Innate Immunity Quiz: TLRs and Complement System
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Innate Immunity Quiz: TLRs and Complement System

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Questions and Answers

What role do Toll-Like Receptors (TLRs) play in the immune system?

  • They initiate innate immune responses. (correct)
  • They solely recognize DAMPs.
  • They directly kill pathogens.
  • They promote the generation of antibodies.
  • Which of the following statements about the Complement system is true?

  • All complement proteins are membrane-bound.
  • Complement activation can trigger a cascade of enzymatic reactions. (correct)
  • Complement proteins are only involved in phagocytosis.
  • Complement solely relies on antibody activation.
  • What triggers the Classical Pathway of complement activation?

  • Microbial surface structures.
  • Pro-inflammatory cytokines.
  • Viral RNA presence.
  • Antibody-antigen complexes. (correct)
  • Which immune response is NOT a consequence of Pattern Recognition Receptors (PRRs) detecting PAMPs?

    <p>Activation of adaptive immune cells.</p> Signup and view all the answers

    What are DAMPs and how do they contribute to the immune response?

    <p>They are released during cell injury and activate the immune system.</p> Signup and view all the answers

    What is the primary function of the Alternative Pathway of complement activation?

    <p>Activated by microbial surface structures.</p> Signup and view all the answers

    Which of the following best describes opsonization in the context of the complement system?

    <p>Coating of pathogens to enhance phagocytosis.</p> Signup and view all the answers

    Which of the following best describes the cascade of activation in the complement system?

    <p>Each activated component activates multiple downstream components.</p> Signup and view all the answers

    What triggers the lectin pathway of complement activation?

    <p>Binding of lectins to mannose residues on pathogen glycoproteins</p> Signup and view all the answers

    What is the role of C3a and C5a in the immune system?

    <p>They act as powerful anaphylatoxins causing mast cell degranulation.</p> Signup and view all the answers

    What effect does C3b have during the immune response?

    <p>Promotes phagocytosis by being recognized by complement receptor 1.</p> Signup and view all the answers

    What is the primary function of the membrane attack complex (MAC)?

    <p>To promote the lysis of bacterial and virus-infected cells.</p> Signup and view all the answers

    Which of the following is a characteristic of cytokines?

    <p>Cytokines show redundancy where multiple cytokines can produce similar effects.</p> Signup and view all the answers

    What type of interactions can cytokines have within the immune system?

    <p>They may exhibit synergy, redundancy, and antagonism.</p> Signup and view all the answers

    Which cytokines are classified as pro-inflammatory?

    <p>IL-1, IL-6, TNF-α, IFNγ</p> Signup and view all the answers

    What does the term 'pleiotropic' refer to in relation to cytokines?

    <p>Having multiple effects on different cell types.</p> Signup and view all the answers

    What role does IL-6 play in the immune response?

    <p>Promotes acute phase proteins from the liver</p> Signup and view all the answers

    Which cytokine is mainly responsible for promoting Th1 polarization of helper T cells?

    <p>IL-12</p> Signup and view all the answers

    What function does TGF-β serve in the immune system?

    <p>Inhibits effector T cell function and promotes Treg differentiation</p> Signup and view all the answers

    Which cytokine is primarily produced in response to viral infection?

    <p>Type 1 Interferon (IFN-α, β)</p> Signup and view all the answers

    What is the main function of IL-2 in the immune response?

    <p>Facilitates clonal expansion of antigen-stimulated T cells</p> Signup and view all the answers

    Which cytokine inhibits the production of pro-inflammatory cytokines by dendritic cells?

    <p>IL-10</p> Signup and view all the answers

    What does IL-4 promote in the immune system?

    <p>Class switching to IgE</p> Signup and view all the answers

    What is a primary characteristic of inflammation?

    <p>It is a non-specific response to protect against various types of harm.</p> Signup and view all the answers

    Which of the following is NOT a cardinal sign of inflammation?

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

    What is the primary role of vasodilation during inflammation?

    <p>To increase blood flow to the affected area</p> Signup and view all the answers

    Which type of immune cell is typically recruited first during the inflammatory response?

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

    The process of leukocyte exiting the blood vessels is known as:

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

    In the inflammatory response, what is an effect of increased vascular permeability?

    <p>Swelling due to fluid accumulation</p> Signup and view all the answers

    What signal induces the expression of E-selectin on endothelial cells during inflammation?

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

    Which chemokine is primarily responsible for directing neutrophil migration during inflammation?

