Complement System Overview
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Questions and Answers

Which of the following complement proteins is synthesized by mast cells?

  • C4
  • C3
  • C1q (correct)
  • C6

    • What is the approximate serum concentration of C3 in humans?

  • 480 µg/mL
  • 20 µg/mL
  • 1300 µg/mL (correct)
  • 600 µg/mL

    • Which component of the complement system has a molecular weight of 24 kDa?

  • FD (correct)
  • C1q
  • C3
  • C2

    • What critical feature does C3 possess that allows it to bind to microbes?

    <p>A reactive thioester side-chain</p> Signup and view all the answers

    Which complement pathway is described as an 'evolutionarily ancient innate pathway'?

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

    How does C3 get activated in healthy normal animals?

    <p>Through spontaneous breakdown into C3a and C3b</p> Signup and view all the answers

    Which of the following statements is true regarding complement proteins?

    <p>Complement proteins account for 5% to 10% of total blood serum proteins.</p> Signup and view all the answers

    What is the function of the thioester group in C3 during the activation process?

    <p>To prevent unwanted binding to normal cells</p> Signup and view all the answers

    What is the effect of factor P (FP or properdin) on the C3 convertase complex?

    <p>It forms a stable C3bBbP complex, increasing its half-life.</p> Signup and view all the answers

    Which pathway accounts for 80% to 90% of complement activation?

    <p>The alternative complement pathway</p> Signup and view all the answers

    Which protease is activated by mannose-binding lectin (MBL) after it binds to microbial carbohydrates?

    <p>MASP-2</p> Signup and view all the answers

    What does the lectin pathway primarily react to?

    <p>Bacterial PAMPs</p> Signup and view all the answers

    What component is formed when MBL activates MASP-2, cleaving C4?

    <p>C4a and C4b</p> Signup and view all the answers

    Which component binds to C4b to form the C4b2 complex?

    <p>C2</p> Signup and view all the answers

    What is the characteristic feature of the family of proteins known as defense collagens?

    <p>Collagen-like region and carbohydrate recognition domain</p> Signup and view all the answers

    What is the half-life of the unstable C3 convertase complex C3bBb?

    <p>5 minutes</p> Signup and view all the answers

    What is required to activate C1 in the classical complement pathway?

    <p>Paired antigen-bound molecules of IgM</p> Signup and view all the answers

    What is the role of C1s after it is activated?

    <p>To cleave C4 into C4a and C4b</p> Signup and view all the answers

    What complex is formed when C4b binds to C2?

    <p>C4b2 complex</p> Signup and view all the answers

    What potential outcome can result from blocked inhibitory processes of complement activation?

    <p>Uncontrolled complement activation leading to inflammation</p> Signup and view all the answers

    What is formed after C5 is cleaved by the C3bBb convertase?

    <p>C5a and C5b complex</p> Signup and view all the answers

    What role does the C5b67 complex play in the complement pathway?

    <p>It inserts into the microbial cell wall</p> Signup and view all the answers

    Which of the following peptides bind to C5 after C3b is involved?

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

    What type of cells can C1q bind to directly, aside from immune complexes?

    <p>Apoptotic and necrotic cells</p> Signup and view all the answers

    What is the primary role of the complement system in the immune response?

    <p>To kill pathogens immediately upon their entry into the body.</p> Signup and view all the answers

    How does the complement system get activated?

    <p>Through the binding of pathogen-associated molecular patterns or antibodies.</p> Signup and view all the answers

    Which pathways are involved in the activation of the complement system?

    <p>Alternative, lectin, and classical pathways.</p> Signup and view all the answers

    What role does the complement system play in inflammation regulation?

    <p>It regulates inflammation as part of its defense role.</p> Signup and view all the answers

    Which complement pathways are classified as innate immunity responses?

    <p>The alternative and lectin pathways.</p> Signup and view all the answers

    What could happen if the complement system is not properly regulated?

    <p>Increased risk of inflammation or autoimmunity.</p> Signup and view all the answers

    Which statement correctly describes the relationship between the classical pathway of the complement system and antibodies?

    <p>The classical pathway is triggered by antigen-bound antibodies.</p> Signup and view all the answers

    What additional function does the complement system provide beyond pathogen elimination?

    <p>It aids in tissue regeneration and lipid metabolism.</p> Signup and view all the answers

    What is the role of the terminal complement complex (TCC) in microbial cell membranes?

    <p>It inserts into membranes and creates pores for osmotic lysis.</p> Signup and view all the answers

    What triggers the inflammatory response associated with complement activation?

