Podcast
Questions and Answers
What role does C5a primarily play in the immune response?
What role does C5a primarily play in the immune response?
Which component is directly responsible for forming the membrane attack complex (MAC)?
Which component is directly responsible for forming the membrane attack complex (MAC)?
How does C3b contribute to the immune response?
How does C3b contribute to the immune response?
What is a consequence of the action of the membrane attack complex (MAC) on bacteria?
What is a consequence of the action of the membrane attack complex (MAC) on bacteria?
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What mechanism prevents the complement system from damaging host cells?
What mechanism prevents the complement system from damaging host cells?
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What is one of the main functions of the complement system?
What is one of the main functions of the complement system?
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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 proteases are part of the C1 complex in the classical pathway?
Which proteases are part of the C1 complex in the classical pathway?
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What is the outcome of the hydrolysis of C3 in the alternative pathway?
What is the outcome of the hydrolysis of C3 in the alternative pathway?
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Which component is necessary to form C4bC2a in both the classical and lectin pathways?
Which component is necessary to form C4bC2a in both the classical and lectin pathways?
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Which factor does not need an antibody to initiate the alternative pathway?
Which factor does not need an antibody to initiate the alternative pathway?
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What forms the C5 convertase in the terminal complement pathway from the alternative pathway?
What forms the C5 convertase in the terminal complement pathway from the alternative pathway?
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What is the role of C1r in the classical pathway?
What is the role of C1r in the classical pathway?
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Study Notes
Complement System Basics
- Part of the innate immune system
- Found in blood plasma
- Produced in the liver
Roles of Complement
- Killing (lysis) of foreign cells: Forms pores in bacterial membranes causing cell death and leakage.
- Tagging foreign material (opsonization): Marks foreign cells for phagocytosis by immune cells. C3b and C4b are opsonins.
- Pro-inflammatory signaling and chemoattraction: Triggers inflammation by attracting immune cells to the site of infection. C3a and C5a are anaphylatoxins.
Complement Pathways
- Classical, Lectin, and Alternative pathways all converge to form a C3 convertase which activates the terminal pathway.
- All pathways lead to membrane attack complex (MAC) formation.
Classical Pathway
- Initiated by antibodies bound to pathogens. (antibodies first in the process!)
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C1 complex: C1q (hexamer), C1r, and C1s. Six globular heads of C1q bind to Fc regions of antibodies.
- Activation: 2 antibodies binding-> activation of C1r and C1s.
- Cleavage: C1r cleaves C1s, which then cleaves C4 into C4a and C4b, and C2 into C2a and C2b.
- C4b binds to bacterial surface; C2a and C2b bind with C4b to form C4b2a (classical C3 convertase).
- Can also bind directly to bacterial surfaces like lipoteichoic acids.
Lectin Pathway
- Initiated by lectins binding to carbohydrates on pathogens. (lectins bind to pathogen carbohydrates!)
- Mannose-binding lectin (MBL): Produced by the liver, especially during inflammation. Binds to repeating mannose sugars on bacterial and fungal surfaces. (MBL bind to bacteria!)
- MBL-associated serine protease (MASP): Cleaves C2 and C4, ultimately forming C4b2a -- the C3 convertase. (C3 convertase is formed also in this pathway!)
Alternative Pathway
- Does not require antibodies or microbes. (starts without an antibody)
- C3 hydrolysis: C3 in the blood spontaneously hydrolyzes to C3(H2O).
- Factor B and Factor D: C3(H2O) binds to Factor B; Factor D cleaves Factor B into Bb and Ba.
- C3 convertase formation: C3(H2O)Bb (initial C3 convertase) binds C3b; Factor D cleaves Factor B in C3bB complex. This results in C3bBb, the C3 convertase. (final form of C3 convertase!)
- Amplification loop: C3b bound to microbial surfaces forms C3 convertase, initiating an amplification loop.
Terminal Complement Pathway
- C5 convertase formation: C3 convertase (from any pathway) binds another C3b to form the C5 convertase.
- C5 cleavage: Cleaves C5 into C5a (anaphylatoxin, pro-inflammatory, recruits immune cells) and C5b (initiates MAC formation).
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MAC assembly: C5b recruits C6, C7, C8, and multiple C9 molecules to form a membrane pore in the pathogen's membrane.
- Bacterial death: MAC formation creates holes in bacterial membranes, causing cell lysis.
Complement Function
- Opsonization: Tags microbes for phagocytosis.
- Inflammation: C3a and C5a are anaphylatoxins that attract and activate immune cells.
- Lysis: Forms MAC to directly kill many types of bacteria.
Avoiding Complement Activation on Self-Cells
- Self-cells express inhibitors (e.g., CD59) to prevent MAC formation.
Implications of Complement Deficiencies
- Individuals with deficiencies in terminal complement components are at increased risk of recurrent infections.
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Description
Test your knowledge on the complement system in immunology. This quiz covers essential components such as C5a, C3b, and the membrane attack complex (MAC), along with their roles in the immune response. Dive into the mechanisms that prevent damage to host cells while understanding the implications for bacterial infections.
