免疫球蛋白的结构与功能的关系课件

,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,此处编辑母版单击标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,学到很多东西的诀窍，就是一下子不要学很多。 - 洛 克,*,免疫球蛋白的结构与功能的关系,幽默来自智慧，恶语来自无能,免疫球蛋白的结构与功能的关系免疫球蛋白的结构与功能的关系幽默来自智慧，恶语来自无能Immunoglobulin Structure-Function Relationship免疫球蛋白的结构与功能的关系Signalling antigen receptors on B cells - bifunctional antigen-binding secreted molecules（B 细胞表面受体和分泌的抗体）,Structural conservation and infinite variability - domain structure（结构上不仅保守而且无限可变的）.,The Immunoglobulin Gene Superfamily （免疫球蛋白的超家族）,The immunoglobulin fold （免疫球蛋白的折叠）,Framework and complementarity determining regions - hypervariable loops （框架结构和可变区）,Modes of interactions with antigens （与抗原相互作用的模型）,Effector mechanisms and isotype role of the Fc. （Fc 区的作用）,Multimeric antibodies and multimerisation,Characteristics and properties of each Ig isotype,Ig receptors and their functionsImmunoglobulin Structure-Function Relationship,小学语文教材所选的内容是十分贴合小学生的年龄特点的，文章内容十分优美、生动，?x起来也朗朗上口，但从教学的情况来看，尽管他们能够流利地朗读文章，却缺少对美的感悟，本文就对此提出了解决的方法。,一、引导小学生从文章优美的文字中体会美,小学语文教学的内容是十分生动且丰富的，教材选择的题材也是非常多样化的，有记叙文，也有散文和诗歌。一般来讲，记叙文会选择一些比较形象生动的内容；而诗歌在文字上十分精练，但表达的思想却十分明了；散文的句式则十分简洁、优美。小学生因为年龄较小，在对文章的体会上，可能有一定的局限性，这需要老师去积极引导，让学生认真地朗读课文，并找出其中自己认为具有美感的句子，说出自己的感受，通过这样的方式，不仅能够对提升小学生的语感有很大的帮助，同时还能让小学生在分享与体会的同时得到美的熏陶。,如在教学美丽的小兴安岭这篇文章时，文章对秋天的描述运用了比喻和拟人的修辞手法，如“秋天，枫树的叶子火一般红，秋风吹来，落叶在林间飞舞”，通过“火一般红”和“飞舞”这两个词将枫叶的状态生动地表现出来。教师在教学这类句子的时候，需要引导小学生对这样的句子反复进行朗读，体会文字的美感，并且引导他们分析句子的结构和所用的修辞手法，让小学生通过分析来学习如何能够更生动地描述一个东西或一件事情，这对于他们对文字的运用也是有很大的帮助的。在语文教学中，只有对文字反复研读，认真分析，才能体会到其中真正的美，因此，在小学语文教学过程中，教师需要从这方面给予学生更多的引导，以帮助他们更好地学习，从优美的文字中感受到美。,二、引导小学生从反复的诵读中感受美,要想使小学生体会到语文文章的美，反复进行诵读并且对课文的内容有透彻的理解是必不可少的，但在诵读的过程中，不能过于生硬，这样只会使文章失去原本的美感，通过有感情地朗读，能够使小学生更好地把握与体会文章的内容和其中的美。所谓有感情地朗读指的是在能够流利地通读文章的前提下将文章的内容传神地朗读出来，读音和表情的运用能够与文章所表达的意思相符，在不同的句子中，能够读出不同语调，使文章的风格和情感能够被很好地表达出来，让听的人能够被强烈吸引且有所感悟，但这是基于对文章有充分了解，能够体会作者所想表达的思想感情的基础上的。,因为小学生理解能力有限，这就需要教师针对实际情况加以引导，首先让学生对文章反复进行朗读，教师可叫几名同学单独进行朗读，指出他们在朗读过程中存在的问题，引导他们在什么样的地方应该以什么样的情感去朗读，这样的方式不仅使学生能够认识到自身所存在的不足之处，还能够对文章有更深刻的理解，其他同学在听的过程中也可以联系自身的不足之处进行改正。总之，文章的美是需要在朗读的过程中去感受和体会的，教师要对小学生在这方面多进行引导。,三、引导小学生在情感的把握和理解中感悟美,在义务教育语文课程标准中，对小学语文教学有明确的描述：教师需要帮助学生对教学内容有更深的理解和体验，让他们能够有一定的感悟和思考。在语文的学习中，情感的理解是十分重要的一个因素，如果不能够对情感有很好的把握，只能使文章变得平淡无奇，发挥不了其真正的作用。在学习的过程中，小学生需要通过反复的朗读与体会去把握文字的美感以及文章所要表达的思想感情，并且还要对文章的背景有一定的了解，明确作者写文章的出发点，只有这样才能够对文章的情感有更深刻的理解与感悟。,在文学作品中的人物、场景通常是十分生动且真实的，为使学生能够更好地理解，教师可在课堂中将文章的场景进行还原，将角色分配给学生进行扮演，通过这样的方式，使小学生有身临其境之感，也能够更好地把握文章的情感。另外，这样的教学方式也符合小学生的年龄特点，对于调动课堂气氛和他们学习的积极性是有很大的帮助的。,总而言之，小学生对语文教学内容中美的体会与感悟是十分重要的，这不仅能够提高他们的语言和文字表达能力，同时还能使他们对文章有更深刻的理解，但这需要教师对他们积极进行引导，本文介绍了具体的操作方法。,创新是事物发展过程中量的积累，是量变过程。