1 / 24

Transplant Immunobiology

Transplant Immunobiology. Douglas Stahura DO Grandview Hospital November 6, 2002. Goals. Review definitions Review basic mechanisms of immunologic system Understand T-cell immunity Review transplant medications and mechanisms. Definitions.

eedwin
Télécharger la présentation

Transplant Immunobiology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Transplant Immunobiology Douglas Stahura DO Grandview Hospital November 6, 2002

  2. Goals • Review definitions • Review basic mechanisms of immunologic system • Understand T-cell immunity • Review transplant medications and mechanisms

  3. Definitions • Autograft – transplantation of one’s own tissue to another site • Syngraft – transplantation of graft between two genetically identical individuals • Allograft – transplantation of graft between individuals of the same species • Xenograft – transplantation of graft between individuals of different species

  4. Definitions • Alloantigens – antigens recognized as foreign on allografts • Alloreactive – lymphocytes that recognize and respond to alloantigens

  5. Definitions • Major Histocompatibility Complex (MHC) • In humans, known as HLA system • Central role in antigen recognition • Principal immunologic function of MHC gene product is to present antigens as fragments of foreign proteins, forming complexes that can be recognized by T lymphocytes

  6. MHC • MHC molecules are membrane associated • Antigen-specific T lymphocytes recognize fragments of antigens only when bound to the surface of other cells that bear MHC molecules • Mature T lymphocytes recognize and react to foreign antigens and not to self • Clonal deletion • Self tolerance

  7. MHC • Located on short arm of chromosome 6 • Six separate genes; • Class I = HLA-A,B,C • Class II = DR,DQ,DP • Each gene is represented by one of two codominant alleles (paternal +maternal) • Haplotype – alleles of HLA system passed to offspring via meiosis

  8. MHC • HLA Class I • Found on all nucleated cells • Function as immunorecognition site for endogenously synthesized foreign protein antigens • Recognized by CD8+ T cells

  9. MHC • HLA Class II • Found on APC (antigen presenting cells) • B monocytes, macrophages, dendritic cells, mesangial cells, Kupffer’s cells, alveolar type 2 cells • central role in the initiation of the immune response to transplantation antigens

  10. T cell activation

  11. T cell activation Allorecognition – recognition of TRANSPLANT antigens by T cells TCR – T cell receptor “recognizes” MHC/antigen complex CD3 complex initiates intracellular signalling

  12. T cell activation • CD3 complex – five peptide chain closely arrayed in cell membrane alongside TCR • TCR binding induces conformational change in CD3 which initiates intracellular signal pathways

  13. T cell activation • Accessory molecules • Stabilize the interaction between cytotoxic T cells and their target cell • Provide a non-antigen “second” signal for T cell activation • Adhesion molecules enhance antigen recognition by increasing affinity between T cell and MHC cell • TCR recognition without accessory molecule co-stimulation results in clonal anergy or apoptosis

  14. T cell Costimulation

  15. Immunosuppressive Medications • Drugs target the cellular mechanisms that are known • Signal ONE • Calcineurin inhibitors • Cylosporine (Sandimmune, Neoral) • Tacrolimus (FK506, Prograf) • Monoclonal Antibodies • OKT3 – targets CD3 molecule • Polyclonal Antibodies (ALG) • Thymoglobulin

  16. Immunosuppressive Medications • Signal Two – no currently approved • Signal Three • Sirolimus (Rapamycin) • Monoclonal Ab that target IL-2 receptors • Anti-metabolite • Azathioprine (Imuran) nonspecific inhibitor of purine synthesis • Mycophenolate mofetil (Cellcept) lymphocyte selective inhibitor of de novo purine synthesis

  17. Immunosuppressive Medications • Corticosteroids • Blocks T-cell and APC cytokine and cytokine receptor expression (inhibits transcription) • Blocks migration of lymphocytes to tissues (anti-inflammatory)

More Related