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15 Cards in this Set
- Front
- Back
Complement System
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- set of 9 blood proteins that enhance function of both adaptive and innate responses of infection
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Antimicrobial Properties of Complement Proteins
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1. Opsonization (C3b)
2. Lysis of bacteria (forms pore on bacterial membrane) 3. Amplification of inflammatory responses (anaphylatoxins C5a and C3a --> incr vasc permeability, chemotaxis, attract --phils) |
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Classic Pathway
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1. C1 recognizes Ag-AB (with IgM and IgG) complex thru Fc and binds to it
2. This Ag-Ab + C1 complex cleaves C4+C2 complex = C3 convertase (C4b24b) C3a (C4a and C2a) are released as anaphylatoxins 3. This C3 convertase complex binds to cell membrane and cleaves C3 into C3a and C3b 4. C3 convertase splits many C3 mcls --> amplification 5. C3b + C3 convertase bound to cell membrane (C4bC2b)= C4b3b2b (C5 convertase) 6. C5 convertase then splits C5 into C5a and C5b fragments 7. C6, C7, C8, and C9 then attach = C5-C9 membrane attack complex --> C5bC6C7C8 + many C9s 8. Bacteria lyses/disentigrates |
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Anaphylatoxins: what do they do and what are they?
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C3a and C5a:
- incr permeability: leaky capillaries - induce muscle contraction (degranulation) - induce mast cells to release histamine (allergic rxn, kills parasites) - chemotaxis of neutrophils and monocytes out of capillaries into tissues C3b is also an opsonin, so enhances phagocytosis bc phag cells have receptor for it |
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Complement Pathway
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- NO AB COMPLEX REQUIRED
1. In presence of LPS, peptidoglycan, techoic acid- C3 is hydrolysized 2. C3b on surface of bacterial cells is recognized by Factor B 3. Factpr D cleaves Factor B = C3bBb, release of Ba 4. C3bBb is recognized by Properdin, which stimulates C3 convertase (C3bBbP) 5. C3 convertase cleaves and activates many C3 mcls --> amplification and C5 convertase 6. C3bBbP3b (extra 3b from addition of another activated C3b) 7. C5-C9 form MAC 8. Cell lysis and bursts |
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C3 and C5 Convertase For Classic and Alternative
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Classic:
C3: C4b2b C5: C4b2b3b Alternative: C3:C3BbP C5: C3bBbP3b |
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How are bacteria killed by complement/MAC?
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MAC forms a pore on bacterial cell membrane
K+ and Cl- flow out H2O and Na+ flow in Cell lysis |
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Defensins: what and who has?
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small cyesteine rich proteins found in inverts and verts
active vs. bact, fungi, and env and non enveloped viruses cells in immune system have these peptides to aid in killing phagocytosed bact (ex. in neutrophils and almost all epithelial cells) bind to microbial cell membrane and form pore like membrane defects that llow efflux of essential nutrients PORE: LEAK AND LYSE |
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Defensins: main function?
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penetrate bacterial cell membrane and lyse bact cells
forms pore like structure allowing efflux of K and Cl and influx of Na and water |
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chemokines
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low molec weight proteins that stimulate leukocyte (WBC) movement/chemotaxis
blood --> tissue |
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cytokines
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proteins that act thru specific receptors
regulate and activate immune responses |
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cytokines important for inflammation
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IL-1 : induces fever --> hypothalamus, incr T --> most pathogens cannot multiply well, but immune cells can
TNF: tumor necrosis factor alpha |
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Inflammation and Heart Disease
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incr. of C reactive protein in response to inflammation
activates complement chain |
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Coronary Heart Disease
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most common disease of heart
characterized by hardening and narrowing of coronary arteries due to plaque build up = artherosclerosis plaque: cholesterol and other lipids blood flow and oxygen supply to heart can be reduced or even fully blocked with growing plaque plaques may rupture and cause clots that block arteries |
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Process of artherosclerosis
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oxidized LDL binds to endothelial cell, lining and damaging vessel walls
macrophages engulf but cannot breakdown -->full and lyse |