Ch. 6 Complement Flashcards
What is the full name of C3 convertase for the classical pathway?
C4b2a
What is the full name of C5 convertase for the classical pathway?
C4b2a3b
How is the classical pathway initiated?
by antibody binding (IgM or IgG)
How is the lectin pathway initiated?
lectin binds to microbial surfaces
How is the alternative tickover pathway inititated?
when C3 undergoes spontaneous hydrolytic cleavage in serum
What does the CR1 (CD35) receptor bind and what is the outcome?
- RBCs with Cr1 bind complexes and take them to the liver
- removal of C3b-opsonized immune complexes by liver
- neutrophil phagocytosis
What does the CR2 (CD21) receptor bind and what is the outcome?
Binds C3b breakdown products
-promotes uptake of antigens by B cells and FDCs; ehancement of B cell activation and B cell coreceptor
What does the CR3 (CD11b with CD18) do?
promotes phagocytosis and extravasation
What does the C3aR/C5aR do?
- stimulates release of proinflammatory cytokines and granule components form basophils, eosinophils, neutrophils;
- induce acute phase response protein synthesis in liver
- induced neutrophil respiratory burst
What are the three ways complement enhances host defenses against infection?
- MAC-induced cell death
- Promotion of Inflammation
- Promotion of opsonization
Which anaphylatoxins bind to receptors on granulocytes, mast cells, and endothelial cells and trigger cascades that secrete IL-6 and TNF-a?
C3a, C4a, C5a
What are three separate ways that complement promotes opsonization/phagocytosis?
a. Opsonized microbes easier to ingest/destroy
b. Apoptotic cells express the phospholipid phosphatidyl serine and fragmented DNA on their surface, which binds C1q
c. Opsonized immune complexes easier to clear
i. C3b binds to CR1 on erythrocytes and is carried to the liver and spleen
What are two ways that complement is passively regulated?
- protein stability
- cell-surface composition
Protein stability regulation
ex. short half-life of C3 convertase unless stabilized by properdin
Cell-surface composition regulation
i. Self cells possess different carbohydrate structures (sialic acid) that are more effectively bound by fluid-phase proteases that destroy C3b
1. These more readily inactivate C3b through hydrolysis, protecting self cells
C1INH: Membrane bound or soluble? How it regulates complement?
o Serine protease inhibitor (serpin) by binding to and poisoning proteases
o Promotes dissociation of C1 complex by inhibiting proteases C1r and C1s
o MASP-2 of lectin pathway
DAF: Membrane bound or soluble? How it regulates complement?
o Decay accelerating factor promote decay of C3 convertases
Membrane bound
CR1: membrane bound or soluble?
membrane bound
C4BP
o Soluble components that bind sialic acid/ heparin/heparan sulfate present on the surface of our cells
Factor H
o Soluble components that bind sialic acid/heparin/heparan sulfate present on the surface of our cells
Factor I
soluble, constitutively active serine protease that cleaves membrane-associated C3b & C4b into inactive fragments
o Decay of C3 convertase leads to C3b and C4b left behind, which are still catalytically active
o Activity is controlled by the presence of decay factors or Membrane Cofactor of Proteolysis (MCP)
Protectin
inhibits the MAC attack
o Binds C5b678 complexes deposited on host cells
Prevents their insertion into the plasma membrane
Also blocks C9 recruitment, preventing MAC formation
Vitronectin
o Soluble protein that binds fluid phase C5b67 to prevent insertion into host cell plasma membranes
Carboxypeptidase N,B, and R
inactivate the anaphylatoxins C3a and C5a
Carboxypeptidases = enzymes that remove amino acids from the carboxyl end of peptides
Enzymes remove arginine residues from the C termini of C3a & C5a
Makes them inactive (des-Arg forms, “without Arginine”)
Helps to shut down unnecessary or dangerous chemotaxis & inflammation induction
