Complement System Flashcards
(117 cards)
1
Q
The classical pathway forms _______ complexes.
A
antigen:antibody
2
Q
Membrane cofactor protein (MCP) promotes:
A
C3b and C4b inactivation
3
Q
What kind of bond gets exposed by a protease during the cleavage of C3 into C3a and C3b?
A
thioester bond (nucleophile)
4
Q
A C5 convertase is composed of ___.
A
C3b+Bb+C3b
5
Q
C3 convertase directly leads to the activation of which proteins of the complement system?
A
C3a, C5a, C3b
6
Q
What is the formula for the C1 complex?
A
C1q:C1r(2):C1s(2)
7
Q
The cleavage of C4 and C2 by C1s forms the _____.
A
C4b2a complex
8
Q
What does C4b do?
A
binds to pathogen and starts the opsonization process; binds C2 for cleavage by C1s
9
Q
C1s cleaves ___ and then cleaves ___.
A
C4; C2
10
Q
Why does complement activation work to destroy bacterial cells but not allow the destruction of our own cells?
A
because the factors that regulate the complement pathway are bound to the membrane of normal cells to block the complement cascade from happening
11
Q
Kallikrein can lead to the activation of _____, which causes vasodilation, nonvascular smooth muscle contraction, edema, and activation of the complement cascade.
A
bradykinin
12
Q
The release of serum into the tissues, marked by swelling, is called ____.
A
wheal
13
Q
DAF ____ the association of factor B with C3b, thereby preventing the formation of additional C3 convertase.
A
blocks
14
Q
Which active component of the terminal complement components allows insertion into the cell membrane to begin formation of the MAC?
A
C8
15
Q
At which level is the alternative pathway continuously activated?
A
low level
16
Q
What is C1r responsible for?
A
it cleaves C1s to active protease
17
Q
The C4b/C2a complex is responsible for cleaving ___.
A
C3
18
Q
Does the alternative pathway rely on pathogen-binding antibodies?
A
NO
19
Q
What is a prothrombotic state, in regards to complement-mediated cell injury?
A
exposure of subendothelial collagens and release of von Willebrand factor and fibrinogen formation
20
Q
Ficolins have a very similar structure to MBL. However, they bind _____.
A
carbohydrates
21
Q
The globular heads of ___ bind to the surface of the cell to bind with the antibodies/immunoglobulins.
A
C1q
22
Q
What does C4a do?
A
weak inflammatory activity
23
Q
Which protein causes opsonization?
A
C3b
24
Q
MBL and ficolin function the SAME, but contain different ___.
A
domains
25
What happens when C3b binds to CR1 on a macrophage?
nothing; bacteria cannot be phagocytosed
26
What is C1q responsible for?
it binds directly to pathogen surfaces or indirectly to antibody bound to the pathogen, allowing the auto-activation of C1r
27
C4 gets cleaved into ___ and ___.
C4b; C4a
28
How is the therapeutic inhibition of C5 complement by Eculizumab clinically significant?
Eculizumab blocks C5 convertase in converting C5 into C5a; C5a initiates the MAC complex that forms pores and lyses cells; by blocking the formation of C5a, the MAC complex is not formed (thereby keeping host cells intact)
29
In the alternative pathway, C3 is cleaved into C3b. What is the role of C3b?
it binds to pathogen surface; binds factor B for cleavage by factor D
30
The Classic Complement Pathway is triggered by the activation of the ___ complex.
C1
31
_____ promotes removal of particles via complement receptors on host cells, and leads to assembly of the membrane attack complex.
Opsonization
32
Inflammation is marked by:
capillary dilation, leukocytic infiltration, redness, heat, and pain
33
We have a genetic predisposition to which kind of immunity?
innate immunity
34
DAF inhibits the assembly of classical and alternative pathway _____.
C3 convertases
35
When lectins bind to carbohydrates, which pathway is engaged?
lectin pathway (LP)
36
Upon binding of MBL to the bacterial surface, ____ and ____ become activated and then activate the complement system by cleaving C4 and C2.
MASP-1; MASP-2
37
The classical pathway utilizes the _____ complex, whereas the lectin pathway utilizes the _____ complex.
