第二十四章-免疫多样性Immune-div课件.ppt

1、Immune diversity24.1 Introduction24.2 Clonal selection amplifies lymphocytes that respond to individual antigens24.3 Immunoglobulin genes are assembled from their parts in lymphocytes24.4 Light chains are assembled by a single recombination24.5 Heavy chains are assembled by two recombinations24.6 Re

2、combination generates extensive diversity24.7 Avian immunoglobulins are assembled from pseudogenes24.8 Immune recombination uses two types of consensus sequence24.9 Recombination generates deletions or inversions24.10 The RAG proteins catalyze breakage and reunion24.11 Allelic exclusion is triggered

3、 by productive rearrangement24.12 DNA recombination causes class switching24.13 Early heavy chain expression can be changed by RNA processing24.14 Somatic mutation generates additional diversity24.15 B cell development and memory24.16 T-cell receptors are related to immunoglobulins24.17 The major hi

4、stocompatibility locus codes for many genes of the immune systemAntigen is any molecule whose entry into an organism provokes synthesis of an antibody(immunoglobulin).Superfamily is a set of genes all related by presumed descent from a common ancestor,but now showing considerable variation.T cells a

5、re lymphocytes of the T(thymic)lineage;may be subdivided into several functional types.They carry TcR(T-cell receptor)and are involved in the cell-mediated immune response.24.1 IntroductionFigure 24.1 Humoral immunity is conferred by the binding of free antibodies to antigens to form antigen-antibod

6、y complexes that are removed from the bloodstream by macrophages or that are attacked directly by the complement proteins.24.1 IntroductionFigure 24.2 In cell-mediated immunity,killer T cells use the T-cell receptor to recognize a fragment of the foreign antigen which is presented on the surface of

7、the target cell by the MHC protein.24.1 IntroductionHapten is a small molecule that acts as an antigen when conjugated to a protein.24.2 Clonal selection amplifies lymphocytes that respond to individual antigens Figure 24.3 The pool of immature lymphocytes contains B cells and T cells making antibod

8、ies and receptors with a variety of specificities.Reaction with an antigen leads to clonal expansion of the lymphocyte with the antibody(B cell)or receptor(T cell)that can recognize the antigen.24.2 Clonal selection amplifies lymphocytes that respond to individual antigensC genes code for the consta

9、nt regions of immunoglobulin protein chains.V gene is sequence coding for the major part of the variable(N-terminal)region of an immunoglobulin chain.24.3 Immunoglobulin genes are assembled from their parts in lymphocytes Figure 24.4 Heavy and light chains combine to generate an immunoglobulin with

10、several discrete domains.24.3 Immunoglobulin genes are assembled from their parts in lymphocytesFigure 24.4 Heavy and light chains combine to generate an immunoglobulin with several discrete domains.24.3 Immunoglobulin genes are assembled from their parts in lymphocytesTable 24.1 Each immunoglobulin

11、 family consists of a cluster of V genes linked to its C gene(s).24.3 Immunoglobulin genes are assembled from their parts in lymphocytes FamilyV GenesC GenesManMouseManMouseLambda64Kappa100098Figure 24.5 The lambda C gene segment is preceded by a J segment,so that V-J recombination generates a funct

12、ional lambda light-chain gene.24.3 Immunoglobulin genes are assembled from their parts in lymphocytesFigure 24.6 The kappa C gene segment is preceded by multiple J segments in the germ line.V-J joining may recognize any one of the J segments,which is then spliced to the C gene segment during RNA pro

13、cessing.24.3 Immunoglobulin genes are assembled from their parts in lymphocytesFigure 24.7 Heavy genes are assembled by sequential joining reactions.First a D segment is joined to a J segment;then a V gene segment is joined to the D segment.24.3 Immunoglobulin genes are assembled from their parts in

14、 lymphocytesFigure 24.8 The lambda family consists of V gene segments linked to a small number of J-C gene segments.24.4 The diversity of germline information Figure 24.9 The human and mouse kappa families consist of V gene segments linked to 5 J segments connected to a single C gene segment.24.4 Th

15、e diversity of germline information Figure 24.10 A single gene cluster in man contains all the information for heavy-chain gene assembly.24.4 The diversity of germline information Figure 24.11 The chicken lambda light locus has 25 V pseudogenes upstream of the single functional V-J-C region.But sequ

16、ences derived from the pseudogenes are found in active rearranged V-J-C genes.24.4 The diversity of germline information Figure 24.12 Consensus sequences are present in inverted orientation at each pair of recombining sites.One member of each pair has a spacing of 12 bp between its components;the ot

