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 (A)</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. (A)</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. (B)</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. (A)</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. (A)</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. (D)</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. (A)</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. (C)</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. (C)</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. (A)</p> Signup and view all the answers

Which cells do NKT cells share characteristics with?

<p>Both CTL and NK cells. (D)</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. (C)</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. (A)</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. (C)</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. (C)</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. (C)</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. (B)</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) (A)</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 (C)</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 (D)</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 (C)</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 (B)</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. (C)</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. (C)</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 (B)</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. (A)</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 (A)</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. (A)</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. (C)</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. (A)</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 (C)</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. (C)</p> Signup and view all the answers

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

<p>Nitric oxide (B)</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 (A)</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. (A)</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. (D)</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. (B)</p> Signup and view all the answers

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

<p>By week 8 (A)</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 (B)</p> Signup and view all the answers

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

<p>Vg1Vd2 TCRs (D)</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. (B)</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 (B)</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. (C)</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. (B)</p> Signup and view all the answers

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

<p>Large proteins (A)</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. (A)</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. (A)</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. (B)</p> Signup and view all the answers

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

<p>Thymus (C)</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. (B)</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. (C)</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. (C)</p> Signup and view all the answers

Flashcards

NKT cells' rapid response

NKT cells react quickly, acting as a primary defense against bacterial and viral infections.

NKT cell Ag recognition

NKT cells recognize glycolipids and glycosphingolipids presented on CD1d molecules by antigen-presenting cells.

Invariant NKT cells

NKT cells with a unique TCR; the alpha chain is mostly unchanging, while the beta chain shows some variation.

NKT cell activation

NKT cell activation can be direct, through activation by certain pathogen-derived glycolipid Ags, or indirect, from microbes lacking these glycolipid antigens.

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NKT cell effector function

Activated NKT cells primarily secrete cytokines and chemokines, playing a key role in innate immunity.

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gd T cell effector functions

gd T cells, activated by antigens, produce cytokines that activate NK cells and macrophages, support the differentiation of other T cells, and affect antibody production by B cells.

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gd T cell cytokine secretion

Activated gd T cells release molecules that direct leukocyte movement and tissue repair.

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gd T cell wound healing

gd T cells can prompt skin cells to produce molecules that aid in wound closure.

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gd T cell vs. ab T cell memory

Unlike ab T cells, gd T cells do not exhibit immunological memory.

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gd T cell antigen presentation

gd T cells can act as antigen-presenting cells to ab T cells.

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gd T cell development timing

gd T cells are among the first T cells produced during fetal development.

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NKT cell characteristics

NKT cells have similarities to both cytotoxic T cells and natural killer cells.

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NKT cell location

NKT cells are found throughout the body, where other T and NK cells reside.

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NKT cell activation speed

NKT cells can quickly release cytokines after activation, without needing to mature into effector cells.

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NKT cell cytokine role

Activated NKT cells primarily secrete cytokines and chemokines that play a key role in innate immunity.

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gd T cells role

gd T cells are a type of T cell that plays a role in innate immunity, responding to antigens from pathogens or stressed cells. Unlike T cells with other types of receptors, gd T cells can quickly respond, and are often the first line of defense.

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gd T cell antigens

gd T cells recognize a wider variety of antigens than other T cells. These can include intact proteins, peptides, lipids, and other molecules from pathogens or stressed cells.

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gd T cell location in the body

gd T cells are primarily found in the skin and mucosal tissues, rather than in secondary lymphoid organs like other T cells.

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gd T cell vs. ab T cell response

gd T cells respond more quickly than other T cells. They often act quickly in response to threats, even without prior activation signals (costimulation).

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gd T cells and immune memory

Unlike other T cells (like ab T-cells), gd T cells do not provide lasting immunity (memory).

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gd T cell effector functions

Activated gd T cells produce cytokines that help activate other immune cells (like NK cells and macrophages), support the development of other T cells, and influence antibody production.

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NKT cell characteristics

NKT cells share traits of both cytotoxic T cells and natural killer cells.

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NKT Cell Activation Speed

NKT cells can release cytokines quickly after activation without needing to develop into effector cells.

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gd T cell development timing

gd T cells are some of the first T cells produced during fetal development.

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gd T cell location

gd T cells are often found in the skin and mucosal tissues, unlike other T cells that are more common in lymph nodes and spleen.

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gd T cell vs. ab T-cell memory

gd T cells don't develop immunological memory like conventional T cells, while ab T cells produce memory cells.

