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1、熟悉免疫系统的概念及组成 ,熟悉免疫器官(组成及其在免疫系统中的地位和作用),熟悉免疫细胞(概念、种类),掌握T、B淋巴细胞的表面标志、功能及亚群,了解T、 B淋巴细胞的发育成熟及分布,了解淋巴细胞再循环,熟悉NK细胞及M等免疫细胞的免疫生物学功能。,免疫器官 (Immune organs)免疫细胞 (Immune cells)免疫分子 (Immune molecules),免疫系统的基本组成 Basic Components of the Immune System,2-1 造血干细胞的分化途径,免疫细胞(Immune cell): 与应答有关的细胞,包括前体细胞。,(特异性免疫),(非特异
2、性免疫),分为执行特异性免疫和非特异性免疫的细胞,2-2粒细胞系 (Granulocytes),中性粒细胞,嗜酸性粒细胞,嗜碱性粒细胞,主要形态学特点:胞浆含有明显的胞浆颗粒。,50%70%,1%3%,1%,在普通光学显微镜下观察Giemsa染色血涂片,中性粒细胞呈淡藕荷色,多叶核,胞浆中含有大量的细胞颗粒。透射电镜下其胞浆颗粒清晰可辨。,I 中性粒细胞 ( Neutrophil ),RBC,Neutrophils represent 60-70% of leukocytes in the peripheral blood. Their granules contain alkaline ph
3、osphatase, lysozame, lactoferrin etc.,They are the earliest phagocytic cells to appear in the bacterial infection and are prominent constituent of pus.,II 嗜酸性粒细胞 (Eosinophil),在普通光学显微镜下观察Giemsa 染色的血涂片,嗜酸性粒细胞胞核为双叶状,胞浆中含有大量深红色细胞颗粒。透射电镜下其胞浆颗粒呈结晶状。,Eosinophils represent 2-4% of peripheral blood white cel
4、ls. Their granules contain histaminase, acid phosphatase, and major basic protein. They are important in destroying parasites, phagocytosing Ag-bound complexes, and combating histamine levels during allergic reaction.,嗜酸粒细胞占外周血白细胞的24%。 颗粒中含有组织胺酶,酸性磷酸酶,碱性蛋白。在消灭寄生虫,吞噬抗原抗体复合物起重要的作用,在过敏反应中有抗组胺的作用。,The r
5、ole of Eosinophils in Allergic inflammation,Eosinophils have Fcreceptor for IgE and cause cytotoxicity to large multicellular parasites coated with specific IgE antibody, analogous to Kcells.,Histopathology of bladder shows eggs of Schistosoma haematobium surrounded by intense infiltrates of eosinop
6、hils,III 嗜碱性粒细胞 ( Basophil ),在普通光学显微镜下观察Giemsa染色的血涂片,嗜碱性粒细胞胞浆中布满深蓝色细胞颗粒。透射电镜下胞浆颗粒中充满致密物质。,Basophils represent 1% of peripheral blood white cells. Their granules contain histamine, heparin, and chemotactic factors for neutrophils and eosinophils. They are similar to mast cells in that they participat
7、e in IgE-mediated hypersensitive responses.,Basophils,IV 肥大细胞 (mast cell),组织中的肥大细胞含有大量致密细胞颗粒(左)。Crohn氏病患者肠粘膜组织的肥大细胞自发释放颗粒的内容物,留下许多细胞颗粒空穴(右)。,肥大细胞形态大,胞核较小;胞质内充满大量粗大而具有异染性的圆形嗜碱性颗粒;这种颗粒被伊红染成红色。,静息肥大细胞,激活后 5 分钟,激活后 60 分钟,2-3Dendritic cells (树突细胞),Dendritic cells are bone marrow-derived cells specialized
8、 to present antigen to B or T cells in order to initiate a primary immune response.,树突细胞是骨髓衍生的专职提呈抗原至B 或T细胞,启动初期免疫反应,Dendritic Cells,Bone marrow Blood Tissue,Blooddendritic cell,Monocyte,Indeterminatecell,Dendritic cell,Macrphage,Mycloid precursor,Pluripotent stem cell,?,I 郎格汉斯细胞 ( Langerhans cells
