Immunological Tolerance 1 Factors affecting tolerance role of

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免疫耐受 Immunological Tolerance 1

免疫耐受 Immunological Tolerance 1

Factors affecting tolerance role of antigen Factors which affect response Favor immune response Favor

Factors affecting tolerance role of antigen Factors which affect response Favor immune response Favor tolerance Ø Physical form of antigen Ø Large, aggregated, complex molecules, properly processed Ø soluble, aggregate-free, simple small molecules, not processed Ø Route of injection Ø Subcutaneous or intramuscular Ø Oral or, sometimes, intravenous Ø Dose of antigen Ø Optimal dose Ø Very large or very small dose

Factors affecting tolerance the role of host Factors that affect response Favor immune response

Factors affecting tolerance the role of host Factors that affect response Favor immune response Favor tolerance Ø Age of responding animal Ø Fully differentiated; memory T & B cells Ø Newborn (mice), immunologically immature Ø Differentiation state of cells Ø Older, immunologically mature Ø Relative undifferentiated B cell with only Ig. M, T cells in the thymic cortex

Immunologic features of tolerance Ø It is an antigen-induced, active process Ø Like immunologic

Immunologic features of tolerance Ø It is an antigen-induced, active process Ø Like immunologic memory, it is antigen specific Ø Like immunologic memory, it can exist in B cells, T cells or both Ø Like immunologic memory, its easier to induce and lasts longer in T cells than in B cell

Tolerance in T and B cells

Tolerance in T and B cells

High and low dose tolerance

High and low dose tolerance

Host age and antigen dose affect tolerance newborn adult

Host age and antigen dose affect tolerance newborn adult

Mechanism of tolerance induction Ø Clonal deletion Thymus: negative selection Ø Bone marrow: Ig.

Mechanism of tolerance induction Ø Clonal deletion Thymus: negative selection Ø Bone marrow: Ig. M+, Ig. D- B cells encountering self antigen Ø Ø Clonal anergy Lack of co-stimulatory(B 7) molecules Ø Exposure to large amounts of antigen Ø Improper antigen presentation Ø Lack of antigenic stimulus Ø Ø Receptor editing Anti-idiotype antibodies Suppressor T cells

Clonal deletion: negative selection in the thymus

Clonal deletion: negative selection in the thymus

Negative selection of B cells in bone marrow

Negative selection of B cells in bone marrow

Clonal anergy in T cells

Clonal anergy in T cells

Clonal anergy in B cells

Clonal anergy in B cells

Tolerance due to lack of helper T cells

Tolerance due to lack of helper T cells

Receptor editing among B cells

Receptor editing among B cells

Antiidiotype antibody in tolerance

Antiidiotype antibody in tolerance

Breakdown of tolerance Ø Immunosuppression Ø Ø Lack of antigen exposure Ø Ø Lack

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

Immunological Tolerance 1 Factors affecting tolerance role ofImmunological Tolerance 1 Factors affecting tolerance role of
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