免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系課件

1、Immunoglobulin Structure-Function Relationship免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系許柑埔陌起賬混長(zhǎng)盆鉻魯衍碴院數(shù)材炒割真膏琴主戍醉哭黃筐眾腫離確秘免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Signalling antigen receptors on B cells - bifunctional antigen-binding secreted molecules（B 細(xì)胞表面受體和分泌的抗體）Structural conservation and infinite variability - domain structure（結(jié)構(gòu)上不僅保守

2、而且無限可變的）.The Immunoglobulin Gene Superfamily （免疫球蛋白的超家族）The immunoglobulin fold （免疫球蛋白的折疊）Framework and complementarity determining regions - hypervariable loops （框架結(jié)構(gòu)和可變區(qū)）Modes of interactions with antigens （與抗原相互作用的模型）Effector mechanisms and isotype role of the Fc. （Fc 區(qū)的作用）Multimeric antibodies a

3、nd multimerisationCharacteristics and properties of each Ig isotypeIg receptors and their functionsImmunoglobulin Structure-Function Relationship刀蘿曹淹橋隱擅涉床格袱詢鴻烴蒸概翔軒棠呸靈檔昌沽浴羌匹仟拷拷燥裴免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Cell surface antigen receptor on B cells B 細(xì)胞表面受體和分泌的抗體Allows B cells to sense their antigenic

4、environmentConnects extracellular space with intracellular signalling machinerySecreted antibody （抗體）Neutralisation （中和作用）Arming/recruiting effector cells （激活或者誘導(dǎo)功能細(xì)胞）Complement fixation （幫助機(jī)體對(duì)抗原的清除）Immunoglobulin Structure-Function Relationship裂印濟(jì)濱蜘羨楓撐辯峪桑搐賢嘗泥詢調(diào)爛爛烤計(jì)指匪惠涼遁菱制筐柜孩考免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與

5、功能的關(guān)系Immunoglobulins are Bifunctional ProteinsImmunoglobulins must interact with a small number of specialised molecules - （免疫球蛋白必須與特殊分子相互作用）Fc receptors on cells （細(xì)胞表面的Fc受體）Complement proteins （輔助蛋白）Intracellular cell signalling molecules （細(xì)胞內(nèi)信號(hào)轉(zhuǎn)導(dǎo)分子）whilst simultaneously recognising an infinite arr

6、ay of antigenic determinants. （同時(shí)能夠識(shí)別無限抗原族）很沒間粥局煞攙芽匪歉牟蛻幀腫滌奔班滓癥藉幌獲蹭狙遵隧廉熄馭冀團(tuán)彭免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Structural conservation and a capacity for infinite variability in a single molecule is provided by a DOMAIN structure.（結(jié)構(gòu)上不僅保守而且無限可變的- 抗體結(jié)構(gòu)域）Ig domains are derived from a single ancestral gene tha

7、t has duplicated, diversified and been modified to endow an assortment of functional qualities on a common basic structure（Ig結(jié)構(gòu)域源于一個(gè)原始基因，復(fù)制，多元化，修飾等）Ig domains are not restricted to immunoglobulins （Ig 結(jié)構(gòu)域不僅僅局限于免疫球蛋白）.The most striking characteristic of the Ig domain is a disulphide bond - linked str

8、ucture of 110 amino acids long（Ig結(jié)構(gòu)域最明顯的特點(diǎn)是其雙硫鍵，連接了110個(gè)氨基酸）.Immunoglobulin domains姚踩跑襪洋塘藕雙哇杠庫竄牛涵冪撥操態(tài)惕忙鍵瞞榮未伺骸侯貪質(zhì)右扣凡免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系The genes encoding Ig domains are not restricted to Ig genes.Although first discovered in immunoglobulins, they are found in a superfamily of related genes, p

9、articularly those encoding proteins crucial to cell-cell interactions and molecular recognition systems.IgSF molecules are found in most cell types and are present across taxonomic boundariesIg gene superfamily - IgSF沉境獻(xiàn)非綿涼禁蜒帳奔抒醒嘻裙責(zé)賃繳廢碾痕互靠榷檻雄人眷橋篷令主冪免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系A(chǔ)ntibodies are Proteins

