C4 Flashcards
1
Q
- coined the term “complement” because it complements the action of antibody in destroying microorganisms.
A
Paul Ehrlich
2
Q
Heat labile series of more than 30 plasma proteins
A
complement”
3
Q
named with a (?) followed by a (?)
A
capital C
number
4
Q
- results from the cleavage of a larger precursor by a protease
A
small letter
5
Q
complement” example
A
C3a/ C3b
6
Q
- designated as b
A
Larger fragment
7
Q
- designated as a
A
Smaller fragment
8
Q
Exception:
A
C2 fragments
9
Q
Larger- (?), smaller fragment- (?)
A
C2a
C2b
10
Q
Proteins and glycoproteins synthesized mainly by liver
A
COMPONENTS
11
Q
Most circulate in the serum functionally inactive forms
A
COMPONENTS
12
Q
Produces a cascade phenomenon where the product of one reaction is the enzymatic catalyst of the next
A
COMPONENTS
13
Q
(?) soluble and cell-bound proteins
A
30
14
Q
FUNCTIONS OF COMPLEMENT
A
- Lysis of cells, bacteria and viruses
- Opsonization
- Triggers specific cell functions, inflammation and secretion of immunoregulatory molecules
- Immune clearance: removal of immune complexes and deposition in the spleen and liver
15
Q
Biological Functions
A
- Anaphylatoxin
- Increase Capillary Permeability
- Chemotaxis
- Virus neutralization
- Opsonization
16
Q
Main Complement Component Involved Opsonization
A
C3b
17
Q
Main Complement Component Involved Anaphylatoxin
A
C3a, C4a, C5a
18
Q
Main Complement Component Involved Increase Capillary Permeability
A
Role of C2b fragment
19
Q
Main Complement Component Involved Chemotaxis
A
C5a
20
Q
Main Complement Component Involved Virus neutralization
A
C4
21
Q
They bind to receptors on mast cells and basophils
A
Anaphylatoxin
22
Q
Induce degranulation and release of influx mediators including histamine
A
Anaphylatoxin
23
Q
small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells.
A
Anaphylatoxin
24
Q
Can lead to edema if complement is not controlled
A
Increase Capillary Permeability
25
Attract cells and play important role in recruitment of cells to an influx site
C5a
26
Enhances neutralization of viruses by homologous antibodies
C4
27
C3b on particles such as bacteria or an Ab-Ab complex promotes the attachment and ultimate ingestion of the particles.
C3b
28
CLASSICAL Initiated by:
Antigen-antibody complex
29
ALTERNATE/ALTERNATIVE/PROPERDIN Initiated by:
1. Aggregates of IgA
2. Yeast cell or zymogen
3. CVF
4. LPS
30
LECTIN Initiated by:
With mannose and other similar sugars in the cell wall
31
Recognition event which will initiate complement cascade
INITIATION PHASE
32
Classical and alternate pathway differ at this phase
INITIATION PHASE
33
Activation of early components culminate in activation of C3 which is the critical component
AMPLIFICATION/ ACTIVATION PHASE
34
Classical and alternate pathway differ at this phase
AMPLIFICATION/ ACTIVATION PHASE
35
Culminates in target cell lysis
MEMBRANE ATTACK PHASE
36
Classical and alternate pathway is the same at this phase
MEMBRANE ATTACK PHASE
37
Phases of Complement Activation
38
Initiation of Pathways
39
Activation of the Complement
40
Bonding of C1 complex (C1q, C1r, C1s) to antibodies bound to an antigen on the surface of a bacterial cell.
Classic Pathway
41
Contact with a foreign surface such as the polysaccharide coating of a microorganism
Alternative
42
Covalent bonding of a small amount of C3b to hydroxyl groups on cell surface carbohydrates and proteins.
Alternative
43
Activated by low-grade cleavage of C3 in plasma
Alternative
44
Binding of the complex of mannose binding lectin and associated serine proteases (MASP1 and MASP2) to arrays of mannose groups on the surface of a bacterial cell.
Mannose Binding
45
Major effector mechanisms of antibody-mediated immunity.
