1 / 36

Chapter16 Immunological Tolerance

Chapter16 Immunological Tolerance. Contents. Part Ⅰ Introduction PartⅡ Mechanisms of Self Tolerance Part Ⅲ Factors affecting Induced Tolerance PartⅣ Clinical Significance of Immunological Tolerance. PartⅠ Introduction.

tpruett
Download Presentation

Chapter16 Immunological Tolerance

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. Chapter16 Immunological Tolerance

  2. Contents PartⅠ Introduction PartⅡ Mechanisms of Self Tolerance PartⅢ Factors affecting Induced Tolerance PartⅣ Clinical Significance of Immunological Tolerance

  3. PartⅠ Introduction • Owen first observed immunological tolerance to allogenic antigen in fetal period in 1945

  4. cattle of dizygotic twin

  5. Experiment of Medawar on immunological tolerance

  6. Definition: A type of specific unresponsiveness to an antigen induced by the exposure of specific lymphocytes to that antigen, but response to other antigens. • Tolerogens: antigens that induce tolerance • Types: self-tolerance induced tolerance

  7. General features of immunological tolerance • Tolerance is antigenic specific and results from the recognition of antigens by specific lymphocytes. • Normal individuals are tolerant of their own antigens(self antigen)----- Self-tolerance. • Foreign antigens may be administered in ways that preferentially inhibit immune response by inducing tolerance in specific lymphocytes---antigen induction.

  8. Immunologic features of tolerance • It is an antigen-induced, active process • Like immunologic memory, it is antigen specific • Like immunologic memory, it can exist in B cells, T cells or both • Like immunologic memory, it's easier to induce and last longer in T cells than in B cells

  9. Tolerance in T and B cells

  10. Difference of Immuologic tolerance & immunodeficiency, immunosuppression Immunodeficiency:Deficiency in the production of humoral and /or cell-mediated immunity---non-specificity to Ag Immunosuppression: Suppression of immune responses to antigens. This can be achieved by various means, including physical, chemical----non-specificity to Ag

  11. Part II Mechanism of Self Tolerance

  12. 1. Central tolerance: Central tolerance occurs in the central lymphoid organs as a consequence of immature self-reactive lymphocytes recognizing ubiquitous self-antigen. 2. Peripheral tolerance: tolerance was induced in peripheral organs as a result of mature self-reactive lymphocytes encountering tissue-specific self antigens under particular conditions

  13. 1. Central tolerance Clonal deletion (apoptotic cell death) During maturation of T lymphocytes in the thymus or B lymphocytes in the bone marrow, immature lymphocytes that recognize ubiquitous self-antigen with high affinity are deleted bynegative selection

  14. Clonal deletion:negative selection of T cells in the thymus

  15. Negative selection of B cells inbone marrow

  16. 2. Peripheral tolerance 1.Peripheral tolerance of T cells ① Clonal anergy functional inactivation without cell death: lack of co-stimulatory signal

  17. ②clonal ignorance: self-reactive lymphocytes remain viable and functional but do not react to the self antigens in any detectable way.

  18. ③ Immunologically privileged sites ④ Regulatory T cells CD4+CD25+ Treg: TGF- , IL-10 ⑤AICD(activation-induced cell death) Repeated stimulation of lymphocytes by persistent antigens results in death of the activated cells by a process of apoptosis. FasL on activated T cell binds to Fas on activated T cell and then induces T cell apoptosis.

  19. 2) Peripheral tolerance of B cells • ①Clonal deletion • ②Lack of Th cells • ③Clonal anergy • ④Receptor editing

  20. Part III Factors affecting tolerance induction • Role of antigen • Role of the host

  21. 1.role of antigens (1)Types of antigen • Large, aggregated, complex molecules, properly processed-immune response • soluble, aggregate-free, simple small molecules, not processed-tolerance (2)Dosage of antigen • Optical dosage-immune response • Very high or very low-tolerance (3)Portal of entry • Subcutaneous or intramuscular-immune response • Oral or intravenous-tolerance (4) features of determinant

  22. Immune response Low-zone tolerance high-zone tolerance T、B cell T cells 抗体滴度 TD-Ag TI-Ag TD-Ag Concentration of antigen

  23. 2.Role of the host (1)Ages • Adult, immunologically mature---Immune response • Embryo and newborn , immunologically immature---immunological tolerance (2) Differentiation state of cells • Fully differentiated; memory T & B cells—Immune response • Relative undifferentiated B cell with only IgM, T cells in the thymic cortex---immunological tolerance (3) Species,Heredity,Gender, Health

  24. Host age and antigen dose affect tolerance newborn adult

  25. PartⅣ Clinical Significance of immunological tolerance

  26. 1. To induce immunological tolerance • Prevent the rejection of organ allografts and xenografts • Treat autoimmune diseases • Treat allergic diseases

  27. 2. To terminate immunological tolerance • To treat tumor: enhance first signal or second signal • To treat infection diseases

  28. Summary • Definition of immunological tolerance • Features of immunological tolerance • Induction of immunological tolerance • Mechanism of immunological tolerance • Clinical application of immunological tolerance

More Related