    <p>CXCL8</p> Signup and view all the answers

    Recruitment of which immune cell type occurs last in the series during the inflammatory response?

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

    What is the primary role of CCL2 and CCL7 in inflammation?

    <p>They bind to CCR2 to recruit monocytes.</p> Signup and view all the answers

    Which of the following is NOT a prominent systemic manifestation of inflammation?

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

    What is a major change observed during the acute phase response in inflammation?

    <p>Increase of acute phase proteins in the serum</p> Signup and view all the answers

    Which cytokines are considered the 'master cytokines' influencing inflammation?

    <p>IL-1 and TNF</p> Signup and view all the answers

    Which condition is termed the systemic inflammatory response?

    <p>Sepsis and septic shock</p> Signup and view all the answers

    What is the impact of chemical mediators on vasodilation?

    <p>They increase blood flow to injured tissues.</p> Signup and view all the answers

    How does local injury affect the systemic response?

    <p>It can lead to pronounced systemic manifestations.</p> Signup and view all the answers

    What common treatment targets the effects of inflammation?

    <p>Anti-inflammatory drugs</p> Signup and view all the answers

    Study Notes

    Toll-Like Receptors (TLRs)

    • Detect Pathogen-Associated Molecular Patterns (PAMPs)
    • Found on the surface of cells of the innate immune system
    • Crucial for detecting microbial infections

    Pattern Recognition Receptors (PRRs)

    • Recognize PAMPs and Damage-Associated Molecular Patterns (DAMPs)
    • Activate innate immune responses:
      • Aid phagocytosis
      • Activate innate cells
      • Promote inflammatory mediators

    Danger Associated Molecular Patterns (DAMPs)

    • Host proteins released during cell injury
    • Activate the immune system

    Complement

    • A collection of soluble proteins that activate upon injury.
    • Aids the immune system by:
      • Promoting phagocytosis through opsonisation.
      • Induce inflammatory responses.
      • Directly kill pathogens.

    Activation of Complement

    • Activation of one component triggers an enzyme cascade.

    Overview of Complement Pathways

    • Classical Pathway: Triggered by the presence of an antibody-antigen complex
    • Alternative Pathway: Triggered by microbial surface structures e.g. LPS
    • Lectin Pathway: Triggered by mannose residues on pathogen glycoproteins binding to host lectins
    • Common Feature: Activation of C3 convertase which converts C3 into C3a and C3b

    Complement: Inflammation

    • C3a and C5a are powerful anaphylatoxins
    • Cause mast cell degranulation
    • Promote vasodilation and increase vascular permeability
    • C5a is chemotactic factor

    Complement: Opsonisation

    • C3b attaches to the outside of the microbe
    • Is recognised by complement receptor 1 (CR1) on phagocytes
    • Promotes phagocytosis and destruction of the pathogen

    Complement: Membrane Attack Complex (MAC)

    • C5b triggers the formation of MAC (C5b6789)
    • Causes lysis of bacterial, virus-infected, or tumour cells
    • Contains multiple copies of C9

    Soluble Mediators: Cytokines

    • Soluble proteins produced by a variety of cell types.
    • Critical for innate and adaptive immune responses.
    • Their expression can be perturbed in immune, inflammatory, and infectious disease states.
    • Actions can be autocrine, paracrine, or endocrine.
    • Include proinflammatory (e.g., IL-1, IL-6, TNF-α, IFNγ), anti-inflammatory (e.g., TGF-β, IL-10), and involved in cell growth and differentiation (e.g., colony-stimulating factors (CSFs) and stem cell factor).

    Cytokine Properties

    • Pleiotropic: Having more than one effect
    • Redundancy: Several cytokines can have the same effect
    • Synergy: The effect of two cytokines may be greater than the sum of each effect
    • Antagonism: One cytokine may inhibit the response to another cytokine
    • Cytokine Networks: Cytokines enhance or suppress the production of others generating complex cytokine networks.

