cmi2014-chapter-8-lymphocytedevelopmentppt课件.ppt
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1、Cellular and Molecular Immunology,Xian-Hui He Department of Immunobiology Jinan University 2014-11,1,Chapter 8 The Development and Survival of Lymphocytes,Development of B lymphocytes. The development of T lymphocytes in the thymus. Positive and negative selection of T cells. Survival and maturation
2、 of lymphocytes in peripheral lymphoid tissues.,Part III The development of mature lymphocyte receptor repertoires,2,中枢耐受的形成,1. Development of B lymphocytes. B淋巴细胞的发育,3,Development of B lymphocytes.,8-1 B淋巴细胞由骨髓中的造血干细胞 (HSC) 所产生. hematopoietic stem cells (HSC) .,骨髓中产生BCR,骨髓中阴性选择,在外周活化,成为浆细胞和记忆细胞,4,D
3、evelopment of B lymphocytes.,B细胞早期发育依赖于骨髓基质细胞 (stromal cells) .,骨髓基质细胞表达B细胞发育所需的IL-7、CXCL12、VCAM-1、SCF,5,晚期祖B细胞,多能干细胞,前B细胞,未成熟B细胞,早期祖B细胞,淋巴样干细胞,Development of B lymphocytes.,8-2 B细胞发育始于重链基因的重排, 重链与替代轻链组成前B受体 (Pre-B receptor).,6,大前B细胞,多能干细胞,小前B细胞,未成熟B细胞,晚期祖B细胞,早期祖B细胞,成熟B细胞,重链重排,前B受体,轻链重排,IgM表达,IgD表达,
4、Development of B lymphocytes.,8-3 前B受体检测重链的成功重排, 从而传递信号触发轻链重排,完成Pro-B到Pre-B的转换.,7,Development of B lymphocytes.,8,Development of B lymphocytes.,8-4 前B受体传递信号抑制重链基因的进一步重排,完成等位基因排斥(allelic exclusion).,9,Development of B lymphocytes.,8-5 Pre-B细胞重排轻链基因,在细胞表面表达Ig. 轻链等位基因排斥; isotypic exclusion: or 轻链基因可以重复
5、重排,直到产生有功能的轻链蛋白,10,Development of B lymphocytes.,8-6 未成熟的前B细胞在离开骨髓前检测自身反应性. 阴性选择:不与自身抗原反应的B细胞发育成熟 中枢耐受 (central tolerance)形成的主要机制 cell death by apoptosis or clonal deletion (克隆删除) the production of a new receptor by a process known as receptor editing (受体编辑) the induction of a permanent state of unr
6、esponsiveness, or anergy, to antigen (失能) immunological ignorance (免疫忽视),11,12,无自身反应性,多价自身分子,可溶自身分子,低亲和力非交联 自身分子,成熟B细胞,凋亡或产生无自身 反应性成熟B细胞,失能B细胞,克隆忽略 成熟B细胞,2. The development of T lymphocytes in the thymus. T淋巴细胞在胸腺中的发育,13,The development of T lymphocytes in the thymus.,14,The development of T lymphoc
7、ytes in the thymus.,8-7 T细胞的祖细胞源于骨髓,但所有重要发育事件在胸腺进行. 在胸腺中发育的T细胞称为胸腺细胞(thymocytes),髓质,皮质,(基质stroma),(基质stroma),15,The development of T lymphocytes in the thymus.,在胸腺中发育的T细胞称为胸腺细胞(thymocytes) 裸鼠(Nude mice): 上皮细胞终末分化所需的转录因子Foxn1基因缺陷, 无胸腺(无T细胞,有B细胞) Human DiGeorge syndrome: 无胸腺(无T细胞,有B细胞) 严重联合免疫缺陷(SCID):
8、无T、无B (抗原受体基因重排缺陷),16,The development of T lymphocytes in the thymus.,8-8 T细胞前体在胸腺大量扩增,但大部分死亡. 98% thymocytes 凋亡,17,The development of T lymphocytes in the thymus.,8-9 不同细胞表面分子的表达显示胸腺细胞处于不同发育阶段.,18,19,T细胞受体(TCR)的发育: TCR 基因先重排,成功重排的链与替代轻链pT组成pre-TCR TCR 基因随后重排,表达有功能TCR, 经历选择过程。,成功重排的链与替代轻链pT组成pre-TCR
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