10、 that Recognize Specific Antigens 抗體能夠特異性的識(shí)別抗原現(xiàn)澗腔疇旁撿各知效英肅追官衙餃怖磁氮酋韓菩揚(yáng)奴喀冉仔就營(yíng)簽瑤伶盧免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Epitopes（抗原決定簇 ）: Antigen Regions that Interact with Antibodies謬宛悟孽虛虜旬彤鴿微劣宗氓男澈隧變駒駒葷熄拓頒簧踞陷茲所藹懼健幸免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Consequences of Antibody Binding抗體結(jié)合效應(yīng)侈氮喜限摹孤信砷唯蹬盲沿比毆氛儈捍寐票剎原諜咐第侖止由飽姓裁裳滿免

11、疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CLVLSSSSSSSSCH3CH2CH1VHFcFabF(ab)2Domains are folded, compact, protease resistant structuresDomain Structure of Immunoglobulins免疫球蛋白的結(jié)構(gòu)域Pepsin cleavage sites - 1 x (Fab)2 & 1 x FcPapain cleavage sites - 2 x Fab 1 x FcLight chain Cdomainsk or lHeavy chain Cdomainsa, d, e, g

12、, or m爬鼓蛹景答癥域痙仕欠葉因遇術(shù)踏遵瘴藉命攝叛俗烽罰帥駛芯戰(zhàn)妹謬賞漏免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3滇缺濘燥伊役卷鬧拖匿燈窿蔚注艘瓤蘿神白寫眩串寬若肩興市棋觀攬棒道免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2鴕跺份瓢私熒患鰓全所攤豎蟬擾肺幅雨禮鼠肅忿蚊人六笆迢返韶掖始卑撞免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2CH1殆瓜漁煎潰挺考桔鑼懼位蕪額茲蓋桑手灌跟不諜帽輪缸遙崖瞎溜分澗悟摹免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2CH1VH1褲漓策佬醛頃獻(xiàn)墳惹瞥羌蠱燈棉三暮夢(mèng)翔肚拇煽外獸糙

13、劇鋁瘓倆隆獸風(fēng)咱免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2CH1VH1VL瓶冀仙鏈用聘龐臀掘獲瘧職層化腕綁闊盜劇樣幾饅偽砒翰豢樓撐疆龔島隆免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2CH1VH1CLVL結(jié)焉瑯促崩嘔踏吏堵釉氫濫版狀逆膝纖千將聶層畫捻示吐貞況賃核類況辰免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2CH1VH1CLVL盼霉呂鈕瑤皿闌頁冊(cè)冒孝鼠傍恤損冒賽洽角遺畜張琳過塹茹厲靡洶寡胚浸免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系HingeCH3CH2CH1VH1VLCLElbow目菏恬肄歇絕埠濾祟嘉龜豌

14、忙蜂獨(dú)耶批營(yíng)繭誨晉涌圃略峨袖掘武竊州石夢(mèng)免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2FbFvFvFvFbFvHingeElbowCH3CH2FbFvFlexibility andmotion of immunoglobulins鮮梧筒鄲蔫祁溺馭刑啥次怪阻廓顧梭軋顫任藤碴止送遮齲粕謄兩凡鎖危學(xué)免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系HingeFvFbFabCH3CH2CH1VH1VLCLFcElbowCarbohydrate溝垃柯釣拋導(dǎo)勻跌容潑沫相繁蔫演膊縷忱獨(dú)鵝述逢趟邪潰雹黔肢鈴源涯初免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系The Imm

15、unoglobulin FoldThe characteristic structural motif of all Ig domainsBarrel under constructionA barrel made of a sheet of staves arranged in a folded over sheetA b barrel of 7 (CL) or 8 (VL) polypeptide strands connected by loops and arranged to enclose a hydrophobic interiorSingle VL domain休圾浦利彈記共冰

16、亥陋咖卸誘逗欲算蝦貸鹼詩諄耀慕蚤礫豪訂墟薛炳拉潮免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Unfolded VL region showing 8 antiparallel b-pleated sheets connected by loops.NH2COOHSSThe Immunoglobulin Fold淪甥缽扇苛川糕藤膳銀死裴旅錘修甜羔慎豎肆揀疹咒暖繳勁函卯鏟勉峙孺免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Immunoglobulins must interact with a finite number of specialised molecules -E

17、asily explained by a common Fc region irrespective of specificity- whilst simultaneously recognising an infinite array of antigenic determinants.In immunoglobulins, what is the structural basis for the infinite diversity needed to match the antigenic universe?Immunoglobulins are Bifunctional Protein

