Cells and organs in the immune system

1. Cells and organs in the immune system

2. Hematopoiesis • Cells of the immune system • Organs of the immune system • Systemic function of the immune system

3. An infection that begins in one area of the body eventually involves cells, organs, and tissues that may be distant from the site of pathogen invasion. Antigen from distant sites can arrive at lymph nodes via lymph and dendritic cells, thereby assuring activation of T cells and B cells and release of these cells and their products to the circulation. Inflammatory processes bring lymphocytes and other leukocytes to the site of infection. • Thus, although dispersed through-out the body, the components of the immune system communicate and collaborate to produce an effective response to infection.

4. All leukocytes develop from a common multipotent hematopoietic stem cell during hematopoiesis.造血干细胞是存在于造血组织中的一群原始造血细胞。在人胚胎第2周时可出现于卵黄囊，第四周开始转移至胚肝，妊娠5个月后，骨髓开始造血，出生后骨髓成为造血干细胞的主要来源。 • Various hematopoietic growth factors (cytokines) induce proliferation and differentiation of the different blood cells. • Hematopoiesis Can Be Studied In Vitro

8. Organs of the Immune System • The immune organs can be classified functionallyinto two main groups. • The primary lymphoid organs provideappropriate microenvironments for the development andmaturation of lymphocytes. • The secondary lymphoid organstrap antigen from defined tissues or vascular spaces and aresites where mature lymphocytes can interact effectively withthat antigen.

9. Primary lymphoid organs • Thymus: The thymus is the site of T-cell development and maturation. • Bursa: In birds , bursa is the site of B-cell origin and development. • bone marrow:In humans and mice, bone marrow is the site of B-cell origin and development.

10. secondary lymphoid organs • Lymph nodes: lymph nodes are specialized for trapping antigen from local tissues. • Spleen: the spleen specializes in filtering blood and trapping blood-borne antigens. The structure of spleen The function of spleen • mucosal-associated lymphoid tissue

11. thymus • The thymus is a flat, bilobed organ situated above the heart. Each lobule is organized into two compartments: the outer compartment, or cortex, is densely packed with immature T cells, called thymocytes, whereas the inner compartment, or medulla, is sparsely populated with thymocytes. • 生理性胸腺萎缩 • 胸腺的功能

12. 生理性胸腺萎缩 • The thymus reaches its maximal size at puberty and then atrophies, with a significant decrease in both cortical and medullary cells and an increase in the total fat content of the organ.

13. Both the cortex and medulla of the thymus are crisscrossed by a three-dimensional stromal-cell network composed of epithelial cells, dendritic cells, and macrophages, which make up the framework of the organ and contribute to the growth and maturation of thymocytes. • T细胞由皮质向髓质迁移的过程也是T细胞由不成熟向成熟的发育过程。随着细胞从皮质层向髓质的迁移，细胞也会逐渐变为成熟的T细胞。

14. The function of thymus • 胸腺是T细胞分化成熟的场所，在这个过程中，只有大约1%的细胞能最终发育成熟； • 髓质内的网状上皮细胞可分泌胸腺激素，这些物质是构成胸腺微环境的重要因素，对于T细胞的分化和调节起到重要的作用； • 形成对自身抗原的耐受性——维持自身的稳定。在T细胞成熟的过程中能与自身抗原物质发生反应的克隆都被清除掉了。

15. Bursa(腔上囊及类器官) • 腔上囊是鸟类特有的器官，它是鸟类B淋巴细胞成熟的部位； • 腔上囊作用的发现。

16. Bone • 骨髓是人和哺乳类动物的造血器官，同时也是各种免疫细胞的发源地，其中含有具强大分化潜能的多能干细胞，能分化为造血干细胞和淋巴干细胞； • 骨髓功能缺陷时可导致机体免疫功能的缺陷； • 骨髓被认为是高等哺乳动物B细胞成熟的部位。

18. lymphatic systemand Lymph nodes • A lymph node can be divided into three roughly concentric regions: the cortex, the paracortex, and the medulla. • Lymph nodes are encapsulated bean shaped structures containing a reticular network packed with lymphocytes, macrophages, and dendritic cells. • 淋巴结的生理作用

19. Lymphatic vessels • Small lymphatic capillaries opening into the tissue spaces pick up interstitial tissue fluid and carry it into progressively larger lymphatic vessels, which carry the fluid, now called lymph, into regional lymph nodes. As lymph leaves the nodes, it is carried through larger efferent lymphatic vessels, which eventually drain into the circulatory system at the thoracic duct or right lymph duct.

