免疫耐受 Immunological课件.pptVIP

Chapter 13 Immunological  Tolerance (3) I. Introduction Concept Natural tolerance Acquired tolerance II. Factors Affecting Tolerogenicing of Antigen III. Mechanisms of Tolerance Induction IV. Clinical significance of immunologic tolerance Concept Immunological tolerance is a state of unresponsiveness that is specific for a particular antigen; it is induced by prior exposure to that antigen. II. Factors Affecting Tolerogenicing of Ag 1. The structure of antigen 2. The antigen dosage 3. The route of administration Low –zone tolerance High –zone tolerance Tolerance cells T cells T and B cells Speeds 24 hours slow ( 1-2 weeks) Time long (months) short (weeks) Antigens TD-Ag (low-dose) all Ag (high-dose) Experimental induction of tolerance at low and high doses of antigen Serum anti-BAS Response to secondary immunogenic dose of BSA% of control Priming dose of BSA,g 100% 10-12 10-9 10-6 10-3 1.0 Low-zone tolerance High-zone tolerance Immunity Control: signal Immunogenic Dose of BSA III. Mechanisms of Tolerance Induction 1. Clonal deletion therapy Central thymic tolerance to self Ags-positive and negative selection. 2. Clonal anergy a.? Lack of signal of activation can cause unresponsiveness b. The blocking of immunocompetent cells c. Lack of helper cells 3. The Suppressant effect of various cells Mechanisms of Tolerance Induction Clonal deletion: physically deleting cells from the repertoire at come stage during their lifespan. Clonal anergy: downregulating the intrinsic mechaism of the immune response. Suppression: inhibiting cellular activity through interaction with other cells, such as those producing inhibitory cytokines or idiotype-specific lymphocytes which recognize the antigen receptor i