同时创新又是创造，是事物的突变，是一个全新事物和方法，是事物发展过程中的质变。物理的实验教学能够很好的体现这一质变过程。我们下面就在物理实验教学中来探索创新教育的具体实施。,一、更新实验教学的思路、做好物理实验,实验是物理教学的基础，它具有生动形象的特点，有利于激发学生的好奇心和求知欲，实验的一个重要特点是“动手操作，动眼观察，动脑思考”。在物理实验中，为了达到探索的目的，需要将观察、思维和操作紧密结合起来，它可以满足学生操作的欲望，但又不是单调的机械动作，因此可以将学生的操作兴趣转化为探索的兴趣，从而形成稳定的学习动机和认知兴趣。又由于实验本身的特点，它又成为物理教学中培养学生开拓意识和创新能力的重要途径。,二、实验教学方法的改革,1、观察是创新的前提。我们在实验教学中首先应该使学生知道：所谓观察就是要有目的地辨明观察对象的主要特征，注意发现引起变化的条件和原因，其次,要使学生了解观察是要经过一定的努力，克服一定的困难，才能发现问题，才能得到对事物的正确认识和正确的结论。需要指出的是：在教学中应该让学生知道，观察事物是科学方法中提取大量事实的第一步，也是我们要进行任何创造和超越的第一步，我们所需要的不仅仅是大家观察到的结果，更重要的是观察这个活动的本身，观察在生活中无处不在。比如观察水的沸腾实验中要求学生注意观察在给水加热的过程中，能看到什么?在此基础上引导同学讨论观察的方法和应注意的问题。,2、在实验中创新。实验就是在人工控制条件下使物理现象重复出现供人们观察的工作。通过实验，能够对物理事实获得具体的明确的认识，有助于理解物理概念和规律。那么在这里学习的就不是色散的知识，更重要的学习了这种探索事实根本的方法实验。实验中要有实事求是的科学态度。教育学生每做一个实验应该：了解实验目的，正确使用仪器，作必要的记录，得出相应的结论整理好实验器材。根据实验观察到的现象和结果得出结论，做出正确的实验报告。向学生适当介绍一些物理学大师所做的物理实验以及所取得的成绩，而在以后的学习中能够运用这些方法来探索知识。,3、重视方法的总结，动手动脑。科学方法提出这样几个步骤：收集大量资料，证据；总结分析；得出结论；提出意见和建议。实验做完了，结果出来了，我们的实验是不是就结束了？没有。应用才是我们的最终目的，这也完全符合唯物主义方法论中关于从实践到理论再由理论到实践的辨证原则。,当学生做了基本实验后，教师应当对学生实验提出较高层次的要求做验证性的和设计性的实验。比如在做完测平均速度的实验后应该总结实验时所采用的物理方法：控制变量的方法，这种方法在物理的实验中是最常用的，是应该掌握的。这样在学完密度知识后根据实验室所能提供的器材可以要求学生解决如何测金属块的密度问题，学生可以根据控制变量的方法提出设计方案，也可以提出一些具体问题，自己设计实验方法进行实验。这不仅对前面知识的应用，也是一种对物理方法的使用。,三、运用现代技术手段、辅助实验教学,物理作为一门实验性很强的学科，在实验教学的过程中，我们也遇到了有的实验在课堂上无法通过实际操作演示来完成。例如“大气压强”这堂课是初中物理的难点和重点。教师可以运用多媒体进行辅助教学，在一节课内就轻松自如地完成了原来需要两课时的内容，学生对基木概念掌握的牢固程度以及运用的灵活性，都远远超过了用传统教学手段进行教学的效果。测试表明，教学质量比用传统方法授课提高了一倍以上。一般来说，教师讲授马德堡半球实验时，把两个马德堡半球合在一起，抽掉里面的空气后叫一个学生拉一下，拉不开，就证明大气压强的存在。但是，究竟大气压强有多大？学生没有感受，印象不深。采用多媒体，可以在课堂里模拟300多年前的马德堡半球实验，分拉两个半球的马匹从2匹增加到4匹、8匹，直到16匹，再配以紧张而有节奏的马赛进行曲伴奏，直到“啪”的一声，把两个半球拉开，声像并茂，把学生带入了现场实验情景，所有学生都十分投入。采用多媒体对马德堡半球进行剖析讲解，强化了学生对大气从四面八方施压给半球的基本概念的理解。以往教师做测量大气压强量值的托里拆利演示实验时，由于无法改变教室里的大气压强，只能凭嘴讲：随着大气压强的变化，管内水银柱的高度也会发生相应变化。而运用多媒体后，就能模拟这一过程。运用大气压强原理制成的活塞式抽水机及离心式抽水机，不少教师因为这部分不作考试内容，往往就略去不讲，即使讲，也只能在挂图上讲解，学生往往一知半解，无法看到抽水机的动态工作过程。而多媒体却方便地解决了这一问题。以讲解活塞式抽水机工作原理为例，当活塞提起时，圆桶内形成一个低压区，下边大气压强将阀门冲开，使整个圆桶内形成低压区，外面的大气压就把水压入桶内。这一动态过程是在一瞬间完成的，而运用多媒体教学即可视学生理解程度，随时停顿或放慢速度，以便讲解清楚。这样，就化难为易，使所有的学生都能一目了然地掌握抽水机的工作原理。,总之，创新教育能使学生学会学习，开发智力提高素质，增加了锻炼的机会，增强了适应社会发展的意识。而其在物理实验教学中的具体实施，也会给我们培养大量的适应现代化社会需要的人材提供一个可行的方式方法。,免疫球蛋白的结构与功能的关系幽默来自智慧，恶语来自无能免疫球,1,免疫球蛋白的结构与功能的关系课件,免疫球蛋白的结构与功能的关系课件,免疫球蛋白的结构与功能的关系课件,免疫球蛋白的结构与功能的关系课件,Structural conservation,and,a capacity for infinite variability in a single molecule is provided by a,DOMAIN,structure.,（结构上不仅保守而且无限可变的,-,抗体结构域）,Ig domains are derived from a single ancestral gene that has duplicated, diversified and been modified to endow an assortment of functional qualities on a common basic structure,（,Ig,结构域源于一个原始基因，复制，多元化，修饰等）,Ig domains are not restricted to