C1q, C1r, C1s; MASP-1/MASP-2 (MBL)
38
The release of ____ promotes cell activation (mast cell degranulation) or migration to the inflammatory site (chemotaxis).
anaphylatoxins
39
Which active component of the terminal complement components initiates the assembly of the membrane-attack complex?
C5b
40
Which proteins of the complement system mediate inflammation and phagocyte recruitment?
C3a, C5a
41
__ is the active enzyme of C3 convertase C3bBb and C5 convertase C3b2Bb.
Bb
42
DAF accelerates the _____ of Bb from C3b in formed C3 convertase (C3bBb), which stops the production of additional C3b.
dissociation
43
___ gets bound to the surface of the pathogen, coating its surface, after being attacked by a nucleophilic group.
C3b
44
Which pathway does the natural, spontaneous complement mechanism engage?
alternative pathway (AP)
45
____ serves as a mechanism initiating the elimination of noxious agents and damaged tissues.
Inflammation
46
C4b2a facilities the amplification of C3b for opsonization. How?
one molecule of C4b2a can cleave thousands of C3 molecules into C3b, which stick to the bacterial surface and coat it
47
Which protein initiates the effector pathway?
C5b
48
____ is a plasma protein that stabilizes the C3 convertase C3bBb on bacterial cells.
Properdin
49
What is the ultimate goal of complement system pathways?
to lead to the membrane attack complex (MAC)
50
The alternative pathway ____ contain the antibody-binding first step.
DOES NOT
51
On which targets does the complement system become activated on?
apoptotic cells, tissue debris, pathogens
52
In _____ immunity, natural antibodies are replaced by specific antibodies.
adaptive
53
___ and ___ dissociate C3 convertases on human cells.
DAF; MCP
54
What deposits C3b onto the bacterial cell surface in the alternative complement pathway?
C3 convertase of the classical or lectin pathways
55
The cleavage of C5 into C5b and C5a generates ___ and ___, respectively.
membrane attack complex (MAC); a potent pro-inflammatory mediator
56
Which immune system (innate/adaptive) involves lymphocytes (T and B cells) that can recognize and deactivate specific antigens?
adaptive immune system
57
Which factor cleaves bound factor B when it is bound to C3b?
Factor D
58
Elements from which immune system (innate/adaptive) include mucous secretions, complement proteins, and neutrophils, macrophages, and dendritic cells?
innate immune system
59
What are the terminal complement components?
C5b, C6, C7, C8, C9
60
When opsonization and destruction happens to normal cells and not bacterial cells it can cause an ______.
autoimmune disease
61
Bound factor B is cleaved by factor D and then the C3bBb complex cleaves many ___.
C3 molecules
62
C3a and C5a are ______.
anaphylatoxins
63
C3 and MCP are made in the ____.
liver
64
Which pathway does the binding of a targeted, naturally occurring antibody engage?
classical pathway (CP)
65
Complement triggers:
1) phagocytosis
2) inflammation
3) membrane attack
66
What are the two complements?
membrane perturbation and inflammation
67
C3a mediates intermediate ______.
inflammation
68
The central component of the complement system is _____.
complement fixation
69
Each of the cleavage steps in the production of C3b leads to _____, and staggering proportions of the protein.
amplification
70
How is the complement system activated mechanistically?
1) natural - spontaneous turnover of C3 engages the alternative pathway
2) antibody binding - engages the classical pathway
3) lectin to carbohydrate binding - engages the lectin pathway
71
Do MBL and ficolins have the same basic function? Do they utilize the same enzyme?
YES; NO
72
Complement is activated by a series of ____ that are ____ and create this cascade.
proteins; enzymes
73
C1 is a complex of _____.
C1q, C1r & C1s
74
Which protein of the complement system binds to complement receptors on phagocytes, opsonizes pathogens, and removes immune complexes?
C3b
75
What is C1s responsible for?
it cleaves C4 and C2
76
The biological activities and the regulatory proteins of the lectin pathway and the classical pathway are ____.
the same
77
___ initiates amplification via the alternative pathway, and binds C5 for cleavage by C2b.
C3b
78
C4b2a is an active _____, which cleaves C3 into C3a and C3b, where C3b binds to the microbial surface.
