12年执医考微生疫必考总结

　 第 一 单元　微生物的基本概念1.非细胞型微生物：病毒2.原核细胞型微生物：细菌3.真核细胞型微生物：真菌第 二 单元　细菌的形态与结构细菌的基本结构细胞壁肽聚糖由聚糖支架与四肽侧链及五肽交联桥共同构成功能：菌体固有形态。脂多糖是革阴细菌内毒素主要成分溶菌酶：切断聚糖支架的β-1，4糖苷键，抑制细菌细胞壁的合成。青霉素：切断四肽侧链与五肽交联桥之间的连接，抑制细菌细胞壁的合成质粒：是细菌染色体外的遗传物质。非细菌生命活动所必须。（1）F质粒：编码细菌性菌毛（2）R质粒：控制细菌耐药性细菌的特殊结构1.荚膜：抗吞噬。2.鞭毛：运动。3.芽胞：增强细菌抵抗外界不良环境的能力。是灭菌效果的指征。4.菌毛普通菌毛：粘附作用性菌毛遗传物质的传递，由F质粒表达初染：结晶紫染液媒染：卢戈氏碘液脱色：95% 的乙醇复染：稀释复红液。）

　第三单元　细菌的生理细菌生长繁殖的条件大多数细菌的最适pH为pH7.2～7.6。结核杆菌pH6.6～6.8，霍乱弧菌pH8.8～9.0繁殖方式：二分裂方式进行无性繁殖细菌的分解和合成代谢1.热原质：细菌在代谢过程中产生的一种物质，注入人或动物体内可引起发热反应细菌毒素的区别细菌的分解代谢试验1.糖发酵试验：乳糖发酵试验常用于鉴别肠道致病菌与非致病菌大肠杆菌IMViC试验结果为：，产气杆菌为细菌的人工培养菌落：由单个细菌在固体培养基中生长繁殖，形成的肉眼可见的细菌集团第四单元　消毒与灭菌紫外线260～270nm，最佳波长为265～266nm杀菌机理：使同一条DNA链上相邻的两个嘧啶碱基共价结合而形成嘧啶二聚体，干扰细菌DNA的复制与转录，导致细菌死亡或突变

