Transcript Slide 1
Transplantation • therapy for terminal organ failure or tissue damage by transfer of healthy organ or tissue (graft) • donor - the individual who provides the graft is called the and is called either the • recipient or the host - the individual who receives the graft 1 Common transplants Organs heart, lungs, kidney,liver, pancreas, small intestine... Tissues & cells cornea, skin, Langerhan’s islets, bone marrow, blood transfusion, blood vessels, bone, heart valve... Graft AUTOGRAFT skin ISOGRAFT from genetically identical individual ALLOGRAFT from genetically different individual of the same species XENOGRAFT individual from one species to other species Transplantation • Autotransplantation • Isotransplantation • Allotransplantation • Xenotransplantation no immune response or graft rejection immune response and graft rejection MHC differences induce immune response and allograft rejection 5 Alloantigens (histocompatibility antigens) graft molecules recognized as foreign and causing rejection Alloreactive lymphocytes, alloreactive Abs lymphocytes and Abs reacting against alloantigens WHAT ARE TRANSPLANTATION ANTIGENS? Relative degree of Antigens polymorphism -----------------------------------------------------------------------------1) ABO blood group Limited 2) Major histocompatibility complex (MHC) Very high 3) Minor histocompatibility antigens (non-MHC antigens) Limited 4) Xenoantigens Extremely high Direct allorecognition Downloaded from: StudentConsult (on 13 January 2011 08:40 PM) © 2005 Elsevier Graft rejection after direct immune recognition Langerhansove ćelije kožnog kalema Migracija u lokalni LČ i aktivacija efektorskih T-ćelija Efektorske T-ćelije odlaze u kalem Reakcija odbacivanja Indirect allorecognition Downloaded from: StudentConsult (on 13 January 2011 08:40 PM) © 2005 Elsevier More T cells are activated in the immune response to graft than in an infection INFECTION TRANSPLANTATION T foreign peptide self peptide APC T T T APC T T Injury mechanisms during graft rejection CYTOKINES activation and proliferation Th (IFN-γ) CD4 B NK MF CTL CD8 At free radicals activation and proliferation Elimination of graft cells Complement activation DC Allograft rejection Hyperacute (few hours) Pre-formed Abs to blood type Ags and MHC molecules Acute (few days/weeks) Chronic (several months to years) Downloaded from: StudentConsult (on 13 January 2011 08:40 PM) © 2005 Elsevier Allograft rejection Hyperacute (few hours) Pre-formed Abs to blood type Ags and MHC molecules Acute (few days/weeks) Vascular (Abs to MHC molecules) Cellular (T cells and macrophages) Chronic (several months to years) Downloaded from: StudentConsult (on 13 January 2011 08:40 PM) © 2005 Elsevier Allograft rejection Hyperacute (few hours) Pre-formed Abs to blood type Ags and MHC molecules Acute (few days/weeks) Vascular (Abs to MHC molecules) Cellular (T cells and macrophages) Chronic (several months to years) Tissue fibrosis and blood vessel walls thickening (TGF-β) Downloaded from: StudentConsult (on 13 January 2011 08:40 PM) © 2005 Elsevier Bone marrow transplantation Graft-versus-host disease – GVHD in bone marrow transplantation 21 Testing for donor-recipient compatibility • ABO blood typing • Tissue typing: HLA matching • Screening for the presence of preformed antibodies • Cross-matching 22 Prevention and treatment of allograft rejection Immunosuppressive drugs - Corticosteroids (anti-inflammatory effect) -Cyclosporin A, Tacrolimus... (block T cell activation and cytokine production) -Mycophenolate mofetil (blocks lymphocyte proliferation by blocking guanine synthesis) -Rapamycin (blocks lymphocyte proliferation by inhibiting IL-2 signalling) - Abs to TCR (CD3) and co-stimulatory molecules (CTLA4) 1. Transplantation of tissue or organ from gennetically different individual from the same species is called 2. Transplantation from an individual from different species is called 3. Antigens recognized during rejection are 4. Main alloantigens during rejection are a. hyperacute rejection 5. Allo-MHC molecules could be recognized by 6. Direct alloantigen recognition means that 7. Indirect alloantigen recognition happen when recipient’s APC e. MHC molecules 8. Allograft rejection due to pre-formed recipient’s Abs is called h. processes and presents alloantigens 9. In prevention and treatment of graft rejection we use 10. In bone marrow transplantation d 1.____ f 2.____ j 3.____ e 4.____ b 5.____ b. direct and indirect recognition c. recipient’s T cells recognize allo-MHC molekule on donor’s cells d. allotransplantation f. xenotransplantation g. imunosuppressive therapy i. donor’s T cells react to recipient MHC molecules j. alloantigens and xenoantigens c 6.____ h 7.____ a 8.____ g 9.____ i 10.___