9、),上皮组织中的LC(1,普通光镜)捕捉外来抗原后即进入引流淋巴结的T细胞区,成为IDC(2,扫描电镜照片)。,II 并指状树突细胞(interdigitating DC),IDC表达高水平的II类MHC分子和共刺激分子B7,具有激活T细胞的能力 (外周淋巴组织)。,B cells,FDC,III 滤泡树突细胞(folicular DC, FDC),淋巴滤泡内的FDC通过Fc受体和补体受体捕获被致敏的抗原,并将其递呈给B细胞,2-4单核巨噬细胞,(monocytes and macrophages),lysosome,lysosome,Nucleus,Nucleus,Phagosome,Mon
10、ocyte,Macrophage,Phagosome,Phagosome,Phagosome,Pseudopodia,The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissue.,Monocyte,Macrophage,The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissu
11、e.,lysosome,lysosome,Nucleus,Nucleus,Phagosome,Phagosome,Phagosome,Phagosome,Pseudopodia, 单核细胞 Monocyte ( blood ) 库普弗细胞 Kupffer cells ( liver ) 肾小球间质细胞 Mesangial cells ( kidney glomerulus ) 小神经胶质细胞 Microglia ( brain ) 肺泡巨噬细胞 Alveolar macrophages ( lung ) 组织细胞 Histiocyte ( connective tissue ),Macroph
12、age,-Different names in different tissues,单 核 巨 噬 细 胞,单核细胞体积较大,蹄状核(左,普通光镜)。透射电镜显示其高尔基体发达、粒体丰富、胞浆颗粒明显(中)。扫描电镜显示腹腔巨噬细胞粘附于玻璃表面(右)。,Macrophages Ingest and Degrade antigens,bacteria,Long pseudopodia,(A),(B),Macrophages Ingest and Degrade antigens,2-5 Lymphocytes(淋巴细胞),Lymphocytes are a class of white blo
13、od cells that bear variable cell surface receptors for antigens. There are two main classes of lymphocytes- B and T cells-which mediate humoral and cellular immunity respectively.,I 淋巴细胞的一般特点 ( General characteristics of lymphocytes),未活化淋巴细胞直径67微米,浆/核比例很小(左,普通光镜)。投射电镜显示未活化淋巴细胞胞核致密,胞浆中细胞器很少(右)。,Resti
14、ng lymphocytes have little cytoplasm and condensed nuclear chromatin. Upon activation, the cell enlarges to form a lymphoblast and then proliferates and differentiates into an antigen-specific effector cell.,Small lymphocyte (T or B)6 m,lymphoblast (T or B)15 m,Plasma cell (B)15 m,Memory cell ( T or
15、 B),NK,Lymphocyte subsets,T CELLS,B CELLS,Common Lymphoidprecurs0r,T HELPER CELLS,CYTOTOXIC T CELLS,PLASMA CELLS,Activate B cellsAnd macrophages,Kill virusInfected cells,Produce antibodies,II 淋巴细胞分群 ( Classification of lymphocytes),1、T 淋巴细胞,T lymphocyte derive their name from their site of maturatio
16、n in the thymus.,MHC/抗原肽,补体,运铁蛋白,TCR,CD35,CD28,B7-2,CD4,CD8,MHC-II/I,IL-2,CD71,CD58(LAF-3),CD2,or,FcmR,FcgR,抗体,(1) T 细 胞 表 面 受 体,组织胺,白细胞分化抗原:CD抗原(cluster of differentiation,),是指血细胞在分化成熟为不同谱系、分化的不同阶段及细胞活化过程中,出现或消失的细胞表面标记分子。 白细胞分化抗原除表达在白细胞之外,还表达在红系、巨核和血小板谱系。白细胞分化抗原还广泛分布于非造血细胞如血管内皮细胞、成纤维细胞、上皮细胞、神经内分泌细胞