　 外毒素（exotoxin） 内毒素（endotoxin）

　产生细菌 G+及少数G-菌 只有革兰阴性菌产生

　释放方式 生活状态下释放 死亡裂解释放

　化学组成 蛋白质 脂多糖

　抗原性质 强，可转变成类毒素 弱，不能形成类毒素

　耐热性质 不耐热 极强

　致病性质 选择性作用，毒性强 引起全身反应 第五单元　噬菌体噬菌体的生物学特性DNA或RNA毒性噬菌体吸附、穿入、脱壳、生物合成及组装成熟释放温和噬菌体前噬菌体：整合在细菌染色体上的噬菌体基因片段。溶原性细菌：染色体上携带整合的前噬菌体基因的细菌第六单元　细菌的遗传与变异细菌遗传物质1.细菌染色体：环状双股DNA2.质粒：染色体外的遗传物质（1）F质粒：编码细菌性菌毛（2）R质粒：控制细菌耐药性（3）col质粒：编码大肠杆菌素（4）Vi质粒：决定细菌毒力的大小细菌变异的机制1.基因突变2.基因的转移与重组转化游离的DNA片段感受态直接进入受体菌转导通过性菌毛将遗传物质（质粒或细菌的染色体）传递给受体菌溶原性转换温和噬菌体以前噬菌体的形式与宿主菌染色体发生整合白喉杆菌：白喉外毒素；肉毒梭菌：肉毒毒素；产气荚膜梭菌：α毒素第七单元　细菌的感染与免疫医学.全.在线.网.站.提供胃内无细菌寄生正常情况下对人体有益无害条件致病菌1.寄生异位菌群失调机体的免疫力低下菌群失调宿主的非特异性免疫力一、非特异性免疫的组成（1）屏障结构；（2）吞噬细胞2.不完全吞噬：病原菌被吞噬但未被杀灭，并由吞噬细胞携带转移到机体的其它部位，引起扩散；（3）非特异性体液因素1.补体：旁路途径活化在抗体形成前即发挥防御作用。2.溶菌酶：破坏细菌细胞壁的肽聚糖成分。3.防御素：使细菌细胞膜发生不可逆损伤二、胞外菌感染、胞内菌感染及外毒素致病的免疫特点1.胞外菌感染：细菌的清除主要依赖机体的体液免疫。2.胞内菌感染：清除主要依赖细胞免疫作用。3.毒血症：外毒素清除依赖体液免疫中的抗毒素的中和作用感染的发生与发展第八单元　细菌感染的检查方法与防治原则血清学诊断抗体效价5.酶免疫吸附试验免疫荧光试验人工主动免疫和人工被动免疫第九单元　球　菌化脓性球菌葡萄球菌属、链球菌属和奈瑟球菌属葡萄球菌属革阳，无荚膜、无鞭毛、不形成芽胞3.致病性葡萄球菌：金黄色葡萄球菌，凝固酶阳性，分解甘露醇链球菌属甲型溶血性链球菌：（不完全溶血）。乙型溶血性链球菌：（完全溶血）。丙型链球菌：血平皿上菌落周围无溶血环链球菌溶血素：链球菌溶血素O，链球菌溶血素S。三、所致疾病（一）A群乙型溶血性链球菌所致疾病有三大类1.化脓性感染：扁桃体化脓、淋巴管炎等2.中毒性疾病：猩红热3.变态反应性疾病：急性肾小球肾炎、风湿热（二）甲型溶血性链球菌所致疾病: 感染性心内膜炎活动性风湿热患者血清中抗链球菌溶血素O抗体效价显著升高肺炎球菌属2.血平皿上形成α溶血（甲型溶血）。5.溶菌试验及菊糖发酵试验可用来鉴别肺炎球菌和甲型溶血性链球菌脑膜炎奈瑟菌巧克力色培养基培养荚膜：增强细菌抗吞噬细胞的吞噬作用。菌毛：增强细菌粘附于易感细胞的表面内毒素：引起发热及低血压性休克淋病奈瑟菌IgA1蛋白酶：破坏粘膜表面IgA11%硝酸银滴眼可预防新生儿淋球菌性结膜炎第十单元　肠道杆菌革兰阴性杆菌埃希、志贺和沙门肠道杆菌的共同特征志贺 菌体抗原（O抗原）鞭毛抗原（H抗原） 不分解乳糖埃希菌属致病性大肠杆菌1.肠产毒性2.肠侵袭性3.肠致病型4.肠出血型饮用水的卫生标准：每升水的大肠菌群数不得超过3个每饮水中，细菌总数不得超过100个志贺菌属细菌性痢疾1.痢疾志贺菌（A群）2.福氏志贺菌（B群）3.鲍氏志贺菌（C群）4.宋内志贺菌（D群）3.内毒素：毒性强烈，是志贺菌主要致病物质1.肠 壁：进内毒素吸收甚至中毒性休克。2.肠粘膜：出现脓血便。3.肠壁植物神经：沙门菌属伤寒杆菌1.Vi抗原：抗吞噬细胞吞噬作用2.肠毒素：外毒素3.内毒素：体温升高，白细胞数下降、休克1. 肠热症标本采集原则：发病 1周内取血液，第1～3周内：取骨髓，发病2～3周时：取粪便或尿液肥达氏反应O凝集相当IgM与H凝集医学.全在.线第十一单元　弧菌属本属细菌与肠杆菌科的主要不同点是氧化酶试验阳性及位于菌体一端的单根鞭毛霍乱弧菌革阴有菌毛，单端单根鞭毛，暗视野显微镜下呈鱼群样穿梭运动3.霍乱肠毒素：毒性强烈的外毒素霍乱肠毒素激活腺苷酸环化酶使ATP不断转化为cAMP，导致cAMP浓度增高，肠粘膜细胞分泌增多，出现水样便副溶血性弧菌嗜盐性细菌，主要引起食物中毒医学 全在.线提供第十二单元　厌氧性细菌厌氧芽胞梭菌属破伤风梭菌、肉毒梭菌、产气荚膜梭菌和艰难梭菌破伤风梭菌“鼓槌状”。致病物质破伤风痉挛毒素和溶血素破伤风痉挛毒素的致病机理：作用于脊髓前角运动细胞，封闭了抑制性中间神经元释放抑制性神经介质，导致骨骼肌强直性收缩，出现破伤风特有的苦笑面容和角弓反张等临床症状破伤风的易感条件：1.窄而深的伤口；2.局部组织供血供氧不足；3.伴有需氧菌及兼性厌氧菌的混合感染产气荚膜梭菌“汹涌发酵” 1.主要致病物质：肠毒素：增加肠壁通透性，引起腹泻。α毒素：作用类似于卵磷脂酶，溶解血细胞和血管内皮细胞，造成血管通透性增加，形成水肿。气性坏疽食物中毒肉毒梭菌网球拍状肉毒毒素：作用于颅脑神经核、外周神经-肌肉接头处，阻碍乙酰胆碱的释放，导致肌肉弛缓性麻痹无芽胞厌氧菌正常菌第十三单元　棒状杆菌属白喉棒状杆菌革阳，无菌毛、无荚膜、不形成芽孢白喉外毒素第十四单元　分枝杆菌属细胞壁含有大量脂质又称抗酸杆菌有结核分枝杆菌和麻风分枝杆菌结核分枝杆菌无荚膜、无鞭毛、无芽胞1.抗结核免疫是一种带菌免疫红肿硬结直径 结果分析 5mm 阳性，机体细胞免疫功能正常，曾感染（或接种）过结核杆菌（疫苗） 15mm 强阳性，可能存在活动性结核病灶 阴性 未感染过结核杆菌 麻风分枝杆菌革兰染色及抗酸染色均阳性瘤型麻风：主要侵犯细胞免疫功能低下者的皮肤及粘膜，形成麻风结节第十五单元　放线菌属和奴卡菌属放线菌属内源性感染硫磺样颗粒奴卡菌属不属于人体正常菌群，不引起内源性感染第十六单元　动物源性细菌人畜共患病布鲁菌属：布氏杆菌；耶尔森菌属：鼠疫耶氏菌芽胞杆菌属：炭疽芽胞杆菌布鲁菌属耶尔森菌属鼠疫耶氏菌肺鼠疫：吸入染菌的尘埃黑死病芽孢杆菌属炭疽芽孢杆菌炭疽毒素：直接损伤微血管内皮细胞，增加血管通透性，血液粘稠度增高导致感染性休克及DIC第十七单元　其他细菌流感嗜血杆菌巧克力色培养基百日咳鲍特菌百日咳病程：（1）卡他期；（2）痉咳期；（3）恢复期幽门螺杆菌尿素酶试验（本菌含有丰富的尿素酶）幽门螺杆菌呈弧形，S形或海鸥状，有鞭毛，革兰染色阴性。微需氧，营养要求高。幽门螺杆菌尿素酶丰富，是鉴定的主要依据。幽门螺杆菌与人类慢性胃炎，消化性溃疡及胃癌等有着密切的关系嗜肺军团菌胞内寄生菌假单胞菌属铜绿假单胞菌俗称绿脓杆菌，，耐受多种化学消毒剂及抗生素第十八单元　支原体缺少细胞壁的原核细胞型微生物，细胞膜含胆固醇，可通过滤菌器，以二分裂的方式繁殖，是目前所知能在无生命培养基中繁殖的最小微生物支原体油煎蛋样菌落主要致病型支原体1.肺炎支原体：原发性非典型肺炎。2.溶脲脲原体：除衣原体外，是引起非淋球菌性尿道炎的主要病原体第十九单元　立克次体1.严格细胞内寄生，含DNA和RNA两种核酸，以二分裂法繁殖。2.具有细胞壁结构，革阴，大小介于细菌和病毒之间。3.培养方法：动物接种、鸡胚接种和细胞培养。