17、her has 23 bp spacing.24.5 Recombination between V and C gene segments generates deletions and rearrangements Figure 24.13 Breakage and reunion at consensus sequences generates immunoglobulin genes.24.5 Recombination between V and C gene segments generates deletions and rearrangementsFigure 24.14 Pr

18、ocessing of coding ends introduces variability at the junction.24.5 Recombination between V and C gene segments generates deletions and rearrangementsFigure 15.8 Reciprocal recombination between direct repeats excises the material between them;each product of recombination has one copy of the direct

19、 repeat.24.5 Recombination between V and C gene segments generates deletions and rearrangementsFigure 15.9 Reciprocal recombination between inverted repeats inverts the region between them.24.5 Recombination between V and C gene segments generates deletions and rearrangementsFigure 24.15 A V gene pr

20、omoter is inactive until recombination brings it into the proximity of an enhancer in the C gene segment.The enhancer is active only in B lymphocytes.24.5 Recombination between V and C gene segments generates deletions and rearrangementsAllelic exclusion describes the expression in any particular ly

21、mphocyte of only one allele coding for the expressed immunoglobulin.24.6 Allelic exclusion is triggered by productive rearrangement Figure 24.16 A successful rearrangement to produce an active light or heavy chain suppresses further rearrangements of the same type,and results in allelic exclusion.24

22、.6 Allelic exclusion is triggered by productive rearrangementClass switching is a change in the expression of the C region of an immunoglobulin heavy chain during lymphocyte differentiation.24.7 DNA recombination causes class switching Figure 24.17 Immunoglobulin type and function is determined by t

23、he heavy chain.J is a joining protein in IgM;all other Ig types exist as tetramers.24.7 DNA recombination causes class switchingFigure 24.10 A single gene cluster in man contains all the information for heavy-chain gene assembly.24.7 DNA recombination causes class switchingFigure 24.18 Class switchi

24、ng of heavy genes may occur by recombination between switch regions(S),deleting the material between the recombining S sites.Successive switches may occur.24.7 DNA recombination causes class switchingFigure 24.1 Humoral immunity is conferred by the binding of free antibodies to antigens to form anti

25、gen-antibody complexes that are removed from the bloodstream by macrophages or that are attacked directly by the complement proteins.24.7 DNA recombination causes class switchingFigure 24.19 The 3 end controls the use of splicing junctions so that alternative forms of the heavy gene are expressed.24

26、.7 DNA recombination causes class switchingHybridoma is a cell line produced by fusing a myeloma with a lymphocyte;it continues indefinitely to express the immunoglobulins of both parents.Somatic mutation is a mutation occurring in a somatic cell,and therefore affecting only its daughter cells;it is

27、 not inherited by descendants of the organism.24.8 Somatic mutation generates additional diversity Figure 24.20 B cell differentiation is responsible for acquired immunity.Pre-B cells are converted to B cells by Ig gene rearrangement.Initial exposure to antigen provokes both the primary response and

28、 storage of memory cells.Subsequent exposure to antigen provokes the secondary response of the memory cells.24.9 B cell development and memory Figure 24.21 B cell development proceeds through sequential stages.24.9 B cell development and memoryFigure 24.16 A successful rearrangement to produce an ac

29、tive light or heavy chain suppresses further rearrangements of the same type,and results in allelic exclusion.24.9 B cell development and memoryFigure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer(H2L2)linked to two copies of the signal-transducing heterodimer(Igab).24.9 B

30、 cell development and memoryFigure 24.23 The gd receptor is synthesized early in T-cell development.TCR ab is synthesized later and is responsible for classical cell-mediated immunity,in which target antigen and host histocompatibility antigen are recognized together.24.10 T-cell receptors are relat

31、ed to immunoglobulins Figure 24.2 In cell-mediated immunity,killer T cells use the T-cell receptor to recognize a fragment of the foreign antigen which is presented on the surface of the target cell by the MHC protein.24.10 T-cell receptors are related to immunoglobulinsFigure 24.24 The human TCRa l

32、ocus has interspersed a and d segments.A Vd segment is located within the Va cluster.The D-J-Cd segments lie between the V gene segments and the J-Ca segments.The mouse locus is similar,but has more Vd segments.24.10 T-cell receptors are related to immunoglobulinsFigure 24.25 The TCRb locus contains

33、 many V gene segments spread over 500 kb,and lying 280 kb upstream of the two D-J-C clusters.24.10 T-cell receptors are related to immunoglobulinsFigure 24.14 Processing of coding ends introduces variability at the junction.24.10 T-cell receptors are related to immunoglobulinsFigure 24.13 Breakage a