17、等。,(2) 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),无胸腺的裸鼠是T细胞选择性缺陷的天然动物模型,Tumors formed by Rat1 cells expressing myr-p110. Nude mice were injected on the left flank with 1X106 Rat-1A cells expressing myr-p110 and on the right flank with an equal number of control Rat-1
18、A cells. This picture was taken 10 days post inoculation.,2、B 淋巴细胞,The B lymphocyte derived its letter designation from its sit of maturation, in the bursa of Fabricius in birds, the name turned out to be apt, for bone marrow is its major site of maturation in a number of mammalian species, includin
19、g humans and mice.,抗原,补体 (C3bi ),CD23,CD28,B7-2,CD40,IL-5,FcmR,(1) B 细 胞 表 面 受 体,IL-2,IgM,IgE,CD21,IL-4,CD32,IgG,补体 (C3b,C4b ),CD40-L,B cell is one of the two major types of lymphocytes. The antigen receptor on of B cells is a cell-surface Ig. On activation by Ag, B cells differentiate into plasma c
20、ells producing Ab molecules of the same Ag specificity as the receptor.,免疫球蛋白(Immunoglobulin Ig),活化B细胞(Activated B cell),浆细胞(plasma cell),ANTIGEN,(2) 原发性B细胞缺陷病:,某种原因使B细胞发育停滞先天性B细胞缺乏或分化成熟障碍。,B细胞免疫缺陷,B细胞发育障碍或者缺乏T细胞帮助均可导致体液免疫应答缺陷。临床表现为反复的胞外寄生菌感染。,性联无免疫球蛋白血症(XLA)Bruton 病,a1 a2 b g,白蛋白,球蛋白,(a) (b) (c),T、
21、B 细胞联合免疫缺陷 Severe Combined Immunodeficiency,SCID,人 NK 细 胞(大颗粒淋巴细胞),3、NK 细胞 (Natural Killer cells),NK cells are large granular non-T non-B lymphocytes.,NK cells are important in innate immunity to viruses and other intracellular pathogens, as well as in antibody-dependent cell mediated cytotoxicity.
22、They also kill certain tumor cells.,NK,靶细胞,NK,杀伤,靶细胞,介导 ADCC(antibody-dependent cell-mediated cytotoxicity),NKCR,杀伤病原体 (viruses and other intracellular pathogens),An NK cell (N) attached to a target cell T. The NK cell will kill the now helpless target cell quickly,2 免 疫 器 官,Organs of the Immune Sys
23、tem,Organs of the Immune System,外周免疫器官 (Peripheral lymphoid organ),中枢免疫器官 (Central lymphoid organ),淋巴细胞发育成熟的场所骨髓(bone marrow)、胸腺(thymus),淋巴细胞定居和发挥功能的场所脾(spleen)、淋巴结(lymphoid nodes)黏膜相关淋巴组织(MALT),外周免疫器官 (Peripheral lymphoid organ),Organ or tissue that provides a microenvironment necessary for lymphoc
24、ytes maturation,中枢免疫器官 (Central lymphoid organ),淋巴细胞发育成熟的场所骨髓(bone marrow)、胸腺(thymus),淋巴细胞定居和发挥功能的场所脾(spleen)、淋巴结(lymphoid nodes)黏膜相关淋巴组织(MALT),2-6中枢免疫器官 (Central lymphoid organ),I 骨髓和法氏囊 (Bone Marrow and bursa of Fabricius),1 免疫细胞生成场所2 B细胞成熟基地,法氏囊(Bursa of Fabricius),Bruce Glick and Charlie Chang,皮