C3 convertase
79
A Type 1 allergic reaction elicits the _____ response.
wheal and flare
80
What happens to the bacterial cell membrane when the MAC is completed and forms a pore?
depolarization
81
What does C2b do?
it is the precursor to vasoactive C2 kinin
82
How many subunits is C1q (part of the C1 complex) made up of?
6
83
Which type of cells are attracted to cells that have been opsoninized?
phagocytic
84
C3b acts as an ____.
opsonin
85
Does the lectin pathway lead to the same kind of opsonization utilizing the C3 convertase as the classical and alternative pathways?
YES
86
MASP-1 and MASP-2 are associated with ____.
carbohydrate binding
87
The antigen:antibody complexes activate ____, which then targets _____.
C1q, C1r & C1s complex; C4 and C2
88
Which proteins lead to local inflammation?
C5a, C3a
89
What does C2a do?
it is the active enzyme of classical pathway C3/C5 convertase; cleaves C3 and C5
90
C3b facilitates the removal of immune complexes, which means it activates the ______ components.
terminal complement
91
C1 esterase inhibitors block angioedema on two levels; at ___ and ___.
Factor XIIa/Plasmin; Kallikrein
92
After binding of the C1 complex and immunoglobulin, a conformational change results for ____.
C1r (which then goes on to cleave C1s)
93
The redness of skin resulting from the dilation of blood vessels is called ____.
flare
94
Complement-mediated endothelial cell injury creates a ____ state.
prothrombotic
95
What do mast cells release during degranulation?
histamine
96
Which molecule polymerizes on the C5b678 complex to form a pore on the membrane?
C9
97
The addition of C3b to the C3 convertase produces ___.
C5 convertase (C3b2Bb)
98
The classical pathway, lectin pathway, and alternative pathway all converge at what enzyme?
C3 convertase
99
C4a ____ the opsonization process, whereas C3b ____ it.
initiates; amplifies
100
What happens when C5a binds to the CR1 receptor on the cell membrane of a macrophage?
the macrophage will be activated and can phagocytose the bacterium
101
CD59 (protectin) prevents formation of _____ and is widely expressed on host cell membranes.
membrane attack complex (MAC)
102
C3bBb is a __ convertase and C3b2Bb is a __ convertase.
C3; C5
103
The complement system becomes activated ____ of a prior adaptive immune system.
independently
104
C3 gets cleaved into ___ and ___. What do each of the subunits do?
C3a (recruits phagocytes)
| C3b (tags bacterium for destruction)
105
DAF inhibits the formation of C3 complement components, thereby preventing the formation of ____ in the cell membrane.
complement-mediated pores
106
C3b starts the opsonization process by _____ it.
amplifying
107
The complement system and activation of complement is part of the ____ immune system.
innate
108
Which opsonizing antigen has the most important opsonizing activity?
C3b
109
The ____ pathway is homologous to the classical pathway, but uses opsonins, mannose-binding lectin (MBL), and ficolin instead of C1q.
Lectin Pathway
110
The membrane protein that displaces Bb from C3b and C2a from C4b is called _____.
decay-accelerating factor (DAF)
111
The adaptive immune system contains genetically encoded _____ that produce a variety of proteins that can recognize specific antigens.
proteins
112
What do the terminal complement components do?
form the membrane-attack complex, lyse certain pathogens and cells
113
The C4b2a convertase leads to the C3 convertase, which can lead to the production of the _____.
C5 convertase
114
C2 gets cleaved into ___ and ___ by ____.
C2a; C2b; C1s
115
Why is the alternative pathway activated at a low level?
because C3 is mildly unstable in an aqueous environment, spontaneous C3 hydrolysis occurs (breakdown of thioester bond)
116
What are the two major functions of the complement system?
1) alters the membrane of pathogens + cellular debris (opsonization) to promote removal
2) enhances the inflammatory response that promote activation or migration of WBCs to site
117
C5b binds __ and __ to form the ____ complex.
C6; C7; C5b67
