Immunologic tolerance


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Immunologic tolerance

  1. 1. IMMUNOLOGICTOLERANCE By:- Robin Gulati
  2. 2. ContentsDefinitionCentral tolerancePeripheral toleranceBack up mechanisms
  3. 3. What is Immunologic Tolerance?State in which the individual is incapable of developing an immune response to a specific antigen.Self tolerance: refers to the lack of individual’s antigens.Affects the ability to live in harmony with our own cells and tissues.
  4. 4. Classification Immunologic tolerance Central Peripheraltolerance tolerance
  5. 5. Central ToleranceRefers to death (deletion) of self-reactive T- and B-lymphocyte clones during their maturation in the central lymphoid organs (the thymus for T cells and the bone marrow for B cells).Experiments with transgenic mice provide abundant evidence that T lymphocytes that bear receptors for self antigens undergo apoptosis within the thymus during the process of T-cell maturation
  6. 6.  T-cells that bear receptors for self antigen undergo apoptosis within the thymus during the process of T-cell maturation. Many autologous protein antigen are processed and presented by thymic antigen- presenting cells in association with self MHC (major histocompatibility complex) proteins. Developing T-cells having high affinity receptors for such antigens are negatively selected, or deleted, and therefore the peripheral T-cell pooling is lacking or deficient in self reactive cells. The developing thymocytes express high levels of Fas causing negative selection.
  7. 7. Clonal deletion of T-cells also affects B- cells.When developing B-cells encounter a membrane-bound antigen within the bone marrow, they undergo apoptosis.No self antigen present in the thymus: T- cells and B-cells slip into the periphery.B-cells bearing receptors for thyroglobulin, collagen and DNA can be found in the periphery.
  8. 8. PERIPHERAL TOLERANCET-cells that escape intrathymic negative selection can cause tissue injury unless they are deleted or muzzled in the peripheral tissues.3 “back up” mechanisms that silence such potentially autoreactive T-cells are:- 1.Clonal deletion by activation-induced cell death 2.Clonal anergy 3.Peripheral suppression by T-cells
  9. 9. 1. Clonal deletion by activation- induced cell deathMechanism to prevent uncontrolled T-cell activation during normal immune response involves apoptotic death of activated T- cells by Fas-Fas ligand system.Expression of Fas (CD95) is upregulated in antigen activated T-cells.Engagement of Fas by Fas L, coexpressed on activated T-cells, dampens the immune response by inducing apoptosis of activated T-cells.
  10. 10. The self antigens that are abundant in the peripheral tissues cause repeated and persistent stimulation of self-antigen-specific T-cells leading eventually to their elimination via Fas mediated apoptotis.
  11. 11. 2.Clonal anergyRefers to a prolonged or irreversible functional inactivation of lymphocytes, induced by encounter with antigens under certain conditions.
  12. 12. Activation of T-cells requires 2 signals:- a.Recognition of peptide antigen in association with self MHC molecules on the surface of antigen-presenting cells and set of costimulatory signals provided by antigen-presenting cells. b.To initiate second signals, certain T-cells associated molecules, such as CD28, must bind to their ligand, a negative signal is delivered, and the cell becomes anergic.
  13. 13. Such a cell then fails to be activated even if the relevant antigen is presented by component antigen presenting cells that can deliver costimulation.Since costimulatory molecules are not expressed or are weekly expressed on most normal tissues, the encounter between auto reactive T-cells and their specific antigen leads to clonal anergy.Also affects B-cells.
  14. 14. B-cells encounter antigen in the absence of specific helper T-cells, the antigen-receptor complex is down regulated, and such cells never re-express their immunoglobin receptors.Such cells are unable to respond to subsequent antigenic stimulation.
  15. 15. 3.Peripheral stimulation of T-cellsFocus is on suppressor T-cells with the ability to downregulate the function of other autoreactive T-cells.Molecular mechanisms by which suppressor T-cells recognize antigens and exert their suppressive effects are little understood.Some evidence is that peripheral suppression of autoreactivity may be mediated, in part, by the regulated secretion of cytokinesis.
  16. 16. Tolerance of self-reactive T-cells is extremely important for prevention of autoimmune disease.
  17. 17. THANK YOU!