immunoglobulins,（,Ig,结构域不仅仅局限于免疫球蛋白）,.,The most striking characteristic of the Ig domain is a disulphide bond - linked structure of 110 amino acids long,（,Ig,结构域最明显的特点是其双硫键，连接了,110,个氨基酸）,.,Immunoglobulin domains,Structural conservation and a,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, particularly 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 boundaries,Ig gene superfamily - IgSF,The genes encoding Ig domains,Antibodies are Proteins that Recognize Specific Antigens,抗体能够特异性的识别抗原,Antibodies are Proteins that R,8,Epitopes,（抗原,决定簇,）,: Antigen Regions that Interact with Antibodies,Epitopes（抗原决定簇 ）: Antigen Regi,9,Consequences of Antibody Binding,抗体结合,效应,Consequences of Antibody Bindi,10,C,L,V,L,S,S,S,S,S,S,S,S,C,H,3,C,H,2,C,H,1,V,H,Fc,Fab,F(ab),2,Domains are folded, compact, protease resistant structures,Domain Structure of Immunoglobulins,免疫球蛋白的结构域,Pepsin cleavage sites - 1 x (Fab),2,& 1 x Fc,Papain cleavage sites - 2 x Fab 1 x Fc,Light chain C,domains,k,or,l,Heavy chain C,domains,a, d, e, g,or,m,CLVLSSSSSSSSCH3CH2CH1VHFcFabF(,CH3,CH3,CH3,CH2,CH3CH2,CH3,CH2,CH1,CH3CH2CH1,CH3,CH2,CH1,VH1,CH3CH2CH1VH1,CH3,CH2,CH1,VH1,VL,CH3CH2CH1VH1VL,CH3,CH2,CH1,VH1,CL,VL,CH3CH2CH1VH1CLVL,CH3,CH2,CH1,VH1,CL,VL,CH3CH2CH1VH1CLVL,Hinge,CH3,CH2,CH1,VH1,VL,CL,Elbow,HingeCH3CH2CH1VH1VLCLElbow,C,H,3,C,H,2,Fb,Fv,Fv,Fv,Fb,Fv,Hinge,Elbow,C,H,3,C,H,2,Fb,Fv,Flexibility and,motion of immunoglobulins,CH3CH2FbFvFvFvFbFvHingeElbowCH,Hinge,Fv,Fb,Fab,CH3,CH2,CH1,VH1,VL,CL,Fc,Elbow,Carbohydrate,HingeFvFbFabCH3CH2CH1VH1VLCLFc,The Immunoglobulin Fold,The characteristic structural motif of all Ig domains,Barrel under construction,A barrel made of a sheet of staves arranged in a folded over sheet,A,b,barrel of 7 (C,L,) or 8 (V,L,) polypeptide strands connected by loops and arranged to enclose a hydrophobic interior,Single V,L,domain,The Immunoglobulin FoldThe cha,Unfolded V,L,region showing 8 antiparallel,b,-pleated sheets connected by loops.,NH,2,COOH,S,S,The Immunoglobulin Fold,Unfolded VL region showing 8 a,Immunoglobulins must interact with a finite number of specialised molecules -,Easily 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 Proteins,Immunoglobulins must interact,Amino acid No.,Variability,80,100,60,40,20,20,40,60,80,100,120,Cytochromes C,Variability of amino acids in related proteins,Wu & Kabat 1970,Amino acid No.,Variability,80,100,60,40,20,20,40,60,80,100,120,Human,Ig heavy,chains,Amino acid No.Variability80100,FR1,FR2,FR3,FR4,CDR2,CDR3,CDR1,Distinct regions of high variability and conservation led to the concept of a,FRAMEWORK,(FR), on which hypervariable