    <p>The release of small peptides such as C5a.</p> Signup and view all the answers

    Which of the following statements about C5a is correct?

    <p>It activates mast cells to degranulate and release histamine.</p> Signup and view all the answers

    Which complement peptide is known to disrupt bacterial membranes and kill bacteria?

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

    What is the significance of the structure observed in TCC through electron microscopy?

    <p>It represents the poly C9 formation on microbial surfaces.</p> Signup and view all the answers

    How does substrate modulation affect the complement system?

    <p>It allows proteases to cleave factors only when proteins are bound.</p> Signup and view all the answers

    What are anaphylatoxins and which peptides are classified as such?

    <p>Peptides that can cause anaphylaxis at high levels; C3a, C5a</p> Signup and view all the answers

    What is the function of the C5b678 complex?

    <p>It polymerizes C9 to form components of the TCC.</p> Signup and view all the answers

    Study Notes

    Complement System

    • The complement system is a series of proteins that work together to kill pathogens.
    • It is a key component of the innate immune system and can kill pathogens quickly.
    • Complement is a network of proteins, proteases, serum proteins, receptors, and regulators that all work together.
    • It is activated by the presence of either pathogen-associated molecular patterns (PAMPs) or by antigen-bound antibodies.
    • The system is tightly regulated and disturbances can result in inflammation or autoimmunity.

    Functions of the Complement System

    • The complement system has many functions including:
      • killing pathogens
      • alerting the immune system to invaders
      • regulating inflammation
      • removing damaged or altered cells
      • regulating adaptive immune responses
      • clearing antigen-antibody complexes
      • blood vessel formation
      • mobilization of stem cells
      • tissue regeneration
      • lipid metabolism

    Complement Activation Pathways

    • There are three main pathways for complement activation:
      • Alternative Pathway
        • activated by microbial cell walls
        • triggered by C3, the most abundant complement component in serum
        • C3 spontaneously breaks down into C3a and C3b
        • C3b binds to microbes and marks them for destruction
      • Lectin Pathway
        • activated by the binding of soluble pattern-recognition molecules (lectins) to microbial carbohydrates
        • triggered by the presence of bacterial PAMPs
        • lectins bind to microbes and activate proteases that activate complement
        • mannose-binding lectin (MBL) and ficolins are the main lectins
      • Classical Pathway
        • activated by antibodies
        • is an adaptive pathway
        • triggered by antigen-bound IgM or paired, antigen-bound IgG molecules
        • C1 binds to antibody and is then activated, cleaving C4 into C4a and C4b
        • C2 binds to C4b, creating a complex that acts as a protease to cleave C3

    Amplification Pathway

    • All surface-bound C3 convertases (from the alternative, lectin, or classical pathway) can trigger the amplification pathway.
    • C5 binds to C3b and is then cleaved by C3bBb.
    • This generates C5b that can bind to C6 and C7, forming a complex that inserts into the microbial cell wall.
    • C8 then binds, followed by polymerization of 12-18 C9 molecules to form the terminal complement complex (TCC).
    • The TCC forms a pore in the microbial cell membrane, causing osmotic lysis.

    Complement Proteins

    • Complement proteins are either labeled numerically (e.g., C1, C2, C3) or designated as "factors" by letters of the alphabet (FB, FD, FP, etc.).
    • They account for 5% to 10% of the proteins in blood serum.
    • Their size varies from 24 kDa for factor D (FD) to 460 kDa for C1q.
    • Complement proteins are synthesized at multiple sites, including the liver, macrophages, and mast cells.

    Substrate Modulation

    • Substrate modulation is one way that the complement system is regulated.
    • A target for a protease cannot be cleaved unless it is first bound to another protein.
    • Examples include the cleavage of factors C2, B, and C5 only after they have bound to C4, C3, and C3, respectively.

    Biological Consequences of Complement Activation

    • C5a, a small released peptide, has potent inflammatory effects.
      • It can degranulate mast cells and stimulate platelets to release histamine and serotonin.
      • It attracts neutrophils and macrophages.
      • It increases vascular permeability.
    • C3a can kill bacteria by disrupting cell membranes.

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    Complement System: Innate Defense Mechanisms PDF

    Description

    Explore the essential functions and activation pathways of the complement system, a crucial component of the innate immune response. This quiz examines the roles and regulation of complement proteins in pathogen elimination and immune system alertness. Test your knowledge on how this network of proteins contributes to various immune functions.

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