CHAPTER III – COMPLEMENT Flashcards
1
Q
COMPLEMENT Meaning -
A
to Help or to make Complete
2
Q
COMPLEMENT year
A
1890s
3
Q
Coined the term:
A
Paul Ehrlich
4
Q
Elucidate the control of the complement; Novel price
A
Jules Bordet
5
Q
A primary part of the
A
Innate immune response
6
Q
Substance under the
A
humoral-mediated immunity
7
Q
Group of
A
30 different proteins
8
Q
Designation
A
• Numerals (C1-C9)
• Letter symbols (factor D)
9
Q
Cleavage Products – enzyme activation
A
a and b
10
Q
named with a capital C followed by a
A
number
11
Q
- results from the cleavage of a larger precursor by a protease
A
small letter
12
Q
Ex. C3a/ C3b
• Larger fragment- designated as
• Smaller fragment- designated as
A
b
a
13
Q
Exception:
A
C2 fragments
14
Q
Larger-
smaller fragment-
A
C2a
C2b
15
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
16
Q
Proteins and glycoproteins synthesized mainly by
A
liver hepatocytes
17
Q
Most circulate in the serum functionally inactive forms as
A
proenzymes or zymogens
18
Q
PRODUCES A
A
CASCADE PHENOMENON
19
Q
WHERE THE PRODUCT OF ONE REACTION IS THE (?) OF THE NEXT
A
ENZYMATIC CATALYST
20
Q
Heat Labile: destroyed when heated at
A
56°C for 30 mins
21
Q
Anaphylatoxin
A
C3a, C4a, C5a
22
Q
Increase Capillary Permeability
A
Role of C2b fragment
23
Q
Chemotaxis
A
C5a
24
Q
Virus neutralization
A
C4
25
Opsonization
C3b
26
They bind to receptors on mast cells and basophils
Anaphylatoxin
27
Induce degranulation and release of influx mediators including histamine
Anaphylatoxin
28
Can lead to edema if complement is not controlled
Increase Capillary Permeability
29
Attract cells and play important role in recruitment of wbc cells to an influx site
Chemotaxis
30
Enhances neutralization of viruses by homologous antibodies
Virus neutralization
31
C3b on particles such as bacteria or an Ab-Ab complex promotes the attachment and ultimate ingestion of the particles.
Opsonization
32
Initiated by: Antigen-antibody complex
CLASSICAL
33
First to be studied
CLASSICAL
34
Initiated by:
1. Aggregates of IgA
2. Yeast cell or zymogen
3. CVF
4. LPS
ALTERNATE/ ALTERNATIVE/ PROPERDIN LECTIN
35
Initiated by: With mannose and other similar sugars in the cell wall
LECTIN
36
Ab-dependent
CLASSICAL
37
ALTERNATE/ ALTERNATIVE/ PROPERDIN LECTIN
LECTIN
Ab-independent
38
Biological Functions
39
Initiation of Pathways
40
Phases of Complement Activation
41
Recognition event which will initiate complement cascade
INITIATION PHASE
42
Classical and alternate pathway differ at this phase
INITIATION PHASE
43
Activation of early components culminate in activation of C3 which is the critical component
AMPLIFICATION / ACTIVATION PHASE
44
Classical and alternate pathway differ at this phase
AMPLIFICATION / ACTIVATION PHASE
45
Culminates in target cell lysis
MEMBRANE ATTACK PHASE
46
Classical and alternate pathway is the same at this phase
MEMBRANE ATTACK PHASE
47
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
48
IgM or IgG
CLASSICAL PATHWAY
49
Ag-Ab-IgM: conformational change in Fc : exposing a binding site for C1
CLASSICAL PATHWAY
50
Antibody is not required
ALTERNATIVE PATHWAY
51
Innate immunity
ALTERNATIVE PATHWAY
52
4 serum proteins: C3, factor B, factor D and properdin + C5 + C6789
ALTERNATIVE PATHWAY
53
Initiated by cell-surface constituents that are foreign to the host (gram + and gram - bacterial cell walls)
ALTERNATIVE PATHWAY
54
: proteins that recognize and bind to specific carbohydrate targets
Lectins
55
After initiation proceeds thru action of CA and C2 to produce C5 convertase
LECTIN PATHWAY
56
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
57
3 pathways : active C5 convertase to cleave C5 --- C5a and C5b (initiates the final steps to form MAC)
Membrane Attack Complex
58
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
59
105
C1 inhibitor (C1INH)
60
240
C1 inhibitor (C1INH)
61
Dissociates C1r and C1s from C1q
C1 inhibitor (C1INH)
62
88
Factor I
63
35
Factor I
64
Cleaves C3b and C4b
Factor I
65
150
Factor H
66
300-450
Factor H
67
Cofactor with I to inactivate C3b
Factor H
68
prevents binding of B to C3b
Factor H
69
520
C4-binding protein
70
250
C4-binding protein
71
Acts as a cofactor with I to inactivate C4b
C4-binding protein
72
84
S protein (vitronectin)
73
500
S protein (vitronectin)
74
Prevents attachment of the C5b67 complex to cell membranes
S protein (vitronectin)
75
165,000 to 280,000
CR1 or Complement Regulator 1
76
It is found mainly on peripheral blood cells, including neutrophils, monocytes, macrophages, erythrocytes, eosinophils, B lymphocytes, some T lymphocytes, and follicular dendritic cells.
CR1 or Complement Regulator 1
77
It binds C3b and C4b but has the greatest affinity for C3b
CR1 or Complement Regulator 1
78
CD45
CR1 or Complement Regulator 1
79
50,000 to 70,000
Membrane Cofactor Protein
80
found on virtually all epithelial and endothelial cells except erythrocytes.