20. 淋巴结是免疫反应的发生部位 • As antigen is carried into a regional node by the lymph, it is trapped, processed, and presented together with class II MHC molecules by dendritic cells in the paracortex, resulting in the activation of TH cells. The initial activation of B cells is also thought to take place within the T-cell-rich paracortex. Once activated, TH and B cells form small foci (病灶) consisting largely of proliferating B cells at the edges of the paracortex. Some B cells within the foci differentiate into plasma cells secreting IgM and IgG.

21. The outermost layer, the cortex, contains lymphocytes (mostly B cells), macro-phages, and follicular dendritic cells arranged in primary follicles(滤泡). • Beneath the cortex is the paracortex, which is populated largely by T lymphocytes and also contains interdigitating dendritic cells thought to have migrated from tissues to the node. • The innermost layer of a lymph node, the medulla, is more sparsely populated with lymphoid-lineage cells; many are plasma cells actively secreting antibody molecules.

22. The structure of spleen

23. 滤过作用：体内约90%的循环血液要流经脾脏，脾脏中的 M可吞噬和清除血液中的病原体，以及衰老死亡的自身红细胞、白细胞、某些蜕变细胞及免疫复合物等，从而使血液得到净化。 • T 细胞和 B 细胞细胞定居的场所。 • 免疫应答发生的场所：血液中的病原体等抗原性异物经血液循环进入脾脏，除被 M摄取并降解为抗原肽，导致 T、B 细胞活化、增殖，产生效应T细胞和浆细胞。脾脏是针对来自血液中抗原异物的免疫应答场所，也是体内产生抗体的主要器官。 • 合成某些生物活性物质，如补体、干扰素等。

24. 粘膜相关淋巴组织（mucosa-associated lymphoid tissue，MALT） • The mucous membranes lining the digestive, respiratory, and urogenital systems have a combined surface area of about 400 m2 (nearly the size of a basketball court) and are the major sites of entry for most pathogens. • 粘膜相关淋巴组织，乃无被膜的淋巴组织，主要指呼吸道、肠道及泌尿生殖道粘膜固有层和上皮细胞下散在的淋巴组织，以及某些带有生发中心的器官化的淋巴组织，MALT 主要包括鼻相关淋巴组织、肠相关淋巴组织和支气管相关淋巴组织。 如扁桃体、小肠的派氏集合淋巴结（Peyer’s patch）、阑尾等。

25. Cells of the immune system • Lymphocytes are the central cells of the immune system, responsible for adaptive immunity and the immunologic attributes of diversity, specificity, memory, and self/nonself recognition. • The other types of white blood cells play important roles, engulfing and destroying microorganisms, presenting antigens, and secreting cytokines.

26. Lymphoid cells • Antigen presenting cells, APC • Granulocytic and red cells • 淋巴细胞和APC的相互作用

27. Electron micrograph of an antigen-presenting macrophage (right) associating with a T lymphocyte.

28. Lymphocytes • Lymphocytes constitute 20%–40% of the body’s white bloodcells and 99% of the cells in the lymph. These lymphocytes continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs, thereby integrating the immune system to a high degree. • The lymphocytes can be broadly subdivided into three populations—B cells, T cells, and natural killer cells —on the basis of function and cell-membrane components.

29. natural killer cells • The natural killer cell was first described in 1976,when it was shown that the body contains a small population of large, granular lymphocytes that display cytotoxic activity against a wide range of tumor cells in the absence of any previous immunization with the tumor. • NK cells were subsequently shown to play an important role in host defense both against tumor cells and against cells infected with some, though not all, viruses. • These cells, which constitute 5%–10% of lymphocytes in human peripheral blood, do not express the membrane molecules and receptors that distinguish T- and B-cell lineages.

