Histocompatibility and Transplantation Immunology

Most important HLA is HLA-DQ (class II)

  • How do T cells exert damaging effect on transplanted organ?

    • CD4+ activation: production of cytokines and chemotactic factors → activate and reqruitment of macroohages, NK cells → destruction of graft → cytokines → b cell activation → APC →

    • CD8+

  • Antibody mediaated rejections happens in 2 ways:

    • immediatly after transplant: recipient has pre-existing antibodies to donor’s MHC Ag - or too donor’s blood group

    • kater on and concurrenly with T cell activation

  • Most damaging effect of antibodies on transplanted organs:

    • Regection mediated by complement activation → graft cell lysis via MAC formation

    • activ ation of phagocytes → phagocytosis

    • Activation of NK cells →

  • Types of rejection:

    • Hyper acute

      • within a few hours

      • immune response aginst blood vessels

      • requires pre-exisitng antibodies

      • most commonly against highly vascularised organ

      • most commonly agains ABO blood group antigens

      • Mechanism: Ab binds to endothelial cells → labels for attack by complement and NK cells → phagocytosis by macrophages → inflammation → platelet activation → blockage of blood vessel → hypoxia → death of organ

    • Acute:

      • ‘direct allo-recgnition’

      • takes a few days

      • involves T cells through MHC proteins [T cells see MHC antigen AND the protein it carries]

      • host T cells recognise foreign MHC on transplanted organ → activation

      • The MHC itself is attached, not the antigen

    exam q:

  • Activation of recipient’s T cells often incolve imput from organs own dendritic cells. How?

    • most transplanted organs come from dead people → no proliferation → hypoxia → inflammation → activation of own dentritic cells → (once transplnted) dendritic cells travel to lymph node [dendritic cell trafficking] → express donor’s MHC → meets recipient CD4+ cells in lymph → activation of CD4+ cells → activated cells travel to donor organ → at organ, meet donor MHC → further activation → recruitement of other immune cells (phagocyles, lymohocytes ect) → inflammation

    • happens few days after transplant —> transplant rejection

  • Chronic rejection

    • mechanism not fully understood

    • gradual thickening of blood vessel walls → eventual loos of blood supply → ischemia → organ death → membrane fragments of dying organ MHC antigen taken up by recipient APC → chopped up → presented to CD4+ T cells → cativation of b cells to make antibodies → inflammatory response

    • directed mainly against MHC class 1 fragments of donor

    • called indirect allo-recognition

  • GVHD

    • after transplant, stem cells travel to BM and differeentiate into T cells

    • t cells express donors MHC pattern → recognition of host MHC as foreign → may begin to attack

    • largeely T cell depednednt

    • T cells usually remeoved from stem cell transokant to reduce risk of GVHD

    • Signs and symptoms: skin blistering, rashes, swelling, severe GI complications

    • Treatment: glucocorticoids