCRs typically recognize?

    <p>Glycolipids presented by CD1d</p> Signup and view all the answers

    Which statement best describes the nature of cytokines produced by NKT cells?

    <p>They have powerful effects on αβ T cell differentiation.</p> Signup and view all the answers

    What is a primary characteristic that distinguishes gd T cells from ab T cells in terms of their development?

    <p>gd T cells rearrange TCRgd genes earlier than ab T cells.</p> Signup and view all the answers

    During which stage of development do gd T cells start to be detected in humans?

    <p>By 8 weeks gestation.</p> Signup and view all the answers

    What is one function of cytokines produced by gd T cell effectors?

    <p>They activate NK cells and macrophages.</p> Signup and view all the answers

    Which type of cell do gd T cells NOT appear to have immunological memory?

    <p>gd T cells.</p> Signup and view all the answers

    What role do fetal thymic stromal cells play in gd T cell development?

    <p>They influence gd T cell generation and migration.</p> Signup and view all the answers

    How do NKT cells differ from typical CTL and NK cells after activation?

    <p>NKT cells can secrete cytokines immediately upon activation.</p> Signup and view all the answers

    Which statement correctly describes the thymic selection processes for gd T cells?

    <p>gd T cells undergo positive and negative thymic selections.</p> Signup and view all the answers

    What function does nitric oxide (NO) have in relation to activated gd T cells?

    <p>It is an antimicrobial compound produced by epithelial cells.</p> Signup and view all the answers

    Which cells do NKT cells share characteristics with?

    <p>Both CTL and NK cells.</p> Signup and view all the answers

    What is one of the key additional roles of gd T cells beyond cytokine production?

    <p>They influence leukocyte trafficking and wound healing.</p> Signup and view all the answers

    What is a significant characteristic of gd T cells compared to ab T cells in their recognition of antigens?

    <p>They can respond to a broader range of ligands, including non-protein antigens.</p> Signup and view all the answers

    In which anatomical locations are gd T cells predominantly found?

    <p>Among epithelial cells of the skin and mucosal areas.</p> Signup and view all the answers

    How do gd T cells differ in activation response compared to conventional ab T cells?

    <p>They respond more rapidly and can activate without conventional costimulation.</p> Signup and view all the answers

    What type of TCR structure do gd T cells express?

    <p>TCR composed of TCRg and TCRd chains.</p> Signup and view all the answers

    What is one reason gd T cells are critical in host defense?

    <p>They fill gaps in immune responses that are not recognized by myeloid cells.</p> Signup and view all the answers

    What type of factors do activated gd T cells secrete to stimulate epithelial cell activity?

    <p>Keratinocyte growth factor (KGF)</p> Signup and view all the answers

    Which cell types are influenced by the cytokines produced by gd T cell effectors?

    <p>NK cells and Macrophages</p> Signup and view all the answers

    What is not a feature of gd T cells according to their function?

    <p>Capability for immunological memory</p> Signup and view all the answers

    Which developmental stage do gd T cells reach during human embryonic development?

    <p>By 8 weeks in the fetal stage</p> Signup and view all the answers

    What population of T cells is generated from the same precursor as gd T cells?

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

    Which of the following best describes the activation of NKT cells?

    <p>They can secrete cytokines immediately after activation.</p> Signup and view all the answers

    What role do fetal thymic stromal cells play in the development of gd T cells?

    <p>They influence distinct waves of gd T cell development.</p> Signup and view all the answers

    What type of antigens can gd TCRs bind directly, without the need for presentation by other molecules?

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

    Which statement accurately describes a characteristic of gd TCRs compared to ab TCRs?

    <p>They are often broadly cross-reactive.</p> Signup and view all the answers

    Which types of molecules do some gd T cell subsets specifically respond to in terms of stress?

    <p>Stress-related molecules expressed by sick host cells</p> Signup and view all the answers

    How do the activation processes of gd T cells in peripheral tissues typically differ from those in epidermal and intestinal tissues?

    <p>Epidermal and intestinal gd T cells depend on stress ligand engagement for costimulation.</p> Signup and view all the answers

    What role do antigen-presenting cells (APCs) play in the activation of gd T cells during inflammation?

    <p>They supply stimulatory cytokines and promote activation.</p> Signup and view all the answers

    What is a shared characteristic between some gd T cells and natural killer (NK) cells regarding regulation?

    <p>Some gd T cells express NK inhibitory receptors recognizing MHC class I.</p> Signup and view all the answers

    Which of the following types of molecules are NOT known to be recognized by gd T cells?

    <p>High molecular weight carbohydrates</p> Signup and view all the answers

    Which statement best describes the specificity of certain gd T cell subsets?

