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Inflammation and Wound Healing Exam 1 > Complement System > Flashcards

Complement System Flashcards

1
Q

what is the complement system?

A

a system comprising of many circulating and membrane-fixed proteins

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2
Q

what is the function of the complement system?

A
  • kill microorganisms directly
  • induce inflammation
  • increase phagocytosis by opsonization
  • clear insoluble immune complexes
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3
Q

what are the three steps of activation for the complement system?

A
  1. recognition
  2. enzyme activation
  3. expression of biological activity
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4
Q

what are the three activation pathways?

A
  1. classical pathway
  2. alternate pathway
  3. lectin pathway
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5
Q

what is the similarity between all three activation pathways?

A

they all result in the same complement activation

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6
Q

what is the classical pathway initiated by?

A

antigen-antibody complex

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7
Q

what is the alternate pathway initiated by?

A

cell wall of bacteria and yeasts

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8
Q

what is the lectin pathway initiated by?

A

lectins that bind mannose (MBL)

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9
Q

what are the similarities of the classical and lectin pathways?

A
  • formation of C3 convertase
  • covalent binding of C3b to microbial surface
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10
Q

what are the similarities of the alternative, classical and lectin pathways?

A
  • all three perform cleavage of C3
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11
Q

what is the first step of the classical pathway?

A
  • C1 complex binds to antibody-antigen complex initiating the pathway
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12
Q

what is the C1 complex composed of?

A

C1q
C1r
C1s

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13
Q

what does the C1q portion of the C1 complex need for binding?

A

two molecules of IgG or one molecule of IgM in order to bind to Fc regions and cause a conformational change

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14
Q

what happens once the binding of the C1 complex and antigen-antibody complex causes a conformational change?

A

the activated C1s (C1 esterase) begins enzymatic activity to cleave downstream complement components

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15
Q

what does C1 esterase cleave?

A

cleaves C4 into C4a and C4b first,
then cleaves C2 into C2a and C2b

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16
Q

what is C3 convertase?

A

the bound fragments C4b and C2a combined on the membrane to form a complex

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17
Q

what does the C3 convertase cleave?

A

cleaves C3 into C3a and C3b where c#b is the key molecule

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18
Q

what is the largest amplification step in the classical pathway?

A

C3 convertase cleaving hundreds of C3 molecules

19
Q

what are the components of C5 convertase and what does it cleave?

A

C4bC2aC3b and it cleaves C5 into C5a and C5b

20
Q

what does C5b initiate?

A

the formation of the membrane attack complex (MAC)

21
Q

what are the steps in forming the membrane attack complex?

A
  1. C5b forms the nucleus
  2. C6 binds to C5b
  3. C7 binds to C5bC6
  4. C8 binds to C5bC6C7
  5. C5bC6C7C8 serves as receptor for C9
22
Q

what happens once C9 polymerizes?

A

transforms into poly-C9 tube that inserts into the membrane that allows for ions to escape, water to enter and the cell to lyse

23
Q

what is the initial steps of the Lectin pathway that differ from the classical?

A
  1. mannose-binding lectin (MBL) binds to carbs on the surface of bacteria and yeast
  2. MBL-associated serine proteases (MASP) cleaves C4 into C4a and C4b and C2 into C2a and C2b
  3. C4bC2a forms the C3 convertase complex on membrane
  4. the rest is the same as the classical pathway
24
Q

what is the first step of the alternative pathway?

A

activation by pathogens causes H2O molecules to hydrolyze C3 to C3b

25
Q

what happens after C3b is formed in the alternative pathway?

A

binds to the activators surface forming the nucleus to activate the complement cascade

26
Q

what happens when C3b binds Factor B to form C3bFactorB complex

A

Factor D cleaves C3bFactorB complex forming C3bBb (C3 convertase)

27
Q

what does properdine do?

A

binds to C3bBb to make it more stable complex aka C3bBbP

28
Q

what two complexes cleave C3 to C3b in the alternative pathway and what is the result?

A

C3bBb and C3bBbP cleave C3 to C3b allowing for a large amount of C3b available for Factor B binding

29
Q

what does C3bBbC3b cleave and what does the product initiate?

A

cleaves C5 into C5a and C5b that allows for the formation of the membrane attack complex (same as classical and lectin pathway)

30
Q

how does the complement system induce inflammation?

A

the proteolysis of C3, C4 and C5 release C3a, C4a and C5a which are anaphylatoxins

31
Q

what do anaphylatoxins do?

A
  • strongly stimulate chemotaxis for neutrophils and granulocytes
  • induce expression of adhesion molecules to increase extravasation
  • enhance production of inflammation mediators
32
Q

what is C-Reactive Protein?

A
  • marker to test for inflammation due to its ability to activate the classical pathway by binding to C1q and the phosphocholine on the microbe
33
Q

how does the complement system increase phagocytosis?

A

complement receptors (1,3, and 4) expressed on macrophages, NK cells and granulocytes bind to C3b, iC3b and C4b that are already bound to the microbe

34
Q

how does the complement system aid in the removal of immune complexes?

A
  • complement proteins attach to antibodies in the immune complex triggering the complement cascade that produces C3b
  • C3b acts as a tag for complement receptors on surfaces of macrophages and neutrophils which will engulf and digest the immune complex
35
Q

what is systemic lupus erythematosus and what causes it?

A

impaired ability to clear immune complexes due to a deficiency in complement components C1, C4 and C2

36
Q

what can be causes due to a deficiency in the alternative pathway?

A

increased susceptibility to recurrent infections with pyogenic bacteria (pus-producing)

37
Q

what is decay accelerating factor (DAF)?

A
  • a protein that dissociates the C4bC2a complex inhibiting the formation of C3 convertase in the classical pathway
  • a protein that dissociates the C3bBbC3b complex in the alternate pathway
38
Q

what is C1 INH and what can deficiencies lead to?

A

C1-INH binds to the C1 complex (C1q, C1r, and C1s), preventing uncontrolled activation of the classical complement pathway where deficiencies can lead to angioedema

39
Q

what is angioedema?

A

recurrent, potentially life-threatening episodes of swelling from unregulated complement and bradykinin production due to deficiency in C1-INH

40
Q

how does Factor H regulate the alternate pathway?

A

dissociates C3 convertase by displacing Bb from C3bBb

41
Q

how does Factor 1 and membrane cofactor protein regulate the alternate pathway?

A

cleaves C3b forming an inactive C3b (iC3b)

42
Q

how does C59 regulate the alternate pathway?

A

blocks C9 binding and prevents the formation of membrane attack complex (MAC)

43
Q

how does serum carboxypeptidase regulate the alternate pathway?

A

inactivates anaphylatoxins C3a, C5a and C4a

Inflammation and Wound Healing Exam 1 (13 decks)

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