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What is the complement system?
A part of the immune system comprising 30 soluble and membrane-bound proteins that act in innate and adaptive immunity.
Where are complement proteins synthesized?
In the liver.
How is the complement system activated?
By three pathways: classical, lectin, and alternative.
What triggers the classical pathway?
Antigen-antibody complexes involving IgG or IgM.
How is the lectin pathway activated?
By mannose-binding lectin (MBL) binding to terminal mannose residues on microbial surfaces.
What activates the alternative pathway?
Direct contact with microbial surfaces and C3b deposition.
What is the key enzyme in complement activation?
C3 convertase, which cleaves C3 into C3a and C3b.
What is the function of C5 convertase?
It cleaves C5 into C5a and C5b, initiating the formation of the membrane attack complex (MAC).
What is opsonization?
The process of marking pathogens for phagocytosis by binding opsonins like C3b.
What are anaphylatoxins, and give examples.
Small peptides (C3a, C4a, and C5a) that induce inflammation and attract immune cells.
What is the membrane attack complex (MAC)?
A structure formed by C5b, C6, C7, C8, and multiple C9 proteins that causes cell lysis.
What are the initial components of the classical pathway?
C1 (C1q, C1r, C1s), C2, C3, and C4.
Which immunoglobulin classes activate C1 in the classical pathway?
IgM and IgG (IgG3 > IgG1 > IgG2; IgG4 does not bind).
What is the role of C4b2a in the classical pathway?
It functions as a C3 convertase.
Which components are unique to the alternative pathway?
Factors B, D, and properdin (factor P).
How does properdin stabilize the alternative pathway?
By binding to C3bBb, prolonging its activity.
What is the amplification loop in the alternative pathway?
The continuous activation of C3 by C3bBb to generate more C3b.
What activates the lectin pathway?
MBL binding to mannose residues on bacteria and fungi.
What is MASP, and what is its role?
MBL-associated serine protease (MASP) cleaves C4 and C2 to form C3 convertase.
How does complement enhance B cell responses?
By interacting with complement receptors on B cells to amplify antibody production.
What is the role of complement in removing immune complexes?
It clears complexes from circulation to prevent tissue deposition and inflammation.
How does complement aid in removing necrotic cells?
By tagging damaged cells for clearance by phagocytes.
Why is complement regulation important?
To prevent uncontrolled activation and damage to host tissues.
Name a regulatory protein of the complement system.
Decay-accelerating factor (DAF), which disrupts C3 convertase formation.
What happens in complement deficiency?
Increased susceptibility to infections and autoimmune diseases like systemic lupus erythematosus (SLE).
What diseases are associated with complement deficiencies?
Pyogenic infections, glomerulonephritis, and recurrent bacterial infections.
What role does complement play in sepsis?
Overactivation can lead to excessive inflammation and tissue damage.
What are the three main outcomes of complement activation?
Opsonization, inflammation, and pathogen lysis.
What is the convergence point of all complement pathways?
The cleavage of C3 to form C3a and C3b.
What is the final step of complement activation?
Formation of the membrane attack complex (MAC) leading to cell lysis.
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