Immunology - Lecture 4
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Questions and Answers

What is the role of C3 convertase in pathogen destruction?

  • It directly kills pathogens through enzymatic reactions.
  • It prevents phagocytosis by inhibiting immune responses.
  • It forms a protective shield around pathogens.
  • It marks the pathogen for destruction, enhancing phagocytosis. (correct)

    • Which protein complex is the first in the classical pathway of complement activation?

  • C3 convertase complex.
  • Mannose-binding lectin complex.
  • C1 complex consisting of C1q, C1r, and C1s. (correct)
  • C5 convertase complex.

    • How does mannose-binding lectin (MBL) bind to microbial surfaces?

  • Through non-specific electrostatic interactions.
  • By binding to sialic acid residues on host cells.
  • Through carbohydrate-recognition domains targeting specific sugars. (correct)
  • By neutralizing toxins produced by pathogens.

    • What is the composition of the C5 convertase in the alternative pathway?

    <p>Two C3b subunits and one Bb subunit.</p> Signup and view all the answers

    What carbohydrate structures does MBL primarily target?

    <p>Mannose, fucose, and GlcNAc.</p> Signup and view all the answers

    What is the primary function of the complement system?

    <p>To opsonize and lyse pathogens</p> Signup and view all the answers

    Which component of the complement system is primarily synthesized by the liver?

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

    What initiates the activation of the complement system?

    <p>Contact with pathogens or antibodies bound to pathogens</p> Signup and view all the answers

    What type of proteins are the majority of complement components classified as?

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

    What is the role of zymogens in the complement system?

    <p>Zymogens become active through proteolytic cleavage</p> Signup and view all the answers

    Which of the following complement activation pathways is directly triggered by the presence of pathogens?

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

    What is an essential feature of the complement system's activation process?

    <p>It involves a cascade of enzymatic reactions</p> Signup and view all the answers

    Which of the following statements about the complement system is incorrect?

    <p>All complement proteins are synthesized during an immune response</p> Signup and view all the answers

    What is the function of Factor D in the complement system?

    <p>Cleaves factor B for its activation</p> Signup and view all the answers

    What role does properdin play in the alternative pathway of complement activation?

    <p>Enhances the activity of the alternative C3 convertase</p> Signup and view all the answers

    Which convertase is produced when C3b binds to factor B?

    <p>Alternative C3 convertase</p> Signup and view all the answers

    The cleavage products of C3b interact with which complement receptors?

    <p>CR3 and CR4</p> Signup and view all the answers

    How does the alternative pathway amplify the classical or lectin pathways?

    <p>By producing more C3b molecules</p> Signup and view all the answers

    What distinguishes bacterial surfaces in the context of complement activation?

    <p>They favor properdin binding and lack regulatory proteins</p> Signup and view all the answers

    What is the primary purpose of C3 convertase in the complement activation cascade?

    <p>To cleave C3 into C3a and C3b</p> Signup and view all the answers

    What is the resultant effect of the alternative pathway on C3b levels at pathogen surfaces?

    <p>Coats pathogen surfaces with increased C3b</p> Signup and view all the answers

    What is the role of Factor I in the complement system?

    <p>Inactivates C3b through cleavage</p> Signup and view all the answers

    How does Factor H regulate complement activation?

    <p>By enhancing the cleavage of C3b into iC3b</p> Signup and view all the answers

    Which membrane protein inhibits the alternative C3 convertase?

    <p>DAF (decay-accelerating factor)</p> Signup and view all the answers

    What is the function of the Membrane-Attack Complex (MAC)?

    <p>To form holes in membranes of pathogens</p> Signup and view all the answers

    What triggers an inflammatory response in the complement system?

    <p>Anaphylatoxins C3a and C5a</p> Signup and view all the answers

    Which condition can result from a malfunctioning complement system?

    <p>Autoimmune disorders like lupus</p> Signup and view all the answers

    What is the primary purpose of complement fixation?

