Immunological Tolerance 1 Factors affecting tolerance role of

免疫耐受 Immunological Tolerance 1

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 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 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

High and low dose tolerance

Host age and antigen dose affect tolerance newborn adult

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

Negative selection of B cells in bone marrow

Clonal anergy in T cells

Clonal anergy in B cells

Tolerance due to lack of helper T cells

Receptor editing among B cells

Antiidiotype antibody in tolerance

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