    Cytokine Examples

    • Produced by macrophages/dendritic cells upon stimulation:
      • TNF, IL-1: Induce inflammation, by acting on the endothelial cell
      • IL-6: Induced acute phase proteins from the liver, promotes adaptive immune responses
      • IL-12: Promotes IFN-γ production and Th1 polarisation of helper T cells. Stimulates NK cell activity
      • IL-23 Promotes survival and function of Th17 cells
    • Produced in response to virus:
      • Type 1 Interferon (IFN-α, β) Inhibits viral replication, promotes MHC class I expression and cytotoxic T cells.
    • Produced by helper T cells:
      • IL-2: Clonal expansion of antigen-stimulated T cells, maintenance of regulatory T cells (Treg)
      • IFN-γ: Product of Th1 cells (and NK cells), promotes activation of macrophage to be better killers of intracellular bacteria, increased MHC class I expression
      • IL-4: Th2 cytokine, includes class switching to IgE
      • IL-5: Activates eosinophils
      • IL-17: Th17 cytokine, promotes neutrophil-based inflammation in defense against extracellular pathogens

    Anti-inflammatory Cytokines

    • IL-10 inhibits the production of pro-inflammatory cytokine by dendritic cells; produced by Treg, DC, and macrophages (later response)
    • TGF-β: Promotes differentiation to Treg, inhibitor effector T cell function; produced by Treg and other cells. Can promote wound healing (if chronic fibrosis). But, in the presence of inflammatory cytokines, can promote Th17.

    Inflammation

    • Non-specific, localized, protective tissue response to injury (e.g., infection, trauma, heat).
    • Intended to eliminate or wall off the cause of injury, necrotic cells, and promote tissue repair.
    • Denotes by suffix “-itis”

    Cardinal Signs of Inflammation

    • Redness
    • Heat
    • Swelling
    • Pain
    • Functional Impairment

    Steps in Inflammation

    • Detection of pathogens or danger: (PAMPs, DAMPs) by innate cells results in the release of mediators that cause vascular and cellular responses
    • Vasodilation and increased vascular permeability:
    • Recruitment of additional immune cells: (neutrophils, then monocytes, then lymphocytes)
    • Elimination of trigger:
    • Resolution:

    Inflammation: Vascular Changes

    • Vasodilation: Increases blood flow (red, warm)
    • Increased permeability: Leads to exudation of protein-rich fluid (swelling)
    • Reduced blood velocity:
    • Accumulation of immune cells:

    Recruitment of Effector Cells

    • Recruitment of effector cells to the site of infection is an important step in controlling infection.

    Steps in Cell Recruitment

    • Time: Neutrophils < Monocytes < Lymphocytes

    Neutrophil Recruitment: Rolling

    • Neutrophils are often the first cell recruited.
    • Activation by inflammatory cytokines (e.g., TNFα, IL-1) induces expression of E-selectin on the endothelium.
    • Weak interactions with carbohydrate ligands on the neutrophils, slows movement, causing rolling.

    Neutrophil Recruitment: Adhesion

    • Chemokines induce conformation changes in integrins (e.g., LFA-1), allowing the leukocyte to adhere tightly to the endothelial cells via interactions with their ligands (e.g., ICAM-1, also upregulated by inflammatory cytokines like TNF).
    • Cells cross the blood vessel walls (extravasation).
    • The chemokine CXCL8 (aka IL-8) directs the migration of neutrophils along its concentration gradient.

    Monocyte Recruitment

    • Monocytes are typically recruited (hours) later than neutrophils.
    • CCL2 and CCL7 both bind to CCR2 chemokine receptor and recruit monocytes.

    Inflammation Systemic Effects

    • Ideally, the inflammatory response remains confined to a localised area.
    • Local injury can result in prominent systemic manifestations as inflammatory mediators are released into the circulation.
    • Acute phase response: A group of physiologic processes occurring soon after the onset of inflammation. The most prominent change is a dramatic increase of acute phase proteins in the serum.
    • Alterations in white blood cell count: (leukocytosis or leukopenia)
    • Fever:
    • Sepsis and septic shock: (systemic inflammatory response syndrome) Represents the severe systemic manifestations of inflammation.

    Inflammation: Chemical Mediators

    • Chemical mediators of inflammation impact:
      • Vasodilation
      • Vascular permeability
      • Chemotaxis
      • Fever
      • Pain
      • Tissue Damage
    • Often the target of anti-inflammatory drugs.

    Systemic Effects of Inflammation

    • IL-1 and TNF are considered the “master cytokines”

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    Related Documents

    Innate Immunity PDF

    Description

    Test your understanding of Toll-Like Receptors (TLRs) and the Complement System within the innate immune response. This quiz covers the roles of Pattern Recognition Receptors (PRRs), Danger-Associated Molecular Patterns (DAMPs), and the activation pathways of complement proteins. Explore the intricate mechanisms that protect the body against microbial infections.

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