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

2. INTRODUCTION 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
Autograft the transfer of organ from one part to another in the same individual
Allograft from one individual to another of the same species
Isograft transfer of organ from one individual to his or her identical twin
Xenograft the transfer of organ from one individual to another of different species
Orthotopic graft a graft placed in it normal anatomical position
Heterotopic graft a graft placed at a site different from the organ is normally located.

3. Tissues that can be transplanted
Bones
Tendons
Cornea
Heart valves
Skin of leg
Vein
HAIR, BONE MARROW ETC.

9. 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.

10. Characteristics of MHC
Responsible for strong rejection
MHC class I molecules - almost all nucleated cells
MHC class II molecules – APCs, B cells, Macrophages

11. Antigen processing and display by MHC Molecule

12. 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

13. GRAFT 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

14. GRAFT REJECTION (Contd…)
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

15. 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)

16. 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

17. CELLULAR REJECTION 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

19. Non rejection complications
Transport injury
Drug toxicity
Infection
Malignancy
Recurrence of disease

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

21. HPV induced squamous cell carcinoma Sarcoma
ANOTHER METHOD:
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

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

23. PATIENT SELECTION & EVALUATION (Recipient)
Clinical evaluation; history and physical examination
Immunological evaluation
Infection screening – septic work-up
Others ; CBC, clotting profile, ECG, tumour markers.
1. RECIPIENT
Patient who met the indication for transplant – ORGAN FAILURE
Clinical evaluation; history and physical examination to rule out other diseases and co-morbidities
Immunological evaluation
Blood group
Tissue typing & cross matching
Serology; HIV, Hepatitis, CMV, VDRL
Infection screening – septic work-up
Others ; CBC, clotting profile, FBS, ECG, LFT, RFT, tumour markers.

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

25. 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.
Brain dead donor:
Donors who have been declared brain-dead and whose organs are kept viable by ventilators or other mechanical mechanisms until they can be excised for transplantation.
Hypothermia profunds hypotension, metabolic and endcrine disorders which depresses the CNS
Heart is still beating in donation after brain death donor.
Donation after circulatory death donor have cardiac arrest.

26. 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
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 to exclude circulating antibodies in recipient against HLA expressed by donor.
HLA antibody screening and specificity in recipient before and after transplant to guide immunosuppressive therapy

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

28. Thank you