regions were suspended.,Framework and Hypervariable regions,Amino acid No.,Variability,80,100,60,40,20,20,40,60,80,100,120,Most hypervariable regions coincided with antigen contact points - the,COMPLEMENTARITY DETERMINING REGIONS,(CDRs),FR1FR2FR3FR4CDR2CDR3CDR1Distin,Hypervariable regions,Hypervariable CDRs are located,on loops at the end of the Fv regions,Hypervariable regionsHypervari,Space-filling model of (Fab),2, viewed from above,illustrating the surface location of CDR loops,Light chains,Green,and,brown,Heavy chains,Cyan,and,blue,CDRs,Yellow,Space-filling model of (Fab)2,The framework supports the hypervariable loops,The framework forms a compact,b,barrel/sandwich with a hydrophobic core,The hypervariable loops join, and are more flexible than, the,b,strands,The sequences of the hypervariable loops are highly variable amongst antibodies of different specificities,The variable sequences of the hypervariable loops influences the shape, hydrophobicity and charge at the tip of the antibody,Variable amino acid sequence in the hypervariable loops accounts for the diversity of antigens that can be recognised by a repertoire of antibodies,Hypervariable loops and framework: Summary,The framework supports the hyp,Antigens vary in size and complexity,Protein:,Influenza haemagglutinin,Hapten:,5-(para-nitrophenyl phosphonate)-pentanoic acid.,Antigens vary in size and comp,Antibodies interact with antigens in a variety of ways,Antigen inserts into a pocket in the antibody,Antigen interacts with an extended antibody surface or a groove in the antibody surface,Antibodies interact with antig,C,H,3,C,H,2,Fb,Fv,Fv,Fv,Fb,Fv,Hinge,Elbow,C,H,3,C,H,2,Fb,Fv,Flexibility and,motion of immunoglobulins,CH3CH2FbFvFvFvFbFvHingeElbowCH,30 strongly neutralising McAb,60 strongly neutralising McAb Fab regions,60 weakly neutralising McAb Fab regions,Human Rhinovirus 14,- a common cold virus,30nm,Models of Human Rhinovirus 14 neutralised by monoclonal antibodies,30 strongly neutralising McAb6,Electron micrographs of Antibodies and complement opsonising Epstein Barr Virus (EBV),Negatively stained EBV,EBV coated with a corona of,anti-EBV antibodies,EBV coated with antibodies and activated complement components,Electron micrographs of Antibo,Antibody + complement- mediated,damage to E. coli,Healthy E. coli,Electron micrographs of the effect of antibodies and complement upon bacteria,Antibody + complement- mediate,Non-covalent forces in,antibody - antigen interactions,Electrostatic forces,Attraction between opposite charges,Hydrogen bonds,Hydrogens shared between electronegative atoms,Van