CLASSICAL PATHWAY
46
CLASSICAL PATHWAY
Principal components:
C1-C9
47
CLASSICAL PATHWAY
Activation:
C1, 4, 2, 3, 5, 6, 7, 8 and 9
48
present in the plasma in the largest quantities
C3
49
fixation of (?) is the major quantitative reaction of the complement cascade
C3
50
CLASSICAL PATHWAY
3 major stages:
1. Recognition
2. Amplification of proteolytic complement cascade
3. Membrane attack complex (MAC)
51
Begins with the formation of soluble antigen-antibody complexes or with binding of antibody to antigen on a suitable target such as a bacterial cell
CLASSICAL PATHWAY
52
IgM or IgG
CLASSICAL PATHWAY
53
Ag-Ab-IgM : conformational change in Fc : exposing a binding site for C1
CLASSICAL PATHWAY
54
is the recognition unit that binds to the FC portion of two antibody molecules
C1qrs
55
C1s is activated and cleaves C4 and C2 to form (?), which is known as C3 convertase.
C4b2a
56
C3 convertase cleaves C3 to form (?), known as C5 convertase.
C4b2a3b
57
The combination of (?) is the activation unit.
C4b2a3b
58
(?) cleaves C5.
C5 convertase
59
C5b attracts (?), which bind together, forming the membrane attack complex.
C6, C7, C8, and C9
60
(?) polymerizes to cause lysis of the target cell.
C9
61
Antibody is not required
ALTERNATIVE PATHWAY
62
Innate immunity
ALTERNATIVE PATHWAY
63
ALTERNATIVE PATHWAY
4 serum proteins:
C3, factor B, factor D and properdin
64
Initiated by cell-surface constituents that are foreign to the host (gram + and gram – bacterial cell walls)
ALTERNATIVE PATHWAY
65
Factors capable of activating the alternative pathway
✓ Inulin
✓ Zymosan
✓ Bacterial polysaccharides and endotoxins
✓ Aggregated IgG2, IgA and IgE
66
: proteins that recognize and bind to specific carbohydrate targets
Lectins
67
After initiation proceeds thru action of C4 and C2 to produce C5 convertase
MANNOSE BINDING LECTIN PATHWAY
68
Activated by binding of mannose-binding lectin to mannose residues on glycoproteins or carbohydrates on the surface of microorganisms such as Salmonella, Listeria, Neisseria, Cryptococcus and Candida.
MANNOSE BINDING LECTIN PATHWAY
69
The binding of (?) to two antibody molecules activates the classical pathway, while the alternative pathway is started by hydrolysis of C3.
C1qrs
70
The (?) is triggered by binding of MBP to mannose on bacterial cell walls.
lectin pathway
71
(?) bind to form an activated C1-like complex.
MASP-1, MASP-2, and MASP- 3
72
(?) cleaves C2 and C4 and proceeds like the classical pathway.
MASP-2
73
(?) operate in the alternative pathway.
Factor B and factor D
74
While C3 convertase is formed differently in each pathway, (?) is a key component in each one.
C3
75
The C5 convertase in the alternative pathway consists of (?).
C3bBb3bP
76
In the classical pathway, C5 convertase is made up of (?).
C4b2a3b
77
After (?) is cleaved, the pathway is common to all.
C5
78
3 pathways: active C5 convertase to cleave C5 --- [?] (initiates the final steps to form MAC)
C5a and C5b
79
Forms a large channel through the membrane of the target cell enabling ions and small molecules to diffuse freely across the membrane.
MEMBRANE ATTACK COMPLEX
80
Molecular wt.
410
C1q
81
Molecular wt.
85
C1r
C1s
82
Molecular wt.
205
C4
83
Molecular wt.
102
C2
84
Molecular wt.
190
C3
C5
85
Molecular wt.
110
C6
86
Molecular wt.
100
C7
87
Molecular wt.
150
C8
88
Molecular wt.
70
C9
89
Conc.(ug/mL)
150
C1q
90
Conc.(ug/mL)
50
C1r
C1s
91
Conc.(ug/mL)
300-600
C4
92
Conc.(ug/mL)
25
C2
93
Conc.(ug/mL)
1200
C3
94
Conc.(ug/mL)
80
C5
95
Conc.(ug/mL)
45
C6
96
Conc.(ug/mL)
90
C7
97
Conc.(ug/mL)
55
C8
98
Conc.(ug/mL)
60
C9
99
Binds to Fc region of IgM and IgG
C1q
100
Activates C1s
C1r
101
Cleaves C4 and C2
C1s
102
Part of C3 convertase (C4b)
C4
103
Binds to C4b—forms C3 convertase
C2
104
Key intermediate in all pathways
C3
105
Initiates membrane attack complex
C5
106
Binds to C5b in MAC
C6
107
Binds to C5bC6 in MAC
C7
108
Starts pore formation on membrane
C8
109
Polymerizes to cause cell lysis
C9
110
Molecular wt.