18、s澗昨巴添哆餞戊疾鍍闡摻攝京蹄裹按說絕漚泵協(xié)糧珊阮體虎幀惺粱氣犧撇免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系A(chǔ)mino acid No.Variability8010060402020406080100120Cytochromes CVariability of amino acids in related proteinsWu & Kabat 1970Amino acid No.Variability8010060402020406080100120HumanIg heavychains您研屆蝦苗藤幀宙玖卷釬強(qiáng)嚨勻歷趾鴉洪冉匈歸硼爛渡喜嚴(yán)昂繼狙襯悅矣免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系

19、免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系FR1FR2FR3FR4CDR2CDR3CDR1Distinct regions of high variability and conservation led to the concept of a FRAMEWORK (FR), on which hypervariable regions were suspended.Framework and Hypervariable regionsAmino acid No.Variability8010060402020406080100120Most hypervariable regions coincided

20、with antigen contact points - the COMPLEMENTARITY DETERMINING REGIONS (CDRs)森皆僚署鋸而屢暢皿紫恕貫厲酶濰軟聘認(rèn)鴛靠采屎洋抓柑邁抓冪愚狄憂撤免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Hypervariable regionsHypervariable CDRs are locatedon loops at the end of the Fv regions測(cè)砸所晾違毒寧有異么庸逗畦穩(wěn)祥肖拄貳迫贓嵌樞蘆洗汲滁跑諷泡主叮掐免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Space-filling mo

21、del of (Fab)2, viewed from above,illustrating the surface location of CDR loops Light chainsGreen and brownHeavy chainsCyan and blueCDRsYellow腑聚畜丈語冗峭興子簇筍目棠脈隆迷樞呂桶朗罐斥把撫研召喳濟(jì)嗓隕坤煮免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系The framework supports the hypervariable loopsThe framework forms a compact b barrel/sandwich with

22、 a hydrophobic coreThe hypervariable loops join, and are more flexible than, the b strandsThe sequences of the hypervariable loops are highly variable amongst antibodies of different specificitiesThe variable sequences of the hypervariable loops influences the shape, hydrophobicity and charge at the

23、 tip of the antibodyVariable amino acid sequence in the hypervariable loops accounts for the diversity of antigens that can be recognised by a repertoire of antibodiesHypervariable loops and framework: Summary珊右搽葬搜瑞夸嚏邀用會(huì)匹趕焰漫盔溝垛選癡泥借跑溫告引梅聾填頰詹糕免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系A(chǔ)ntigens vary in size and compl

24、exityProtein:Influenza haemagglutininHapten:5-(para-nitrophenyl phosphonate)-pentanoic acid.遵決祖訃描示廣削部擔(dān)石詳融勘企逾枕朋貿(mào)患帶雁桃炎逗迷綱誅簇幻駿疼免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系A(chǔ)ntibodies interact with antigens in a variety of waysAntigen inserts into a pocket in the antibodyAntigen interacts with an extended antibody surfa

25、ce or a groove in the antibody surface振抹杭悅黎羚歇售跺鋸嬌標(biāo)贅劃樣忱嗜罵褪胃歡泛滋湍靳蝗逗鎢袖礎(chǔ)族奶免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CH3CH2FbFvFvFvFbFvHingeElbowCH3CH2FbFvFlexibility andmotion of immunoglobulins吠蛤賠辯試?yán)试诖慌睦p擊繡蜂湃岸唾故弊蚊卸嘴散僧逢藩臥烏抗飾祟囤腿免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系30 strongly neutralising McAb60 strongly neutralising McAb Fab r

26、egions60 weakly neutralising McAb Fab regionsHuman Rhinovirus 14- a common cold virus30nmModels of Human Rhinovirus 14 neutralised by monoclonal antibodies詩稱紳渝肢廓惰銜坯婿蛇杜紳阿借貉蹄潤(rùn)覽托倉(cāng)樓亦摟在摟眾瑤這塢洋康免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Electron micrographs of Antibodies and complement opsonising Epstein Barr Virus (EBV)

27、Negatively stained EBVEBV coated with a corona ofanti-EBV antibodiesEBV coated with antibodies and activated complement components音渴恩吵方舀脯獰巋沖徊弄于浙迄時(shí)販俘虎浴藕輿午響馮況限者交樸置篩免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系A(chǔ)ntibody + complement- mediated damage to E. coliHealthy E. coliElectron micrographs of the effect of antibodi

28、es and complement upon bacteria舍獄沼伺癌發(fā)儉江旬抨盆懇家傘履卑紹皚異逸礎(chǔ)逾瞞咎丈田佯挑幻是輿蟄免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Non-covalent forces inantibody - antigen interactionsElectrostatic forcesAttraction between opposite chargesHydrogen bondsHydrogens shared between electronegative atomsVan der Waals forcesFluctuations in elect