34、nd reunion at consensus sequences generates immunoglobulin genes.24.10 T-cell receptors are related to immunoglobulinsFigure 24.26 The TCRg locus contains a small number of functional V gene segments(and also some pseudogenes;not shown),lying upstream of the J-C loci.24.10 T-cell receptors are relat

35、ed to immunoglobulinsFigure 24.27 T cell development proceeds through sequential stages.24.10 T-cell receptors are related to immunoglobulinsFigure 24.28 The two chains of the T-cell receptor associate with the polypeptides of the CD3 complex.The variable regions of the TCR are exposed on the cell s

36、urface.The cytoplasmic domains of the z chains of CD3 provide the effector function.24.10 T-cell receptors are related to immunoglobulinsFigure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer(H2L2)linked to two copies of the signal-transducing heterodimer(Igab).24.10 T-cell

37、receptors are related to immunoglobulinsTransplantation antigen is protein coded by a major histocompatibility locus,present on all mammalian cells,involved in interactions between lymphocytes.24.11 The major histocompatibility locus codes for many genes of the immune system Figure 24.29 The histoco

38、mpatibility locus of the mouse contains several loci that were originally defined genetically.Each locus contains many genes.Spaces between clusters that have not been connected are indicated by queries.24.11 The major histocompatibility locus codes for many genes of the immune system Figure 24.30 T

39、he human major histocompatibility locus codes for similar functions to the murine locus,although its detailed organization is different.Genes concerned with nonimmune functions also have been located in this region.24.11 The major histocompatibility locus codes for many genes of the immune system Fi

40、gure 24.31 Class I and class II histocompatibility antigens have a related structure.Class I antigens consist of a single(a)polypeptide,with three external domains(a1,a2,a3),that interacts with b2 microglobulin(b2 m).Class II antigens consist of two(a and b)polypeptides,each with two domains(a1&a2,b

41、1&b2)with a similar overall structure.24.11 The major histocompatibility locus codes for many genes of the immune system Figure 24.32 Each class of MHC genes has a characteristic organization,in which exons represent individual protein domains24.11 The major histocompatibility locus codes for many g

42、enes of the immune system Immunoglobulins and T-cell receptors are proteins that play analogous functions in the roles of B cells and T cells in the immune system.Each immunoglobulin protein is a tetramer containing two identical light chains and two identical heavy chains.Each type of chain is code

43、d by a large cluster of V genes separated from the cluster of D,J,and C segments.Allelic exclusion ensures that a given lymphocyte synthesizes only a single Ig or TCR.24.12 Summary11醉翁亭记 1反复朗读并背诵课文，培养文言语感。2结合注释疏通文义，了解文本内容，掌握文本写作思路。3把握文章的艺术特色，理解虚词在文中的作用。4体会作者的思想感情，理解作者的政治理想。一、导入新课范仲淹因参与改革被贬，于庆历六年写下岳阳

44、楼记，寄托自己“先天下之忧而忧，后天下之乐而乐”的政治理想。实际上，这次改革，受到贬谪的除了范仲淹和滕子京之外，还有范仲淹改革的另一位支持者北宋大文学家、史学家欧阳修。他于庆历五年被贬谪到滁州，也就是今天的安徽省滁州市。也是在此期间，欧阳修在滁州留下了不逊于岳阳楼记的千古名篇醉翁亭记。接下来就让我们一起来学习这篇课文吧！【教学提示】结合前文教学，有利于学生把握本文写作背景，进而加深学生对作品含义的理解。二、教学新课目标导学一：认识作者，了解作品背景作者简介：欧阳修(10071072)，字永叔，自号醉翁，晚年又号“六一居士”。吉州永丰(今属江西)人，因吉州原属庐陵郡，因此他又以“庐陵欧阳修”自居

45、。谥号文忠，世称欧阳文忠公。北宋政治家、文学家、史学家，与韩愈、柳宗元、王安石、苏洵、苏轼、苏辙、曾巩合称“唐宋八大家”。后人又将其与韩愈、柳宗元和苏轼合称“千古文章四大家”。关于“醉翁”与“六一居士”：初谪滁山，自号醉翁。既老而衰且病，将退休于颍水之上，则又更号六一居士。客有问曰：“六一何谓也？”居士曰：“吾家藏书一万卷，集录三代以来金石遗文一千卷，有琴一张，有棋一局，而常置酒一壶。”客曰：“是为五一尔，奈何？”居士曰：“以吾一翁，老于此五物之间，岂不为六一乎？”写作背景：宋仁宗庆历五年(1045年)，参知政事范仲淹等人遭谗离职，欧阳修上书替他们分辩，被贬到滁州做了两年知州。到任以后，他内心