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NKT cell location

NKT cells are found throughout the body, including tissues like peripheral blood, the spleen, liver and lymph nodes.

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gd T cell antigen recognition

gd T cells can directly bind non-peptide antigens, or antigens presented by non-classical MHC class Ib molecules or CD1 molecules.

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gd T cell antigen types

gd T cells react to a broad range of substances, including peptides, proteins, pyrophosphates, phospholipids, lipoproteins, phosphorylated oligonucleotides, and alkyl amines.

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gd T cell subset specificity

Specific gd T cell subsets are targeted against particular pathogen types or stress molecules released from damaged/infected/transformed host cells, like heat shock proteins.

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gd T cell activation

Activation mechanisms of some gd T cells resemble those of NK cells more than ab T cells, as some gd T cells express NK inhibitory receptors, and can be activated without traditional costimulation.

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gd T cell location

gd T cells commonly reside in peripheral tissues like the skin and intestines, often in areas of inflammation.

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gd T cell activation costimulation

Peripheral gd T cell activation may involve conventional CD28-mediated costimulatory signals, whereas gd T cells in the skin and intestines are triggered by co-stimulation from other surface receptors.

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gd T cells and memory

gd T cells, unlike ab T cells, generally do not exhibit immunological memory.

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gd T cell in immune response

gd T cells are part of the faster initial immune response to various threats, responding to stressed/infected cells or pathogens, and helping activate other immune cells via cytokine signaling; hence gd T cells are an adaptive immunity part.

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gd T cell location

gd T cells are primarily found in the skin and mucosal tissues, unlike other T cells, which are more common in secondary lymphoid organs.

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gd T cell antigen recognition

gd T cells recognize a broader range of antigens, including intact proteins, peptides, lipids, and other molecules from pathogens or stressed cells.

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gd T cell response vs. ab T cells

gd T cells respond faster than ab T cells. They can act quickly to threats, even without the traditional activation signals (costimulation).

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gd T cell memory

Unlike ab T cells, gd T cells do not develop immunological memory.

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gd T cell effector function

Activated gd T cells release cytokines to activate other immune cells (NK cells & macrophages), help other T cell development, and influence antibody production.

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gd T cell effector functions

Activated gd T cells produce cytokines that activate NK cells and macrophages, support other T cell differentiation, and influence B cell antibody production.

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gd T cell development timing

gd T cells are among the first T cells produced during fetal development, appearing before the fully developed adaptive immunity from ab T cells.

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NKT cell characteristics

NKT cells have similarities to both cytotoxic T cells and natural killer cells.

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NKT cell activation speed

NKT cells can release cytokines quickly after activation without needing to develop into effector cells.

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NKT cell cytokine role

Activated NKT cells primarily secrete cytokines and chemokines, playing a crucial role in innate immunity.

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gd T cell location

gd T cells are often found in peripheral tissues like skin and mucosal surfaces, unlike other T cells.

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gd T cell vs. ab T cell memory

gd T cells, unlike ab T cells, do not exhibit immunological memory.

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gd T cell location

gd T cells are frequently found in skin and mucosal tissues, unlike other T cells that are more common in lymph nodes and spleen.

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gd T cell antigen recognition

gd T cells can directly recognize non-peptide antigens, or antigens presented by non-classical MHC class Ib molecules or CD1 molecules.

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gd T cell antigen types

gd T cells respond to a wide array of molecules, including peptides, proteins, pyrophosphates, phospholipids, lipoproteins, phosphorylated oligonucleotides, and alkyl amines.

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gd T cell subset specificity

Different subsets of gd T cells are tailored to target specific types of pathogens or stress molecules released from damaged/infected/transformed host cells, like heat-shock proteins.

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gd T cell activation

Activation mechanisms of some gd T cells are more similar to natural killer cells (NK cells) than other ab T cells, with pathways potentially involving NK inhibitory receptors and skipping some traditional costimulation.

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gd T cell activation costimulation

Peripheral gd T cells might be activated by typical CD28 co-stimulation, whereas gd T cells in the skin and intestines are triggered by other surface receptor engagements with stress ligands.

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gd T cell vs. ab T-cell memory

Unlike ab T cells, gd T cells typically do not exhibit immunological memory.

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gd T cell in immune response

gd T cells contribute to the initial immune response by reacting swiftly to stressed/infected cells or pathogens, and support other immune cells via cytokines; hence gd T cells play a part in adaptive immunity.

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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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