29、ron clouds around molecules oppositely polarise neighbouring atomsHydrophobic forcesHydrophobic groups pack together to exclude water (involves Van der Waals forces)愈舊恩莉憋鑿績(jī)波享凹坷昧意熙曾鴛付虛肚欄臆哪朔牛糯親鄙乖壟仆兌知免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Why do antibodies need an Fc region?Detect antigenPrecipitate antigenBlock

30、the active sites of toxins or pathogen-associated moleculesBlock interactions between host and pathogen-associated moleculesThe (Fab)2 fragment can -Inflammatory and effector functions associated with cellsInflammatory and effector functions of complementThe trafficking of antigens into the antigen

31、processing pathwaysbut can not activate龜睜下礙渡擺枷雜梳兩過揮央州舅擅歧稠慌鄧韌基宵長(zhǎng)矚痘虜攔門猖柯襄免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Structure and function of the Fc regionCH3CH2IgA IgD IgGCH4CH3CH2IgE IgMThe hinge region is replaced by an additional Ig domainFc structure is common to all specificities of antibody within an ISOTYPE(

32、although there are allotypes)The structure acts as a receptor for complement proteins and a ligand for cellular binding sites陷蒼擴(kuò)構(gòu)毗歲搪悟眺慫宦用卷薦籍哺嗽懂砸閏術(shù)屯蜜騙沙煌世寥歪焚慰掌免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Monomeric IgMIgM only exists as a monomer on the surface of B cellsCm4 contains the transmembrane and cytoplasmic r

33、egions. These are removed by RNA splicing to produce secreted IgMMonomeric IgM has a very low affinity for antigenCm4Cm3Cm2Cm1N.B. Only constant heavy chain domains are shown帳朝港直鹼夏扇義翰滑邑橇村慷劍忱擲紐徘閘公訛紐峽型階表帕益蓖瑰鴉免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系Cm3 binds C1q to initiate activation of the classical complement p

34、athwayCm1 binds C3b to facilitate uptake of opsonised antigens by macrophagesCm4 mediates multimerisation (Cm3 may also be involved)Cm4Cm3Cm2Cm1N.B. Only constant heavy chain domains are shownPolymeric IgMIgM forms pentamers and hexamers玻距夜海呼視意才恫并食檢原舷堤褪卜繕漆柔多棄侗百換廣灑最陶武瞄嶼免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系CCC

35、CCCMultimerisation of IgMCm4Cm3Cm2CCCm4Cm3Cm2CCCm4Cm3Cm2CCCm4Cm3Cm2CCCm4Cm3Cm2CCssssssCCss1. Two IgM monomers in the ER(Fc regions only shown)2. Cysteines in the J chain form disulphide bonds with cysteines from each monomer to form a dimer3. A J chain detaches leaving the dimer disulphide bonded.4.

36、 A J chain captures another IgM monomer and joins it to the dimer.5. The cycle is repeated twice more6. The J chain remains attached to the IgM pentamer.糖圣頗屠嗅段縮璃胃果壕露嶼翁詢鼎鄂膚互侶屬癌蓉叫酌提賴蠱帳剁曬眠免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系A(chǔ)ntigen-induced conformational changes in IgMPlanar or Starfish conformation found in s

37、olution.Does not fix complementStaple or crab conformation of IgMConformation change induced by binding to antigen.Efficient at fixing complement莫檢淘香象寂荒燃賂綠廖聲孰診愉團(tuán)柯茄閡纖取雜擇粗羊荒希梗履調(diào)曲笑免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系IgM facts and figuresHeavy chain:m - MuHalf-life: 5 to 10 days% of Ig in serum:10Serum level (m

38、gml-1): 0.25 - 3.1Complement activation:+ by classical pathwayInteractions with cells: Phagocytes via C3b receptorsEpithelial cells via polymeric Ig receptorTransplacental transfer: NoAffinity for antigen:Monomeric IgM - low affinity - valency of 2Pentameric IgM - high avidity - valency of 10釣佐溪謗壟疑簽

39、辦四阿亮悄叢摻框肄佛俊野五依針峨撩糾溝偵入稼懈爆譜免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系IgD facts and figuresIgD is co-expressed with IgM on B cells due to differential RNA splicingLevel of expression exceeds IgM on nave B cellsIgD plasma cells are found in the nasal mucosa - however the function of IgD in host defence is unknown - k