4.对多种抗生素敏感。5.吸血的节肢动物既是立克次体的寄生宿主（储存宿主） 同时也是其传播媒介。6.大多是人畜共患病的病原体。Q热柯克斯体：蜱为传播媒介医学.全.在线.网.站.提供第二十单元　衣原体能通过滤菌器，专性细胞内寄生，以二分裂方式进行增殖并具有独特的增殖周期的原核细胞型微生增殖周期中可观察到两种不同的颗粒结构（1）原体：球形，小而致密，是发育成熟的衣原体，具有高度感染性；（2）网状体：大而疏松，由原体在细胞空泡中发育而成，不具有感染性，是衣原体的繁殖体主要病原性衣原体一、沙眼衣原体二、肺炎衣原体第二十一单元　螺旋体钩端螺旋体革阴，着色较难。常用镀银染色法密螺旋体梅毒螺旋体苍白螺旋体镀银染色法一期梅毒：硬性下疳二期梅毒：全身皮疹三期梅毒：自身损伤疏螺旋体伯氏疏螺旋体镀银染色法染色。是莱姆病的病原体，传播媒介是蜱第二十二单元　真　菌真核细胞型微生物，有典型的细胞核和完善的细胞器。不含叶绿素、无根、茎、叶的分化真菌在三大类微生物中个体最大。分为单细胞和多细胞真菌两大类。单细胞真菌的特点：又称为酵母菌，以出芽的方式繁殖。多细胞真菌的特点：又称为霉菌，由孢子出芽繁殖形成。不同种类霉菌的菌丝和孢子形态不同，是鉴别真菌的重要标志（一）菌丝：孢子长出芽管，逐渐延长呈丝状体，称为菌丝。菌丝延伸分枝，交织成团，称为菌丝体。（二）孢子：孢子是真菌的繁殖器官，一条菌丝上可形成多个孢子区别要点 真菌孢子 细菌芽胞 产生数目 一条菌丝可产生多个 一个细菌只形成一个 抵抗力 不强,60～70℃短时死亡 强,煮沸短时间内不会死亡 生物功能 重要的繁殖方式 非繁殖方式 主要致病性真菌一、皮肤癣真菌二、白假丝酵母菌（白色念珠菌）粘膜感染以鹅口疮最为多见三、新生（型）隐球菌鸽粪第二十三单元　病毒的基本性状病毒的大小和形态 专性活细胞内寄生，以复制的方式增殖病毒体是结构完整的具有感染性的病毒颗粒病毒的结构和化学组成病毒体主要由核酸和蛋白质组成3.脂类和糖：病毒脂类构成包膜的主要成分，因此脂溶剂可破坏病毒包膜，使其失去感染性。糖类参与构成病毒刺突成分病毒的增殖包括：吸附和穿入，脱壳，生物合成，组装成熟和释放四个步骤理化因素对病毒的影响朊粒传染性海绵状脑病医学全在.线提供第二十四单元　病毒的感染和免疫病毒的传播方式病毒的感染类型慢性感染潜伏感染 慢发病毒感染出现慢性进行性疾病，最终为致死性的感染。如麻疹病毒引起的亚急性硬化性全脑炎，朊粒引起的库鲁病等病毒的致病机制溶细胞性感染、稳定状态感染和整合感染抗病毒免疫干扰素刺激宿主细胞产生抗病毒蛋白，抑制病毒蛋白质的合成干扰素的抗病毒作用是间接抑制作用分类：人类干扰素分为α、β及γ三型，分别由白细胞、成纤维细胞及淋巴细胞产生。α、β干扰素属于I型干扰素，γ干扰素属于II型干扰素I型干扰素抗病毒作用强于II型；而II型干扰素的免疫调节功能和抑制肿瘤细胞的功能强于I型第二十五单元　病毒的感染的检查方法与防治原则病毒感染的检查方法常用的血清学诊断方有中和试验、补体结合试验和血凝抑制试验第二十六单元　呼吸道病毒正粘病毒--流行性感冒病毒1）核心：RNA聚合酶；分节段的单股负链RNA。2）基质蛋白（M蛋白）：位于病毒包膜与核心之间，抗原性稳定，具有型特异性。3）包膜：糖蛋白刺突：血凝素（HA）和神经氨酸酶（NA）。HA和NA抗原性不稳定，易发生变异，是流感病毒分亚型的依据副粘病毒麻疹病毒麻疹是儿童时期最为常见的急性出疹性传染病亚急性硬化性全脑炎腮腺炎病毒腮腺肿大青春期感染者可引起睾丸炎、卵巢炎等并发症其它呼吸道病毒风疹病毒腺病毒无包膜的双股DNA病毒可引起细胞转化和肿瘤形成第二十七单元　肠道病毒主要的传播途径是粪-口传播脊髓灰质炎病毒I、II、III三个血清型，三型间无交叉免疫反应病毒可侵犯脊髓前角运动神经细胞，引起迟缓性肢体麻痹，感染多见于儿童，故又称为小儿麻痹柯萨奇病毒与埃可病毒无菌性脑膜炎疱疹性咽炎、胸痛、心肌炎、心包炎、手足口病轮状病毒片段组成的双股RNA第二十八单元　肝炎病毒乙型肝炎病毒（HBV）形态与结构：Dane颗粒具有双层衣壳。病毒外衣壳，相当于一般病毒的胞膜。内衣壳包裹HBV的DNA和DNA聚合酶。病毒基因组为不完整的环状双股DNA，完整的单链为负链，较短的单链为正链表面抗原（HBsAg）:是Dane颗粒外衣壳的组成成分是HBV感染的主要标志核心抗原（HBcAg）：为内衣壳成分，其外由HBsAg覆盖，故不易在血循环中检测到。HBcAg抗原性强，能刺激机体产生抗-HBc抗体，但无保护作用。抗-HBc IgM抗体阳性常提示HBV处于复制状态e抗原（HBeAg）：是HBV丙型肝炎病毒（HCV）丁型肝炎病毒（HDV）小球形颗粒：是HBV合成过剩的外衣壳蛋白戊型肝炎病毒（HEV）核酸为单股正链RNA第二十九单元　虫媒病毒流行性乙型脑炎病毒三带喙库蚊幼猪是乙脑病毒传播环节中最主要的中间宿主或扩散宿主登革病毒伊蚊传播登革出血热/登革休克综合征通常发生于以往有过登革病毒感染病史的人，再次感染登革病毒的成人或儿童第三十单元　出血热病毒汉坦病毒：单股负链RNA包膜上有血凝素刺突有明显的区域性和季节性肾综合征出血热汉坦病毒肺综合征第三十一单元　疱疹病毒单纯疱疹病毒（HSV）单纯疱疹病毒-I型和II型病毒经口腔，呼吸道和生殖器粘膜以及破损皮肤侵入人体1.原发感染：6个月后的婴儿，容易发生HSV-1的原发感染。最常见的是齿口炎，在牙龈、咽颊部粘膜产生成群疱疹。HSV-2原发感染多发生在性生活后，表现为生殖器疱疹2.潜伏与再发 HSV-1可潜伏于三叉神经节和颈上迷走神经节；HSV-2潜伏于骶神经节。水痘-带状疱疹病毒（VZV）VZV只有一个血清型。人是VZV的唯一自然宿主，皮肤是病毒的主要靶细胞儿童初次感染引起水痘潜伏于脊髓后根神经节或颅神经的感觉神经节中巨细胞病毒CMV体内感染上皮细胞、白细胞和精子细胞等；体外只能在人成纤维细胞中增殖在宫颈癌、前列腺癌、结肠癌和Kapsi肉瘤等组织中检测出CMV的DNA序列EB病毒（EBV）一种嗜B细胞的人疱疹病毒，主要侵犯B细胞传染性单核细胞增多症：表现为发热、淋巴结肿大、脾肿大、肝功能紊乱以及外周血单核细胞显著增多非洲儿童恶性淋巴瘤：又称Burkitt淋巴瘤EBV与鼻咽癌医学 全在.线提供第三十二单元　反转录病毒人类免疫缺陷病毒（HIV ）gp120:识别宿主细胞表面受体，并与之结合，完成病毒的吸附gp41:促进病毒包膜与宿主细胞膜之间的融合，介导病毒穿入阳性者必须用免疫印迹（Western blot analysis）法作确证试验第三十三单元　其他病毒狂犬病毒弹状病毒科狂犬病毒属的一种嗜神经病毒33-2），对狂犬病毒的诊断很有价值。吞咽或饮水时喉头肌肉发生痉挛，故又称恐水症。第1，3，7，14，28天各肌肉注射1ml。人乳头瘤病毒宫颈癌：侵犯中枢神经系统，恐水症，固定毒株制备疫苗。每小时3mm速度作向心性扩展，一般不入血。病理主要是急性弥漫性脑脊髓炎，嗜酸性包涵体称内基小体。临表：潜伏1-3个月。1.前驱期：类似感冒，蚁走异样感觉。2.兴奋期：恐水症神清。3.麻痹期：全身弛缓性瘫痪。伤口处理：1.肥皂水和新洁尔灭冲洗半小时但不能合用。2.挤出污血碘酊反复涂拭。3.局部抗狂犬病免疫血清浸润40IU/kg。接种：5针30日内，0、3、7、14、30，各2ml。严重者10针，0～6日个一针，10、14、30、90，再各一针

