Innate Immunity and Inflammation 2
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Innate Immunity and Inflammation 2

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Questions and Answers

What is a common effect of both C5a and C3a?

  • Decreased histamine release
  • Vasodilation (correct)
  • Increased heart rate
  • Reduced vascular permeability

    • Which cells in particular does C5a act as a chemotactic agent for?

  • B cells and T cells
  • Eosinophils and basophils
  • Natural killer cells and dendritic cells
  • Neutrophils and macrophages (correct)

    • What is a consequence of inadequate complement proteins (C2, C3, C4, C5, MBL, MAC complex)?

  • Enhanced resistance to viral infections
  • Reduced risk of parasitic infections
  • Vulnerability to bacterial infection (correct)
  • Increased risk of fungal infections

    • Which condition is associated with deficiencies in C1q?

    <p>Systemic lupus erythematosus</p> Signup and view all the answers

    What role does C1q play in relation to macrophages and apoptotic bodies?

    <p>Helps macrophages to clear apoptotic bodies</p> Signup and view all the answers

    What is the proposed role of self-antigens in the development of autoimmunity?

    <p>Continual presence increases the likelihood of developing autoimmunity</p> Signup and view all the answers

    What makes the alternative pathway the first responder in complement activation?

    <p>It can be activated spontaneously by hydrolysis of C3</p> Signup and view all the answers

    What process likely licenses NK cells to ensure their NKIRs are functional?

    <p>Presentation of antigens by dendritic cells</p> Signup and view all the answers

    In what circumstance do NK cells not kill a cell?

    <p>When a cell expresses mostly normal MHC-I proteins</p> Signup and view all the answers

    What happens when NKARs 'over-rule' the NKIRs?

    <p>NK cell kills the abnormal cell</p> Signup and view all the answers

    How do NKARs kill the cell when activated?

    <p>All of the above</p> Signup and view all the answers

    What is the function of perforin in the mechanism of NKAR killing?

    <p>Poking holes in the membrane</p> Signup and view all the answers

    Natural killer cells predominantly kill...

    <p>Cancer cells or virally-infected cells</p> Signup and view all the answers

    Which cells protect the body from indiscriminate NK-killing and tissue damage?

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

    What are the main ligands for RLRs that activate NF-KB?

    <p>Double-stranded RNA</p> Signup and view all the answers

    What happens when a DAMP activates NLRP3?

    <p>Formation of inflammasome</p> Signup and view all the answers

    What is the effect of IL-1 release from macrophages?

    <p>Amplifies the inflammatory response</p> Signup and view all the answers

    What is the function of an inflammasome?

    <p>Activation of caspase 1</p> Signup and view all the answers

    What is the cellular effect when a cell undergoes pyroptosis?

    <p>Lysis and release of more DAMPs</p> Signup and view all the answers

    What is the function of NLRP3 when it detects diverse signals such as DAMPs and PAMPs?

    <p>Activates pro-IL-1 to IL-1</p> Signup and view all the answers

    Continual presence of self-antigens (ie. nuclear material) in extracellular space can increase the risk of developing _______

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

    Which of the following cells are important PAMP and DAMP detectors?

    <p>All of the above</p> Signup and view all the answers

    Epithelial and endothelial cells can detect PAMPs and DAMPs

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

    What is the major cellular source of IL-1?

    <p>Macrophages/monocytes, dendritic cells, keratinocytes</p> Signup and view all the answers

    Which cytokine has redundant and pleiotropic effects?

    <p>All of the above</p> Signup and view all the answers

    What is the mechanism of fever generation?

    <p>Peripheral vasoconstriction and shivering</p> Signup and view all the answers

    Which cell type is NOT an important cellular source of IL-1?

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

    What is one of the local functions of IL-1?

    <p>Increased vascular permeability</p> Signup and view all the answers

    What is the major cellular source of TNF-alpha?

    <p>Macrophages/monocytes, dendritic cells, mast cells</p> Signup and view all the answers

    What is the general role for CRP in acute inflammation?

    <p>All of the above</p> Signup and view all the answers

    Ferritin, Hepcidin, MBL and SAA are all examples of....

    <p>Acute phase proteins</p> Signup and view all the answers

    Which of the following effectors change the hypothalamic set point for body temperature?

