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15 Cards in this Set
- Front
- Back
What is classical pathway of complement?
What is alternative pathway of complement? |
classical--initiated when immunoglobin binds to antigen.
alternative--"always" on. pre-existing-->eliminates certain groups of pathogens. |
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What are the main components of the classical pathway?
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-C1(q,r,s)
-C2-C9 |
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What is structure and role of C1q?
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Role--
Molecule binds IgG-->Fc of IgG undergoes conformational change, increasing affinity for binding C1q-->C1q undergoes conformational change-->causes C1r to self-cleave and activate-->C1r cleaves/activates C1s Structure-- 18 subunits--can bind 6 molecules of IgG! 6 globular proteins connected by fibers of a triple helix. C1q is part of C1 complex, which is: C1q, C1r (2), C1s(2), and Ca+. |
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What is mechanism of classical pathway?
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Pathogen cell enters-->IgG binds "site 1" on pathogenic cell-->C1 complex binds IgG (C1q of C1 binds Ch2 on IgG)-->C1q undergoes conformational change-->C1r cleaves/activates itself-->C1r cleaves/activates C1s-->C1s cleaves C4 and C2-->C4b, C2a form C4,2 complex (one C1s--form lots of C4,2 complexes--"amplification")-->C4, 2 complex binds to "site 2" on pathogenic cell-->C4,2 cleaves C3 into C3a and C3b fragments-->One C3b binds to cell surface, another binds to C4,2 complex-->forms C4,2,3 complex-->new complex is specific for C5-->cleaves C5 into C5a and C5b fragments-->C5b, C6-C9 get together and form MAC (C6-C9 have post-trans modification--mannose cov. bound to tryptophan)-->MAC binds to "site 3" on path. cell-->MAC opens channels on path cell-->kills cell by lysis!
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What are the main components of the alternative pathway?
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-C3-C9
-B,D,H,I,P |
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What is mechanism of alternative pathway?
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i. C3 reacts with water to make C3—H2O.
ii. C3—H2O complexes with B and D to make C3 convertase. D is activated and becomes an active proteolytic enzyme. iii. C3 convertase cleaves C3 to make C3a and C3b. C3b can either not bind to a surface, bind to a non-activating surface, or bind to an activating surface. 1. C3b can react with water and be inactivated by H and I. 2. C3b can bind to a non-activating surface and be inactivated by H and I. 3. C3b can bind to a pathogenic surface and allow the alternative pathway to continue. iv. C3b bound to a pathogenic surface acquires a site specific for factor B. D joins the complex to activate B. B’s activation launches the alternative pathway. v. Bb binds to C3b to form the C3b-Bb complex, which is specific for C3. vi. C3b-Bb activates C3. vii. The newly formed C3b can bind to a surface for immune adherence or bind to C3b-Bb to form the C3bn-Bb complex, which is specific for C5. viii. P joins the unstable C3bn-Bb complex to form the stable C3bn-P-Bb complex, which cleaves C5. ix. The rest of the alternative pathway follows just as the classical pathway does. |
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Know the role of proteolysis in the complement pathway
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. Proteolysis is required at every step in the both the classical and alternative pathways. Cleaved proteins become active and in turn activate the next proteins in the cascade.
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What are the roles of C3b, C3a, and C5a in classical pathway?
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C3b--"immune adherence"-- binds to pathogen cell AND receptors on leukocytes/macrophages-->pathogenic cell phagocytized!
C3a (4a, 5a)--"anaphylatoxins"--increase vasc. permeability, smooth muscle contraction, and his release. C5a--"anaphylatoxin"--also, a "chemotactic factor"-->induces migration of leukocytes to infection. -->makes a "cloud" around the bacteria--directs WBC's to site. |
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What is the role of the thioester in complement in classical pathway?
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-Thioester is post-translational modification--links cysteine and glutamine.
-Present on certain complement proteins (C3 and C4) -When C3, C4 are cleaved/activated-->His moves to cleave thioester-->makes unstable bond b/w his and glutamine-->unstable bond reacts easily with any "R-OH" structures-->If H20, will form inactive protein (favored if not close to any surface)-->if protein or sugar, will become bound to C3b, C4b (favored if close to surface)-->can react w/protein/sugar on nearby surfaces-->how C3b, C4b can bind to bacteria! |
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What is role of C3?
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C3 has lots of jobs:
1) binds B and D 2) is cleaved into C3a->anaphylatoxin C3b-->discriminate b/w friendly/unfriendly surfaces -->binds to receptors on leuks/pathogens-->"immune adherence" -->makes covalent links to tons of sufaces -->binds to C4,2--changes its specificity -->binds to Bb--makes C3bBb complex -->binds directly to C3bBb complex--changes its specificity HUGE role in both pathways! |
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How is complement pathway regulated?
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1) C3, C4 are unstable--don't last long after being cleaved.
2) C3a-C5a, Ba--inactivated by removal of C-terminal arginines by serum carboxypeptidase B. 3) Factors H/I--inhibit C3b Decay Accelerating Factor--prevents C3b from binding to healthy cells (erythrocytes) and having them destroyed-->these cells have decay-acc. factor, which accelerates C3b destruction by H, I. |
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What is role of Membrane attack complex (MAC)?
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Binds to pathogenic cell-->opens channels in its surface-->lysis!
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What is role of Decay-accelerating factor?
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-Keeps C3b from destroying good, healthy cells!
-erythrocytes (and most cells in blood) have this factor attached to membranes-->accelerates rate of destruction of C3b by H and I. |
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What is role of C-reactive protein?
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-present in severe inflammations.
CRP can substitute for IgG in activating the classical pathway. It binds to a pathogen and then binds to C1q, starting the classical pathway cascade. |
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What the heck is paroxysmal nocturnal hemoglobinuria? What causes it?
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--Lack of Decay-accelerating factor
Infection present in body-->urine turns red at night! Why? -Pathogen from infection creates tons of C3b-->"immune adherence" happens-->erythrocytes have no decay accelerating factor-->RBC's are lysed by leukocytes-->heme released-->red urine! |