Term
| Name the major serine proteases. |
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Definition
| C1r, C1s, C2a, Factor B (Bb), Factor D, MASP 1, MASP 2 |
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Term
| what are the substrate binding molecules? |
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Definition
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Term
| What molecules are part of the MAC complex. Which is most important for perforating membrane? |
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Definition
| C5b, C6, C7, C8, C9. C9 most responsible for punching membrane holes. |
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Term
| What are the bioactive fragments and what are their main roles? |
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Definition
C3a, C5a, C3b, iC3b, C4a
Involved in opsonization and inflammatory response |
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Term
| What are some key regulators? |
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Definition
-properidin (only + regulator)
-C1 inhibitor (C1INH)
-Factor I (only protease inhibitor)
-Factor H
-C4BP
-MCP (membrane cofactor protein) or CD46
-DAF/CD55
-S protein
-CD59 |
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Term
| what are the complement receptors? |
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Definition
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Term
| What are the main anaphylatoxins? |
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Definition
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Term
| what molecules are responsible for opsonization? |
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Definition
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Term
| what molecules are responsible for cell lysis? |
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Definition
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Term
| what are main inflammatory proteins? |
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Definition
| C3a, C5a, and to lesser extent C4a |
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Term
| How does complement alert the adaptive immunity to pathogen invasion? |
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Definition
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Term
| name the pathways in order of decreasing age. |
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Definition
-alternative (oldest)
-lectin (middle)
-classical (youngest, arose around time of adaptive immunity) |
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Term
| what structural element do C3, C4, and C5 have in common? |
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Definition
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Term
| what is a positive regulator in the complement system and what function does it play? |
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Definition
| Properdin. Stabilizes the alternative pathway (C3b, Factor B) so it won't be inactivated. |
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Term
| Name the molecules that initiate each pathway. |
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Definition
Classical: antibody bound to pathogen, joined by C1 complex
Lectin: lectin/MBP, pathogen, MASP1 & MASP2
Alternative: spontaneous C3b activation with pathogen, soon to be joined by Factor B
Each pathway converges on C3 |
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Term
| what mechanisms keep C3 from making covalent bonds all over the body? |
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Definition
-first off, when in plasma the C3b thioester bond is inactivated via hydrolysis
-regulatory proteins also prevent its binding willy nilly; lack of stabilization proteins impedes bonding, too |
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Term
| What comprises the C3 convertase in the classical versus alternative pathway? |
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Definition
Classical: C2a,4b
Alternative: C3b, Bb |
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Term
| In the classical pathway what type of Abs are needed? |
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Definition
IgG1, IgG3 (inflammatory Abs), or IgM (antigen-bound) are capable of activating complement when antigen is BOUND
The C1 complex needs at least 2 Abs bound before C1q activates C1r via cleaving |
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Term
| where does the C1 complex bind on antibodies? |
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Definition
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Term
| how does alternative pathway begin? |
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Definition
| Tickover, or spontaneous cleavage of C3 thioester bond to yield C3(H20), which is able to bind Factor B. The conformational change enables Factor D to cleave it into Bb and Ba. Bb remains with C3(H20) and is the fluid C3 convertase. A little fluid C3 convertase goes a long way in cleaving C3-->C3a and C3b. One molecule of Factor B can cleave many C3 whose fragments go into circulation and bind. Alternative pathway shows amplification of response |
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Term
| what molecules make up the classical pathway C3 and C5 convertases? |
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Definition
CLASSICAL
C3 convertase= C4b, C2a
C5 convertase= C4b, C2a, C3b
Active protease is C2a |
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Term
| what molecules make up the alternative pathway C3 and C5 convertases? |
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Definition
ALTERNATIVE:
C3 convertase= C3bBb
C5 convertase= C3bBbC3b
Active protease is Bb |
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Term
| What is precursor of complement activation pathways? |
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Definition
C3 & B were precursors for both active and classical pathways. C4 evolved from C3 and C2 evolved from B, as they specialized.
C3-->C4
B-->C2 |
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Term
| where are C4 and Factor 4 encoded in the genome? |
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Definition
| in the MHC. significance yet to be determined, but still an interesting finding |
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Term
| describe the lectin pathway. |
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Definition
Mannan-Binding Protein (MBP) binds mannose resides on microbe, and then forms complex with MASP1 and MASP2.
MASP-1 cleaves/activates MASP-2 AND directly cleaves C3 -->C3a and C3b.
Activated MASP-2 goes on to cleave C4 and C2, thus helping to create C4bC2a c3 convertase, as found in classical pathway. C5 convertase same as in classical pathway. |
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Term
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Definition
| inhibits C1 complex, specifically halts the C1r and C1s protease activity. CLASSICAL PATHWAY INHIBITOR |
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Term
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Definition
| the only protease regulator; proteolytically cleaves C3b and C4b |
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Term
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Definition
causes dissoaciation of alternative pathway's C3 convertase (C3b,Bb)subunits
Co-Factor for Factor I mediated cleavage of C3b |
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Term
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Definition
| causes dissociation of classical pathway C3 convertase (C4b,C2a)subunits. Also a cofactor for Factor I mediated cleavage of C4b |
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Term
| what does Membrane Cofactor protein (MCP) or CD46 do? |
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Definition
| cofactor for factor I mediated cleavage of C3b and C4b |
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Term
| what does DAF (decay accelerating factor)/CD55 do? |
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Definition
| causes dissociation of C3 convertase subunits |
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Term
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Definition
| Blocks C9 binding and prevents formation of MAC |
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Term
| What does type I complement receptor (CR1/CD35) do? |
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Definition
-membrane protein
-causes dissociation of C3 convertase subunits
-cofactor for Factor I mediated cleavage of C4b and C3b |
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Term
| what are proteins function as cofactors of Factor I? |
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Definition
-Factor H (alternative, stabilizes C3b cleavage)
-C4BP (classical, aids in C4b cleavage)
-MCP/CD46 (cofactor for FI cleavage)
-CR1 (dissociation of C3 convertase, coFactor for Factor I) |
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Term
| what are the functions of inhibitors of complement cascade? |
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Definition
-block responses to self tissue
-prevent C' from being used up
-limit responses to keep inflammation to a minimum |
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Term
| what is a key protein in C3 degradation? |
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Definition
| Factor I: C3b-->iC3b + C3f-->C3dg + C3c |
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Term
| what function does C3b lose once cleaved by Factor I? |
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Definition
| iC3b maintains its opsonizing power, but is no longer able to recruit Factor B to form the C3 convertase |
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Term
| what receptor is the most important for phagocytosis? |
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Definition
| CR1...helps to stimulate eosinophils, macrophas=ges, PMNs, B, FDCs |
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Term
| what does CR1 bind and what role does it play? |
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Definition
C4b/C3b/iC3b
phagocytosis; immune complex clearance |
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Term
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Definition
binds iC3b
functions: phagocytosis and opsonization |
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Term
| what does CR2 bing and main functions does it play? |
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Definition
C3d receptor
involved in activation, proliferation of B cells;C3d helps to lower threshold for B cell activation by antigen |
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Term
| what molecules are responsible for opsonization and phagocytosis? |
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Definition
-C3b
-C4b
-iC3b
-CR1 = C3b receptor on phagocyte |
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