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Transplant Immunology
Adi Alherbish
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Outline Pre-sensitization: - B cells
Ischemia-reperfusion injury/ innate immune response: - TLR - Complement - NK cells Afferent arm: - APC - TH cells Efferent arm: - Cytopathic T cells, T-reg - B cells, Plasma cells
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Meet the Characters Adkinson: Middleton's Allergy: Principles and Practice, 7th ed.
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B cells
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Sensitization Events Exposure to non- self HLA antigens
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Mature B cells Memory B cells Plasma cells
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Methods of Antibody Detection
Clin J Am Soc Nephrol 1: 404–414, 2006
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Luminex
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Ischemia Reperfusion Injury
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TLR HSP-70 HSP-60 TEC APCs
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Immune Response to Post Ischemic Kidney
Jang et al, Clinical Immunology (2009) 130, 41–50
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C3 wild type mice C3 -/- deficient mice
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B cell- mediated rejection
IRI
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NK Cells Role in Acute and Chronic Allograft Rejection
IFG
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HLA
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MHC I: Nucleated cells
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MHC II: B cells, APCs
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Interferon Endothelial cells MHC I MHC I MHC II
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Minor Histocombpatibility Antigens (miH)
MICA MICB located in close proximity to the HLA-B locus and encode for 62 kDa cell-surface glycoproteins which share limited sequence homologies with HLA class I molecules and are not associated with b2-microglobulin
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T cells
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T Lymphocytes Maturation in Thymus
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Direct Allorecognition
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Indirect Allorecogintion
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Semi-direct Allorecognition
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Calcium- Calcineurin Pathway
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N Engl J Med Jun 18;338(25):
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J Am Soc Nephrol 18: 2252–2261, 2007
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Belatacept (CTLA-4- Ig)
N Engl J Med Jun 18;338(25):
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+ Basiliximab MMF steroids
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LFA-3–Ig, a dimeric fusion protein consisting of the CD2-binding portion of the human lymphocyte function-associated antigen-3 (LFA-3) linked to the Fc portion of human IgG1 complement-mediated lysis interruption of CD2’s interactions with LFA-3 limiting helper T cell adhesion to antigen-presenting cells disrupting the engagement of effector T cell receptor engagement with antigen and major histocompatibility complex molecules
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Increased C5aR expression in TCMR infiltrating cells
Protocol Bx IF/TA Increased C5aR expression in TCMR infiltrating cells
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Vehicle treated recipient
C5aRA Increased apoptosis in control group 1 day after transplant
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