der Waals forces,Fluctuations in electron clouds around molecules oppositely polarise neighbouring atoms,Hydrophobic forces,Hydrophobic groups pack together to exclude water (involves Van der Waals forces),Non-covalent forces inElectros,Why do antibodies need an Fc region?,Detect antigen,Precipitate antigen,Block the active sites of toxins or pathogen-associated molecules,Block interactions between host and pathogen-associated molecules,The (Fab),2,fragment can -,Inflammatory and effector functions associated with cells,Inflammatory and effector functions of complement,The trafficking of antigens into the antigen processing pathways,but can not activate,Why do antibodies need an Fc r,Structure and function of the Fc region,C,H,3,C,H,2,IgA IgD IgG,C,H,4,C,H,3,C,H,2,IgE IgM,The hinge region is replaced by an additional Ig domain,Fc structure is common to all specificities of antibody within an,ISOTYPE,(although there are allotypes),The structure acts as a receptor for complement proteins and a ligand for cellular binding sites,Structure and function of the,Monomeric IgM,IgM only exists as a monomer on the surface of B cells,C,m,4 contains the transmembrane and cytoplasmic regions. These are removed by RNA splicing to produce secreted IgM,Monomeric IgM has a very low affinity for antigen,C,m,4,C,m,3,C,m,2,C,m,1,N.B. Only constant heavy chain domains are shown,Monomeric IgMIgM only exists a,C,m,3 binds C1q to initiate activation of the classical complement pathway,C,m,1 binds C3b to facilitate uptake of opsonised antigens by macrophages,C,m,4 mediates multimerisation (C,m,3 may also be involved),C,m,4,C,m,3,C,m,2,C,m,1,N.B. Only constant heavy chain domains are shown,Polymeric IgM,IgM forms pentamers and hexamers,Cm3 binds C1q to initiate acti,C,C,C,C,C,C,Multimerisation of IgM,C,m,4,C,m,3,C,m,2,C,C,C,m,4,C,m,3,C,m,2,C,C,C,m,4,C,m,3,C,m,2,C,C,C,m,4,C,m,3,C,m,2,C,C,C,m,4,C,m,3,C,m,2,C,C,s,s,s,s,s,s,C,C,s,s,1. 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 dimer,3. A J chain detaches leaving the dimer disulphide bonded.,4. A J chain captures another IgM monomer and joins it to the dimer.,5. The cycle is repeated twice more,6. The J chain remains attached to the IgM pentamer.,CCCCCCMultimerisation of IgMCm,Antigen-induced conformational changes in IgM,Planar or Starfish conformation found in solution.,Does not fix complement,Staple or crab conformation of IgM,Conformation change induced by binding to antigen.,Efficient at fixing complement,Antigen-induced conformational,IgM facts and figures,Heavy chain:,m,- Mu,Half-life:,5 to 10 days,% of Ig in