    <p>They can counter a specific group of pathogens based on V segment usage.</p> Signup and view all the answers

    What cytokine does activated gd T cells induce epithelial cells to produce?

    <p>Nitric oxide</p> Signup and view all the answers

    Which growth factor is secreted by activated gd T cells to aid in wound healing?

    <p>Keratinocyte Growth Factor</p> Signup and view all the answers

    What differentiates gd T cells from ab T cells in their development origin?

    <p>gd T cells emerge from the same precursor as ab T cells and NK cells.</p> Signup and view all the answers

    Which statement accurately describes the relationship between gd T cells and immunological memory?

    <p>gd T cells do not possess features of immunological memory.</p> Signup and view all the answers

    What is a known influence of cytokines produced by gd T cell effectors on other immune cells?

    <p>They promote the differentiation of ab T cells into Th1, Th2, or Th17 effectors.</p> Signup and view all the answers

    During what gestational period are gd TCRgd genes detected in thymocytes of humans?

    <p>By week 8</p> Signup and view all the answers

    Which type of signaling pathway differs between gd T cells and ab T cells upon TCR stimulation?

    <p>The pathways linking TCR stimulation to cytokine production</p> Signup and view all the answers

    Which type of TCRs are predominantly found on intestinal gd T cells?

    <p>Vg1Vd2 TCRs</p> Signup and view all the answers

    What is a key difference between gd TCRs and ab TCRs in terms of antigen recognition?

    <p>gd TCRs can bind directly to non-peptide antigens without presentation.</p> Signup and view all the answers

    Which of the following molecules are recognized by some gd T cell subsets specific to stress?

    <p>Heat shock proteins</p> Signup and view all the answers

    How do gd T cells differ in their activation in peripheral tissues compared to epidermal and intestinal tissues?

    <p>Epidermal and intestinal gd T cells are costimulated primarily through stress ligands.</p> Signup and view all the answers

    Which role do antigen-presenting cells (APCs) play in the activation of gd T cells during inflammation?

    <p>APCs provide stimulatory cytokines or unknown intercellular contacts.</p> Signup and view all the answers

    Which of the following molecules are NOT typically recognized by gd T cells?

    <p>Large proteins</p> Signup and view all the answers

    What characteristic of gd T cell subsets defined by V segment usage allows them to target specific types of pathogens?

    <p>Competence to respond to stress-related antigens.</p> Signup and view all the answers

    What mechanism do some gd T cells use for activation that differs from conventional ab T cell activation?

    <p>They can be activated with phosphorylated metabolites without additional costimulation.</p> Signup and view all the answers

    Which statement correctly describes a major function of gd T cells in host defense?

    <p>They can respond to a broad range of antigens without MHC involvement.</p> Signup and view all the answers

    What anatomical location is NOT commonly associated with high concentrations of gd T cells?

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

    Which of the following accurately describes the nature of gd T cell TCRs?

    <p>They can recognize both soluble and cell-bound ligands.</p> Signup and view all the answers

    What is a characteristic response of gd T cells upon activation compared to ab T cells?

    <p>They often respond in smaller numbers and more rapidly.</p> Signup and view all the answers

    Which broad category of antigens can gd T cells recognize that is usually not addressed by ab T cells?

    <p>Non-protein antigens such as lipids and phosphorylated nucleotides.</p> Signup and view all the answers

    Study Notes

    γδ T Cells: Overview

    • γδ T cells are a minority in humans and mice but a majority in ruminants (cows, sheep, pigs).
    • They express TCRs composed of TCRγ and TCRδ chains plus the CD3 complex.
    • They have either homodimeric CD8αα coreceptors or no coreceptor; thus, they are referred to as double-negative peripheral T cells.

    γδ T Cells: Overview

    • γδ TCRs interact with ligands similarly as pattern recognition receptors (PRRs).
    • They can respond to antigens from various pathogens or stressed host cells.
    • Direct recognition means they do not require MHC or peptide Ag processing by APCs.
    • Intact proteins, peptides, lipids, and phosphorylated nucleotides can all be TCRγδ ligands. They can be soluble or bound to a cell surface.
    • Some stress molecules are recognized by γδ T cells but not by other cells like macrophages or neutrophils, filling a role in host defense.
    • γδ T cells proliferate and differentiate into γδ Th (helper) and γδ CTL (cytotoxic-like) effectors, like αβ T cells.
    • Activation is usually faster, with smaller numbers and often occurs without typical costimulation.

    γδ Τ Cells: Anatomical Distribution

    • The distribution is different from αβ T cells.
    • They are found in small numbers in secondary lymphoid tissues and the thymus.
    • They are interspersed with epithelial cells in the skin (SALT) and mucosal tissues (MALT).
    • This means they are at the forefront of initial contact with pathogens or injurious substances.
    • Unlike αβ T cells, γδ T cells are often resident in a particular tissue type. They show a "canonical" TCR containing specific V gene segments.

