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

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

5 MHC differences induce immune response and allograft rejection

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 ) ABO blood group 2) Major histocompatibility complex (MHC) 3) Minor histocompatibility antigens (non-MHC antigens) 4) Xenoantigens Limited Very high Limited Extremely high

Direct allorecognition

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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

Downloaded from: StudentConsult (on 13 January :40 PM) © 2005 Elsevier Indirect allorecognition

More T cells are activated in the immune response to graft than in an infection APC T T T T T TRANSPLANTATION APC T INFECTION self peptide foreign peptide

Elimination of graft cells CYTOKINES (IFN-γ) free radicals MF DC CTL Th MHC II MHC I CD4 CD8 activation and proliferation activation and proliferation B At Complement activation NK Injury mechanisms during graft rejection

Allograft rejection Hyperacute (few hours) Pre-formed Abs to blood type Ags and MHC molecules Acute (few days/weeks) Chronic (several months to years)

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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)

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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)

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Bone marrow transplantation

21 Graft-versus-host disease – GVHD in bone marrow transplantation

22 Testing for donor-recipient compatibility ABO blood typing Tissue typing: HLA matching Screening for the presence of pre- formed antibodies Cross-matching

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)

alloantigens and xenoantigensj.In bone marrow transplantation10. donor’s T cells react to recipient MHC molecules i.In prevention and treatment of graft rejection we use 9. processes and presents alloantigensh.Allograft rejection due to pre-formed recipient’s Abs is called 8. imunosuppressive therapyg.Indirect alloantigen recognition happen when recipient’s APC 7. xenotransplantationf.Direct alloantigen recognition means that 6. MHC moleculese.Allo-MHC molecules could be recognized by 5. allotransplantationd.Main alloantigens during rejection are4. recipient’s T cells recognize allo-MHC molekule on donor’s cells c.Antigens recognized during rejection are 3. direct and indirect recognitionb.Transplantation from an individual from different species is called 2. hyperacute rejectiona.Transplantation of tissue or organ from gennetically different individual from the same species is called 1. 1.____2.____3.____4.____5.____6.____7.____8.____9.____10.___ dfjebchagi