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SFM - Biochem - Quiz 2 > (L21) CIS - Basic Complement System > Flashcards

(L21) CIS - Basic Complement System Flashcards

1
Q

What are the different pathways of compliment activation and what is activating factor of each pathway?

L21 S18

A

Classical pathway:
-Ab binds pathogen and C1 recognizes Ab activating C2 and C4

Lectin pathway:
-MBL binds pathogen mannose and MBL activates C2 and C4

Alternative pathway:
C3 spontaneously degrades and C3b binds pathogen

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2
Q

What are the effector mechanisms of complement?

L21 S18

A

MAC (membrane attack complex) leading to cell lysis

Opsonization with C3b leading to phagocytosis

Production of anaphylatoxins (C3a, C4a, C5a) leading to vasodilation and degranulation

Clearance of Ab immune complexes

Enhancement of immune response (C3d binding CR2 of B cells)

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3
Q

What is the first step of complement cascade and what does this look like in each pathway?

L21 S18

A

Classical and lectin:
-C1 (classical) or MBL (lectin) convert C2 and C4 into C2a and C4b which binds pathogen and form C3 convertase (C4bC2a)

Alternative:
-C3 spontaneously cleaves (tickover) into C3b which bind pathogen. C3b converts factor B into Bb forming alternative C3 convertase (C3bBb)

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4
Q

What is the second step of complement cascade and what does this look like in each pathway?

L21 S18

A

Classical and lectin:
-C3 convertase (C4bC2a) converts C3 into C3b. C3b binds C3 convertase forming C5 convertase (C4BC2aC3B)

Alternative:
-alternative C3 convertase (C3bBb) converts C3 to C3b. C3b binds C3 convertase forming C5 convertase (C3bBbC3b)

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5
Q

What is the last step of complement cascade and what does this look like in each pathway?

L21 S18

A

Shared by all pathways:

  • C5 convertase converts C5 to C5b
  • C5b inserts into membrane
  • C5b mediates insertion of C6, C7, and C8 into memabrane
  • C5-8 insert numerous C9 forming a pore in membrane called the MAC (membrane attack complex)
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6
Q

What are the roles of Factor B, Factor D, and properdin?

L21 S7-8

A

Factor B:
-used in formation of alternative pathway C3 convertase in activated form (Bb)

Factor D:
-activates Factor B to Bb

Properdin:
-stabilizes alternative pathway C3 convertase

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7
Q

What is MCP and what complement pathways does it affect?

L21 S19-20

A

Cofactor for factor I based degradation of C3b and C4b (all pathways)

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8
Q

What is DAF and what complement pathways does it affect?

L21 S19-20

A

Destabilizes C3/C5 contvertases (all pathway)

This protein is membrane bound and found on host cells preventing complement activation against host cells

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9
Q

What is CR1 and what complement pathways does it affect?

L21 S19-20

A

Decay accelerating activity of C3 and C5 convertase (all pathways)

-and-

Cofactor for factor I based degradation of C3b and C4b (all pathways)

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10
Q

What is C4BP and what complement pathways does it affect?

L21 S19-20

A

C4 binding protein

Decay accelerating activity of classical C3 convertase (classical and lectin)

-and-

Cofactor for factor I based degradation of C4b only (classical and lectin)

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11
Q

What is Factor H and what complement pathways does it affect?

L21 S19-20

A

Decay accelerating activity for alternative C3 convertase

-and-

Cofactor for factor I based degradation of alternative pathway C3 and C5 convertases

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12
Q

What is Factor I and what complement pathways does it affect?

L21 S19-20

A

Degradation of C3b and C4b mediated by cofactors (MCP, CR1, factor H, and C4BP)

This protein soluble and found serum preventing complement activation against host cells

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13
Q

What is CD59 and what complement pathways does it affect?

L21 S19-20

A

Prevents C9 from interacting with C5b-8 thus preventing insertion and MAC formation

Membrane bound

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14
Q

What is C1-INH and what complement pathways does it affect?

L21 S19-20

A

Inactivates C1 (classical) and MASP-1/2 (lectin)

Also inactivates kallikrein which converts kininogen to bradykinin, a vasodilator

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15
Q

What is vitronectin (S-protein) and what complement pathways does it affect?

L21 S19-20

A

Binds to C5b-7 inhibiting C9 polymerization and MAC formation

Soluble

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16
Q

What is clusterin and what complement pathways does it affect?

L21 S19-20

A

Binds to C5b-7 inhibiting C9 binding and MAC formation

Soluble

17
Q

What are anaphylatoxins and what are their functions?

L21 S23

A

C3a and C5a

Activates mast cells/basophils, neutrophils, and monocytes/Mφ

Increased production of pro-inflammatory factors, chemotaxis, extravasation (adhesion molecules and vasoactive substances), and phagocytic killing functions (ROS/RNS)

18
Q

What is the most effective anaphylatoxin?

L21 S24

A

C5a

19
Q

How does the immune system lead to glomerular disease?

L21 S25

A

Immune complexes deposit in kidneys creating inflammation via effector mechanisms:

  • C5a (neutrophil chemotaxis)
  • MAC formation (protease release)
  • ROS production
  • inflammatory cytokines

Abs can also directly bind Ag in kidneys

20
Q

How does the immune system lead to vasculitis?

L21 S25

A

Deposition of immune complexes in vessel wall leading to complement activation and secretion of inflammatory cytokines

Abs can also directly bind Ag on vessel wall

21
Q

What is hereditary angioedema (HAE) and what is responsible?

L21 S30

A

Defect in C1-INH

C1-INH regulates C1 and plasma kallikrein

Without functional C1-INH, plasma complement is continuously activated and kallikrein converts kininogen to bradykinin (causing swelling)

22
Q

What is paroxysmal nocturnal hemoglobinuria (PNH) and what is responsible?

L21 S33

A

Loss of GPI anchor proteins that regulate complement activity against host cells (DAF/CD55 and CD59)

Without these proteins, RBCs are susceptible to hemolysis by MAC complex.

Name comes from the fact that urine becomes more concentrated at night and the presence of hemoglobin in the urine becomes more noticeable.

23
Q

What is the therapy for PNH and what are the assocaited risks of this treatment?

L21 S36

A

Treatment with monoclonal antibodies for C3 and C5 (Compstatin and Eculizumab respectively).

Treatment results in complement deficiency which leads to increased susceptibility of infection.

SFM - Biochem - Quiz 2 (23 decks)

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