6 - COMPLEMENT SYSTEM Flashcards

(164 cards)

1
Q

What humoral mechanism of nonspecific immunity consists of about nine main serum proteins that act in a cascade to lyse cells

A

complement system

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2
Q

What organ is the primary source of most complement components

A

liver

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3
Q

What complement component is produced by intestinal epithelial cells

A

C1

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4
Q

What complement factor is produced in adipose tissue

A

Factor D

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5
Q

What complement pathway is initiated by antigen antibody complexes

A

classical pathway

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6
Q

What immunoglobulin class is most efficient at activating the classical complement pathway

A

IgM

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7
Q

What immunoglobulin subclasses can activate the classical complement pathway

A

IgG1 + IgG2 + IgG3 + IgG4 with IgG4 being weak

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8
Q

Which immunoglobulins are generally poor activators or incapable of classical pathway activation

A

IgG4 + IgA + IgE + IgD

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9
Q

What complement pathway is initiated by mannose binding lectin carbohydrate interactions

A

lectin + MBL pathway

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10
Q

What complement pathway is initiated by spontaneous hydrolysis of C3 and by microbial surfaces

A

alternative pathway

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11
Q

What immunoglobulins are most commonly associated with alternative pathway activators

A

IgA aggregates

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12
Q

What pattern recognition molecule that binds to mannose initiates the lectin pathway

A

mannose binding lectin + MBL

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13
Q

What serine proteases associated with MBL cleave C4 and C2

A

MASP 1 + MASP 2

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14
Q

What is the order of discovery for the nine classical pathway components

A

C1–C9

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15
Q

What is the order of activation in the classical pathway

A

C1→C4→C2→C3→C5→C6→C7→C8→C9

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16
Q

What complement component is the key convergence point for all three pathways

A

C3

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17
Q

What cleaved complement fragment serves as a major opsonin

A

C3b

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18
Q

What other complement fragments besides C3b can act as opsonins

A

C4b + iC3b + C3dg

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19
Q

What complement fragment is a potent chemotaxin for leukocytes

A

C5a

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20
Q

What ions are required for certain complement pathways

A

calcium + magnesium

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21
Q

What group of complement fragments act as anaphylatoxins

A

C3a + C4a + C5a

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22
Q

Which anaphylatoxin has the strongest biologic activity

A

C5a

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23
Q

What small peptide anaphylatoxin increases vascular permeability + contracts smooth muscle + and triggers histamine release

