BIOLOGYofCOMPLEMENT. BIOLOGYDIAGNOSIS COMPLEMENT.
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Transcript of BIOLOGYofCOMPLEMENT. BIOLOGYDIAGNOSIS COMPLEMENT.
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BIOLOGYBIOLOGY
ofof
COMPLEMENTCOMPLEMENT
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BIOLOGYBIOLOGYDIAGNOSISDIAGNOSIS
COMPLEMENTCOMPLEMENT
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= C4d
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= C4d C3 injury
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= C4d C3 injury
MBL
ApoptoticCMV cells
CRP
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= C4d C3 injury
MBL
ApoptoticCMV cells
CRPRegulators
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= C4d C3 injury
MBL
ApoptoticCMV cells
CRPRegulators
protection
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C1
C4
C2
C3MBL
B
C5
Classical
Lectin
Alternative
Three Pathways of Complement ActivationThree Pathways of Complement Activation
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C1
C4
C2
C3MBL
B
C5
Classical
Lectin
Alternative
Three Pathways of Complement ActivationThree Pathways of Complement Activation
a
a
a
b
b
b
b
a
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C1 C2 C5 C6 C7 C8 C9C4 C30.6 mg/ml1.3 mg/ml
C4b
C2a
C3b
Bb
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C1 C2 C5 C6 C7 C8 C9C4 C30.6 mg/ml1.3 mg/ml
C1inh
Factor IC4bp CR1
MCP
Factor IDAF CR1
MCP
C4bp
Factor IDAF CR1Factor H
CD59Clusterin
VitronectinC
4bC
2a
C3b
Bb
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C3b > C4b CR1iC3b > iC4b CR3
C3d > C4d CR2
FUNCTIONFUNCTION
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C4d vs C3d STAININGC4d vs C3d STAINING
0
1
2
3
4
0 1 2 3 4
C3d
C4d
FemaleMaleATGAM
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ATGAM
Thymoglobulin
(Horse polyclonal)
(Rabbit polyclonal)
C4d+ / Total
C4d DepositionC4d DepositionATGAM vs ThymoglobulinATGAM vs Thymoglobulin
9 / 9
0 / 8
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C Reactive Protein Activation of Complement
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CRP- Complement Complexes in Renal TransplantRecipients
ÑÑ
ÑÑ
J J J JH
H
H
H
F F F
F
B B B BÉÉ
É
É
ÇÇ
Ç
Ç
ÅÅ Å
Å3
33
3
â
before day3 before day3 0
50
100
150
200
250
Time Relative to Transplantation
Ñ
Ñ
Ñ
ÑJ
J
J JH
H
H
H
F
F
F
F
B B B B
É
É
É
É
Ç
Ç
Ç
Ç
Å
Å
Å
Å
3
3
3
3â
0
50
100
150
200
250
C4b C3b C4d C3d
J Immunol 157: 473 '96
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ANTIBODY ASSOCIATED REJECTION
7 years after transplantation anti-DR7 and DRw53
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ANTIBODY ASSOCIATED REJECTION
after plasmapheresis plus IVIg anti-DR7 and DRw53 undetectable
C4d C3d
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B
B
Ñ
Ñ
H
H
Ç
Ç
J J
ÉÉ
4 hr 8 hr0
10
20
30
40
50
60
70B iC3b
Ñ (+IL-1)
H C3d
Ç (+IL-1)
J ICAM
É (+IL-1)
Clearance of iC3b and C3dClearance of iC3b and C3dfrom Human Endothelial Cells in vitro
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“SUBLYTIC” MACLEUKOCYTE ACTIVATION BY
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MAC
Endothelial
ACTIVATION OF ENDOTHELIAL CELL BY MAC
W-P
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MAC
Endothelial
ACTIVATION OF ENDOTHELIAL CELL BY MAC
P-selectinvWfCD63
TissueFactor
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MAC
Endothelial
ACTIVATION OF ENDOTHELIAL CELL BY MAC
P-selectinvWfCD63
TissueFactor
Synthesis
PAFMCP-1
bFGF
P-selectin
TissueFactor
PDGF
IL-8
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MAC
Endothelial
P-selectinvWfCD63
TissueFactor
Synthesis
PAFMCP-1
bFGF
P-selectin
TissueFactor
PDGF
IL-8
Monocyte/Macrophage
Patelet
P-selectinbFGFPDGF
vWfTissueFactor
TNF
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B. Wasowska et al 2001 Transplantation 71, 727.
vWf
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Ig Knock Out Recipients
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0
10
20
30
40
50
60
70
80
90
100
SLENormal
Tan et al. Arth & Rheum 40: 1601-1611, 1997
1:3201:1601:801:40
Operating Characteristics of Operating Characteristics of ANA Immunofluorescence AssaysANA Immunofluorescence Assays
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HUMORAL IMMUNITY IN HUMORAL IMMUNITY IN CARDIAC TRANSPLANTSCARDIAC TRANSPLANTS
Cardiac Surgery:J. Conte Cardiology:D Carter, EK Kasper, D Judge Immunogenetics:D Lucas, MS Leffell, AA Zachary Bioengineering:J Haun, R AlevriadouPathology:RH Hruban, ER Rodriguez, WM Baldwin III