2.  Transplantation is the process of taking cells, tissues, or organs, called a,graft, from one individual and placing them into a different individual.  The individual who provides the graft is called the donor, and the individual who receives the graft is called either the recipient or the host

3.  Transplantation Transfer of cells, tissues, or organs  1 st human kidney transplant 1935 Patient died to mistake in blood typing

4.  Immunosuppressive Agents ○ Delay or prevent rejection ○ Majority of these have overall immunosuppressive effect ○ New methods being developed Inducing specific tolerance to graft without suppressing other immune responses

5. Different types of Transplants  Autograft ○ Self tissue transferred from one part of body to another  Isograft ○ Tissue transferred between genetically identical individuals  Allograft ○ Tissue transferred between genetically different members of same species Most of our transplants  Xenograft ○ Tissue transferred between different species

6. Allograft Rejection (a) Acceptance of an autograft is completed within 12–14 days (b) First-set rejection of an allograft begins 7–10 days after grafting, with full rejection occurring by10–14 days. (c) Second-set rejection of an allograft begins within 3–4 days, with full rejection by 5–6 days. The cellular infiltrate that invades an allograft (b, c) contains lymphocytes, phagocytes, and other inflammatory cells

8.  T cells can transfer allograft rejection. When T cells derived from an allograft- primed mouse are transferred to an unprimed syngeneic mouse, the recipient mounts a second-set rejection to an initial allograft from the original allogeneic strain.

9.  T cells play key role in allograft rejection Both CD4+ and CD8+ populations present

10. The Immunology of Allogeneic Transplantation  Allogeneic MHC molecules are presented for recognition by the T cells of a graft recipient in two fundamentally different ways 1. Direct and 2. Indirect

12. Direct presentation in transplantation  Graft dendritic cell is induced to mature, express co-stimulatory molecules (B7).  DC in lymph node activates allo-MHC recognizing CD4+ T cells and/or CD8+ T cells  Activated T cells expand and then home to sites of inflammation where they find allo-MHC on graft cells and secrete cytokines/kill graft cells  This is the critical pathway for CD8 T cell response

13. Indirect presentation in transplantation  Dendritic cells, monocytes, or B cells of host enter sites of inflammation of graft, pick up antigens (e.g. allo-MHCs), and load peptides from these allo-MHC onto their own MHC, migrate to lymph nodes and activate T cells  CD4+ T cells are activated and then migrate to sites of inflammation where they are activated by host macrophages presenting graft antigens, leads to inflammatory reaction and tissue damage Also, important for production of antibodies to MHC molecules

14. Clinical Manifestations of Graft Rejections  Hyperacute ○ Within hours Pre-existing recipient antibodies Graft never become vascularized  Acute ○ Within weeks ○ T cell immune response (CD4 and/or CD8 T cells)  Chronic ○ Months to years ○ Mechanism uncertain by DTH

16. Immunosuppressive Therapy . Azathioprine Help lower T cell proliferation  Methotrexate Folic acid antagonist – blocks purine synthesis  Corticosteroids Reduces inflammation  X-irradiation of recipient before grafting  Antibodies specific for immune cells to keep them at lower numbers