　第 一 单元　绪　论免疫器官胸腺骨髓法氏囊（禽类）外周脾脏淋巴结粘膜免疫系统皮肤免疫系统免疫学的中心法则:免疫系统与神经系统有类似之处，具有：记忆性、特异性、反应性第 二 单元　抗　原基本概念抗原Ag2.抗原的性能 1）免疫原性：产生抗体。2）反应原性是指能够与相应免疫应答产物发生特异性结合的性能1.抗原决定簇：是抗原分子中决定抗原特异性的特殊化学基团，它是TCR/BCR及抗体特异结合的基本单位，又称表位。表位的性质、数目及空间构象决定着抗原的特异性抗原的分类根据产生抗体是否需T细胞参与1.胸腺依赖性抗原 T-Ag；2.胸腺非依赖性抗原 T-Ag。异嗜性抗原A族溶血性链球菌的细胞膜与人的肾脏和心肌具有共同抗原，感染后可因交叉反应而引起肾小球肾炎或心肌炎超抗原Sg：T细胞的识别不受MHC分子的限制佐剂非特异免疫增强剂，与抗原一起或预先注入机体后，可增强机体对抗原的免疫应答能力

　第 三 单元　免疫器官1.免疫器官：1）中枢免疫器官：骨髓（腔上囊）、胸腺、法氏囊（禽类）2）外周免疫器官： 脾、淋巴结及黏膜相关淋巴组织 2.免疫细胞：淋巴细胞 T、B淋巴细胞）；单核细胞/巨噬细胞；树突状细胞；自然杀伤细胞（NK细胞）；粒细胞1.中枢免疫器官：骨髓除T细胞外的所有血细胞发育成熟的场所胸腺：T细胞发育成熟的场所第四单元　免疫细胞T细胞的膜表面分子CD2（SRBC受体）：所有成熟T细胞表面的分子，可以结合绵羊红细胞，形成玫瑰花环CD3（T3）分子与TCR形成稳定的复合物结构，存在所有成熟T细胞表面，起信号转导作用CD4（T4）：与MHC II类分子结合，HIV受体。CD8（T8）：与MHCI类分子结合T细胞亚群按功能分类：）CD4+T细胞辅助性T细胞TTh1细胞免疫应答，在迟发型超敏反应中发挥重要作用。Th2体液免疫应答CD8+T细胞细胞毒性T细胞（Tc，CTL）：特异性杀伤靶细胞（肿瘤或病毒）作用的T细胞The kiss of death。T细胞功能对病毒感染细胞和肿瘤细胞的杀伤作用（Tc）辅助免疫细胞行使功能（Th1，Th2）抑制免疫细胞的功能（Ts）迟发型超敏反应分泌细胞因子记忆功能（Tm）T细胞识别抗原的MHC限制现象T淋巴细胞与树突状细胞MHC：主要组织相容性复合体受遗传控制的代表个体特异性的同种异型抗原系统B细胞B细胞抗原受体BCR ：膜表面的免疫球蛋白（SmIg），鉴别B细胞的抗原性标志CD19 CD20 ：人B细胞特有表面标志CD40：协同刺激分子受体。与CD4+ T细胞表面CD40L结合产生B细胞活化第二信号，使B细胞激活CD80（B7）：分子存在B细胞和其他APC表面受体是T细胞表面的CD28。二者结合产生T细胞活化第二信号B细胞亚类B1为非特异免疫细胞B2为特异免疫细胞B2细胞功能分化为浆细胞产生抗体ADCC（抗体依赖性细胞介导的细胞毒作用）作用：肿瘤细胞等与IgG结合，与NK.吞噬细胞Fc受体结合，增强其对靶细胞的杀伤作用自然杀伤细胞（NK细胞）具有天然杀伤功能和ADCC效应的淋巴细胞NK细胞表面的杀伤抑制受体（KIR），能够传递不许杀伤的信号。这些受体识别的对象是靶细胞表面的 MHC-I 分子。因此，正常表达 MHC-I 类分子的细胞一般不会被NK细胞杀伤抗原呈递细胞APC能够摄取加工处理抗原，再将其呈递给淋巴细胞的一类免疫细胞专职APC ：表达MHC－II类分子；激活CD4+ T细胞；诱导免疫应答4.B细胞内源性抗原呈递过程：细胞（肿瘤细胞或病毒感染细胞）自身合成的抗原，经加工修饰成抗原肽，与MHC I类分子结合成抗原肽-MHC I类分子复合物表达于APC表面，被CD8+ T细胞识别。外源性抗原呈递过程：APC吞入后，在胞内降解为小分子抗原肽，与MHC-II类分子形成抗原肽—MHCII类分子复合物表达于表面被CD4+ T细胞识别。免疫细胞的功能分类1）APC：B细胞、 Mf 、DC2）ARCB细胞：直接识别抗原T细胞：不能直接识别抗原，只能识别抗原和MHC的复合物3）具有杀伤功能的细胞Tc（细胞毒性T细胞NK（自然杀伤细胞单核巨噬细胞ADCC效应细胞（NK、粒细胞、肥大细胞、单核巨噬细胞等）LAK第五单元　免疫球蛋白免疫球蛋白（Ig）是指具有抗体活性或化学结构与抗体相似的球蛋白。抗体（Ab）是B细胞识别抗原后增殖分化为浆细胞所产生的一种蛋白质，主要存在于血清等体液中，能与相应抗原特异性地结合，具有免疫功能免疫球蛋白的结构所有Ig的基本单位都是四条肽链组成的对称结构。两条重链（H）和两条轻链（L）。根据氨基酸排列顺序的不同分为可变区（V）和恒定区（C）。分类： IgG、IgA、IgM、IgD、IgE，