serum:,10,Serum level (mgml,-1,):,0.25 - 3.1,Complement activation:,+ by classical pathway,Interactions with cells:,Phagocytes via C3b receptorsEpithelial cells via polymeric Ig receptor,Transplacental transfer:,No,Affinity for antigen:,Monomeric IgM - low affinity - valency of 2Pentameric IgM - high avidity - valency of 10,IgM facts and figuresHeavy cha,IgD facts and figures,IgD is co-expressed with IgM on B cells due to differential RNA splicing,Level of expression exceeds IgM on nave B cells,IgD plasma cells are found in the nasal mucosa - however the function of IgD in host defence is unknown - knockout mice inconclusive,Ligation of IgD with antigen can activate, delete or anergise B cells,Extended hinge region confers susceptibility to proteolytic degradation,Heavy chain:,d,- Delta,Half-life:,2 to 8 days,% of Ig in serum:,0.2,Serum level (mgml,-1,):,0.03 - 0.4,Complement activation:,No,Interactions with cells:,T cells via lectin like IgD receptor,Transplacental transfer:,No,IgD facts and figuresIgD is co,IgA dimerisation and secretion,IgA is the major isotype of antibody secreted at mucosal sufaces,Exists in serum as a monomer, but more usually as a J chain-linked dimer, that is formed in a similar manner to IgM pentamers.,J,C,C,S,S,S,S,C,C,S,S,S,S,C,C,s,s,IgA exists in two subclasses,IgA1 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,IgA dimerisation and secretion,Epithelial,cell,J,C,C,S,S,S,S,C,C,S,S,S,S,C,C,s,s,Secretory IgA and transcytosis,B,J,C,C,S,S,S,S,C,C,S,S,S,S,C,C,s,s,J,C,C,S,S,S,S,C,C,S,S,S,S,C,C,s,s,J,C,C,S,S,S,S,C,C,S,S,S,S,C,C,s,s,pIgR & IgA are,internalised,Stalk of the pIgR is degraded to release IgA containing part of the pIgR - the secretory component,J,C,C,S,S,S,S,C,C,S,S,S,S,C,C,s,s,IgA and pIgR are transported to the apical surface in vesicles,B cells located in the submucosa,produce dimeric IgA,Polymeric Ig receptors are expressed on the basolateral surface of epithelial cells to capture IgA produced in the mucosa,EpithelialJCCSSSSCCSSSSCCssSec,IgA facts and figures,Heavy chains:,a,1,or,a,2 - Alpha 1 or 2,Half-life:,IgA1 5 - 7 daysIgA2 4 - 6 days,Serum levels (mgml,-1,):,IgA1 1.4 - 4.2IgA2 0.2 - 0.5,% of Ig in serum:,IgA1 11 - 14IgA2 1 - 4,Complement activation:,IgA1,-,by alternative and lectin pathwayIgA2 - No,Interactions with cells:,Epithelial cells by pIgRPhagocytes by IgA receptor,Transplacental transfer:,No,To 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 facilitating phagocytosis,IgA facts and figuresHeavy cha,IgE facts and figures,IgE appears late in evolution in accordance with its role in protecting