Immunology Unit 2 - The complement system

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44 Terms

1
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What is the definition of the complement system?

System of proteins largely produced by the liver and mostly found in blood

2
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Where are complement proteins found?

Mostly blood, but can be found at other sites, including inside cells

3
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What outcomes come from the cascade of active enzymes and accessory proteins in the complement system?

Lysis - direct destruction of bacteria

Inflammation - release of anaphylatoxins to increase local inflammation and fight infections

Opsonization - coating a surface with C3b and C4b to increase uptake by phagocytic cells

4
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What three pathways are activated by compliment?

  1. alternative 

  2. lectin

  3. classical 

5
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In the classical pathway, what binds to the antigen-antibody complex to activate C4?

C1qC1rC1s

6
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C1q binds to _______ antibodies

multiple

7
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What is the complement cascade initiation of the classical pathway?

  1. globular head of C1q binds to antibodies

  2. C1r undergoes conformational change & cleaves C1r and C1s

  3. Active C1s cleaves C4 to C4a + C4b

  4. C4b binds C2 which is cleaved to C2a/b by C1s

  5. C4b/C2a bind to C3 and cleave it to C3a and C3b

8
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What two components make C3 convertase in the classical and lectin pathway?

C4b and C2a

9
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What cleaves C4 to create C4a and C4b in the classical pathway 

Active C1s

10
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What are the first antibodies of the classical pathway?

IgM

11
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What is the complement cascade initiation of the lectin pathway?

  1. Globular heads of MBL bind to bacterial carbohydrates 

  2. MASP1/2 undergo conformational change-cleaves MASP1 and MASP2

  3. Active MASP1/2 cleaves C4 to C4a and C4b

  4. C4b binds C2 which is cleaved to C2a/b by C1s

  5. C4b/C2a bind C3 and cleave it to C3a and C3b

12
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What cleaves C4 to create C4a and C4b in the lectin pathway 

MASP1/2

13
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What is the complement cascade initiation of the alternative pathway?

  1. C3 is hydrolyzed by water in the blood-creating pseudo-C3b

  2. Factor B binds to C3(H2O)

  3. Factor D cleaves Factor B to Ba and Bb

  4. C3(H2O)Bb bind to C3 and cleave it to C3a and C3b

  5. C3b/Bb attaches to a surface

  6. Properdin stabilizes the C3 convertase

  7. C3bBb binds to C5 and cleaves it into C5a and C5b

14
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What create C3 convertase in the alternative pathway?

C3H2O and Bb

15
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What role does Factor B play in alternative pathway?

stabilization

16
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For all 3 pathways there are 2 stages. What are they and what shows which is which?

  1. Initiation

  2. Amplification

It goes from initiation to amplification once C3 is bound to C3 convertase 

17
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All 3 pathways lead to one common factor that brings them together. What is this?

C5

18
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What does MAC stand for?

Membrane Attack complex

19
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Where can cascade happen?

Anywhere compliment activates

20
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_______ increases inflammation

Anaphylatoxins

21
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C3a and C5a will bind to what in a transmembrane protein to activate anaphylatoxin signaling?

C3aR or C5aR

22
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Anaphylatoxin signaling and inflammatory response is carried out by what?

Macrophage - chemotaxis, phagocytosis, cytokine 

Basophil - degranulation

Eosinophil - degranulation,chemotaxis

Neutrophil - degranulation, chemotaxis, phagocytosis

Mast cell - degranulation, chemotaxis 

23
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What increases phagocytic uptake?

Opsonization

24
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What is opsonization?

when opsonins coat a pathogen with macrophages and neutrophils to “tag” it for destruction by phagocytes

25
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Other than bacteria, what can compliment opsonize?

deposited immune complexes, viruses, apoptotic cells, host cells

26
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What will happen is C1/C2/C4 had a deficiency?

Failure to clear ICs, apoptotic cells

27
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What will happen is C3 had a deficiency?

Lack bacterial clearance

28
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What will happen is C5-C9 had a deficiency?

Loss of bacterial lysis

29
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What will happen is MBL had a deficiency?

No binding lectins 

30
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What will happen is Factor B & D had a deficiency?

Loss of AP

31
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What will happen is properdin had a deficiency?

X-linked 

32
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What are examples of CR1s?

Erythrocytes, neutrophils, monocytes, macrophages, eosinophils, FDCs, B cells, some T cells

33
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What are examples of CR2s?

B cells and FDCs

34
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What are examples of CR3s?

Monocytes, macrophages, neutrophils, eosinophils, NK cells, T cells, FDCs

35
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What are examples of CR4s?

Monocytes, macrophages, neutrophils, dendritic cells, NK cells, T cells

36
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CD59 does what to regulate compliment?

protection 

37
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CD55 does what to regulate compliment?

decay accelerator

38
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CD46 does what to regulate compliment?

membrane cofactor 

39
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What occurs during displacing C1 proteases?

C1q binds to antigen-antibody complex to activate C1r and C1s. C1 inhibitor dissociates C1r and C1s from the active C1 complex 

40
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What occurs during inactivating C4?

C4b2b is the active C3 convertase. DAF,C4BP, and CR1 displace C2b from the C4b2b complex. C4 bound by C4BP or MCP is cleaved by soluble protease 1 to inactive forms of C4c and C4d

41
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What occurs during inactivating C3?

C5 is cleaved into C5a and C5b. CR1 and H displace C3b. Cr1 and H act as cofactors in the cleavage of C3b

42
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What stops the MAC?

CD59 prevents final assembly of the membrane attack complex at the C8 to C9 stage

43
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What in the cell cleaves and chops up C3 and C5

lysosome 

44
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Pathogens can take advantage of ____ for cell entry

CD46