　重链： γ、 α、 μ、 δ、 ε免疫球蛋白的水解片段木瓜蛋白酶水解 IgG得到两个相同的Fab段和一个Fc段胃蛋白酶裂解 IgG得到一个具有双价活性的F（ab’）2 段和若干个小分子多肽碎片（pFc’） 免疫球蛋白的类型Ig的同种型IgG 分 IgG1， IgG2， IgG3， IgG4。IgA 分 IgA1， IgA2免疫球蛋白的功能IgM、IgE分CH1.CH2.CH3.CH4（二）C区的功能：1.激活补体IgM，IgG1~3 + Ag 经典途径激活补体IgG4、IgA、IgE 的凝聚物可经旁路途径激活补体结合细胞表面的Fc受体 （细胞亲嗜性）3.调理作用：颗粒性抗原-IgG促吞噬细胞的吞噬5. ADCC（抗体依赖性细胞介导的细胞毒作用）作用：肿瘤细胞等与IgG结合，与NK.吞噬 细胞Fc受体结合，增强其对靶细胞的杀伤作用6.介导I型超敏反应：IgE穿过胎盘和黏膜五类免疫球蛋白的特性与功能一、IgG生后3个月开始合成IgG多为单体，半衰期长约为23天，含量最高IgG1、IgG2和IgG3的CH2能通过经典途径激活补体IgG是唯一能通过胎盘的抗体通过Fc段与吞噬细胞表面FcR结合二、IgM为五聚体最大的Ig，称巨球蛋白。不能通过血管壁，对防止菌血症作用重要天然血型抗体是IgMIgM胚胎晚期已能合成，也是感染后最早产生的抗体。IgM是B细胞抗原受体的主要成分三、IgA分为血清型和分泌型两种血清型IgA主要由肠系膜淋巴组织中的浆细胞产生，存在于血清中。分泌型IgA（SIgA）是由呼吸道、消化道、泌尿生殖道等处的黏膜固有层中浆细胞产生。是黏膜局部抗感染的重要物质四、IgD2.膜结合型即mIgD 是B细胞的重要表面标志，也是BCR重要组成成分B细胞的分化过程中首先出现mIgM，后来出现mIgD ，他的出现标志着B细胞成熟了五、IgE由黏膜固有层中浆细胞产生。种系进化过程中出现最晚， 含量最低IgE的CH2和CH3功能区可与肥大细胞、嗜碱性粒细胞上的高亲和力Fcε受体结合，（因此又称亲细胞抗体），引起I型超敏反应第六单元　补体系统一组经活化后具有酶活性的不耐热的蛋白质补体激活的途径补体活化的经典途径分为识别阶段、活化阶段和膜攻击阶段三个阶段激活物：1.免疫复合物是经典激活途径的主要激活物质。2.C1仅与IgM的CH3区或IgG1-3的CH2区结合才能活化；激活条件：每一个C1分子必须同时与两个以上Ig的Fc段结合才能被激活游离或可溶性抗体不能通过经典途径激活补体补体攻膜单位C5b678复合物补体活化的MBL途径旁路（替代）途径替代途径是补体系统重要的放大机制B细胞介导的体液免疫应答B细胞识别的抗原可分为TD抗原和TI抗原比较项目 经典途径 旁路途径 MBP途径 激活物 抗原-抗体复合物 细菌脂多糖、凝聚的IgA/IgG4等 病原微生物表面甘露糖残基 补体成分 C1—C9 B、D、P因子

　C3C5—C9 MBL、MASP-1，2

　C2—C9 所需离子 Ca2+，Mg2+

　Mg2+ Ca2+ C3转化酶 C4b2b

　C3bBb C4b2b C5转化酶 C4b2b3b

　C3bnBb C4b2b3b 作　用 在特异性体液免疫应答的效应阶段发挥作用 参与非特异性免疫，在感染早期发挥作用 参与非特异性免疫，在感染早期发挥作用 第七单元　细胞因子细胞因子（CK）是由细胞分泌的具有生物活性的小分子蛋白物质的统称单核因子、淋巴因子、集落刺激因子等细胞因子的种类：1.白介素 IL-2；2.干扰素 IFN-γ；3.肿瘤坏死因子 TNF-α；4.集落刺激因子 CSF，EPO （促红细胞生成素）；5.生长因子TGF- b细胞因子的生物学活性1.抗感染和抗肿瘤。2.参与和调节炎症反应。3.调节免疫。4.刺激造血

