Term
| What proteins in the horseshoe crab are homologous to vertebrate complement proteins? |
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Definition
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Term
| What types of molecules can activate the vertebrate complement system? |
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Definition
PAMPs
antibodies + microbial antigens
coagulation/fibrinolytic components |
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Term
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Definition
| punches holes in the microbial cell membranes, resulting in osmotic lysis |
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Term
| What are the 3 complement pathways? |
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Definition
Alternative Pathway
Lectin-Binding Pathway
Classical Pathway |
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Term
| Which are the oldest complement genes? |
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Definition
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Term
| Duplications of C3 led to... |
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Definition
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Term
| Duplication of Bf led to.... |
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Definition
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Term
| The classical pathway developed as a result of... |
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Definition
| duplication events leading to C6,C7,C8 & C9 |
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Term
| Chickens lack the complement genes for... |
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Definition
| C2, C9, MASP1, Factor P (properdin) |
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Term
| Zebrafish lack the complement genes for... |
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Definition
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Term
| Which complement proteins are produced by the liver? |
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Definition
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Term
| Which complement proteins are produced by macrophages? |
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Definition
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Term
| Neutrophils are capable of producing & storing... |
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Definition
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Term
| Host cells are rich in sialic acid, allowing _____ to bind to C3b |
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Definition
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Term
| What happens to C3a produced by the spontaneous degradation of C3 in the alternative pathway? |
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Definition
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Term
| Which complement receptors is iC3b able to bind to? |
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Definition
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Term
| Describe the construction of an anchor molecule |
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Definition
1. C5 binds to C3b on microbial cell surfaces
2. C3bBb or C4bC2b cleaves C5
3. C5a is released into humoral fluid
4. C6 & C7 bind to C5b forming C5b67
5. Complex formed is inserted into membrane |
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Term
| Describe the assembly of the MAC |
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Definition
C8 & C9 bind to C5b67 complex
MAC is created, acting as a pore which inhibits osmotic regulation of the microbial cell |
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Term
| What activates the lectin-binding pathway? |
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Definition
| MBL or ficolins bind to microbial cell wall, activating a MASP2 complex |
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Term
| MASP2 is critical for the lectin-binding pathway and also... |
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Definition
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Term
| What activates the classical pathway? |
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Definition
IgM or IgG produced during the acquired immune response attach to the microbial surface, resulting in a conformational change which exposes the Fc region of the antibody
(the Fc region contains complement-binding sites) |
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Term
| What is the most important regulator of the classical pathway? What does it do? |
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Definition
C1-INH
-blocks C1r & C1s, preventing C4bC2b assembly |
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Term
| What proteins are able to accelerate the decay of C3 & C5 convertases? |
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Definition
CD55
Hf
If
C4-binding protein
CR1 (CD35) |
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Term
| Which proteins block the insertion of of C5b678 into the microbial cell mmb? |
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Definition
vitronectin
clusterin
CD59 (protectin) |
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Term
| What ligands does CR1 bind? What effect does their binding have on the immune response? |
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Definition
C3b
C4b
iC3b
-allows the complexes to be removed by the spleen & liver |
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Term
| Where are CR1 receptors found in primates? |
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Definition
90% are on RBCs
10% are on phagocytic cells |
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Term
| What ligands does CR2 bind? What effect does this have? |
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Definition
C3d
-CD19/CR2 complex is formed, releasing a signal to increase activation of B cells in response to microbial presence |
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Term
| What ligands does CR3 bind? What effect does this have? |
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Definition
iC3b
-mediates phagocytosis & cytotoxicity |
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Term
| What ligands does CR4 bind? What effect does this have? |
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Definition
breakdown products of C3
-mediates phagocytosis, cytotoxicity, clotting |
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Term
| Where are C3aR & C5aR found? What happens when they bind to C3a and C5a? |
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Definition
mast cells
eosinophils
basophils
degranulation, release of vasoactive compounds |
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Term
| What ligand does C1qR bind? What effect does this have? |
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Definition
C1q
-mediates phagocytosis of apoptotic bodies
-mediates macrophage differentiation
-mediates DC migration |
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Term
| What ligands does CRIg bind? What effect does this have? |
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Definition
C3b & iC3b
phagocytosis of pathogens in the blood |
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Term
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Definition
| tissue macrophages e.g. Kupffer cells |
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Term
| C1q can act as an opsonin for... |
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Definition
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Term
| C3b & C4b can act as opsonins for..... |
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Definition
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Term
| Which complement proteins have vasoactive properties? |
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Definition
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Term
| What are the anaphylactic effects of C3a & C5a? (5) |
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Definition
-mast cell/eosinophil degranulation
-platelet release of vasoactive compounds
-increased vascular permeability
-neutrophil release of lysosomal enzymes
-macrophage release of thromboxane |
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Term
| Which C3 breakdown product is bacteriolytic? |
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Definition
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Term
| What causes BLAD in cattle? |
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Definition
| SNP in CD18 reduces B2 expression, preventing leukocyte adhesion |
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Term
| What causes glomerulonephritis? |
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Definition
| SNP in Hf leading to excess C3b being deposited in the kidneys |
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Term
| SNPs in which complement genes increases the risk of asthma? |
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Definition
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Term
| Which component of the coagulation-fibrinolysis process acts strictly as a C3 convertase? |
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Definition
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Term
| Which components of the coagulation-fibrinolysis process act as C3 & C5 convertases? |
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Definition
Factors X, XI, IX
thrombin
plasmin |
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Term
| How does Streptococci M affect complement activation? |
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Definition
| masks C3b binding sites, preventing opsonization |
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Term
| How does Staph aureus affect complement activation? |
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Definition
| produces fibrinogen-binding protein which changes the shape of C3b, preventing interaction with Bf |
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Term
| How does Salmonella enterica affect complement activation? |
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Definition
| Rck gene prevents MAC from being inserted into bacterial mmb |
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Term
| How does E coli affect complement activation? |
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Definition
produces Stx which activates the complement system
-binds to Hf, downregulates CD59 in kidney cells, increases C3b production
-MACs on renal cells lead to hemolytic uremic syndrome |
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