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Questions and Answers
What is the function of C1inh in the classical pathway?
What is the function of C1inh in the classical pathway?
What condition is associated with C1inh deficiency?
What condition is associated with C1inh deficiency?
Which of the following binds to C4b in regulating the classical pathway?
Which of the following binds to C4b in regulating the classical pathway?
Which of the following complexes represents the C3 convertase in the classical pathway?
Which of the following complexes represents the C3 convertase in the classical pathway?
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What role does Decay Accelerating Factor (DAF) play in the regulation of the classical pathway?
What role does Decay Accelerating Factor (DAF) play in the regulation of the classical pathway?
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What is the trigger for the classical pathway of complement activation?
What is the trigger for the classical pathway of complement activation?
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What initiates the alternative pathway of complement activation?
What initiates the alternative pathway of complement activation?
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Which pathway of complement activation is primarily associated with the innate immune response?
Which pathway of complement activation is primarily associated with the innate immune response?
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Which protein is involved in the cleavage of factor B in the alternative pathway?
Which protein is involved in the cleavage of factor B in the alternative pathway?
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What is the role of C1 in the classical pathway of complement activation?
What is the role of C1 in the classical pathway of complement activation?
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What is the end result of all three complement activation pathways?
What is the end result of all three complement activation pathways?
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What is the role of C3bBb in the alternative pathway?
What is the role of C3bBb in the alternative pathway?
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Which pathway involves the binding of mannan-binding lectin to pathogens?
Which pathway involves the binding of mannan-binding lectin to pathogens?
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The alternative pathway of complement activation primarily amplifies which pathways?
The alternative pathway of complement activation primarily amplifies which pathways?
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What is the main function of soluble regulatory proteins in complement activation?
What is the main function of soluble regulatory proteins in complement activation?
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Which component is NOT part of the C1 complex in the classical pathway?
Which component is NOT part of the C1 complex in the classical pathway?
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What is the primary function of the lectin pathway in the complement system?
What is the primary function of the lectin pathway in the complement system?
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What type of proteins are C1inh and similar regulators classified as?
What type of proteins are C1inh and similar regulators classified as?
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Which statement correctly describes the components involved in the complement activation process?
Which statement correctly describes the components involved in the complement activation process?
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During which step is regulation exerted in the classical pathway of complement activation?
During which step is regulation exerted in the classical pathway of complement activation?
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What is a direct consequence of C3b binding to host cell surfaces?
What is a direct consequence of C3b binding to host cell surfaces?
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What happens to C1 after it binds to an antibody?
What happens to C1 after it binds to an antibody?
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What is the role of C4b in the classical pathway?
What is the role of C4b in the classical pathway?
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Which complex is considered the C3 convertase of the classical pathway?
Which complex is considered the C3 convertase of the classical pathway?
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What initiates the formation of the Membrane Attack Complex (MAC)?
What initiates the formation of the Membrane Attack Complex (MAC)?
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How does C3b function in the complement pathway?
How does C3b function in the complement pathway?
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What is a characteristic feature of the MBL pathway?
What is a characteristic feature of the MBL pathway?
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Which factor is responsible for cleaving C4 in the MBL pathway?
Which factor is responsible for cleaving C4 in the MBL pathway?
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What initiates the alternative pathway of the complement system?
What initiates the alternative pathway of the complement system?
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What is the role of Factor I in the regulation of complement pathways?
What is the role of Factor I in the regulation of complement pathways?
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Which component is NOT a co-factor for Factor I in the inactivation of C3b?
Which component is NOT a co-factor for Factor I in the inactivation of C3b?
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Which protein prevents the formation of the membrane attack complex (MAC)?
Which protein prevents the formation of the membrane attack complex (MAC)?
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What happens to C3b when bound by Factor H, DAF, or CR1?
What happens to C3b when bound by Factor H, DAF, or CR1?
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C4b can be inactivated to generate which inactive products?
C4b can be inactivated to generate which inactive products?
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Which pathway is specifically inactivated by DAF, Factor H, or CR1?
Which pathway is specifically inactivated by DAF, Factor H, or CR1?
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Which statement about the complement activation pathways is correct?
Which statement about the complement activation pathways is correct?
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What does CD59 specifically inhibit?
