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Transplant Immunology

Transplant Immunology. WHY TRANSPLANT TISSUES OR ORGANS? Replace dysfunctional/nonfunctional tissue or organs ------------------------------------------------------------------------------ - High technology medicine Specialized healthcare professionals Specialized facilities

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Transplant Immunology

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  1. Transplant Immunology

  2. WHY TRANSPLANT TISSUES OR ORGANS? Replace dysfunctional/nonfunctional tissue or organs ------------------------------------------------------------------------------ - High technology medicine Specialized healthcare professionals Specialized facilities Specialized support Pathology Radiology - Life saving - Very Expensive ------------------------------------------------------------------------------

  3. DEFINITIONS OF TYPES OF TRANSPLANTS: ---------------------------------------------------------------------- Classification scheme: depends upon: - the species of donor and recipient - same or different? - genetic similarity of donor & recipient (assuming both are form the same species) - identical versus - non-identical ----------------------------------------------------------------------

  4. NOMENCLATURE: Donor (graft) & Recipient (host) • Same Genetically Type of • Species Identical transplant /tissue • ------------------------------------------------------------------------------ • Self-> Self Yes Yes Autologous graft • Autograft • Twin A -> B* Yes Yes Isogeneic graft(syngeneic) • Isograft (syngeneic graft) • Person • A --> B Yes No Allogeneic graft • Allograft** • Species • A --> B No No Xenogeneic graft • Xenograft • ------------------------------------------------------------------------------ • * Also applies to individuals of an inbred strain (e.g., inbred mice) • ** Most common type of transplant in humans IMPORTANT!

  5. IMPORTANT! WHAT ARE THE RULES OF TRANSPLANTATION? Type of Graft Graft fate without immunosuppression of the recipient (host) ---------------------------------------------------------- Autograft Accepted IsograftAccepted AllograftRejected* XenograftRejected* ---------------------------------------------------------- * Graft (donor) and Host (recipient) are antigenically dissimilar

  6. Tissue Autograftt

  7. Twin “A” TWIN “B” Tissue Isograft (syngeneic graft)

  8. Tissue Allogeneic graft (allograft)

  9. Tissue Xenograft

  10. CLASSIFICATION BY GRAFT LOCATION Orthograft: transplanted organ is placed in the normal organ location (heart) Heterotopic: transplanted organ is placed in an unnatural location (kidney in pelvis)

  11. WHAT ARE THE TRANSPLANTATION ANTIGENS? Transplantation Relative Antigens Polymorphism ------------------------------------------------------------------------------ 1) ABO Limited 2) Major histocompatibility Very high complex (MHC)* 3) Minor histocompatibility Limited antigens(non-MHC antigens) 4) Xenoantigens Extremely high ------------------------------------------------------------------------------ * Human MHC = HLA Complex, class I and class II MHC IMPORTANT!

  12. IMPORTANT

  13. CONCEPT: ------------------------------------------------------------------------------ - the greater the difference in peptide sequences between graft and recipient - the stronger the immune response to the graft (donor) ------------------------------------------------------------------------------

  14. HOW CAN FOREIGN CLASS II MHC PRESENT PEPTIDES TO HOST TCRs?

  15. Classification of the phases of tissue rejection Minutes- Hours Days Weeks Months Years Hyper- acute Acute Subacute Chronic

  16. Yes No Hyper- acute Acute Subacute Chronic Minutes- Hours Days Weeks Months Years Pre-existing immunity to graft antigens CMI Antibody + CMI Antibody CMI

  17. TIME TO TISSUE REJECTION IN MICE -------------------------------------------------------------------------- Skin graft in mice strain A --> Immune strain B response First set rejection 11 - 15 days Primary Second set rejection 6 - 8 days Secondary --------------------------------------------------------------------------- IMPORTANT

  18. First Kidney Transplant Surgery: 1950

  19. Transplantation From Kidney to Stem cell

  20. History of Transplantation in Iran

  21. 1st kidney transplantation in 1967 in Shiraz Dr. Sanadi Zadeh

  22. 1985 2 transplantation teams were organized and started to work actively 274 kidney transplant in 2 years