    <p>To enhance phagocytosis by tagging pathogens</p> Signup and view all the answers

    What effect does the presence of sialic acid on bacteria have on the complement system?

    <p>Inhibits complement activation</p> Signup and view all the answers

    What is the role of complement component C3 in the immune response?

    <p>It cleaves to form C3a and C3b, promoting opsonization.</p> Signup and view all the answers

    Which pathway of the complement system is initiated by spontaneous hydrolysis of C3?

    <p>Alternative pathway</p> Signup and view all the answers

    Which component is primarily involved in forming the membrane attack complex?

    <p>C5b</p> Signup and view all the answers

    What is the function of the lectin pathway in the complement system?

    <p>It binds to specific carbohydrate structures on microbes.</p> Signup and view all the answers

    How are inactive complement proteins designated?

    <p>By a simple number designation.</p> Signup and view all the answers

    What does the term 'opsonin' refer to in the context of the complement system?

    <p>A molecule that enhances phagocytosis of pathogens.</p> Signup and view all the answers

    What is the primary function of C5 in the complement system?

    <p>To form C5a and C5b for the membrane-attack complex.</p> Signup and view all the answers

    Which components are part of the classical pathway of the complement system?

    <p>C1, C4, C2</p> Signup and view all the answers

    What is meant by 'complement fixation'?

    <p>The irreversible binding of complement proteins to pathogens.</p> Signup and view all the answers

    Which of the following is NOT a product of complement protein cleavage?

    <p>C1s</p> Signup and view all the answers

    What initiates the activation of the classical pathway?

    <p>Binding of antibodies to antigens.</p> Signup and view all the answers

    What is the main function of mannose-binding lectin (MBL) in the complement system?

    <p>To bind to specific carbohydrates on microbes.</p> Signup and view all the answers

    What is essential for the phagocytic cells to recognize pathogens in the context of complement activation?

    <p>Opsonization by complement components.</p> Signup and view all the answers

    Which effect does C3a have within the complement system?

    <p>It triggers degranulation of inflammatory cells.</p> Signup and view all the answers

    Study Notes

    The Complement System

    • What is the Complement System?
      • A system of soluble plasma proteins produced mainly by the liver.
      • These proteins act to opsonize and lyse pathogens.
      • Composed of over 30 proteins that circulate in inactive forms.
      • Essential component of the innate immune system.
      • ‘Activated’ in the presence of pathogens or antibodies bound to pathogens.

    Complement Activation Pathways

    • How is the Complement System activated?
      • Three pathways lead to complement activation:
        • Contact with pathogens: Alternative pathway
        • Lectin pathway: Activated by soluble carbohydrate-binding proteins like mannose-binding lectin (MBL) and ficolins.
        • Classical pathway: Activated when component C1 recognizes microbial surface directly or binds to antibodies already bound to pathogen.

    Complement Nomenclature

    • How are complement proteins named?
      • Designated by letter C followed by a number.
      • Inactive complement proteins (aka zymogens) have a simple number designation (e.g. C1 or C2).
      • Products of cleavage reactions are designated by adding a lowercase letter (e.g. C3 cleaves to produce C3a and C3b).

    Key Components of the Complement System

    • Function of each key component:
      • C1 (C1q, C1r, C1s): Protease involved in cleaving C2 and C4.
      • C2: Cleaved by C1 or MASP-2 to form C2b fragment of classical C3 convertase.
      • C3: Cleaved to form C3a (anaphylatoxin) and C3b (opsonin), also functions in forming alternative C3 convertase.
      • C4: Cleaved by either C1 or MASP-2 to form C4b fragment of classical C3 convertase.
      • C5: Cleaved by C3 convertase to form C5a (anaphylatoxin) and C5b (initiates formation of membrane-attack complex).
      • C6, C7, C8, C9: Involved in the formation of the Membrane-Attack Complex (MAC) which disrupts cell membranes.