A

C5a

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24
Q

What is the first complement pathway to be discovered

A

classical pathway

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25
What is the most recently described complement pathway
lectin + MBL pathway
26
What is the most evolutionarily ancient complement pathway
alternative pathway
27
What pathway provides a bridge between innate and adaptive immunity
LECTIN
28
What pathway is particularly important as a defense mechanism in early life
alternative pathway
29
What pathway is most effective against certain viral infections
lectin pathway
30
What recognition unit characterizes the classical pathway
C1qrs
31
What recognition units are characteristic of the lectin pathway
MBL + MASP
32
What recognition components are characteristic of the alternative pathway
Factor B + Factor D + Factor P
33
What molecule is the recognition unit of the classical pathway that binds to the Fc region of IgM and IgG
C1q
34
What component of the classical pathway activates C1s
C1r
35
What component of the classical pathway cleaves C4 and C2
C1s
36
What component of the classical pathway is part of the C3 convertase and is the second most abundant complement protein
C4
37
What component of the classical pathway binds to C4b to form the C3 convertase
C2
38
What component of the complement pathway is the pivotal intermediate in all three pathways
C3
39
What component of the complement pathway is the most abundant serum protein
C3
40
What complement component initiates formation of the membrane attack complex
C5
41
What complement protein binds to C5b in the membrane attack complex
C6
42
What complement protein binds to C5bC6 in the membrane attack complex
C7
43
What complement protein starts the formation of the transmembrane pore in the MAC
C8
44
What complement protein polymerizes to form the lytic pore in the MAC
C9
45
What component of the alternative pathway binds to C3b to form the C3 convertase
Factor B
46
What component of the alternative pathway cleaves Factor B
Factor D
47
What component of the alternative pathway stabilizes the C3 and C5 convertases
properdin
48
What pattern recognition protein in the lectin pathway binds mannose on microbial surfaces
mannose binding lectin + MBL
49
What protease of the lectin pathway helps cleave C4 and C2
MASP 1
50
What protease of the lectin pathway primarily cleaves C4 and C2
MASP 2
51
What is the C3 convertase of the classical pathway
C4b2a
52
What is the C5 convertase of the classical pathway
C4b2a3b
53
What is the C3 convertase of the lectin pathway
C4b2a
54
What is the C5 convertase of the lectin pathway
C4b2a3b
55
What is the C3 convertase of the alternative pathway
iC3bBb
56
What is the C5 convertase of the alternative pathway
iC3bBb3b
57
What inhibitor dissociates C1r and C1s from C1q
C1 inhibitor + C1INH
58
What regulator cleaves C3b and C4b
Factor I
59
What cofactor for Factor I inactivates C3b and prevents Factor B binding
Factor H
60
What soluble regulator is the principal controller of the alternative pathway
Factor H
61
What regulator acts as a cofactor with Factor I to inactivate C4b
C4 binding protein
62
What protein prevents attachment of the C5b C6 C7 complex to the membrane
S protein + vitronectin
63
What membrane regulator dissociates Bb or C2b from C3 convertase sites
DAF + CD55
64
What membrane regulator prevents insertion of C9 into the membrane
MIRL + CD59
65
What receptor on many blood cells binds C3b and C4b and mediates immune complex transport
CR1 + CD35
66
What regulatory protein on most epithelial and endothelial cells is the most efficient cofactor for Factor I mediated C3b cleavage
MCP + CD46
67
What structural feature of C1q includes six globular heads and a collagen like tail
modular trimeric structure
68
What metal ion is required for properdin mediated stabilization of alternative pathway convertases
magnesium
69
What feature of the alternative pathway allows it to bypass C1qrs + C4 + and C2
starting from C3 hydrolysis
70
What process initiates activation of the alternative pathway
spontaneous hydrolysis of native C3
71
What is the relative size of complement fragments b versus a in most cases
fragment b is larger than fragment a
72
What two complement fragments are produced when C3 is cleaved
C3a + C3b
73
What two complement fragments are produced when C4 is cleaved
C4a + C4b
74
What two complement fragments are produced when C5 is cleaved
C5a + C5b
75
What group of components forms the membrane attack complex
C5b + C6 + C7 + C8 + C9
76
What is the terminal complex formed by C5b through C9
C5b 9 + MAC
77
What approximate pore size does the MAC produce in the target membrane
70–100 Angstroms
78
What physiologic change in the target cell leads to lysis after MAC insertion
influx of water + loss of electrolytes
79
What complement component greatly accelerates lysis when present in the MAC
C9
80
What clinical consequence is relatively mild even in C9 deficiency
recurrent infections + not severe lysis defects
81
What disease is associated with C1 deficiency
lupus like syndrome + recurrent infections
82
What disease is associated with C2 deficiency
lupus like syndrome + recurrent infections + atherosclerosis
83
What is the most common complement deficiency
C2 deficiency
84
What is the most serious or severe complement deficiency
C3 deficiency
85
What disease pattern is associated with C3 deficiency
severe recurrent infections + glomerulonephritis
86
What complement deficiency is associated with Neisseria infections
C5–C8 + C9 deficiency
87
What disease is associated with C1INH deficiency
hereditary angioedema
88
What disease is associated with DAF or CD55 deficiency
paroxysmal nocturnal hemoglobinuria
89
What deficiency is associated with MIRL or CD59 deficiency
paroxysmal nocturnal hemoglobinuria
90
What deficiency is associated with Factor H or Factor I deficiency
severe recurrent infections + thrombotic + inflammatory complications
91
What deficiency is associated with MBL deficiency
increased susceptibility to pneumococcal disease + infections
92
What deficiency is associated with properdin deficiency
Neisseria infections
93
What complement protein is often used as the most sensitive marker of disease activity in systemic inflammation
C3
94