　第八单元 白细胞分化抗原和粘附分子白细胞分化抗原LDA细胞表面标志CD分子细胞膜表面的分化抗原群CD3分子：三种二聚体组成的复合物与TCR形成TCR- CD3复合物，转导TCR特异性识别抗原所产生的活化信号，促进T细胞活化CD28与CD80或CD86结合后产生协同刺激信号，使T细胞活化。CD152与CD80或CD86结合后，可抑制活化的T细胞扩增，对T细胞介导的免疫应答其负调节作用4.CD4和CD8T细胞的膜分子，属于Ig超家族成员。CD4+：Th1/ Th2 辅助性T细胞。CD8+：分为：Tc细胞：细胞毒性T细胞；Ts细胞：抑制性T细胞CD4-MHC II类抗原，HIV（人类免疫缺陷病毒）的受体。CD8MHC I类抗原粘附分子粘附分子在炎症和免疫中的作用细胞发育和胚胎发育，如T细胞在胸腺的发育细胞迁移和器官定位，如淋巴细胞归巢细胞凋亡：如FAS（CD95）和FASL（CD178）的相互作用

　第九单元　主要组织相容性复合体及其编码分子人的主要组织相容性抗原称白细胞抗原HLA人MHC基因MHC-HLA位于第6对染色体短臂遗传特征：MHC基因为单元型遗传方式，共显性表达。子女与父母有一半HLA相同。子女间1/4机率完全相同，完全不同；1/2机率一半HLA相同。MHC的共显性表达四、MHC结合的分子：MHC I 类分子结合抗原多肽（8-10个氨基酸）、TCR、CD8分子、杀伤细胞抑制性受体（KIR）。MHC II 类分子结合抗原多肽（13-18个氨基酸）、TCR、 CD4分子五、MHC的细胞分布：I类抗原分布于大部分组织细胞。II类抗原分布于B细胞、单核巨噬细胞、树突状细胞、活化的T细胞六、MHC功能1.介导T细胞的抗原识别2.调控NK细胞功能3.T细胞在胸腺的分化4.免疫应答的遗传控制5.移植排斥6.与某些疾病具有连锁关系介导T细胞的抗原识别MHC I类抗原介导内源性抗原的呈递MHC II类抗原介导外源性抗原的呈递第十单元　免疫应答适应性免疫应答的主要特性1.识别自身与非己的特性2.特异性3.记忆性抗原提呈细胞对抗原的加工处理和提呈抗原提呈细胞（APC）：摄取、加工、处理抗原并将抗原信息提呈给淋巴细胞专职APC：主要包括巨噬细胞，树突状细胞和B细胞。能够提呈MHC II 分子和抗原肽复合物B细胞介导的体液免疫应答TD抗原诱导的体液免疫应答ThCD4+ Th2）细胞、APC参与B细胞活化需要双信号 MHC II分子 抗原肽复合物→表达到APC细胞表面→T细胞CD4+Th2，相互识别结合→第一信号： BCR中的mIg（mIgM和mIgD）识别抗原，经Iga/Igβ（CD79a 和CD79b）传递第一活化信号。第二信号：来自于Th细胞，包括：1.Th细胞的膜分子：CD40L，LFA-1， CD28，ICAM-1等2.Th细胞分泌的细胞因子：IL-2，IL-4，IL-5，IFN-γ等TI抗原诱导的体液免疫应答TI-1抗原（LPS，聚合鞭毛）TI-2抗原：（肺炎球菌夹膜多糖）特点：只能诱导IgM类抗体， 无免疫记忆。初次和再次免疫应答没有差别胚胎期首先合成IgM ，出生后3个月开始合成IgG，4-6个月开始合成IgA初次应答中主要为IgM再次应答中产生的抗体主要为IgGT细胞介导的细胞免疫应答2.CD4+T细胞活化，增殖，分化T细胞的活化剂第一信号：TCR对MHCII－抗原肽复合物的识别，CD3分子将第一信号传递到细胞内第二信号：CD28识别专职APC上的B7分子，又称协同刺激信号TCR识别抗原肽的MHC限制性3.CD8+Tc细胞的活化，增殖，分化CD8+ Tc细胞也被称作细胞毒性淋巴细胞（CTL）。第一信号：TCR识别MHC-I/抗原肽复合物第二信号：协同刺激信号，此外，活化的Th1细胞提供的细胞因子IL-2， IL-12CD8+T细胞活化——效应性Tc细胞（CTL）特异性杀伤携带抗原的细胞。机制：通过穿孔素、丝氨酸蛋白酶、FasL-Fas蛋白表达使靶细胞溶解破坏和发生凋亡第十一单元　免疫应答的调节分子水平的免疫调节MHC分子限制T细胞对抗原的识别：Th细胞与APC细胞的MHC基因型一致时， Th细胞才能被激活细胞水平的免疫调节作用APC（抗原提呈细胞）的免疫调节作用T细胞的免疫调节作用第十二单元　免疫耐受医学全在线免疫活性细胞接触抗原性物质时所表现的一种特异性的免疫无应答状态第十三单元　超敏反应型超敏反应速发型超敏反应型超敏反应细胞毒型超敏反应