30. thymus dependent cell • T细胞的主要类群 • T细胞的表面标志 • T细胞的表面受体 • T细胞的个体发育 • T细胞的免疫缺陷

31. T细胞免疫缺陷表现为体液与细胞免疫应答无能，患者反复发生致命性病毒、霉菌、分枝杆菌和寄生虫感染。T细胞免疫缺陷表现为体液与细胞免疫应答无能，患者反复发生致命性病毒、霉菌、分枝杆菌和寄生虫感染。 先天性胸腺发育不全（DiGeorge 综合症） A child with DiGeorge syndrome showing characteristic dysplasia of ears and mouth and abnormally long distance between the eyes.

32. 无胸腺的裸鼠是T细胞选择性缺陷的天然动物模型无胸腺的裸鼠是T细胞选择性缺陷的天然动物模型

33. （一）T细胞的主要类群 T 细 胞 类 群 细 胞 毒 性 T 细 胞 抑 制 性 T 细 胞 辅 助 性 T 细 胞 反 抑 制 性 T 细 胞

34. 1、辅助性T细胞(help T cells,Th) 少量抗体产生 大剂量X射线 无抗体产生 植入T、B细胞 导致T、B淋巴 细胞被杀死 实验说明的问题 大量抗体产生 植入T细胞 植入B细胞

35. 这个实验证明：T细胞具有辅助B细胞产生抗体的能力。它还可以辅助其它免疫细胞发挥作用。我们将这类T细胞称为辅助性T细胞（helper T cells TH）。它占所有T细胞总数的40~60%。TH是AIDS的受体细胞。 • Th细胞可根据它分泌的细胞因子的类型不同分成两个亚群：Th1和Th2。

38. 3、抑制性T细胞 • 在T细胞类群中有一类T细胞，它可以抑制其它免疫细胞（TH、B）的活性，防止机体产生过高的免疫应答。这一类T细胞我们称为抑制性T细胞（suppressor T cells TS）。 • 抑制性T细胞不是独立的亚群，只是功能含义上的命名。具有抑制功能的T细胞既可表达CD4＋也可表达CD8＋标志。 它约占T细胞总量的5~10%。

39. 2、 cytotoxic T lymphocyte, CTLs 细胞毒性T细胞是T细胞的主要效应形式。 作用方式： • 通过与靶细胞细胞后释放成孔蛋白使靶细胞膜受损，从而导致靶细胞的破裂； • 向靶细胞内释放物质，诱导靶细胞发生细胞凋亡。 所以我们将此类细胞称为细胞毒性T细胞。

41. 4、反抑制性T细胞 这类细胞的主要作用是防止Ts细胞的活性过高，抑制Ts细胞的活性，从而使机体的细胞免疫处于一种合适的程度。

42. （二）T细胞的表面标志 细胞表面存在多种分子，根据这些分子我们可以将T细胞区分为不同的类型。在这些分子中最重要的是CD（cluster of differentation）抗原。

44. （三）T细胞表面受体 • T细胞表面受体（T cell receptor TCR）也是存在于T细胞表面的一类分子。它的作用是结合外来抗原的抗原决定簇。 • 绵羊红细胞表面分子受体：它可以与绵羊红细胞发生结合，在显微镜下观察类似玫瑰花环。 • 有丝分裂原受体：这些受体可与PHA和ConA，这些物质与T细胞结合后能促进细胞分裂。

48. TCR的结构 • TCR由α、β两条异二聚体组成的TCR αβ。两条肽链都是由膜外区、穿膜区及胞浆区组成。 • TCR属于Ig超家庭，膜外区包括可变区和恒定区。

49. （四）T细胞个体发育 • 胸腺细胞在胸腺内经历了严格的选择过程，即发生在胸腺皮质的阳性选择（positive selection）和发生在皮-髓交界处的阴性选择（negative selection）。 • 为什么在T细胞发育的过程中会经历选择过程？ • 进入胸腺的前T细胞，约95%在皮质发生凋亡，仅不足5%的胸腺细胞继续向髓质迁移，分化为成熟T细胞，最后（大约仅1%）进入外周免疫器官。

50. 为了满足T细胞的功能需要