What complement component is reduced in severe liver disease and in SLE with renal involvement
C4
95
What laboratory assay detects complement activation through immune complex mediated fixation
complement fixation test
96
What general assay detects complement activation via antigen-antibody-complement-dependent lysis of indicator cells
complement fixation assay
97
What source of complement is commonly used in the complement fixation test
guinea pig complement
98
What is the indicator system in the complement fixation assay
sheep red blood cells coated with anti-sheep antibody
99
What result pattern indicates a positive complement fixation test
no hemolysis
100
What result pattern indicates a negative complement fixation test
hemolysis
101
What outcome in the complement fixation assay means complement was consumed by antigen-antibody complexes
no hemolysis
102
What outcome in the complement fixation assay means complement was available to lyse antibody-coated sheep red blood cells
hemolysis
103
What term is used for the antibody that coats the sheep red blood cells in the indicator system
hemolysin or amboceptor
104
What automated or turbidity-based method is frequently used to measure individual complement components
nephelometry
105
What quantitative method involves antigen-antibody-precipitin-ring formation to measure complement proteins
radial immunodiffusion or RID
106
What two complement components are most commonly measured in routine clinical practice
C3 and C4
107
What standard method is used to quantitate classical-pathway hemolytic activity
CH50 assay
108
What substance is measured in the CH50 assay when it lysed 50 percent of sensitized sheep erythrocytes
patient serum titer causing 50 percent lysis
109
What model system uses antibody-sensitized sheep erythrocytes as target cells
CH50 assay system
110
What modified hemolytic assay measures the functional activity of the alternative pathway
AH50 assay
111
What two ions are manipulated to block the classical pathway and selectively activate the alternative pathway
calcium and magnesium via EGTA and MgCl2
112
What chelating agent is used with magnesium to block calcium-dependent classical-pathway activation
EGTA
113
What test measures binding of immune complexes to C1q
C1q-binding assay
114
What elevated result in the C1q-binding assay indicates circulating immune complexes
high C1q-binding values
115
What clinical use is suggested for the C1q-binding assay in certain leukemias
prognostic tool in acute myelogenous leukemia
116
What term is used for soluble chemical messengers that regulate immune-cell communication and behavior
cytokines
117
What immune functions do cytokines orchestrate
innate and adaptive immunity
118
What subset of cytokines is produced by T cells and historically termed lymphokines
T-cell-derived cytokines
119
What subset of cytokines is produced by monocytes and macrophages and historically termed monokines
monocyte-derived cytokines
120
What six major groups categorize cytokines
interleukins chemokines colony-stimulating factors tumor necrosis factors transforming growth factors interferons
121
What four cytokines are key proinflammatory mediators
TNF-alpha IL-1 IL-6 IFN-gamma
122
What functional group mediates chemotaxis and leukocyte trafficking
chemokines
123
What cytokines of innate immunity include IL-1 IL-6 IL-10 IL-12 IL-15 IL-18 TNF and type I interferons
innate cytokines
124
What cytokines of adaptive immunity include IFN-gamma IL-2 IL-4 IL-5 IL-13 lymphotoxin and TGF-beta
adaptive cytokines
125
What three cytokines are major anti-inflammatory mediators
TGF-beta IL-10 IL-13
126
What term describes one cytokine having multiple effects
pleiotropy
127
What term describes multiple cytokines having similar effects
redundancy
128
What term describes cooperative cytokine interaction
synergy
129
What term describes opposing cytokine effects
antagonism
130
What pathologic state involves massive cytokine overproduction
cytokine storm
131
What clinical consequence can result from cytokine storm
shock multiorgan failure death
132
What proinflammatory cytokines are produced early by monocytes macrophages dendritic cells
IL-1alpha IL-1beta
133
What term describes IL-1 as fever-inducing
endogenous pyrogen
134
What molecules induced by IL-1 recruit leukocytes
adhesion molecules chemokines IL-6
135
What process allows leukocyte passage through endothelium
diapedesis
136
What cytokine is a T and B cell growth factor and activates NK cells
IL-2
137
What cytokine promotes Th2 differentiation and IgG1 IgE production
IL-4
138
What cytokine stimulates hematopoiesis
IL-3
139
What cytokine induces acute-phase reactants
IL-6
140
What cytokines are TNF-alpha and TNF-beta
tumor necrosis factors
141
What cytokine is also called cachectin
TNF-alpha
142
What stimulus induces TNF-alpha
lipopolysaccharide
143
What condition may result from excess TNF-alpha
septic shock
144
What TNF cytokine is lymphotoxin
TNF-beta
145
What interferons inhibit viral replication
type I interferons
146
What interferon is leukocyte interferon
IFN-alpha
147
What interferon is from fibroblasts epithelial cells
IFN-beta
148
What effect of type I interferons enhances killing of infected cells
increased recognition
149
What clinical use of IFN-beta
multiple sclerosis treatment
150
What clinical uses of IFN-alpha
hepatitis C Kaposi sarcoma leukemias lymphomas
151
What interferon is key Th1 cytokine
IFN-gamma
152
What effect of IFN-gamma on macrophages
activation
153
What cells activated by IFN-gamma
Th1 CD8 NK
154
What cytokine upregulates MHC I and II
IFN-gamma
155
What cytokine regulates proliferation differentiation apoptosis inflammation
TGF-beta
156
What role of TGF-beta
anti-inflammatory regulation
157
What T cell development process regulated by TGF-beta
CD8 expression control
158
What cytokines inhibited by TGF-beta
IL-12 IFN-gamma
159
What mucosal process influenced by TGF-beta
oral tolerance
160
What cells recruited by ECF-A
eosinophils
161
What cells recruited by NCF-A
neutrophils
162
What protease activates C3 and mucus production
tryptase
163
What mediators cause bronchoconstriction secretion permeability
leukotrienes PAF
164
What cytokines produced in type I hypersensitivity
IL-1 IL-3 IL-4 IL-5 IL-6 IL-9 IL-13 GM-CSF TNF-alpha