Natural Killer Cells and COVID-19 (L7)
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How does the number of natural killer cells change as COVID-19 infection severity increases?

  • It increases during the acute phase.
  • It fluctuates without a clear trend.
  • It remains constant throughout the infection.
  • It decreases as the infection becomes more severe. (correct)

    • What is the lifespan of neutrophils under normal conditions?

  • 6 hours (correct)
  • 24 days
  • 12 hours
  • 24 hours

    • What occurs to natural killer cell activation after receiving an mRNA vaccine?

  • There is an initial spike followed by a decrease. (correct)
  • There is no change in activation levels.
  • It is suppressed for weeks.
  • It remains permanently elevated.

    • What is the primary role of neutrophils in response to infection?

    <p>They trap infectious agents using neutrophil extracellular traps.</p> Signup and view all the answers

    What is neutrophilia in the context of COVID-19?

    <p>An increase in the number of neutrophils.</p> Signup and view all the answers

    What happens to monocyte levels during an acute infection?

    <p>They increase and may persist after recovery.</p> Signup and view all the answers

    From which precursor do neutrophils differentiate?

    <p>Myeloid precursor</p> Signup and view all the answers

    What type of cells are the first to be recruited to the site of infection?

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

    How is the CD169+ monocyte subpopulation affected by COVID-19?

    <p>It is used as a marker to analyze monocyte presence post-infection.</p> Signup and view all the answers

    What effect does infection have on the lifespan of neutrophils?

    <p>It increases their lifespan.</p> Signup and view all the answers

    What contributes to the cytokine storm observed in COVID-19 patients?

    <p>The role of monocytes and macrophages.</p> Signup and view all the answers

    Which statement about neutrophilia in SARS-CoV-2 patients is true?

    <p>It is directly associated with increased risk of death.</p> Signup and view all the answers

    How many neutrophils are produced daily?

    <p>100 billion</p> Signup and view all the answers

    What long-term changes occur in monocyte subpopulations after COVID-19 infection?

    <p>Changes in sub-populations can persist for months.</p> Signup and view all the answers

    What is a characteristic feature of type 1 interferons?

    <p>They are known for their antiviral effects.</p> Signup and view all the answers

    What condition is now referred to as PASC?

    <p>Post-acute sequelae of Coronavirus-19.</p> Signup and view all the answers

    What is the primary role of plasmacytoid dendritic cells (pDC) in the immune response?

    <p>Generating type 1 interferon</p> Signup and view all the answers

    How does a decrease in pDC correlate with COVID-19?

    <p>It leads to a reduction in type 1 interferon production.</p> Signup and view all the answers

    Which of the following best describes the consequence of low type 1 interferon production in the context of COVID-19?

    <p>Reduced antiviral response</p> Signup and view all the answers

    Which cell type is primarily implicated in the generation of type 1 interferon?

    <p>Plasmacytoid dendritic cells</p> Signup and view all the answers

    What type of immune cells are primarily decreased in number during COVID-19 according to the data?

    <p>Plasmacytoid dendritic cells</p> Signup and view all the answers

    What is a likely result of the low type 1 interferon levels in patients with COVID-19?

    <p>Increased susceptibility to secondary infections</p> Signup and view all the answers

    In the context of COVID-19, a reduction in plasmacytoid dendritic cells could lead to which inflammatory response?

    <p>Hypoinflammatory state</p> Signup and view all the answers

    Which of the following statements is true regarding the function of pDC in viral infections?

    <p>They initiate and shape the immune response through type 1 interferon.</p> Signup and view all the answers

    What is the primary role of plasmacytoid dendritic cells in the immune response?

    <p>Producing type 1 interferons</p> Signup and view all the answers

    What type of receptors do plasmacytoid dendritic cells use to recognize viral RNA?

    <p>Endosomal Toll-like receptor 7</p> Signup and view all the answers

    Why is it important to focus on absolute numbers of dendritic cells in blood during COVID-19 infection?

    <p>Absolute numbers provide a clearer assessment of infection severity.</p> Signup and view all the answers

    What is a characteristic feature of plasmacytoid dendritic cells that supports their function?

    <p>High constitutive levels of IRF-7</p> Signup and view all the answers

    How does dexamethasone affect the function of plasmacytoid dendritic cells in COVID-19?

    <p>It dampens the immune response.</p> Signup and view all the answers

    What kind of DNA do plasmacytoid dendritic cells recognize through their endosomal Toll-like receptor 9?

    <p>Viral DNA</p> Signup and view all the answers

    What measurement is critical for evaluating plasmacytoid dendritic cells in COVID-19 patients?

    <p>pDC numbers per µl of blood</p> Signup and view all the answers

    What defines the capability of plasmacytoid dendritic cells to respond rapidly to viral infections?

    <p>Constitutive expression of IRF-7</p> Signup and view all the answers

    What is one mechanism by which coronaviruses inhibit type 1 interferons?

    <p>Hiding in double-membraned structures inside cells</p> Signup and view all the answers

    Which statement correctly describes the immune response in uninfected patients?

    <p>CD4 and CD8 T cells are circulating in the absence of infection.</p> Signup and view all the answers

    What characterizes the phenomenon known as 'Trained Immunity'?

    <p>It results in heightened responses based on previous antigen exposure.</p> Signup and view all the answers

    What cytokines are typically produced during a moderate case of COVID-19?