25、质:上皮性网状支架,发育早期胸腺细胞为主髓质:上皮性网状为主,少量胸腺细胞血-胸屏障:皮质毛细血管及其周围具有屏障作用功能:分泌多种激素,促进胸腺细胞分化年龄变化:新生儿胸腺相对较大,至青春期达30-40克,此后胸腺开始萎缩。,II 胸 腺(Thymus),胸腺由胸腺细胞(thymocytes)和胸腺基质细胞(thymic stromal cells)组成,外周淋巴器官,T 细胞发育场所1、出现TCR2、T细胞能识别自身MHC分子3、大部分自身反应性T细胞克隆被清除4、T细胞发育成熟,先天性胸腺发育不全(DiGeorge 综合症),2-7外周淋巴器官 (Peripheral lymphoid
26、organ),粘膜相关淋巴系统 (mucosa-associated lymphoid system),脾脏(spleen),淋巴结(lymphnodes),扁桃体(tonsil),* 高内皮毛细血管后微静脉( High endothelial venule,HEV),HEV are specialized venules found in lymphoid tissues. Lymphocytes migrate from blood into lymphoid tissues by attaching to and migrating across the high endothelial
27、 cells of the vessels.,初级淋巴小结(primary follicle)次级淋巴小结(secondary follicle)= 生发中心(germinal center),Germinal centers in secondary lymphoid tissues are sites of intense B cell proliferation, selection, and death during Ab responses. Germinal centers form around follicular dendritic cell network when act
28、ivated B cells migrate into lymphoid follicles.,*生发中心(germinal center),淋 巴 结 的 基 本 结 构,HEV,髓质淋巴窦,皮质淋巴窦,毛细血管,小梁,输入淋巴管,输出淋巴管,静脉,动脉,髓索,生发中心,髓质,被膜,1、淋巴结,淋巴结被膜外侧有数条输入淋巴管,门处有动、静脉神经和输出淋巴管。实质分为皮质和髓质。靠近被膜的浅层皮质区有生发中心(左)。右图显示生发中心的显微结构,*白髓(white pulp) (1)动脉周围淋巴鞘(periarterial lymphatic sheath,PALS),围绕在动脉周围的弥散淋巴组
29、织,主要由T细胞组成,相当于副皮质区。(2)淋巴小结,主要由B细胞组成,可发展成生发中心,常出现于PALS的一侧。* 红髓(red pulp)占脾实质的2/3,分布于小梁周围及白髓之间。(1)脾索,(2)脾血窦,* 功能滤血、免疫、造血、储血,2、脾 脏 (Spleen),3、粘膜相关淋巴系统 mucosa-associated lymphoid system,MALS,肠 粘 膜 淋 巴 组 织 的 结 构,小肠绒毛细胞,引流淋巴管,粘液层,肌肉层,输出淋巴管,B细胞,T细胞,浆细胞,生发中心,M细胞,肠 道 淋 巴 系 统 免 疫 应 答,Th,巨噬细胞,IgA,sIgA,浆细胞,B,M细
30、胞,上皮细胞,辅助,2-7 淋巴细胞循环 ( Circulation of lymphocytes),Both T and B cells continuously circulate and recirculate, blood to lymph to blood. Approximately 1-2% recirculate every hour. NK cells are only found in blood, spleen and liver.,脾 脏(5小时),血液循环(30分钟),骨髓、上皮腹腔,淋巴结(12小时),粘摸下组织其它组织肝 、大脑,输出淋 巴管,输 入 淋 巴 管,
31、45%,42%,10%,活化淋巴细胞,未活化淋巴细胞,不参加再循环的细胞 ( ?),10%,52%,II 黏附分子与淋巴细胞再循环,Adhesion molecules and lymphocyte circulation,黏附分子( adhesion molecules ),定义:介导细胞与细胞之间、细胞与细胞外基质(extracellular matrix, ECM)之间相互附着的分子 。,功能:与淋巴细胞在体内的循环和归宿密切相关,又称归巢受体(homing receptor)。,粘附分子(Adhesion molecule) 参与细胞与细胞, 或细胞与基质间相互结合,相互作用的膜分子。 大部分粘附分子已被命名为CD分子,粘附分子的功能细胞间相互作用,行使功能,如免疫细胞的协同刺激(costimulation)作用, 炎症过程粒细胞和血管内皮细胞的相互作用。,