What does CD59 specifically inhibit?
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Study Notes
Complement Activation Pathways
- Three pathways activate complement: classical, lectin, and alternative
- Classical pathway: antibody-antigen complexes (adaptive) and pentraxins activate
- Lectin pathway: mannan-binding lectin (MBL) binds carbohydrates on pathogens (innate)
- Alternative pathway: part of the innate immune response, amplifying the classical and MBL pathways
- Final steps converge to create the membrane attack complex (MAC) in all three pathways
Classical Pathway
- Activated by antibody-antigen (Ab:Ag) interactions (adaptive response, most commonly IgM and IgG)
- First step: C1 binds to antibody on the pathogen surface
- C1 has three subunits: C1q, C1r, and C1s (C1r(C1s)2)
- C1q binds to antibody, causing a conformational change
- This activates C1r, which cleaves C1s
- C1s cleaves C4 into C4b and C4a
- C4b binds covalently to the pathogen surface
- C4b binds C2, localizing it on the pathogen surface and allowing C1s to cleave it
- This forms C4b2a, the C3 convertase of the classical pathway
- C3 convertase hydrolyzes C3 molecules
- Some combine to form C5 convertase
Classical Pathway (continued)
- C3b component of C5 convertase binds C5, enabling C4b2a to cleave it
- C5b binds C6, initiating the formation of the membrane-attack complex (MAC)
- C5b then binds C7, C8, and multiple C9 molecules
- This forms the MAC, a pore in the membrane
- Ions and small molecules can freely pass through the pores
- This destabilizes the cell membrane, leading to osmotic instability, swelling, and cell lysis
MBL Pathway
- Antibody-independent, but proceeds like the classical pathway
- Uses C4 and C2
- MBL is present in low concentrations in plasma, increasing during acute-phase response
- MBL binds to mannose residues on pathogen surfaces
- This causes MASP-1 and MASP-2 activation
- MASP-2 cleaves another MASP-2 to generate an active protease
- MASP-2 cleaves plasma protein C4 to C4b, which binds to the pathogen surface
- C4b binds C2, making it susceptible to cleavage by MASP-2
- MASP-2 cleaves C2 to generate C2b, attaching to C4b to form C4b2b (C3 convertase)
- This activates C3, coating the pathogen with C3b
- C3 convertase is covalently bound to the pathogen surface
Alternative Pathway
- Antibody-independent, initiated by cell surface components foreign to the host (e.g., Gram-positive or Gram-negative bacteria)
- C3 spontaneously cleaves to C3b, fragment attaching to the foreign surface
- Factor B binds C3b
- Factor D cleaves Factor B, forming C3bBb (C3 convertase)
- C3bBb cleaves more C3 molecules, further coating the pathogen with C3b
Complement Regulation
- Control proteins regulate the three pathways
- Soluble proteins prevent excessive activation by circulating immune complexes or spontaneous activation
- Cell surface inhibitors protect host cells from complement-mediated attack
- C3b and C4b bind covalently to host cell surfaces
Regulation of the Classical and MBL Pathways
- C3 convertase (C4b2b) is targeted
- Soluble factors (C4BP), CR1 (CD35), and DAF (CD55) bind to C4b and displace C2b, inactivating the convertase.
- C4b bound to C4BP, membrane co-factor of proteolysis (MCP—CD46), or CR1, is cleaved by Factor I, generating inactive C4c and C4d
Regulation of Alternative Pathways
- C3 convertase (C3bBb) is targeted.
- Factor H, DAF, or CR1 inactivate C3bBb by binding C3b and displacing Bb
- In the presence of Factor H, CR1, or MCP, C3b is inactivated by Factor I (iC3b)
Regulation of All Pathways
- CD59 (protectin) prevents MAC formation by inhibiting C9 binding to C5b678 complex
- Inhibitors limit spontaneous activation and protect host cells
- Host cells express inhibitors DAF, MCP, and CD59 (membrane-bound)
- Other inhibitors are serum proteins
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Description
Explore the three critical pathways of complement activation: classical, lectin, and alternative. This quiz examines the mechanisms behind antibody-antigen interactions and the roles of various complement components in the immune response. Understand how these pathways converge to form the membrane attack complex (MAC).