against parasite infections,Most IgE is absorbed onto the high affinity IgE receptors of effector cells,IgE is also closely linked with allergic diseases,Heavy chain:,e,- Epsilon,Half-life:,1 - 5 days,Serum level (mgml,-1,):,0.0001 - 0.0002,% of Ig in serum:,0.004,Complement activation:,No,Interactions with cells:,Via high affinity IgE receptors expressed by mast cells, eosinophils, basophils and Langerhans cellsVia low affinity IgE receptor on B cells and monocytes,Transplacental transfer:,No,IgE facts and figuresIgE appea,The high affinity IgE receptor (Fc,e,RI),a,chain,b,chain,g,2,S,S,S,S,S,S,C,e,1,C,e,1,C,e,2,C,e,2,C,e,3,C,e,3,C,e,4,C,e,4,C,e,1,C,e,1,C,e,2,C,e,2,C,e,3,C,e,3,C,e,4,C,e,4,The IgE - Fc,e,RI interaction is the highest affinity of any Fc receptor with an extremely low dissociation rate.,Binding of IgE to Fc,e,RI increases the half life of IgE,C,e,3 of IgE interacts with the,a,chain of Fc,e,RI causing a conformational change.,The high affinity IgE receptor,IgG facts and figures,Heavy chains:,g,1,g,2,g,3,g,4 - Gamma 1 - 4,Half-life:,IgG1 21 - 24 days IgG2 21 - 24 days IgG3 7 - 8 days IgG4 21 - 24 days,Serum level (mgml,-1,):,IgG15 - 12IgG2 2 - 6IgG3 0.5 - 1IgG4 0.2 - 1,% of Ig in serum:,IgG145 - 53IgG2 11 - 15IgG3 3 - 6IgG4 1 - 4,Complement activation:,IgG1+ IgG2 + IgG3 + IgG4 No,Interactions with cells:,All subclasses via IgG receptors on macrophages and phagocytes,Transplacental transfer:,IgG1+IgG2 +IgG3 +IgG4 +,IgG facts and figuresHeavy cha,Carbohydrate is essential for complement activation,Subtly different hinge regions between subclasses accounts for differing abilities to activate complement,C1q binding motif is located on the C,g,2 domain,Carbohydrate is essential for,Fc,g,receptors,ReceptorCell typeEffect of ligation,Fc,g,RI,Macrophages Neutrophils,Eosinophils, Dendritic cells Uptake, Respiratory burst,Fc,g,RIIA,Macrophages Neutrophils,Eosinophils, PlateletsLangerhans cells Uptake, Granule release,Fc,g,RIIB1,B cells, Mast CellsNo Uptake, Inhibition of stimulation,Fc,g,RIIB2,Macrophages Neutrophils,Eosinophils Uptake, Inhibition of stimulation,Fc,g,RIII,NK cells, Eosinophils,Macrophages, NeutrophilsMast cellsInduction of killing (NK cells),High affinity Fc,g,receptors from the Ig superfamily:,Fcg receptorsReceptorCell typ,The neonatal Fc,g,receptor,The Fc,g,Rn is structurally related to MHC class I,In cows Fc,g,Rn binds maternal IgG in the colostrum at pH 6.5 in the gut. The IgG receptor complex is trancytosed across the gut epithelium and the IgG is released into the foetal blood by the sharp change in pH to 7.4,Some evidence that t