Podcast
Questions and Answers
What is the primary function of Properdin (Factor P) in the complement system?
What is the primary function of Properdin (Factor P) in the complement system?
Which factor is primarily responsible for cleaving Factor B in the complement system?
Which factor is primarily responsible for cleaving Factor B in the complement system?
What is the role of the Membrane Attack Complex (MAC) in the immune response?
What is the role of the Membrane Attack Complex (MAC) in the immune response?
What can happen as a result of deficiencies in complement proteins?
What can happen as a result of deficiencies in complement proteins?
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Which factors are involved in regulating the complement system?
Which factors are involved in regulating the complement system?
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How does overactivation of the complement system affect health?
How does overactivation of the complement system affect health?
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In what ways can complement activation contribute to diseases?
In what ways can complement activation contribute to diseases?
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What role can inhibition of complement activity play in medical treatment?
What role can inhibition of complement activity play in medical treatment?
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What initiates the classical pathway of the complement system?
What initiates the classical pathway of the complement system?
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Which complement protein is central to all three activation pathways?
Which complement protein is central to all three activation pathways?
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The alternative pathway is primarily triggered by which of the following?
The alternative pathway is primarily triggered by which of the following?
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What is the role of C5 in the complement system?
What is the role of C5 in the complement system?
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Which statement about the lectin pathway is true?
Which statement about the lectin pathway is true?
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What does C9 do in the context of the complement system?
What does C9 do in the context of the complement system?
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Which of the following statements about the complement system is incorrect?
Which of the following statements about the complement system is incorrect?
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Which complement protein is involved in the formation of C3 convertase in both the classical and lectin pathways?
Which complement protein is involved in the formation of C3 convertase in both the classical and lectin pathways?
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Study Notes
Introduction to the Complement Pathway
- The complement system is part of the innate immune system.
- It's a complex cascade of proteins that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body.
- It plays a vital role in both inflammation and immune defense.
- The complement system is activated by three major pathways: the classical pathway, the lectin pathway, and the alternative pathway.
Classical Pathway
- Activation is triggered by the binding of antibody (IgG or IgM) to antigens on the surface of a pathogen.
- This binding forms an antigen-antibody complex, acting as a platform for complement protein C1q to bind.
- C1q binding activates a cascade of reactions involving C1r, C1s, and subsequent complement proteins, ultimately leading to the formation of the membrane attack complex (MAC).
- This pathway is antibody-dependent and part of the adaptive immune response.
Lectin Pathway
- Activation is initiated by the binding of mannose-binding lectin (MBL) or ficolins to carbohydrates on the surface of microorganisms.
- MBL or ficolins are pattern recognition molecules, constitutively present in blood and mucus.
- The binding of MBL/ficolin activates a cascade of reactions similar to the classical pathway, resulting in the formation of the MAC.
- This pathway is antibody-independent but part of the innate immune response.
Alternative Pathway
- Activation occurs spontaneously, in the absence of antibodies or previous immune responses, against a microbe or pathogen.
- It's activated by the hydrolysis of C3 to C3(H2O), which then binds to factors B, D, and P.
- The formation of a C3 convertase, C3bBb, amplifies the cascade and leads to the formation of the MAC.
- This pathway is primarily triggered by microbial surfaces or pathogen-associated molecular patterns (PAMPs).
Key Complement Proteins and their Functions
- C3: A crucial component, the 'central hub' of the complement system, cleaved in all three pathways.
- C4: Involved in both the classical and lectin pathways, contributing to C3 convertase formation.
- C5: Key component in the formation of the membrane attack complex (MAC).
- C9: Polymerizes to form the MAC, a pore-forming complex disrupting target cell membranes, causing lysis.
- Factor B: Crucial for alternative pathway C3 convertase formation.
- Factor D: An enzyme that cleaves Factor B.
- Properdin (Factor P): Stabilizes the alternative pathway C3 convertase, leading to MAC formation.
Membrane Attack Complex (MAC)
- The MAC is a complex of complement proteins that inserts into target cell membranes (primarily pathogens).
- The MAC forms a transmembrane pore, disrupting membrane integrity and causing cell lysis.
- Its formation is a critical effector function, helping eliminate foreign invaders.
Regulation of the Complement System
- Tight regulation is essential to prevent host tissue damage.
- Regulatory proteins limit activation to specific target cells.
- These proteins interfere with convertase formation or accelerate component degradation.
- Examples include Factor H, Factor I, and decay-accelerating factor (DAF).
Clinical Significance
- Complement deficiencies increase infection susceptibility.
- Overactivation damages host tissues, contributing to autoimmune diseases and inflammatory disorders.
- Complement activation is implicated in systemic lupus erythematosus, rheumatoid arthritis, and glomerulonephritis.
- Drugs inhibiting complement activation are being developed for inflammatory diseases.
Complement and Disease
- Complement component deficiencies lead to recurrent infections.
- Complement activation contributes to tissue damage in autoimmune disorders.
- Complement activation contributes to inflammatory responses, damaging healthy tissues during hypersensitivity reactions.
- Complement may play a role in cancer development.
- Complement inhibition holds therapeutic potential.
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Description
Explore the intricacies of the complement system, a pivotal aspect of the innate immune response. This quiz delves into the three major activation pathways: classical, lectin, and alternative, and their roles in enhancing immune defense mechanisms. Test your knowledge of the complement proteins and their importance in inflammation and pathogen clearance.