    γδ T Cells: Ag Recognition and Activation

    • γδ TCRs can directly bind to low-molecular-weight non-peptide antigens.
    • Some non-peptide antigens may be presented by non-classical MHC class Ib molecules (or CD1).
    • γδ TCRs are generally less specific than αβ TCRs and can broadly cross-react with various antigens.

    γδ T Cells: Ag Recognition and Activation

    • γδ T cells respond to various bacterial, protozoan, and viral molecules, like peptides, proteins, pyrophosphates, phospholipids, lipoproteins, phosphorylated oligonucleotides, alkyl amines.
    • Specific subsets can recognize or target particular pathogen determinants.
    • γδ T cells can recognize stress molecules that are only prevalent in cells experiencing injury, infection, or cancerous transformation.
    • This broad recognition capability allows γδ T cells to respond to a wide range of threats.
    • Some stress molecules are small pyrophosphate-like molecules while others are peptides or whole proteins released from necrotic cells.

    γδ T Cells: Ag Recognition and Activation

    • γδ T cell activation may resemble NK cell activation as some γδ cells express NK cell inhibitory receptors (for MHC class I).
    • Certain γδ T cells can be activated by phosphorylated metabolites, independent of CD28 or CD40 costimulation.
    • In peripheral tissues, γδ T cells tend to use conventional CD28 costimulation. In the skin and intestines, costimulation may involve other receptors engaged by stress ligands.
    • APCs can help activate cells in inflamed tissue by providing cytokines or unknown intercellular signals.

    γδ T Cells: Effector Functions

    • γδ T cell effectors are similar to αβ T cell effectors, although the signaling pathways differ.
    • γδ T cells, following activation, release cytokines that can activate NK cells and macrophages, cause the differentiation of αβ T helper cells (Th1, Th2, or Th17), and affect isotype switching in B cells.
    • They produce molecules that affect leukocyte trafficking and wound healing.
    • Some activated γδ T cells can cause neighboring epithelial cells to produce nitric oxide (an antimicrobial).
    • Activated γδ T cells produce keratinocyte growth factor (KGF) to stimulate skin repair.
    • Immunological memory is not a feature of γδ T cells.
    • Recent studies suggest γδ T cells can act as antigen-presenting cells (APCs) for αβ T cells.

    NKT Cells: Overview

    • NKT cells are T lineage cells with morphology and function characteristics similar to CTLs and NK cells.
    • They are found in low numbers throughout various tissues including the peripheral blood, spleen, liver, thymus, bone marrow, and lymph nodes.
    • Immediately upon activation, they secrete cytokines.
    • Their rapid response makes them important as a first line of defense against viral and bacterial infections.
    • Their produced cytokines affect the differentiation and function of αβ T cells.

    NKT Cells: Ag Recognition and Activation

    • NKT cells recognize glycolipids, glycosphingolipids, and lipids presented by non-polymorphic CD1d molecules on professional and non-professional APCs.
    • NKT cells have a "semi-invariant" TCRαβ in which the TCRα chain is generally invariant; the TCRβ chain shows diversity.

    NKT Cells: Ag Recognition and Activation

    • Several pathogens and host-derived glycolipids function as NKT cell antigens.
    • Activation of NKT cells recognizing CD1d-restricted glycolipids is direct, requiring no costimulation and cytokine receptor engagement.
    • Microbes lacking those lipids can still activate NKT cells through indirect pathways.
    • Sometimes TCR engagement alone is insufficient; IL-12/IL-18 or IFNα/β receptor engagement may be necessary.

    NKT Cells: Activation (Figures)

    • Visual representations of activation, using panels of diagrams and arrows, displaying activation based on pathogen glycolipid, host glycolipid interactions, etc.

    NKT Cells: Effector Functions

    • The characteristics of activated NKT cells align with innate-immunity cells.
    • NKT cells carry out effector functions immediately without differentiation and their main function is cytokine and chemokine secretion.

    NKT Cells: Development

    • NKT cells are part of the adaptive immune system but share characteristics with innate cells.
    • They develop from the same NK/T precursors that produce αβ and γδ T cells.
    • Their development follows the αβ T cell pathway but diverges at the double positive (DP) stage.
    • IL-15 triggers continued maturation once they are positively selected from thymus non-hematopoietic cells.

    Next Lecture

    • The next chapter is about mucosal and cutaneous immunity.

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    This quiz explores the unique characteristics and functions of γδ T cells in humans, mice, and ruminants. It covers their T-cell receptor composition, their ability to recognize antigens without MHC, and their role in host defense. Test your knowledge on this important component of the immune system.

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