　型超敏反应免疫复合物型超敏反应

　型超敏反应迟发型超敏反应型超敏反应特异性IgE介导的。主要特征：功能紊乱细胞型超敏反应IgG或IgM类细胞溶解或组织损伤型超敏反应IgG或IgM类中等大小可溶性免疫复合物沉积于局部或全身毛细血管基底膜后，中性粒细胞浸润为主肾小球基底膜和关节滑膜型超敏反应由效应T细胞与相应抗原作用后，引起的以单个核细胞浸润和组织细胞损伤为主要特征的炎症反应接触性皮炎型超敏反应IgG或IgM型超敏反应IgG或IgM医学全在线网站第十四单元　自身免疫和自身免疫性疾病自身免疫是指机体免疫系统对自身成分发生免疫应答的现象。自身免疫病是因机体免疫系统对自身成分发生免疫应答而导致的疾病状态。自身免疫性疾病的分类器官特异性自身免疫性疾病：胰岛素依赖性糖尿病IDDM，多发性硬化症MS器官非特异性自身免疫性疾病：又称全身性或系统性自身免疫性疾病，系统性红斑狼疮（SLE）及类风湿关节炎（RA）自身免疫性疾病的致病相关因素自身抗原的出现隐蔽抗原的释放晶状体自身抗原发生改变类风湿因子（RF）免疫调节异常多克隆刺激剂的旁路活化Th1和Th2细胞功能失衡交叉抗原柯萨奇病毒→糖尿病链球菌感染→急性肾小球肾炎，风湿性心脏病遗传因素MHC单型不同：1.DR2与肺出血肺炎综合症有关DR3个体易患重症肌无力.DR4与类风湿有关4.B27与强直性脊柱炎自身免疫病的免疫损伤机制及典型疾病机制相似于、、型超敏反应的发病机制。型常见的自身抗体-免疫复合物引起的自身免疫性疾病系统性红斑狼疮（SLE）T细胞对自身抗原应答引起的炎症性伤害胰岛素依赖型糖尿病（IDDM）第十五单元　免疫缺陷病CD4为HIV的受体，Th细胞为HIV的靶细胞HIV的包膜糖蛋白gp120可与CD4分子高亲和性结合第十六单元　肿瘤免疫肿瘤特异性抗原肿瘤相关抗原第十七单元　移植免疫受者T细胞对供者MHC的直接和间接识别第十九单元　免疫学防治well, with the effectiveness of services to defend the interests of the masses. Third, we should strive to do well. To achieve good practical results, the key is to know the law, to grasp the laws and using laws. Office of economic development, social progress, there are rules to follow. Only act according to the law, to overcome blindness and strengthening initiative, creative. Working in the Office, we should be good at analyzing the essence of things, to find regular thing, change from passive to active, to seek one. Investee 2. establishment of evaluation system. Evaluation system is essentially an incentive mechanism, the evaluation was objective and fair, reasonable, and can stimulate a person's energy, mobilizing people's enthusiasm or be misleading, dampened the enthusiasm of people. At present, the concept of people-oriented people, but to establish and perfect evaluation system is still lagging behind. Work in this area should be seriously caught up. "Three emphasis on" to take advantage of. Is a focus on standards and scientific. A fundamental point of the evaluation criteria, is to keep contact, development, comprehensive eye evaluation of cadres. Office work, both "record" and "potential performance"; both subjective efforts, take another look at the objective condition; both "pragmatic" enough, take another look at the "retreat" level. Second, focus on participating the breadth of the subject. Evaluation of cadres must give full play to democracy, cadres and the masses handing over evaluation. Office work services leadership and service base, serve the people, then nominated the main object will contain a variety of services, so that assessment was accurate and to avoid one-sidedness. Third, pay attention to the seriousness of the conclusion. The use of evaluation findings is mainly embodied in his direction. Permitted to choose one, it would be tantamount to establishing a banner. Evaluation can't take care of the balance, otherwise it would undermine the offset the positive significance of evaluation.

　Office of the party committees at all levels should take the findings as on the cadres ' bonus-penalty, an important basis for future movements, incentive and restraint effect of making evaluations. 3. Prevention of understanding "infidelity". People-centered development, concrete is dialectical,. In practice in the process, to prevent one-sided and still look, from actual people. One is to use dialectical point of view to understand. Humanist is the core of the scientific Outlook on development, remains the development of the scientific Outlook on development emphasizes, is still taking economic construction as the Center. Any departure from the development of thought and action, is a misinterpretation and misunderstanding of people-oriented. Adhere to people-oriented both to overcome one-sidedness of the old, but also to prevent one-sidedness, not accelerating the development of people and the opposition. Must be very clear, people oriented and speeding up development is not opposed, but consistent, we should never bestrengthened password centralized management, enhanced password communication network and the construction of electronic Government Affairs network, strengthen the translation of code cables work, strengthen the management of important files, make sure that the password is absolutely safe, ensure that Cryptography is absolutely clear. History of work to write a history of the original, compiled a book called changde Yearbook, out of a journal of the history of the publication, production of a song of the past after reading forums, changde, a story of people's hard work and exhibition. Archives to go the path of managing archives according to law, strengthen the construction of all types of archives, with the focus on key project archives, private enterprises, credit and Community Archives Archives, making full use of electronic means of technology and network, and promote the standardization and legalization of archives and information. Investee 4. insist on the logistics, will be around strong strong reforms, cadres of service management. Office workers is to be for this, deepen reform, strengthen management, and continuously meet the cadres of the organs function properly and the need for material and cultural life. One is to enhance the logistical support capability. Adapt to the new situation of the market economy, making full use of social power, flexibility in the use of market mechanisms and accelerate the process of marketization and socialization of logistic services. Adhere to the institutionalization of the logistics management, establish and implement a financial management system, trolley management systems, health management systems, security systems, such as the logistics management system, strengthen the management of human, financial, material, and logistical services standardized and institutionalized track. Secondly, we should strengthen the management of construction. Increasing investment, improving the working conditions of organs; overall civilization create an activity, and constantly improve the level of civilization; to promote greening, lighting, purification, flowers, landscaping, Office workers create a good environment for work and life. Third, to improve staff welfare. To in policy allows of range within, trying to for Office cadres workers solution housing, and couples separation, and children employment, aspects of actual difficult provides help, has conditions of place and units, also should appropriate to increased cadres workers of welfare, real do "career left people, feelings left people, appropriate treatment left people", let General Office staff in pay hard efforts of while, feel organization of warm, get due of affordable. Investee 5. insist on the team, will focus on stimulating vitality who care and respect for people. To Office cadres for the cut ... Learning style, strengthen the theoretical knowledge, optimize the structure of knowledge, and continuously improve the quality of cadres and workers. Attention to their physical health, and actively carry out regular wholesome recreational

　well, with the effectiveness of services to defend the interests of the masses. Third, we should strive to do well. To achieve good practical results, the key is to know the law, to grasp the laws and using laws. Office of economic development, social progress, there are rules to follow. Only act according to the law, to overcome blindness and strengthening initiative, creative. Working in the Office, we should be good at analyzing the essence of things, to find regular thing, change from passive to active, to seek one. Investee 2. establishment of evaluation system. Evaluation system is essentially an incentive mechanism, the evaluation was objective and fair, reasonable, and can stimulate a person's energy, mobilizing people's enthusiasm or be misleading, dampened the enthusiasm of people. At present, the concept of people-oriented people, but to establish and perfect evaluation system is still lagging behind. Work in this area should be seriously caught up. "Three emphasis on" to take advantage of. Is a focus on standards and scientific. A fundamental point of the evaluation criteria, is to keep contact, development, comprehensive eye evaluation of cadres. Office work, both "record" and "potential performance"; both subjective efforts, take another look at the objective condition; both "pragmatic" enough, take another look at the "retreat" level. Second, focus on participating the breadth of the subject. Evaluation of cadres must give full play to democracy, cadres and the masses handing over evaluation. Office work services leadership and service base, serve the people, then nominated the main object will contain a variety of services, so that assessment was accurate and to avoid one-sidedness. Third, pay attention to the seriousness of the conclusion. The use of evaluation findings is mainly embodied in his direction. Permitted to choose one, it would be tantamount to establishing a banner. Evaluation can't take care of the balance, otherwise it would undermine the offset the positive significance of evaluation.

