第5章_免疫耐受tolerance.pptVIP

重点： 1.免疫耐受的特点 2.耐受产生的机制 References: Nat. Immunol. 2005,6:327-330. Nat. Rev. Immunol. 2005, 5:772-82. Curr. Opin. Immunol. 2006, 18:184–190 Immunol Rev. 2005，204:116-127. Cell 2008， 133：775－787 Fundamental Immunology. sixth ed. 2008. T细胞不能激活LAT导致克隆失能 LAT: Linker for Activation of T cells 组织细胞不表达协同刺激分子，将诱导耐受 从骨髓出来的B细胞经T1、T2和T3过渡阶段才成熟。在过渡阶段，B细胞仍然是不成熟的细胞。若没有T细胞的帮助，B细胞遭遇抗原会发生克隆清除或anergy，但是不发生受体修正现象。 * Figure 1. A White A/Jax Mouse Carrying an Allogeneic Skin Graft (from a CBA Mouse) Five Months after Transplantation. The A/Jax mouse had received 5 million CBA spleen cells when it was a 17-day-old fetus and had become fully tolerant of CBA histocompatibility antigens. The skin was transplanted five weeks after birth. At this age, normal A/Jax mice would be expected to reject such a graft within 10 days * * Figure 1 | Central-tolerance mechanisms. The affinity of the T-cell receptor (TCR) for self-peptide–MHC ligands is the crucial parameter that drives developmental outcome in the thymus. Progenitors that have no affinity or very low affinity die by neglect. This is thought to be the fate of most thymocytes. If the TCR has a low affinity for self-peptide–MHC, then the progenitor survives and differentiates, a process that is known as positive selection. If the progenitor has a high affinity for selfpeptide– MHC, then several outcomes are possible. First, the progenitor can be selected against, a process that is known as negative selection. The main mechanism of negative selection is clonal deletion, but receptor editing and anergy have also been described. Second, there seem to be mechanisms that select for high-affinity self-reactive cells and result in differentiation into a ‘regulatory’-cell phenotype. It is not known what determines whether a T cell is tolerized by negative selection or is selected to become a regulatory T cell9. IEL, intestinal epithelial lymphocyte; NKT cell, natural killer T cell; TReg cell, CD4+CD25+ regulatory T cell. * Fig.?1.?Model of cyt