Transplantion Graft

1. 1 Transplantion (Graft) Done by Ossama Fanek & Safwan Rawabdeh Supervised by : Dr. Nawaf Shatnawi

2. 2 Definition Is transferring of tissue, to replace the recipient's damaged or absent tissue .

3. 3 Classification Transplantation can be for cell, tissue or organ(s). Can be in the same person, from person to other of the same species or different. 1. Autograft : transfering of tissue to the same person (ex : Skin grafts, vein extraction for CABG, bone and cartilage transplants, and nerve transplants ). 2. Allograft : transplant of an organ or tissue between two genetically non-identical members of the same species. 3. Isograft : A subset of allografts in which organs or tissues are transplanted from a donor to a genetically identical recipient (such as an identical twins) , so they don�t trigger an immune response. 4. Xenograft : transplant of organs or tissue from one species to another. An example are porcine heart valve transplants, which are quite common and successful . Note: Xenotransplantion is often an extremely dangerous type of transplant because of the increased risk of non-compatibility, rejection, and disease carried in the tissue. This is a very serious type of transplant.

4. 4 According to the implanting site : Orthotopic Transplantation: Donor organ is placed in the normal anatomical position (ex: heart, lung, liver). Heterotopic Transplantation: Donor organ is placed in a different site than the normal anatomical position (ex: kidney, pancreas). Paratopic Transplantation : Donor organ is placed close to the original organ.

5. 5 Basic Immunology The main antigens involved in triggering rejection are coded for by a group of genes known as : MHC(Major histocompatibility complex)

6. 6 MHC(Major Histocompatibility Complex) These antigens are the product of genes, which defines the "foreign" nature of a donors tissue to the recipient immune mechanism. In humans, the MHC complex antigens is known as the human leukocyte antigen (HLA) system. It comprises a series of genes located on chromosome 6.

7. 7 Grouped into 3 classes : Class I molecules (named HLA-A, -B, and -C) are found on the membrane of all nucleated cells Class II molecules (named HLA-DR, -DP, and -DQ) are generally expressed by antigen-presenting cells (APCs) such as B lymphocytes, monocytes, and dendritic cells Class III molecules : encoded for other immune component ( complement system, cytokine

8. 8 In a nontransplant setting, the function of the HLA gene product is to present antigens as fragments of foreign proteins that can be recognized by T lymphocytes. In the transplant setting, HLA molecules can initiate rejection and graft damage, via either humoral or cellular mechanisms. Humoral rejection occurs if the recipient has circulating antibodies specific to the donor's HLA from prior exposure (i.e., blood transfusion, previous transplant, or pregnancy), or if posttransplant, the recipient develops antibodies specific to the donor's HLA. The antibodies then bind to the donor's recognized foreign antigens, activating the complement cascade and leading to cell lysis. The blood group antigens of the ABO system, though not part of the HLA system, may also trigger this form of humoral rejection.

9. 9 T- Lymphocytes Thymus is the principal organ responsible for the T cell's maturation. Distinguished from other lymphocyte types, such as B-Cells and natural killer cells (NK cells) by the presence of a special receptor on their cell surface called T-Cell receptors. They can recognized foreign antigen presented by APC(antigen presenting cell). Once presented with an antigen they will produce ILs, and proliferate (cloning).

10. 10 Types of T-Cells : Helper : These cells are also known as CD4+ T cells because they express the CD4 protein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules that are expressed on the surface of Antigen Presenting Cells (APCs) Cytotoxic :These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections Regulatory T cells formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus Natural killer cells.

11. 11 Problems with transplantation REJECTION AVALAIBILITY OF THE TRANSPLANTED TISSUE

12. 12 Why do rejection occurs? Transferred tissue carries antigens Ag presentation to CD8 or CD4 T cell clonal expansion, IL2 production and Ab production by B lymphocyte Activation of all immune component cell lysis and vascular occlusion