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Host and Defense > complement system > Flashcards

complement system Flashcards

1
Q

where are most components of the complement system made?

A

in the liver

  • make up 15% of plasma globulin protein
  • old system of defense
  • *pattern recognition system
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2
Q

what are the initiators of the classical pathway?

A

antibody (IgG and IgM) with C1q complex

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3
Q

initiators of the lectin pathway?

A

mannose with binding lectins

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4
Q

initiators of the alternate pathway

A

C3, properdin

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5
Q

convertase activators

A

label pathogens/antigens with C3b and C5b

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6
Q

opsonins

A

coat pathogens/antigens and target them for phagocytosis

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7
Q

anaphylatoxins

A

initiate and promote inflammation

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8
Q

membrane attack complex

A

form the MAC pore

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9
Q

complement receptors

A

initiate signaling

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10
Q

regulators

A

restrict or halt complement activity

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11
Q

every component of the complement system is what?

A

a protein

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12
Q

missing components cause what?

A

pathogen susceptibility

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13
Q

all three pathways merge at what point?

A

cleavage of C3 to C3a and C3B

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14
Q

the “a” fragment does what?

A

small fragment
no enzyme activity
anaphylatoxin
signaling activity

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15
Q

the “b” fragment does what?

A

large fragment
enzyme activity
opsonin
signaling activity

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16
Q

what complement protein is the exception to the “a/b” rule

A

C2

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17
Q

what is unique about the classical pathway?

A

you must have had exposure to pathogen previously

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18
Q

what iniates the classical pathway?

A

C1q binds to antibody on surface of bacteria and recruits C1r and C1s

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19
Q

what are the two antibodies that can initiate classical pathway?

A

IgG(you need at least two) and IgM

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20
Q

binding of C1q to Ig activates C1r, which does what?

A

cleaves and activates the serine protease C1s forming the C1qr2s2 complex

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21
Q

what is the C3 convertase of the classical pathway?

A

C4b2a

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22
Q

what is the C5 convertase of the classical pathway?

A

C4b2a3b

23
Q

how does the lectin pathway recognize pathogen?

A

the cell surface gylcoproteins that have a terminal monnose residue

24
Q

what is the lectin pathway initiated by?

A

mannose binding lectins(MBL)

and Ficolins

25
Q

the mannose binding lectins binds with what on the surface?

A

mannose and fucose residues

26
Q

the ficolins bind to what on the surface of bacteria?

A

oligosacchardies containing acetylate sugars

27
Q

once the MBLs or ficolins have bound to surface markers they recruit what?

A

MBL associated serine proteases (MASP)

MASP-1 and MASP-2

28
Q

what do MASP-1 and MASP-2 do?

A

cleave complement protein C4

29
Q

once the C4b protein binds to surface the MASP-2 then cuts what?

A

C2 into C2a and C2b

30
Q

what is the C3 convertase of the lectin pathway?

A

C4b2a

31
Q

what is the C5 convertase of the lectin pathway?

A

C4b2a3b

32
Q

what are the three routes of activation?

A
  1. spontaneous C3 hydrolysis
  2. Properdin-pathway binding and C3 recruitment
  3. Proteolytic C3 cleavage
    - thrombin
    - clotting cascade proteases
33
Q

spontaneous hydrolysis of C3 process

A

C3 spontaneously changes conformation to expose its thioester bond

  • C3 thioester bond is unstable in aqueous environements
  • occurs at a low level of constant spont C3 hydrolysis in blood stream and tissues
34
Q

upon hydrolysis of C3 what is the out come?

A

C3b and C3a

-C3b can stay in blood stream or stick to surface of pathogen or cells of the body

35
Q

what is the other way C3b and get on the surface of the pathogen in regards to the alternative pathway?

A

B unit binds to the C3 and then the D unit cuts the B unit into Bb and Ba to give the soluble C3 convertase of iC3Bb

36
Q

what is the soluble alternate pathway C3 convertase?

A

iC3Bb

37
Q

what is the way the second C3 convertase gets formed?

A

surface bound C3b has a B unit attach to it, which in turn allows the D unit to cleave the B unit into Bb and Ba giving the surface bound C3 convertase of C3bBb

38
Q

what are the two C3 convertases of the alternate pathway?

A
  • *iC3Bb (soluble) and initiates alternative pathway

* *C3bBb(membrane bound) drives pathogen C3b opsinization

39
Q

what does properdin do?

A

stabilizes the C3 convertase C3bBb on a pathogen surface and to recruit more C3b

40
Q

what C3 convertase of the alternate pathway initiates the alternative pathway?

A

iC3Bb

41
Q

what C3 convertase of the alternate pathway drives pathogen C3b opsonization?

A

C3bBb

42
Q

what is the C5 convertase of the alternative pathway?

A

(C3b2)Bb

43
Q

complement receptors regulate inflammation how?

A
  • receptors on adaptive and innate cells
  • comp components induce inflamm resp
  • opsonized cells are targeted for destruction by phagocytosis and degranulation
44
Q

anaphylatoxins do what?

A

cause leakage of vasculature and to draw cells(adaptive) to site of infection

45
Q

C5a and C3a can do what?

A

causes degranulation and cause chemotaxis of cells of the innate immune system

46
Q

how does the complement causes phagocytosis of bacteria? also what is the check point in the mechanism?

A

C3b on surface is bound by CR1 on macrophage. If there is no C5a then NO phagocytosis occurs. If there is C5a then the okays phagocytosis
**check point is if C3b is removed before any C5a is made then the cell is not phagocytosed thus self cells that removed C3b are safe.

47
Q

what are the components of the Membrane Attack complex?

A 
C5b
C5
C7
C8
lots of C9
48
Q

how would a blood borne pathogen of the blood get phagocytosed?

A

C3b can bind to the surface of the antibody and then is bound by RBC and taken to a phagocyte

49
Q

how do human cells avoid the MAC?

A

they have CD59 which binds to C5b678 and prevents C9 from binding to complex thus no holes are made

50
Q

what do factor H and I do?

A

remove or inactivate C3b and C5b on self cells

51
Q

what does Decay-Accelerating Factor (DAF) do to C3 convertase of the alternate pathway?

A

removes the Bb from the C3bBb

*hence Decay of C3 convertase

52
Q

what does Membrane Co-factor Protein do?

A

binds to the C3 convertase C3bBb causing the Bb to leave and inactivates the C3b to iC3b

53
Q

in general what do H, I, DAF, and MCP do?

A

leads to C3 convertase depletion and pathogen susceptibility

Host and Defense (26 decks)

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