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Nehal Draz. 1- Autograft: from one area to another, same inbividual, NO IR 2- Syngraft (Isograft; Syngeneic): genetically identical individuals, NO.

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Presentation on theme: "Nehal Draz. 1- Autograft: from one area to another, same inbividual, NO IR 2- Syngraft (Isograft; Syngeneic): genetically identical individuals, NO."— Presentation transcript:

1 Nehal Draz


3 1- Autograft: from one area to another, same inbividual, NO IR 2- Syngraft (Isograft; Syngeneic): genetically identical individuals, NO IR, Histocompatible 3- Allograft (commonest) two genetically dissimilar individuals, same species, Histoincompatible & rejection 4- Xenograft: donor & recipient from different species Histoincompatible & rejection


5 Living graft: from a living donor,e.g. liver segment, kidney, BM Cadaveric graft: from a recently dead individual,e.g. heart, cornea, liver, kidney

6 Bone marrow is the most immunogenic Liver is the least immunogenic depending on: Privileged sites: e.g.cornea No significant IR Lack of lymphatic drainage 2- Different expression of HLA molecules 1- Lack of suitable APCs In some tissues


8 MHC Refers to genes encoding HLA proteins MHC molecules Refers to the protein HLA

9 Allelic polymorphism : The MHC genes represents the most polymorhic genetic system Multiple different allels of the same gene exist in the human population Different allels of the same gene can give Ags with slightly distinct sequences e.g. A gene has 151 allels

10 1- control IR by MHC restriction 2- targets of IR resulting in cytotoxity in graft rejection 3- Certain MHC allels are associated with some diseases e.g. multiple sclerosis &DR2

11 Recipient Tcells can recognize donor allo Ags in the graft by 2 different ways:

12 Recipient Tcells recognize donor;s Ags on donor's MHC molecules on the graft APCs Donor APCs leave the graft & migrate to the regional lymph nodes There they activate recipients Tcells The activated Tcells are carried back to the graft which they attack directly

13 Uptake of donor MHC molecules by the recipient own APCs and presentation to self Tcells on self MHC molecules

14 CD8 Tcells CD4 Tcells - The generated alloreactive CTLS attack graft cells bearing MHC I and destroy them by direct cytotoxicity Secrete cytokines enhancing graft damage: - IL-2: stimulate CTLs - IFNγ: increase allogenic MHC class I &II on graft cells - IL4, 5, 6 stimulate Ab production by Bcells C M I C M I

15 IgG or IgM Foreign GRAFT cell Y 1- Opsonization 2- Complement mediated lysis 3- ADCC destruction MQ NK HUMORAL effector phase. cont

16 1- Hyperacute rejection 2- acute rejection 3- Chronic rejection

17 Within minutes Circulating preformed anti ABO or anti-HLA antibodies Activation of compl. and clotting pathways No treatment Prevention: proper matching

18 Within days or weeks Treatment: immunosuppression Prevention: proper matching TC CD4 YYYY Destroy graft cells Lymphokines activating Infl.& MQ Endothelial injury

19 After months or years No treatment Prevention: proper matching Alloantigen in Vessel wall Proliferation of smooth Muscle cells Gradual lumen narrowing ischemia, Interstial fibrosis Loss of function Delayed type hypersensitivity CYTOKINES

20 Histocompatibility testing Post-operative immunosuppressive therapy Recipient preparation

21 1- ABO typing 2- HLA testing: determination of HLA phenotype for donor & recipient which can be done by: a) microlymphocytotoxicity test b) HLA molecular typing: PCR c) white cell cross matching: mixed lymphocytotoxicity test 3- detection of preformed Abs against donor cells in the serum of the recipient

22 Complete history taking & full clinical examination Treatment of hypertension if present Treatment of infections if present Prophylactic antibiotics Pre-transplantation immunosuppressive therapy

23 The drugs used to suppress the immune system can be divided into 3 categories: Cytotoxic drugs Powerful anti-inflammatory drugs (corticosteroid) Fungal & bacterial derivatives prednisone - Azathioprine - Cyclophosphamide - Cyclosporine A - FK506 - Rapamycin

24 DrugMechanism of action Cyclosporine & FK 506Block Tcell cytokine production RapamycinInhibits IL-2 signaling which inhibits lymphocyte proliferation CorticosteroidsReduce inflammation by inhibiting MQ cytokine secretion Anti IL-2 receptorInhibit T cell proliferation by inhibiting IL-2 binding Anti-CD40 ligandInhibit cellular activation by blocking co-stimulation Monoclonal Ab against Tcell surface markers Depletion of Tcells

25 Infections Malignancies: especially lymphomas & carcinoma of the skin Anaphylaxis or serum sickness Graft verus host disease (GVHD)

26 A successful therapy for tumors derived from marrow precursors such as leukemia & lymphomas It may be also successful in treatment of some primary immunedefficiency disease such as severe forms of thalassemias

27 In leukemia therapy, the source of leukemia must be first destroyed by aggressive cytotoxic chemotherapy. The patient is thus severely immunocompromised Bone marrow cells are highly immunogenic& can elicit a strong IR Therefore, very careful donor/recipient HLA matching is critical

28 If mature donor Tcells are transplanted with the marrow cells, these mature Tcells recognize the tissues of the recipient as foreign causingsevere inflammatory disease called: GVHD Graft Versus Host Disease -Rashes -Diarrhea -Pneumonitis -Liver dysfunction -Wasting -Death

29 1- The most crucial factor is donor selection &MHC compatibility: an identical twin is the ideal donor 2- From poorly matched grafts, T lymphocytes can be removed using monoclonal Abs. to avoid induction of an immune response by the immune competent (mature) donor Tcells against the tissues of the immunocompromised recipient & hence GVHD

30 3-Malignant cells should be eliminated from the recipient blood to avoid recurrence of the underlying malignancy which necessitated the BMT in the first place 4- Methotrexate, cyclosporin & prednisone are often used to control GVHD


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