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Tolerance

Tolerance. Tolerance refers to an antigen induced specific unresponsiveness. Induction of tolerance an experiment of nature. Dizygotic twins in cows. Experimental induction of tolerance. The chimaeric mouse. Factors which affect response. Favor immune response. Favor tolerance.

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Tolerance

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  1. Tolerance Tolerance refers to an antigen induced specific unresponsiveness

  2. Induction of tolerancean experiment of nature Dizygotic twins in cows

  3. Experimental induction of tolerance

  4. The chimaeric mouse

  5. Factors which affect response Favor immune response Favor tolerance Factors affecting tolerance:role of antigen Physical form of antigen Large, aggregated, complex molecules soluble, aggregate-free, simple small molecules Antigen processing properly processed improperly processed Subcutaneous or intra-muscular Oral or, sometimes, intravenous Route of injection Very large or very small dose Dose of antigen Optimal dose

  6. Factors which affect response Favor immune response Favor tolerance Factors affecting tolerance:role of antigen Age of responding animal Adult, immunologically mature Newborn (mice) Immunologically immature Fully differentiated, Memory Differentiation state of cells Undifferentiated B cell with only IgM, T cells in the thymic cortex

  7. 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, its easier to induce and lasts longer in T cells than in B cell

  8. Mechanism of tolerance induction • Clonal deletion • Thymus: negative selection • Bone marrow: IgM+, IgD- B cells encountering self antigen • Clonal anergy • Lack of co-stimulatory(B7) molecules • Exposure to large amounts of antigen • Improper antigen presentation • Lack of antigenic stimulus • Receptor editing • Anti-idiotype antibodies • Suppressor T cells

  9. Clonal deletion:negative selection in the thymus

  10. Negative selection of B cells inbone marrow

  11. Clonal anergy in T cells

  12. Clonal anergy in B cells

  13. Receptor editing among B cells

  14. Antiidiotype antibody in tolerance

  15. Breakdown of tolerance • Immunosuppression • Lack of antigen during differentiation of new clones • Lack of antigen exposure • As above • Cross reactive antigens

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