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Explore the complex biology of complement activation in C4d and C3 injury, MBL, CRP, apoptotic and CMV cells, and various regulatory factors. Understand the three pathways of complement activation and their significance in diagnosis and treatment.
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BIOLOGY of COMPLEMENT
COMPLEMENT DIAGNOSIS BIOLOGY
= C4d
C3 injury = C4d
= C3 injury C4d MBL CRP Apoptotic CMV cells
= C3 injury C4d MBL Regulators CRP Apoptotic CMV cells
protection = C3 injury C4d MBL Regulators CRP Apoptotic CMV cells
Three Pathways of Complement Activation Classical C1 C4 Lectin C2 C5 C3 MBL B Alternative
Three Pathways of Complement Activation Classical C1 C4 b a a Lectin C2 C5 C3 b b a MBL a B b Alternative
C4bC2a C3bBb C3 C4 C1 C2 C5 C6 C7 C8 C9 0.6 mg/ml 1.3 mg/ml
C4bp DAF CR1 Factor I MCP Factor H DAF CR1 Factor I C4bp CR1 Factor I Vitronectin MCP Clusterin C4bC2a C1inh CD59 C3bBb C3 C4 C1 C2 C5 C6 C7 C8 C9 0.6 mg/ml 1.3 mg/ml
FUNCTION C3b > C4b CR1 iC3b > iC4b CR3 C3d > C4d CR2
C4d Deposition ATGAM vs Thymoglobulin C4d+ / Total ATGAM 9 / 9 (Horse polyclonal) Thymoglobulin 0 / 8 (Rabbit polyclonal)
ANTIBODY ASSOCIATED REJECTION 7 years after transplantation anti-DR7 and DRw53
ANTIBODY ASSOCIATED REJECTION after plasmapheresis plus IVIg anti-DR7 and DRw53 undetectable C4d C3d
Clearance of iC3b and C3d from Human Endothelial Cells in vitro
LEUKOCYTE ACTIVATION BY “SUBLYTIC” MAC
ACTIVATION OF ENDOTHELIAL CELL BY MAC MAC W-P Endothelial
ACTIVATION OF ENDOTHELIAL CELL BY MAC MAC CD63 vWf P-selectin Retraction Endothelial Tissue Factor
ACTIVATION OF ENDOTHELIAL CELL BY MAC MAC PAF CD63 vWf P-selectin MCP-1 Synthesis Tissue IL-8 Factor Retraction Endothelial P-selectin Tissue Factor bFGF PDGF
Monocyte/ P-selectin bFGF Macrophage MAC PDGF Patelet vWf Tissue TNFa CD63 vWf PAF Factor P-selectin MCP-1 Synthesis Tissue IL-8 Factor Retraction Endothelial P-selectin Tissue Factor bFGF PDGF
vWf B. Wasowska et al 2001 Transplantation 71, 727.
Operating Characteristics of ANA Immunofluorescence Assays 1:40 1:80 1:160 1:320 Tan et al. Arth & Rheum 40: 1601-1611, 1997
HUMORAL IMMUNITY IN CARDIAC TRANSPLANTS Cardiac Surgery: J. Conte Cardiology: D Carter, EK Kasper, D Judge Immunogenetics: D Lucas, MS Leffell, AA Zachary Bioengineering: J Haun, R Alevriadou Pathology: RH Hruban, ER Rodriguez, WM Baldwin III