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第1 6章 免疫调节

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第1 6章 免疫调节. 第1 5 章 免疫耐受. immunological regulation. Immunological Tolerance. 主要内容. §1.分子水平的免疫调节. § 2. 细胞水平的免疫调节. § 3. 整体和群体水平的免疫调节. § 1. 分子水平的免疫调节. 一、 PTK 参与的激活信号转导和 PTP 的负反馈调节. 二、各种免疫细胞的抑制性受体. ITAM. ITIM. P. P. P. PTK. PTP. 酶. 活化信号. 抑制. 酶. 免疫细胞激活性与抑制性受体. T cell. - PowerPoint PPT Presentation

Text of 第1 6章 免疫调节

  • 16

    immunological regulation15 Immunological Tolerance

  • 3.1.2.

  • 1.PTKPTP

  • CD28 cross linked by B7Costimulatory molecules also associatewith inhibitory receptorsCTLA-4 binds CD28 with a higher affinity than B7 moleculesCo-stimulationinduces CTLA-4The lack of signal 2 to the T cell shuts down the T cell response.

  • PPPAPCPD-1CD28B7-H1B7TPD-1T

  • KLR

  • 2.TT(CD4+CD25+)T

  • T

  • T

  • TCKs

  • 2.

  • apoptosis(activation induced cell death,AICD)

  • 3.--

  • 3.MHCTCR

  • Immunological Tolerance18

  • Introduction

  • 1.3.2.

  • TB1.

  • Owen 1945Ag

  • Induction of tolerancean experiment of natureDizygotic twins in cows

  • chimaeric

  • TB1.

  • T ,B

  • HGG()

  • TTBTD

  • newbornadult

  • TB

  • Negative selection of B cells inbone marrow

  • 1.(clone deletion)

  • Signal 1onlyAnergyThe T cell is unable to produce IL-2 and therefore is unable to proliferate or be clonally selected.Unlike immunosupressive drugs that inhibit ALL specificities of T cell, Signal 1 in the absence of signal 2 causes T cell unresponsiveness to a specific antigenSelf peptide epitopes presentedby a non-classical APC e.g. anepithelial cell

  • 2. TCRAPCTTimmunological ignorance

  • TAg

  • 3. TMHC-IAgclonal anergy)

  • Clonal anergy in T cells

  • Clonal anergy in B cells

  • 4.T,B

  • 5.

  • 6.CKsimmune privileged site

  • 6.(1)

  • ()Stertoli(Immune privilege)

  • IgE.

  • .

  • Introduction:

    Tolerance refers to the specific immunological non-reactivity to an antigen resulting from a previous exposure to the same antigen. While the most important form of tolerance is non-reactivity to self antigens, it is possible to induce tolerance to non-self antigens. When an antigen induces tolerance, it is termed tolerogen.

    Need for tissue and organ graft drove the curiosity to understand the mechanisms of tolerance. The observations a zoologist, Owens, that Dizygotic bovine twins could accept grafts from each other but their siblings from other pregnancies could not tolerate such grafts led Medawar to perform a series of experiments to induce tolerance in mice.Need for tissue and organ graft drove the curiosity to understand the mechanisms of tolerance. The observations a zoologist, Owens, that Dizygotic bovine twins could accept grafts from each other but their siblings from other pregnancies could not tolerate such grafts led Medawar to perform a series of experiments to induce tolerance in mice.He and his collaborators Brent and Billingham under the hypothesis that early exposure to foreign antigens might facilitate tolerance induction performed this experiment.A white (Balb/c) mouse made tolerant to C57Bl (black) mouse tissues.

    Tolerance to tissue and cell antigens can be induced by injection of hemopoietic (stem) cells in neonatal or severely immuno-compromised (by lethal irradiation or drug treatment) animals. Also, grafting of thymus in early life results in tolerance to the donor type cells and tissues. Such animals are known as chimeras. These findings are of significant practical application in bone marrow grafting.

    Induction of tolerance in T cells is easier and requires relatively smaller amounts of tolerogen than tolerance in B cells. Maintenance of immunological tolerance requires persistence of antigen. Tolerance can be broken naturally (as in autoimmune diseases) or artificially (as shown in experimental animals, by xirradiation, certain drug treatments and by exposure to cross reactive antigens).

    Tolerance may be induced to all epitopes or only some epitopes on an antigen and Tolerance to a single antigen may exist at B cell level or T cells level or at both levels.

    Clonal deletion: Functionally immature cells of a clone encountering antigen undergo a programmed cell death. For example, auto-reactive T-cell are eliminated in the thymus following interaction with self antigen during their differentiation (negative selection). Clonal deletion has been shown to occur also in the periphery. B cells expressing only IgM (no IgD) on their surface when exposed to antigen are eliminated.

    Clonal anergy: Auto-reactive T cells when exposed to antigenic peptides that do not possess co-stimulatory molecules (B7-1 or B7-2) become anergic to the antigen. Also, B cells when exposed to large amounts of soluble antigen down regulate their surface IgM and become anergic and short lived. These cells also up regulate Fas molecules on their surface. An interaction of these B cells with Fas-ligand bearing cells result in their death via apoptosis.