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Transplant Immunology

Transplant Immunology. Adi Alherbish. Outline. Pre-sensitization: - B cells Ischemia-reperfusion injury/ innate immune response: - TLR - Complement - NK cells Afferent arm: - APC - T H cells Efferent arm: - Cytopathic T cells, T-reg

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Transplant Immunology

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  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. Mature B cells Memory B cells Plasma cells

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

  8. Luminex

  9. Ischemia Reperfusion Injury

  10. TLR HSP-70 HSP-60 TEC APCs

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

  12. C3 wild type mice C3 -/- deficient mice

  13. B cell- mediated rejection IRI

  14. NK Cells Role in Acute and Chronic Allograft Rejection IFG

  15. HLA

  16. MHC I: Nucleated cells

  17. MHC II: B cells, APCs

  18. Interferon Endothelial cells MHC I MHC I MHC II

  19. 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

  20. T cells

  21. T Lymphocytes Maturation in Thymus

  22. Direct Allorecognition

  23. Indirect Allorecogintion

  24. Semi-direct Allorecognition

  25. Calcium- Calcineurin Pathway

  26. N Engl J Med. 1998 Jun 18;338(25):1813-21.

  27. J Am Soc Nephrol 18: 2252–2261, 2007

  28. Belatacept (CTLA-4- Ig) N Engl J Med. 1998 Jun 18;338(25):1813-21.

  29. + Basiliximab MMF steroids

  30. 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

  31. TCMR Protocol Bx IF/TA Increased C5aR expression in TCMR infiltrating cells

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

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