Membrane Cofactor Protein
81
is the most efficient cofactor for factor Imediated cleavage of C3b
Membrane Cofactor Protein
82
CD46
Membrane Cofactor Protein
83
70,000
DAF or Decayaccelerating factor
84
It is found on peripheral blood cells, on endothelial cells and fibroblasts, and on numerous types of epithelial cells.
DAF or Decayaccelerating factor
85
capable of dissociating both classical and alternative pathway C3 convertases
DAF or Decayaccelerating factor
86
CD55
DAF or Decayaccelerating factor
87
widely distributed on the cell membranes of all circulating blood cells, including red blood cells, and on endothelial, epithelial, and many other types of cell
MIRL or Membrane inhibitor of reactive lysis
88
bind to C8 and prevent insertion of C9 into host cell membranes
MIRL or Membrane inhibitor of reactive lysis
89
CD59
MIRL or Membrane inhibitor of reactive lysis
90
C3b, iC3b, C4b
CR1
91
RBCs, neutrophils, monocytes, macrophages, eosinophils, B and T cells, follicular dendritic cells
CR1
92
Cofactor for factor I
CR1
93
mediates transport of immune complexes
CR1
94
(CD35)
CR1
95
C3dg, C3d, iC3b
CR2
96
B cells, follicular dendritic cells, epithelial cells
CR2
97
B-cell coreceptor for antigen with CD19
CR2
98
(CD21)
CR2
99
iC3b, C3d, C3b
CR3
100
Monocytes, macrophages, neutrophils, NK cells
CR3
101
Adhesion and increased activity of phagocytic cells
CR3
CR4
102
(CD11b/CD18)
CR3
103
(CD11c/CD18)
CR4
104
C3b, C4b
DAF
105
RBCs, neutrophils, platelets, monocytes, endothelial cells, fibroblasts, T cells, B cells, epithelial cells
DAF
106
Dissociates C2b or Bb from binding sites, thus preventing formation of C3 convertase
DAF
107
(CD55)
DAF
108
C8
MIRL
109
RBCs, neutrophils, platelets, monocytes, endothelial cells, epithelial cells
MIRL
110
Prevents insertion of C9 into cell membrane
MIRL
111
(CD59)
MIRL
112
C3b, C4b
MCP
113
Neutrophils, monocytes, macrophages, platelets, T cells, B cells, endothelial cells
MCP
114
Cofactor for factor I cleavage of C3b and C4b
MCP
115
(CD46)
MCP
116
• associated with inflammatory conditions, trauma, or acute illness
INCREASED COMPLEMENT LEVELS
117
• Limited clinical significance
INCREASED COMPLEMENT LEVELS
118
• Low levels of complement suggest one of the following biological effects:
1. Complement has been excessively activated recently.
2. Complement is currently being consumed.
119
• A single complement component is absent because of a genetic defect
DECREASED COMPLEMENT LEVELS
120
HYPOCOMPLEMENTEMIA
DECREASED COMPLEMENT LEVELS
121
• result from the complexing of IgG or IgM antibodies capable of activating complement
HYPOCOMPLEMENTEMIA
122
• associated with diseases that give rise to circulating immune complexes.
HYPOCOMPLEMENTEMIA
123
Lupus-like syndrome; recurrent infections
C1 (q, r, or s)
124
Lupus-like syndrome; recurrent infections; atherosclerosis
C2
125
Severe recurrent infections; glomerulonephritis
C3
126
Lupus-like syndrome
C4
127
Neisseria infections
C5-C8
Properdin
128
No known disease association
C9
129
Hereditary angioedema
C1INH
130
Paroxysmal nocturnal hemoglobinuria
DAF
MIRL
131
Recurrent pyogenic
Factor H or Factor I
132
Pneumococcal diseases, sepsis, Neisseria infections
MBL
133
Pneumococcal diseases
MASP-2
134
Marks the start of Recognition unit CLASSICAL
C1qrs
135
Marks the start of Recognition unit ALTERNATIVE
C3
136
Marks the start of Recognition unit LECTIN
C1-like complex (MASP-1, MASP-2, and MASP)
137
Marks the start of Activation unit CLASSICAL
C4b2a (C3 convertase)
138
Marks the start of Activation unit ALTERNATIVE
C3bBb (C3 convertase)
139
Marks the start of Activation unit LECTIN
C3 convertase
140
Marks the start of Membrane attack complex CLASSICAL
C5b
141
Marks the start of Membrane attack complex ALTERNATIVE
C5b
142
Marks the start of Membrane attack complex LECTIN
C5b
143
C3 convertase CLASSICAL
C4b2a
144
C3 convertase ALTERNATIVE
C3bBb
145
C5 convertase CLASSICAL
C4b2a3b
146
C5 convertase ALTERNATIVE
C3bBb3b
147
Binds to Fc region of IgM and IgG
C1q
148
Activates C1s
C1r
149
Cleaves C4 and C2
C1s
150
Part of C3 convertase (C4b)
C4
151
Binds to C4b—forms C3 convertase
C2
152
Key intermediate in all pathways Initiates membrane attack complex
C3
153
Initiates membrane attack complex
C5
154
Binds to C5bC6 in MAC
C7
155
Starts pore formation on membrane
C8
156
Polymerizes to cause cell lysis
C9
157
Binds to C3b to form C3 convertase
Factor B
158
Cleaves factor B
Factor D
159
Stabilizes C3bBb–C3 convertase
Properdin
160
Binds to mannose
MBL
161
Unknown
MASP-1
162
Cleaves C4 and C2
MASP-2
163
Binds to C5b in MAC
C6
