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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?

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
the mannose binding lectins binds with what on the surface?
mannose and fucose residues
26
the ficolins bind to what on the surface of bacteria?
oligosacchardies containing acetylate sugars
27
once the MBLs or ficolins have bound to surface markers they recruit what?
MBL associated serine proteases (MASP) | MASP-1 and MASP-2
28
what do MASP-1 and MASP-2 do?
cleave complement protein C4
29
once the C4b protein binds to surface the MASP-2 then cuts what?
C2 into C2a and C2b
30
what is the C3 convertase of the lectin pathway?
C4b2a
31
what is the C5 convertase of the lectin pathway?
C4b2a3b
32
what are the three routes of activation?
1. spontaneous C3 hydrolysis 2. Properdin-pathway binding and C3 recruitment 3. Proteolytic C3 cleavage - thrombin - clotting cascade proteases
33
spontaneous hydrolysis of C3 process
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
upon hydrolysis of C3 what is the out come?
C3b and C3a | -C3b can stay in blood stream or stick to surface of pathogen or cells of the body
35
what is the other way C3b and get on the surface of the pathogen in regards to the alternative pathway?
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
what is the soluble alternate pathway C3 convertase?
iC3Bb
37
what is the way the second C3 convertase gets formed?
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
what are the two C3 convertases of the alternate pathway?
* *iC3Bb (soluble) and initiates alternative pathway | * *C3bBb(membrane bound) drives pathogen C3b opsinization
39
what does properdin do?
stabilizes the C3 convertase C3bBb on a pathogen surface and to recruit more C3b
40
what C3 convertase of the alternate pathway initiates the alternative pathway?
iC3Bb
41
what C3 convertase of the alternate pathway drives pathogen C3b opsonization?
C3bBb
42
what is the C5 convertase of the alternative pathway?
(C3b2)Bb
43
complement receptors regulate inflammation how?
- receptors on adaptive and innate cells - comp components induce inflamm resp - opsonized cells are targeted for destruction by phagocytosis and degranulation
44
anaphylatoxins do what?
cause leakage of vasculature and to draw cells(adaptive) to site of infection
45
C5a and C3a can do what?
causes degranulation and cause chemotaxis of cells of the innate immune system
46
how does the complement causes phagocytosis of bacteria? also what is the check point in the mechanism?
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
what are the components of the Membrane Attack complex?
``` C5b C5 C7 C8 lots of C9 ```
48
how would a blood borne pathogen of the blood get phagocytosed?
C3b can bind to the surface of the antibody and then is bound by RBC and taken to a phagocyte
49
how do human cells avoid the MAC?
they have CD59 which binds to C5b678 and prevents C9 from binding to complex thus no holes are made
50
what do factor H and I do?
remove or inactivate C3b and C5b on self cells
51
what does Decay-Accelerating Factor (DAF) do to C3 convertase of the alternate pathway?
removes the Bb from the C3bBb | *hence Decay of C3 convertase
52
what does Membrane Co-factor Protein do?
binds to the C3 convertase C3bBb causing the Bb to leave and inactivates the C3b to iC3b
53
in general what do H, I, DAF, and MCP do?
leads to C3 convertase depletion and pathogen susceptibility

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