Complement System Overview
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Questions and Answers

What role does C5a play in the complement system?

  • It forms part of the MAC assembly complex.
  • It directly lyses bacterial cells.
  • It recruits and activates immune cells. (correct)
  • It binds to microbial cells for opsonization.

    • What mechanism allows the complement system to avoid attacking host cells?

  • Utilization of alternative pathways to target only pathogens.
  • Continuous secretion of C3b to tag foreign cells.
  • Production of antibodies against complement proteins.
  • Presence of specific receptors that inhibit the complement cascade. (correct)

    • What initiates the formation of the Membrane Attack Complex (MAC)?

  • C9 polymerizes into large clusters.
  • C5b binds to C6, C7, and C8. (correct)
  • C3b attaches to cell membranes.
  • C5a recruits C3 convertase to the membrane.

    • How does C3b contribute to the process of opsonization?

    <p>By covalently bonding to microbial cell surfaces. (B)</p> Signup and view all the answers

    What is a key outcome of the complement activation on bacterial membranes?

    <p>Leakage of cytosol and bacterial lysis. (C)</p> Signup and view all the answers

    Which component in the classical pathway begins the activation of complement?

    <p>C1 Complex (D)</p> Signup and view all the answers

    What is the result of C1s cleaving C4 in the classical pathway?

    <p>Formation of C4b and C2a (B)</p> Signup and view all the answers

    What initiates the lectin pathway of complement activation?

    <p>Mannose binding lectin (MBL) (D)</p> Signup and view all the answers

    In the alternative pathway, how is C3(H2O) activated?

    <p>By hydrolysis in blood (A)</p> Signup and view all the answers

    What complex forms the initial C3 convertase in the alternative pathway?

    <p>C3bBb (A)</p> Signup and view all the answers

    The formation of C5 convertase in the alternative pathway includes which components?

    <p>C3b, Bb, and an additional C3b (C)</p> Signup and view all the answers

    Which component does mannose binding lectin primarily bind to for initiation of the lectin pathway?

    <p>Repeating mannose residues (B)</p> Signup and view all the answers

    Which of the following statements is true regarding the roles of the complement system?

    <p>It assists in the lysis of foreign cells and triggers inflammation. (B)</p> Signup and view all the answers

    Flashcards

    C3b

    A molecule that covalently attaches to microbial cells via high reactive thioester bond.

    C5 convertase

    An enzyme complex (C4b2aC3b) that cleaves C5 into C5a and C5b.

    C5a

    A powerful anaphylatoxin that recruits and activates immune cells.

    MAC assembly

    The process where complement proteins (C5b6789) form a pore in the bacterial membrane.

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    Complement inhibitors

    Molecules like CD59 that prevent complement from attacking our own cells.

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    Complement System

    Part of the innate immune system found in blood plasma, produced in the liver.

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    Roles of Complement

    Killing foreign cells, tagging foreign material, and proinflammatory signaling.

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    Classical Pathway

    Complement pathway initiated by antibodies binding to antigens, involving C1 complex activation.

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    Lectin Pathway

    Complement pathway that begins with lectin binding to sugars on pathogens, also involves MASP activation.

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    Alternative Pathway

    Complement activation pathway starting without antibodies, initiated by hydrolyzed C3 in the blood.

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    Membrane Attack Complex (MAC)

    Final product of the complement system that forms pores in target cells, leading to cell lysis.

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    Study Notes

    Complement System Overview

    • Part of the innate immune system
    • Found in blood plasma
    • Produced in the liver

    Roles of Complement

    • Killing (lysis) of foreign cells
    • Tagging foreign material (opsonization)
    • Pro-inflammatory signalling and chemoattraction

    Complement Pathways

    • All pathways converge to form C3 convertase and the membrane attack complex (MAC)

    Classical Pathway

    • Initiated by antibody binding
    • C1 Complex: Composed of C1q, C1r, and C1s. C1q binds to the Fc region of antibodies.
    • Activation: Binding of two or more antibodies to antigen activates C1r and C1s. C1r cleaves C1s, which in turn cleaves C4 and C2.
    • C4b binds to the bacterial surface; C2a and C2b are formed.
    • C4b and C2a combine to form the classical C3 convertase (C4b2a).

    Lectin Pathway

    • Initiated by a lectin (e.g., mannose-binding lectin (MBL))
    • MBL binds to carbohydrates, specifically mannose, on the surface of bacteria and yeast.
    • MBL-associated serine protease (MASP) cleaves C4 and C2, forming the C3 convertase (C4b2a).

    Alternative Pathway

    • Does not require antibody or microbe to initiate
    • C3 is hydrolyzed to C3(H2O)
    • C3(H2O) binds to Factor B, then Factor D cleaves Factor B into Bb and Ba fragments.
    • C3bBb (initial convertase) binds to C3, forming C3bBbC3b (C3 convertase)
    • C3b covalently attaches to the microbial surface activating an amplification loop.

    Terminal Complement Pathway

    • Formation of C5 convertase:
      • From the alternative pathway: C3bBb and another C3b form C3bBbC3b (C5 convertase).
      • From the lectin/classical pathway: C4b2a and another C3b form C4b2aC3b (C5 convertase).
    • C5 cleavage: C5 convertase cleaves C5 into C5a and C5b.
    • C5a: A powerful anaphylatoxin that recruits and activates immune cells.
    • C5b: Initiates the membrane attack complex (MAC) formation.
    • MAC Assembly: C5b recruits C6, C7, C8, and multiple C9 molecules to form a transmembrane pore in the microbial membrane.
    • Bacterial Death: MAC forms pores in the microbial membrane, leading to leakage of cytoplasmic contents, bacterial lysis, and cell wall instability.

    Complement Function

    • Opsonization: C3b and C4b tag microbes, serving as opsonins for recognition by phagocytes.
    • Inflammation: Cleaved 'a' products (e.g., C3a, C4a, C5a) are anaphylatoxins that bind to receptors on immune cells, triggering inflammation (chemotaxis, vasodilation, increased vascular permeability).
    • Lysis: MAC formation leads to direct lysis of invading microbes.

    Complement Regulation

    • Preventing self-damage: Inhibitors prevent complement activation on host cells. Immune cells present complement regulatory proteins, preventing unintended damage to healthy tissue.
    • Example: CD59 on mammalian cells inhibits C5b-C8 complex formation, preventing C9 recruitment.
    • Consequences of deficiency: Individuals with terminal complement deficiencies are at increased risk of recurrent infections.

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    Description

    Explore the intricate details of the complement system, a crucial part of the innate immune response. This quiz covers complement pathways, roles such as opsonization and cell lysis, and the classical and lectin pathways. Test your understanding of how these processes function in immunity.

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