    Microbial Surface Recognition

    • How does the complement system recognize foreign invaders?
      • Lectin pathway: Initiated by soluble carbohydrate-binding proteins like mannose-binding lectin (MBL) and ficolins.
      • Classical pathway: Initiated when complement component C1 (C1q, C1r and C1s) binds to microbial surface directly or binds to antibodies already bound to a pathogen.
      • Alternative pathway: Initiated by spontaneous hydrolysis and activation of C3, which can bind directly to microbial surface.

    C3 Convertase

    • What is the role of C3 convertase?
      • Cleaves C3 into C3a and C3b which leads to all the effector activities of the complement system.

    C3b: Opsonization and Activation

    • What is the importance of C3b?
      • Covalently attaches (complement fixation) to the pathogen surface.
      • Marks the pathogen for destruction (acts as an opsonin) by rendering pathogen more susceptible to phagocytosis.
      • The breakdown occurs through the reaction of enzyme C3 convertase.

    C3 and C5 Convertases of the Complement Pathways

    • C3 Convertase: Serves as a crucial point where the lectin, classical, and alternative pathways converge.
      • Classical C3 convertase: C4b2a
      • Alternative C3 convertase: C3bBb
    • C5 Convertase: Responsible for cleaving C5 to activate the formation of the Membrane Attack Complex.
      • Classical and lectin pathways: Forms C4b2a3b
      • Alternative pathway: Forms C3bBb3b

    The Lectin Pathway

    • What is the lectin pathway?
      • Initiated by soluble carbohydrate-binding proteins like mannose-binding lectin (MBL) and ficolins.
      • Recognizes particular carbohydrates on microbial surfaces.
      • Activates the pathway using MASPs (MBL-associated serine proteases) which trigger the cleavage of complement routines.

    The Classical Pathway

    • What is the classical pathway?
      • Initiated when complement component C1 (C1q, C1r and C1s) recognizes microbial surface directly or binds to antibodies already bound to a pathogen.

    The Alternative Pathway

    • What is the alternative pathway?
      • Initiated by spontaneous hydrolysis and activation of C3, which can bind directly to microbial surface.
      • Enhanced by properdin which stabilizes the C3bBb convertase.

    Complement Receptors

    • How does the complement system interact with cells?
      • Various complement receptors bind to complement proteins fixed on the surface of a pathogen.
      • These receptors allow for recognition and phagocytosis.
      • Macrophages express CR1, which binds to C3b, enhancing recognition and phagocytosis.

    Regulating Complement Activation

    • How is the complement system regulated?
      • Plasma proteins:
        • Factor H: Enhances the cleavage of C3b into iC3b by Factor I.
        • Properdin: (factor P) Stabilizes the C3bBb complex in the alternative pathway.
      • Membrane proteins:
        • DAF (decay-accelerating factor): Breaks down the alternative C3 convertase.
        • MCP (membrane cofactor protein): Binds to C3b and enhances its cleavage to inactive iC3b by factor I.

    Membrane-Attack Complex (MAC)

    • What is the MAC?
      • A complex of complement proteins (C5b, C6, C7, C8, and C9) that forms holes in bacterial and eukaryotic membranes, causing cell lysis.
      • C5b initiates the formation of the MAC.

    Anaphylatoxins: C3a and C5a

    • What are anaphylatoxins?
      • Molecules capable of activating an inflammatory response by triggering degranulation of cells. (e.g., mast cells, basophils)
      • C3a and C5a induce the release of histamine and other inflammatory mediators leading to increased vascular permeability, smooth muscle contraction, and chemotaxis of immune cells.

    Complement System Malfunctions

    • What happens when the complement system malfunctions?
      • Abnormal clearance of bacteria and fungi.
      • Hypersensitivity responses and autoimmune disorders.
      • Increased infection rate due to malfunction of MAC.

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    Lecture 4: The Complement System PDF

    Description

    Explore the intricacies of the Complement System, a crucial part of the innate immune response. This quiz covers its activation pathways, composition, and protein nomenclature, offering a comprehensive understanding of how this system combats pathogens. Test your knowledge of this essential immune component!

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