93
Factor B
111
Conc.(ug/mL)
200
Factor B
112
Binds to C3b to form C3 convertase
Factor B
113
Molecular wt.
24
Factor D
114
Conc.(ug/mL)
2
Factor D
115
Cleaves factor B
Factor D
116
Molecular wt.
55
Properdin
117
Conc.(ug/mL)
15-25
Properdin
118
Stabilizes C3bBb–C3 convertase
Properdin
119
Molecular wt.
200-600
MBL
120
Conc.(ug/mL)
0.0002-10
MBL
121
Binds to mannose
MBL
122
Molecular wt.
93
MASP-1
123
Conc.(ug/mL)
1.5-12
MASP-1
124
Unknown
MASP-1
125
Molecular wt.
76
MASP-2
126
Conc.(ug/mL)
Unknown
MASP-2
127
Cleaves C4 and C2
MASP-2
128
Lupus like syndrome; recurrent infections
C1 (q, r, or s)
129
Lupus like syndrome; recurrent infections; atherosclerosis
C2
130
Severe recurrent infections; glomerulonephritis
C3
131
Lupus like syndrome
C4
132
Neisseria infections
C5-C8
133
No known disease association
C9
134
Hereditary angioedema
C1INH
135
Paroxysmal nocturnal hemoglobinuria
DAF
136
Paroxysmal nocturnal hemoglobinuria
MIRL
137
Recurrent pyogenic infections
Factor H or factor I
138
Pneumococcal disease, sepsis, Neisseria infections
MBL
139
Neisseria infections
Properdin
140
Pneumococcal diseases
MASP-2
141
associated with inflammatory conditions, trauma, or acute illness
INCREASED COMPLEMENT LEVELS
142
Limited clinical significance
INCREASED COMPLEMENT LEVELS
143
Low levels of complement suggest one of the following biological effects:
• Complement has been excessively activated recently.
• Complement is currently being consumed.
• A single complement component is absent because of a genetic defect.
144
result from the complexing of IgG or IgM antibodies capable of activating complement
HYPOCOMPLEMENTEMIA
145
associated with diseases that give rise to circulating immune complexes.
HYPOCOMPLEMENTEMIA
146
The (?) is a series of more than 30 proteins normally found in serum that play a major role in phagocytosis and clearance of foreign antigens from the body.
complement system
147
While the end product of complement activation is lysis, other important events, such as (?) of monocytes and neutrophils take place along the way to enhance host defense mechanisms.
opsonization, increase in vascular permeability, and chemotaxis
148
Most of the proteins of the complement system are inactive enzyme precursors, or (?), that are converted to active enzymes in a very precise order.
zymogens
149
One means of activation is the (?), which is triggered by antigen–antibody combination and involves nine of the proteins.
classical pathway
150
(?) plays a major role in several disease states.
Complement
151
Decreased complement levels or a decline in lytic activity can indicate either (?)
hereditary deficiencies or extreme activation of the system
152
(?) are two conditions that result from missing or very low production of certain regulators.
Paroxysmal nocturnal hemoglobinuria and hereditary angioedema
153
Deficiencies of some components, especially that of C3, may cause an increased risk of (?) due to a lack of clearance of immune complexes.
lifethreatening infection or glomerulonephritis
154
Several laboratory assays have been devised to detect (?).
abnormal complement levels
155
One of these, the (?), uses 50 percent lysis of a standard concentration of antibody-sensitized sheep erythrocytes as an end point.
CH50 hemolytic assay
156
This measures the presence of all proteins involved in the classical pathway.
CH50 hemolytic assay
157
A similar assay, the (?), measures the functioning of the alternative pathway.
AH50 assay
158
Other assays using (?) measure levels of individual components.
RID or ELISA techniques
159
(?) is essential to ensure correct interpretation of laboratory testing.
Proper handling of specimens
160
(?) use complement as a reagent to detect the presence of antigen or antibody.
Complement fixation tests
161
(?) are allowed to combine with a measured amount of complement.
Antigen and antibody
162
Then indicator (?) are added.
sheep red blood cells
163
These are coated with (?) (antisheep cell antibody), and if complement has not been tied up in the first reaction, then lysis of the cells occurs.
hemolysin
164
Thus, (?) is a negative test, indicating that either antigen or antibody was not present.
lysis
165
As in all complement testing, the use of (?) is necessary for accurate results.
standards and control