    <p>PGE2</p> Signup and view all the answers

    What is the main role of Group 1 interferons (IFN-alpha and IFN-beta) in the antiviral response?

    <p>All of the above</p> Signup and view all the answers

    Which cells secrete Group 1 interferons (IFN alpha and IFN beta) in the antiviral response?

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

    How do type I interferons act to provide protection to viral infection?

    <p>By inhibiting viral replication in an autocrine and paracrine fashion</p> Signup and view all the answers

    Study Notes

    Complement System and Chemotaxis

    • C5a and C3a are both potent anaphylatoxins, resulting in increased vascular permeability and recruitment of inflammatory cells.
    • C5a acts as a chemotactic agent specifically for neutrophils, eosinophils, and monocytes.

    Consequences of Inadequate Complement Proteins

    • Deficiencies in complement proteins (C2, C3, C4, C5, MBL, MAC complex) can lead to increased susceptibility to infections and autoimmune diseases.

    C1q and Associated Conditions

    • Deficiencies in C1q are associated with systemic lupus erythematosus (SLE).
    • C1q plays a crucial role in promoting the phagocytosis of apoptotic cells by macrophages.

    Self-Antigens and Autoimmunity

    • Continual presence of self-antigens, such as nuclear material, in the extracellular space can increase the risk of developing autoimmunity.

    Alternative Pathway of Complement Activation

    • The alternative pathway is the first responder in complement activation due to its ability to initiate activation on pathogen surfaces without the need for antibodies.

    NK Cell Functionality

    • Licensing of natural killer (NK) cells occurs through interactions with the major histocompatibility complex (MHC), ensuring their NK inhibitory receptors (NKIRs) are functional.
    • NK cells typically do not kill a cell if it expresses sufficient MHC class I molecules.

    NK Cell Activation and Mechanism of Killing

    • When NK activating receptors (NKARs) over-rule the NKIRs, NK cells are triggered to kill the target cell.
    • NKARs induce cell death through the release of cytotoxic granules, which include perforin.

    Perforin Functionality

    • Perforin functions by creating pores in the target cell membrane, facilitating the entry of granzymes that induce apoptosis.

    Natural Killer Cell Targets

    • Natural killer cells predominantly kill virus-infected cells, tumor cells, and stressed cells.

    Protection Against NK Cell Activity

    • Healthy cells express self-MHC and other protective signals to defend against indiscriminate NK killing and tissue damage.

    Pathogen Detection

    • Main ligands for retinoic acid-inducible gene I-like receptors (RLRs) that activate NF-kB include viral RNA.
    • When damage-associated molecular patterns (DAMPs) activate NLRP3, it triggers an inflammatory response through the formation of an inflammasome.

    IL-1 and Its Effects

    • Release of interleukin-1 (IL-1) from macrophages promotes inflammation, fever, and recruitment of additional immune cells.
    • The inflammasome facilitates the maturation and secretion of IL-1.

    Cellular Outcome of Pyroptosis

    • Pyroptosis results in inflammatory cell death and the release of pro-inflammatory cytokines, differentiating it from apoptosis.

    NLRP3 Functionality

    • NLRP3 acts as a pattern recognition receptor (PRR) detecting both DAMPs and pathogen-associated molecular patterns (PAMPs) to mount an immune response.

    IL-1 Sources and Effects

    • Major source of IL-1 is primarily macrophages; it possesses redundant and pleiotropic effects, influencing various immune responses.
    • Fever generation involves the hypothalamus's set point alteration due to cytokines such as IL-1 and TNF-alpha.

    Other Cytokine Sources

    • Major cellular source of tumor necrosis factor-alpha (TNF-alpha) is activated macrophages.
    • C-reactive protein (CRP) serves as a marker of acute inflammation.

    Acute Phase Proteins

    • Ferritin, hepcidin, mannose-binding lectin (MBL), and serum amyloid A (SAA) are examples of acute-phase proteins produced in response to inflammation.

    Interferon Response

    • Group 1 interferons (IFN-alpha and IFN-beta) are primarily secreted by virus-infected cells and play a critical role in antiviral defense by enhancing the immune response against viral infection.

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