醫(yī)學(xué)免疫學(xué)課件：immunological tolerance

1、Immunological ToleranceImmunological Tolerance DefinitionTypesMechanismsI. DefinitionImmunological tolerance: A specific unresponsiveness of immune system to an antigen that is induced by previous exposure to that antigen.Tolerance is specific unresponsiveness to antigen, resulting from recognition

2、of specific antigens by lymphocytes.Immunological tolerance is different from immunodeficiency or immunosuppression. Immunodeficiency: any condition in which there is deficiency in the production of humoral and /or cell-mediated immunity-non-specificity to AgImmunosuppression: The suppression of imm

3、une responses to antigens. This can be achieved by various means, including physical, chemical and biological means.-non-specificity to AgII. TypesBy tolerogensSelf tolerance Inducible toleranceTolerogens: antigens that induce toleranceSelf tolerance Tolerance to self antigens, in which an individua

4、ls immune system does not attack the normal tissues of the body. Induced tolerance Tolerance to foreign antigens can be induced by exposure to antigens under conditions in which specific clones are suppressed. III. Mechanisms of self tolerance1. Central tolerance Central tolerance occurs in the cent

5、ral lymphoid organs as a consequence of immature lymphocytes recognizing the antigen. 2. Peripheral tolerance The tolerance is induced in peripheral organs as a result of mature lymphocytes encountering specific antigens under particular conditionsI.) Central tolerance: T cells Clonal deletion (apop

6、totic cell death) During maturation of lymphocytes in the thymus for T cell or in the bone marrow for B maturation, immature lymphocytes that recognize ubiquitous self-antigen with high affinity are deleted by negative selectionB cells Clonal deletion Clonal anergyNegative selection of B cells inbon

7、e marrowRceptor editing Abul K. Abbas, Cellular and Molecular Immunology 7th EDITIONII.) Peripheral toleranceT cells 1. Clonal anergy: Functional inactivation without cell death : lack co-stimulatory signal2.Immunological ignorance : Lymphocytes that bind self antigens with relatively low affinity u

8、sually ignore them but in some circumstances become activated. 3. Treg 4. Immunological privilegePrivileged sites: Such as eyes, CNS ( central neural system), placenta, and testis. 5. AICD activation-induced cell deathRepeated stimulation of T cells results in the coexpression of death receptors and

9、 their ligands, and engagement of the death receptors triggers apoptotic death. B cellsClonal deletion Clonal anergyInduction of Immunological ToleranceI. Induction of immunologic tolerance to antigen in fetal period and neonate periodDiscovery of Owen:1945, chimerasExperiment of Medawar II. Inducti

10、on of immunologic tolerance to antigen in adult 1.Antigen and immunologic tolerance 1)concentration of antigens 2)type of antigen 3) features of determinant 4) pathway of antigen entering body 2. Individual and tolerance: Age, Species, Status of host immune sysetemHigh and low dose toleranceFactors

11、affecting tolerancerole of antigenFactors which affect responseFavor immune responseFavor tolerancePhysical form of antigenRoute of injectionDose of antigenLarge, aggregated, complex molecules, properly processedSubcutaneous or intramuscularOptimal dosesoluble, aggregate-free, simple small molecules

12、, not processedOral or, sometimes, intravenousVery large or very small doseFactors affecting tolerancethe role of hostFactors that affect responseFavor immune responseFavor toleranceAge of responding animalDifferentiation state of cellsOlder, immuno-logically matureFully differentiated; memory T & B cellsNewborn (mice), immuno-logically immatur