　Office of the party committees at all levels should take the findings as on the cadres ' bonus-penalty, an important basis for future movements, incentive and restraint effect of making evaluations. 3. Prevention of understanding "infidelity". People-centered development, concrete is dialectical,. In practice in the process, to prevent one-sided and still look, from actual people. One is to use dialectical point of view to understand. Humanist is the core of the scientific Outlook on development, remains the development of the scientific Outlook on development emphasizes, is still taking economic construction as the Center. Any departure from the development of thought and action, is a misinterpretation and misunderstanding of people-oriented. Adhere to people-oriented both to overcome one-sidedness of the old, but also to prevent one-sidedness, not accelerating the development of people and the opposition. Must be very clear, people oriented and speeding up development is not opposed, but consistent, we should never bestrengthened password centralized management, enhanced password communication network and the construction of electronic Government Affairs network, strengthen the translation of code cables work, strengthen the management of important files, make sure that the password is absolutely safe, ensure that Cryptography is absolutely clear. History of work to write a history of the original, compiled a book called changde Yearbook, out of a journal of the history of the publication, production of a song of the past after reading forums, changde, a story of people's hard work and exhibition. Archives to go the path of managing archives according to law, strengthen the construction of all types of archives, with the focus on key project archives, private enterprises, credit and Community Archives Archives, making full use of electronic means of technology and network, and promote the standardization and legalization of archives and information. Investee 4. insist on the logistics, will be around strong strong reforms, cadres of service management. Office workers is to be for this, deepen reform, strengthen management, and continuously meet the cadres of the organs function properly and the need for material and cultural life. One is to enhance the logistical support capability. Adapt to the new situation of the market economy, making full use of social power, flexibility in the use of market mechanisms and accelerate the process of marketization and socialization of logistic services. Adhere to the institutionalization of the logistics management, establish and implement a financial management system, trolley management systems, health management systems, security systems, such as the logistics management system, strengthen the management of human, financial, material, and logistical services standardized and institutionalized track. Secondly, we should strengthen the management of construction. Increasing investment, improving the working conditions of organs; overall civilization create an activity, and constantly improve the level of civilization; to promote greening, lighting, purification, flowers, landscaping, Office workers create a good environment for work and life. Third, to improve staff welfare. To in policy allows of range within, trying to for Office cadres workers solution housing, and couples separation, and children employment, aspects of actual difficult provides help, has conditions of place and units, also should appropriate to increased cadres workers of welfare, real do "career left people, feelings left people, appropriate treatment left people", let General Office staff in pay hard efforts of while, feel organization of warm, get due of affordable. Investee 5. insist on the team, will focus on stimulating vitality who care and respect for people. To Office cadres for the cut ... Learning style, strengthen the theoretical knowledge, optimize the structure of knowledge, and continuously improve the quality of cadres and workers. Attention to their physical health, and actively carry out regular wholesome recreational 医学全在线

　people-oriented in the name of reducing our enthusiasm. Premier Wen Jiabao's Government work report this year, identified as 7% growth, 2.1% lower than last year's 9.1%, but in 8 work remains to accelerate development in the first place ... Work standards. Second is to use the scale of development to understand. Society is evolving, human needs are also changing. Practice of humanism is a long-term process and cannot be achieved overnight. To treat people if you stand still and rigid dogma, it is possible to return to this, see things but not people's old ways. Therefore, we have to follow the development of the times, and continue debugging the humanist perspective, innovative people-oriented way. Under the new historical conditions, we are requested by the times, set up a brand new concept, a high starting point, high standard of armed people, shaping, exercise, people, constantly taking the new connotation of the times. Terms of Office, is to lead the vast numbers of cadres to actively adapt to the knowledge faster and actively adapt to the increasingly high level of leadership situation, actively adapt to the demand of the masses more and more situations, eager to learn, enhance accumulation, efforts, honed the ability to overcome a good service, panic. Third is to use realistic understanding. Adhere to people-oriented must be based on reality, not divorced from reality. Desk no water cups here in Hong Kong, staff need to drink some water to the drinking fountain on a floor, the glass used is a one-time non-cone type. Drink this cup can only hold, cannot be put down. This is not only to save on glass materials, more important is to force you to get drinking water, go back to your seat business.

　Our emphasis on people-oriented, does not imply you can indulge the desires, the comfortable, the pursuit of enjoyment. Office of the party committees at all levels of our comrades, must continue to maintain the style of plain living and hard struggle, to stand up to the tests of temptations, exciting "energy" conservation "disposition" to the spirit of selfless dedication and provide services. Investee 4. clearly defined responsibilities. Putting people first is a common vision of development, everyone is a liability. People-oriented, above and below with the responsibility for coordinating system must be established and hold everyone accountable. First, we must strengthen the leadership. "In its place, its governance, its level, bear the responsibility of the Division." This is the minimum requirement for leaders, is a measure of the basic criteria for whether a leading cadre is competent. Leaders need to "it is an official term for the benefit of" mission, consciously assume responsibility for implementing people-oriented. Director of the Office of the party committees at all levels is the responsibility of the units to implement people-oriented, to manage their people, "plug in own responsibility", effectively enhance the education of leading cadres, cadres and cadres work, efforts to revitalize the Office of human resources, Office work is full of vigor and vitalityactivity, and constantly improve the physical quality of cadres and workers. Broaden the channels into his Office, increase the intensity of writing the open selection of cadres and cadres there, change text structure is not optimal conditions, and continuously improve the overall quality of cadres and workers. The second is to create a relaxed environment. With a deep affection for Office cadres, cadres and the mentality of the concern, attention to their conditions of life, do more work on straighten out emotion, to cheer on, and strive to create a lively and positive working atmosphere. Members of the leading Group Office of the party committees at all levels, more Exchange of ideas with the cadres and workers, with an equal mind, humble attitude of listening, take concrete actions to create a harmonious atmosphere. Thirdly, attention to their growth. Office is the place where talents.

　Leaders at all levels concerned Office cadres, as well as giving them tasks, from yadanzi, so that they get exercise and improve in practice, more political interest and to foster, increase the intensity of promoted use of Office cadres, effort into high office into a high, high, high multiple o