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Transplantation

Medical Biologist Faculty of Education Ishik University 100M Road Erbil-Iraq Tel.: 07504095454
Research Fellow Manchester Fungal Infection Group The University of Manchester Institute of Inflammation and Repair Manchester, UK M13 9NT Tel. 07927133678
GBD Expert Global Burden of Disease IHME Institute for Health Metrics and Evaluation University of Washington Seattle, WA 98121, USA
Dr. Karzan Mohammad PhD. MSc. BSc.

DEFINITION OF TERMS An organ transplant is a surgical procedure in which a failing organ is replaced by a functioning one from a donor with a compatible tissue type. Autograft Allograft Isograft Xenograft
INTRODUCTION

Tissues that can be transplanted

Bones
Tendons
Cornea
Vein
Heart valves
Skin of leg



Major Histocompatibility Complex (MHC)
Major function of MHC- bind to peptide fragments derived from foreign antigen and display them on cell surface for recognition by appropriate T cell. MHC determines the compatibility between donor and recipient for organ transplantation.

Characteristics of MHC

Responsible for strong rejectionMHC class I molecules - almost all nucleated cellsMHC class II molecules – APCs, B cells, Macrophages

Antigen processing and display by MHC Molecule

Major histocompatibility complex MHC: They are clusters of genes on the short arm of chromosome 6 expressed on the cell surface as HLA (Human Leukocyte Antigen) i.e. genes that encode HLA. ABO: These blood group antigen are expressed not only on red blood cells but by most cell types as well. Incompatibility leads to hyperacute rejection

Rejection of transplanted organs is a bigger challenge than the technical expertise required to perform the surgery. It results mainly from HLA and ABO incompatibility through MHC classes. Hyperacute Acute Chronic
GRAFT REJECTION


Hyper acute rejection Immediate graft destruction due to ABO or preformed anti- HLA antibodies. Characterized by intravenous thrombosis and interstitial hemorrhage. Risk factors are previous failed transplant and blood transfusions Kidney transplant is vulnerable to hyperacute rejection
GRAFT REJECTION (Contd…)

Acute rejection Usually occurs during the first 6 months. May be cell mediated (T-cell), antibody mediated or both Characterized by cellular infiltration of the graft(cytotoxic, B- cells, NK cells and macrophages)
GRAFT REJECTION (Contd…)


Chronic Rejection: It occurs after 6 months. Most common cause of graft failure Antibodies play important role Non- immunological factors contribute to the pathogenesis Characterized by myointimal proliferation in graft arteries leading to ischemia and fibrosis
GRAFT REJECTION (Contd…)

It is caused by T-cell mediated reactions. Destruction of grafts occurs by 1. CD8+ CTLs 2. CD4+ helper cells Delayed hypersensitivity is triggered by CD4+ helper cells. 2 pathways 1. Direct pathway 2. Indirect pathway
CELLULAR REJECTION

Non rejection complications

Transport injury Drug toxicity Infection Malignancy Recurrence of disease


Immunosuppressive agents 1. Cyclosporin 2. Azathioprine 3. Steroids 4. Rapamycin 5. Monoclonal antibodies.
METHODS OF INCREASING GRAFT SURVIVAL


Prevention of host T cells from receiving co-stimulatory signals (B7-1&2) from dendritic cells. DISADVANTAGES: EBV induced lymphoma HPV induced squamous cell carcinoma Sarcoma
ANOTHER METHOD:


PRE-OPERATIVE Patient selection and Evaluation Counseling Informed written consent Optimization
PRINCIPLES



1. RECIPIENT Clinical evaluation; history and physical examinationImmunological evaluationInfection screening – septic work-upOthers ; CBC, clotting profile, ECG, tumour markers. PATIENT SELECTION & EVALUATION (Recipient)


Contra-indications for living donor Mental disease Diseased organ Morbidity and mortality risk ABO incompatibility Cross matching incompatibility Transmissible disease
Patient selection & evaluation (DONOR)


II. Deceased donor - Brain dead donors: Normothermic patient. No respiratory effort by the patient. The heart is still beating. No depressant drugs intake should be there while evaluating the patient. Individual should not have any sepsis, cancer (except brain tumour). Not a HIV or hepatitis individual.
Patient selection & evaluation (DONOR)


The tissue typing laboratory carries out 3 tasks : To determine the HLA type of blood for both donor and recipient by PCR. Lymphocyte cross-matching. HLA antibody screening and specificity
TISSUE TYPING


Positive cross matching; Recipient antibodies attacks donor’s.Not suitable for transplant Negative cross matching; Recipient antibodies do not attack donorSuitable for transplantMethods;Micro-cytotoxic assay, mixed lymphocytes, flow cytometry, DNA analysis. CROSS MATCHING

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