Term
| What are the four vital functions of the complement system? What are two important functions related to complement receptors? |
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Definition
1) Opsonization and phagocytosis
2) Stimulation of inflammatory reactions
- attract myeloid cells
- increased adhesion and activation of neutrophils
- mast cell degranulation (hypersensitivity)
3) Complement-mediated cytolysis
4) Clearance of immune complexes
Functions related to CRs:
1) B-cell activation (CR2)
2) Trapping of immune complexes in germinal centers
- FDCs have CR1, CR2, and CR3
- FDCs present antigen to B cells --> affinity maturation of B cells |
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Term
| What is the structural component of C1? |
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Definition
| C1 is a pentamolecular complex consisting of a single C1q, two C1r, and two C1s molecules. |
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Term
| Why can only antibodies bound to antigens and not free circulating antibodies initiate the classical pathway? |
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Definition
| C1q (the first complement in the pathway) must bind to two Ig heavy chains to be activated. Binding to an antigen forces the antibodies to be close together. |
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Term
| Along with the C1 complexes q, r and s, what else must be present to activate the C1 molecules? |
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Definition
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Term
| what are two examples of C5 convertase? |
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Definition
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Term
| What is a C3 convertase made of? |
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Definition
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Term
| What Beta-globulins are in the alternative pathway of complement activation and what do they do? |
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Definition
- C3: spontaneous hydrolysis allows it to bind and opsonize microbial membranes
- Factor B: cleaved by Factor D. Binds with C3b --> C3bBb (a C3 convertase)
- Factor D: a plasma serine protease that cleaves Factor B
- Properidin: stabilizes C3bBb complex on microbial surfaces |
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Term
| What complement causes histamine to release from mast cells? |
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Definition
| C3a (an anaphylatoxin) and also C5a |
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Term
| How does the membrane attack complex (C5b678Poly9) kill cells? |
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Definition
| It disrupts the cell membrane and allows free exchange of water and ions. The entry of water causes osmotic swelling and lysis. Entry of calcium can also induce apoptosis. |
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Term
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Definition
The spontaneous hydrolysis of C3 by water to C3b. C3b exposes the the thioester group which can covalently bind to to protein or polysaccharide on a microbial membrane.
If microbial membrane is not present, the unstable C3b will be inactivated to iC3b. |
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Term
| Describe how the lectin pathway of complement activation works. |
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Definition
| Mannose-binding lectin (MBL) binds to the mannose of microbial polysaccharides. MBL+mannose looks structurally like C1q --> rest of classical pathway from here. |
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Term
| For the type 1 complement receptor (CR1): What is the CD number associated with it? On what cells is it found? What is its function? |
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Definition
CD 35
Found on: Mononuclear phagocytes, neutrophils, B and T cells, RBCs, FDCs, eosinhopihls
Function:
- Promote phagocytosis of C3b- and C4b- coated particles
- Promote dissociation of C3 convertases by acting as cofactor for cleavage of C3b, C4b
- Clearance of immune complexes from circulation |
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Term
| For the type 2 complement receptor (CR2): What is the CD number associated with it? On what cells is it found? What is its function? |
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Definition
CD 21
Found on: B cells, FDCs
Function:
- Enhance B cell activation
- Trapping of antigens in germinal centers
- Receptor for Epstein-Barr Virus |
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Term
| For the type 3 complement receptor (CR3): What is the CD number associated with it? On what cells is it found? What is its function? |
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Definition
Mac-1 or CD11b/CD18
Found on: Mononuclear phagocytes (esp. monocytes), neutrophils, NK cells
Function:
- Phagocytosis of iC3b opsonized microbes
- Enhance leukocyte adhesion to endothelium (binds to ICAM-1)
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Term
| For the type 4 complement receptor (CR4): What is the CD number associated with it? On what cells is it found? What is its function? |
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Definition
CD11c/CD18
Found on: Mononuclear phagocytes (esp. dendritic cells), neutrophils, NK cells
Function:
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Term
| What protein inhibits the assembly of C3 and C5 convertases? How does it work? |
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Definition
Decay Accelerating Facor (DAF) and CR1
They displace C2b from C4b and Bb from C3b to prevent the formation of the convertases. |
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Term
| What proteins inhibit the formation of the MAC? How does it work? |
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Definition
CD59 and S-protein
CD59 prevents C9 from binding
S-protein binds to soluble C5b67 complexes and prevents them from inserting to cell membrane
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Term
| What proteins degrade C3b and C4b from cell surfaces? How do they work? |
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Definition
Factor 1 (with CR1 and Membrance Cofactor Protein, MCP as cofactors)
Factor 1 is a serine protease |
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Term
| What protein inhibits the proteolytic activity of C1r and C1s? How does it work? |
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Definition
C1 Inhibitor
Its a serine protease inhibitor, it binds to C1r and C1s and dissociates them from C1q |
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Term
| Rank the potency of complement proteolytic fragments C3a, C4a, and C5a. |
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Definition
C5a > C3a > C4a
C3a and C5a are anaphylatoxins. |
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Term
| What is the most common complement defiency? And what does it cause? |
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Definition
| C2 deficiency - causes SLE (lupus), dermatomyositis, vasculitis, schonlein-henoch purpura, inflammator bowel disease, glomerulonephritis, juvenile rheumatoid arthitis |
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Term
| Deficiency of what complements/factors can cause increased gram+ bacterial infections? |
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Definition
| C3, Properdin, Factor D deficiency |
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Term
| Deficiency of what complementscan cause increased Neisseria bacterial infections? |
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Definition
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