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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

Tolerance

Tolerance refers to an

antigen induced specific

unresponsiveness

factors affecting tolerance role of antigen

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

factors affecting tolerance role of antigen1

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

immunologic features of tolerance
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
mechanism of tolerance induction
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
breakdown of tolerance
Breakdown of tolerance
  • Immunosuppression
    • Lack of antigen during differentiation of new clones
  • Lack of antigen exposure
    • As above
  • Cross reactive antigens