  23. L.R.D L.U.R.D. cadaveric

  24. 1988 • L.U.R.D program organized and managed successfully • Number of transplant teams grow to < 20

  25. To the end of 2002 => 14888 kidney transplant • Today => 1500 kidney transplant/yr in Iran

  26. THE NUMBER OF RENAL TRANSPLANTS PERFORMED IN IRAN FROM 1984 - 2002

  27. SOURCES OF KIDNEY DONATION IN IRAN ; 1984 - 2002 LURD 79%(N=11 292) LRD 19.2% (N=2746) CAD 1.8%(N=250)

  28. PATIENT AND GRAFT SURVIVAL RATE IN LIVING RELATED (LRD) AND LIVING UNRELATED (LURD) RENAL TRANSPLANTATION In Hashemi Nejad Hospital , Tehran Patient survival % P<0.05 Graft survival LRD (N=469) LURD (N=881) Years Post Transplant

  29. GRAFT SURVIVAL RATES IN HLA IDENTICAL, ONE HLA HAPLOTYPE MATCH AND LIVING UNRELATED RENAL TRANSPLANT In Hashemi Nejad Hospital , Tehran P<0.001 % P=0.35 HLA Identical (n=141) One HLA Haplo (n=307) Living Unrelated (n=881) Years Post Transplant

  30. Other Organ transplants Bone Marrow, Liver & Heart

  31. 1991 1ST BMT in Shariati Hospital (Dr. Ghavamzadeh et al

  32. 1991-2006 Total of 1468 BMT Allogenic 1044 Autologous 324

  33. New Topics Stem cell Human Stem cell Repertoire

  34. What are stem cells? • A stem cell is a cell whose job in the body is not yet determined • Every single cell in the body stems from this type of cell • Stem cells wait for signals to tell them what to become • Until it receives a signal, it must wait patiently and divide slowly • When it receives a signal, begin to differentiate • The signals tell stem cell to turn on certain cell type it supposed to become

  35. These Super cell have a magic clinical potential in tissue repair • They represent the future relief of a wide range of incurable diseases • They could replace defective organ and tissues • They can restore the function of dysfunctional or non functional organs

  36. Where do they come from? Embryonic Sc Adult Sc

  37. Early embryonic stages Some Fetal tissues The Umbilical Cord Several Adult organs • Bone Marrow • Peripheral blood • Fat tissues • Etc…

  38. Adult stem cell? • Every single organ has it’s own stem cell • Bone Marrow • Heamatopoietic stem cell (HSC) • Endothelial stem cell (ESC) • Mesenchymal stem cell (MSC)

  39. Mesenchymal Stem Cells (MSCs) • MSCs are adult stem cells from BM that can differentiate into multiple nonhematopoietic cell lineages. • They can differentiate into osteoblast, adipocytes, chondrocytes, myocytes, cardiomyocytes, astrocytes, oligodenrocytes and neurons. • They have potential to down regulate and inhibit immune response in both recognition and elimination phases

  40. Possible clinical application proposed for MSC include: • stem cell transplantation • Stem cell strategies for the repair of damaged organ and gene therapy • MSCs due to their immunomodulatory potential theoretically, they can be used allogenically

  41. The role of Mesenchymal Stem Cells in relationship with injured somatic tissue and non-immune cells

  42. CAN STEM CELLS BE ISOLATED AND USED? If so under what conditions and restrictions?

  43. The low frequency of MSC in bone marrow necessitate the in vitro expansion prior to clinical use • We evaluated the effect of long term culture on the senescence of these cells • Surprisingly , MSC loses their characteristic after several passages Therefore: It is much better to consider them for therapy early on

  44. BM MSC culture (passage 6)

  45. The goal of our stem cell therapy studies • Assessing the safeness of the stem cell injection • The patients improvement from a clinical point of view • The degree of damaged tissue repair

  46. Mesenchymal Stem Cell therapy for Multiple Sclerosis and Heart Diseases

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