    <p>TNF-alpha, IL-10, and IL-6</p> Signup and view all the answers

    How does ORF3b from SARS-CoV-2 function in relation to the immune response?

    <p>It acts as a potent interferon antagonist.</p> Signup and view all the answers

    What generally happens to lymphocyte production during a severe COVID-19 infection?

    <p>There is a severe decrease in lymphocyte production.</p> Signup and view all the answers

    Why might influenza vaccination provide some level of protection against SARS-CoV-2 infection?

    <p>It induces a broad immune response based on prior exposure.</p> Signup and view all the answers

    What happens to white blood cells during severe COVID-19 infections?

    <p>Frequently, there's an increase in neutrophils.</p> Signup and view all the answers

    Study Notes

    Natural Killer Cells and COVID-19

    • Natural killer cell activation and maturation increase as COVID-19 severity increases.
    • Natural killer cell numbers decrease as the infection becomes more severe.
    • mRNA-based vaccines trigger a spike in natural killer cell activation, which eventually decreases in the days following vaccination.

    Neutrophils and COVID-19

    • Neutrophils are short-lived, but their life can be extended by infection.
    • Neutrophils are phagocytic cells, playing a key role in the early immune response.
    • Neutrophilia (increased neutrophils) is common in COVID-19 patients.
    • Neutropenia (decreased neutrophils) can also occur, contributing to a lower white blood cell count.
    • Neutrophil infiltrates in the lungs have been observed during autopsies of COVID-19 patients.
    • Neutrophil netosis (release of DNA and cell contents) is associated with IL-6 and is a mechanism for trapping infectious agents.

    Monocytes and COVID-19

    • Monocytes differentiate into macrophages and play a significant role in the immune response.
    • Increased levels of circulating monocytes are observed during acute COVID-19 infection and can persist after recovery or even in individuals with post-acute sequelae of COVID-19 (PASC).
    • Monocytes/macrophages contribute to the cytokine storm during COVID-19.
    • Changes in monocyte subpopulations can persist for months after COVID-19, even in individuals without PASC.

    CD169+ Monocytes in COVID-19

    • CD169+ is a marker for a specific monocyte subpopulation.
    • CD169+ monocytes are most affected in COVID-19 compared to the general monocyte marker CD14.
    • In healthy individuals, monocytes represent 5-10% of circulating cells.
    • In recovered COVID-19 patients, the percentage of circulating monocytes remains high.
    • Patients with PASC have significantly higher monocyte counts that persist.

    Type 1 Interferons and Viral Infections

    • Type 1 interferons are antiviral cytokines produced by various cell types.
    • Changes in dendritic cell numbers are observed in COVID-19.
    • Plasmacytoid dendritic cells are the most potent producers of type 1 interferons.

    Plasmacytoid Dendritic Cells: Specialized Virus Experts

    • Plasmacytoid dendritic cells are factories for type 1 interferon production.
    • These cells express Toll-like receptors 7 and 9, recognizing viral RNA and DNA, respectively.
    • They have high constitutive levels of transcription factor IRF-7, enabling rapid interferon alpha production upon viral encounter.
    • Plasmacytoid dendritic cells have an extensive endoplasmic reticulum.

    Plasmacytoid Dendritic Cells and COVID-19

    • Studies have observed decreased numbers of plasmacytoid dendritic cells in COVID-19 patients, potentially contributing to the low type 1 interferon production seen in this disease.
    • Dexamethasone, a corticosteroid used to dampen immune responses, can further impact plasmacytoid dendritic cell numbers and function in COVID-19.

    Coronaviruses Inhibit Type 1 Interferons

    • Coronaviruses have evolved mechanisms to evade the antiviral effects of type 1 interferons.
    • They can hide within double-membraned structures inside cells, evading key pattern recognition receptors (RIG-1 and endosomal Toll-like receptors).
    • Coronaviruses can inhibit the activation of RIG-1, a receptor for double-stranded RNA.
    • They can also inhibit the induction and signaling of type 1 interferons.
    • ORF3b, a protein from SARS-CoV-2, is a potent interferon antagonist.

    T Cell Dynamics in COVID-19

    • In uninfected individuals, CD4 and CD8 T cells circulate normally without causing symptoms.
    • In moderate COVID-19, the immune response is functioning well, leading to epithelial damage and cytokine production (TNF-alpha, IL-6, IL-10, and interferon gamma).
    • Lymphocyte production declines as these cells become activated in the lymph nodes.
    • During severe COVID-19, there is a large decrease in lymphocytes (including CD4 and CD8 T cells), accompanied by an increase in white blood cell count due to increased neutrophils. This is consistent with a cytokine storm.

    Trained Immunity

    • Innate immune cells do not exhibit classical memory like T and B cells.
    • However, evidence suggests that innate immune responses can be enhanced based on prior exposure to antigens. This is known as "trained immunity" or "innate memory".
    • Trained immunity can be demonstrated by increased resistance to infections after vaccination or exposure to particular antigens.
    • Trained immunity is not as long-lasting as classic memory from T and B cells, potentially persisting for months or sometimes longer.

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    Lecture 7 PDF - Sequential Activation Of Immunity In Viral Infection

    Description

    This quiz explores the role of natural killer cells, neutrophils, and monocytes in the context of COVID-19. It covers their activation, response to severity of the disease, and implications related to mRNA vaccines. Test your knowledge of these immune responses in relation to COVID-19.

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