40、nockout mice inconclusiveLigation of IgD with antigen can activate, delete or anergise B cellsExtended hinge region confers susceptibility to proteolytic degradationHeavy chain:d - DeltaHalf-life: 2 to 8 days% of Ig in serum:0.2Serum level (mgml-1): 0.03 - 0.4Complement activation:NoInteractions wit

41、h cells: T cells via lectin like IgD receptorTransplacental transfer: No褪蘭禹佛漢隅犁嘯乍禮搜籍喜鴿咎涎乎椽尚立合艱針齋鍘暖燼譴禱擬惹秒免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系IgA dimerisation and secretion IgA is the major isotype of antibody secreted at mucosal sufacesExists in serum as a monomer, but more usually as a J chain-linked dimer,

42、 that is formed in a similar manner to IgM pentamers.JCCSSSSCCSSSSCCssIgA exists in two subclassesIgA1 is mostly found in serum and made by bone marrow B cells IgA2 is mostly found in mucosal secretions, colostrum and milk and is made by B cells located in the mucosae 媚醚赦郎善遣酚羹供衣折坊霍致租莉耙赫既路泉砒咳擺慚卵片因煩哥庭

43、劉免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系EpithelialcellJCCSSSSCCSSSSCCssSecretory IgA and transcytosisBJCCSSSSCCSSSSCCssJCCSSSSCCSSSSCCssJCCSSSSCCSSSSCCsspIgR & IgA areinternalisedStalk of the pIgR is degraded to release IgA containing part of the pIgR - the secretory componentJCCSSSSCCSSSSCCssIgA and pIgR are

44、transported to the apical surface in vesiclesB cells located in the submucosaproduce dimeric IgAPolymeric Ig receptors are expressed on the basolateral surface of epithelial cells to capture IgA produced in the mucosa洞烘刷找群丟漓縛瘁鈕紹棠官斯揭隋狹生陪世楞冗梢狙肯德切昭捏末結(jié)法免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系IgA facts and figuresHe

45、avy chains:a1 or a2 - Alpha 1 or 2Half-life: IgA1 5 - 7 daysIgA2 4 - 6 daysSerum levels (mgml-1): IgA1 1.4 - 4.2IgA2 0.2 - 0.5% of Ig in serum:IgA1 11 - 14IgA2 1 - 4Complement activation:IgA1 - by alternative and lectin pathwayIgA2 - NoInteractions with cells: Epithelial cells by pIgRPhagocytes by I

46、gA receptorTransplacental transfer: NoTo reduce vulnerability to microbial proteases the hinge region of IgA2 is truncated, and in IgA1 the hinge is heavily glycosylated.IgA is inefficient at causing inflammation and elicits protection by excluding, binding, cross-linking microorganisms and facilita

47、ting phagocytosis鞘姬豆嚇俺慎飽豌貢蔭坷島揩吝缸頒乓吵附江嚏角遙錳奠野芽坦譏師蝎飛免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系IgE facts and figuresIgE appears late in evolution in accordance with its role in protecting against parasite infectionsMost IgE is absorbed onto the high affinity IgE receptors of effector cellsIgE is also closely linked w

48、ith allergic diseases Heavy chain:e - EpsilonHalf-life: 1 - 5 daysSerum level (mgml-1): 0.0001 - 0.0002% of Ig in serum:0.004Complement activation:NoInteractions with cells: Via high affinity IgE receptors expressed by mast cells, eosinophils, basophils and Langerhans cellsVia low affinity IgE recep

49、tor on B cells and monocytesTransplacental transfer: No奏哆狠祟哨晤掣芋恿晃霍減是精搞謎受鍺沽餃眼御莖硒祭悠晰泉籃榜蛔慎免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系The high affinity IgE receptor (FceRI)a chainb chaing2SSSSSSCe1Ce1Ce2Ce2Ce3Ce3Ce4Ce4Ce1Ce1Ce2Ce2Ce3Ce3Ce4Ce4The IgE - FceRI interaction is the highest affinity of any Fc receptor with a

50、n extremely low dissociation rate.Binding of IgE to FceRI increases the half life of IgECe3 of IgE interacts with the a chain of FceRI causing a conformational change.吭波耐蛙鳴躊碾版蘋睦嚴(yán)伴敷允劑整乳謄輩嘲旗捷迢懈兒悄懸迢偶盂平籍免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系免疫球蛋白的結(jié)構(gòu)與功能的關(guān)系IgG facts and figuresHeavy chains:g 1 g 2 g3 g4 - Gamma 1 - 4Half-life: IgG1 21 - 24 days IgG2 21 - 24 days IgG3 7 - 8 days IgG4 21 - 24 daysSerum level (mgml