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Transplant Immunology

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Presentation on theme: "Transplant Immunology"— Presentation transcript:

1 Transplant Immunology
Adi Alherbish

2 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

3 Meet the Characters Adkinson: Middleton's Allergy: Principles and Practice, 7th ed.

4 B cells

5 Sensitization Events Exposure to non- self HLA antigens

6

7

8 Mature B cells Memory B cells Plasma cells

9 Methods of Antibody Detection
Clin J Am Soc Nephrol 1: 404–414, 2006

10 Luminex

11 Ischemia Reperfusion Injury

12 TLR HSP-70 HSP-60 TEC APCs

13 Immune Response to Post Ischemic Kidney
Jang et al, Clinical Immunology (2009) 130, 41–50

14 C3 wild type mice C3 -/- deficient mice

15

16 B cell- mediated rejection
IRI

17 NK Cells Role in Acute and Chronic Allograft Rejection
IFG

18 HLA

19 MHC I: Nucleated cells

20 MHC II: B cells, APCs

21 Interferon Endothelial cells MHC I MHC I MHC II

22 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

23 T cells

24 T Lymphocytes Maturation in Thymus

25 Direct Allorecognition

26 Indirect Allorecogintion

27 Semi-direct Allorecognition

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30 Calcium- Calcineurin Pathway

31

32 N Engl J Med Jun 18;338(25):

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34

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36 J Am Soc Nephrol 18: 2252–2261, 2007

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38 Belatacept (CTLA-4- Ig)
N Engl J Med Jun 18;338(25):

39 + Basiliximab MMF steroids

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43 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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45 Increased C5aR expression in TCMR infiltrating cells
Protocol Bx IF/TA Increased C5aR expression in TCMR infiltrating cells

46 Vehicle treated recipient
C5aRA Increased apoptosis in control group 1 day after transplant

47


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