46、抑郁，但还能发挥“宽简而不扰”的作风，取得了某些政绩。醉翁亭记就是在这个时期写就的。目标导学二：朗读文章，通文顺字1初读文章，结合工具书梳理文章字词。2朗读文章，划分文章节奏，标出节奏划分有疑难的语句。节奏划分示例环滁/皆山也。其/西南诸峰，林壑/尤美，望之/蔚然而深秀者，琅琊也。山行/六七里，渐闻/水声潺潺，而泻出于/两峰之间者，酿泉也。峰回/路转，有亭/翼然临于泉上者，醉翁亭也。作亭者/谁？山之僧/曰/智仙也。名之者/谁？太守/自谓也。太守与客来饮/于此，饮少/辄醉，而/年又最高，故/自号曰/醉翁也。醉翁之意/不在酒，在乎/山水之间也。山水之乐，得之心/而寓之酒也。节奏划分思考“山行/六七

47、里”为什么不能划分为“山/行六七里”？明确：“山行”意指“沿着山路走”，“山行”是个状中短语，不能将其割裂。“望之/蔚然而深秀者”为什么不能划分为“望之蔚然/而深秀者”？明确：“蔚然而深秀”是两个并列的词，不宜割裂，“望之”是总起词语，故应从其后断句。【教学提示】引导学生在反复朗读的过程中划分朗读节奏，在划分节奏的过程中感知文意。对于部分结构复杂的句子，教师可做适当的讲解引导。目标导学三：结合注释，翻译训练1学生结合课下注释和工具书自行疏通文义，并画出不解之处。【教学提示】节奏划分与明确文意相辅相成，若能以节奏划分引导学生明确文意最好；若学生理解有限，亦可在解读文意后把握节奏划分。2以四人小组

48、为单位，组内互助解疑，并尝试用“直译”与“意译”两种方法译读文章。3教师选择疑难句或值得翻译的句子，请学生用两种翻译方法进行翻译。翻译示例：若夫日出而林霏开，云归而岩穴暝，晦明变化者，山间之朝暮也。野芳发而幽香，佳木秀而繁阴，风霜高洁，水落而石出者，山间之四时也。直译法：那太阳一出来，树林里的雾气散开，云雾聚拢，山谷就显得昏暗了，朝则自暗而明，暮则自明而暗，或暗或明，变化不一，这是山间早晚的景色。野花开放，有一股清幽的香味，好的树木枝叶繁茂，形成浓郁的绿荫。天高气爽，霜色洁白，泉水浅了，石底露出水面，这是山中四季的景色。意译法：太阳升起，山林里雾气开始消散，烟云聚拢，山谷又开始显得昏暗，清晨自

49、暗而明，薄暮又自明而暗，如此暗明变化的，就是山中的朝暮。春天野花绽开并散发出阵阵幽香，夏日佳树繁茂并形成一片浓荫，秋天风高气爽，霜色洁白，冬日水枯而石底上露，如此，就是山中的四季。【教学提示】翻译有直译与意译两种方式，直译锻炼学生用语的准确性，但可能会降低译文的美感；意译可加强译文的美感，培养学生的翻译兴趣，但可能会降低译文的准确性。因此，需两种翻译方式都做必要引导。全文直译内容见我的积累本。目标导学四：解读文段，把握文本内容1赏析第一段，说说本文是如何引出“醉翁亭”的位置的，作者在此运用了怎样的艺术手法。明确：首先以“环滁皆山也”五字领起，将滁州的地理环境一笔勾出，点出醉翁亭坐落在群山之中，

50、并纵观滁州全貌，鸟瞰群山环抱之景。接着作者将“镜头”全景移向局部，先写“西南诸峰，林壑尤美”，醉翁亭坐落在有最美的林壑的西南诸峰之中，视野集中到最佳处。再写琅琊山“蔚然而深秀”，点山“秀”，照应上文的“美”。又写酿泉，其名字透出了泉与酒的关系，好泉酿好酒，好酒叫人醉。“醉翁亭”的名字便暗中透出，然后引出“醉翁亭”来。作者利用空间变幻的手法，移步换景，由远及近，为我们描绘了一幅幅山水特写。2第二段主要写了什么？它和第一段有什么联系？明确：第二段利用时间推移，抓住朝暮及四季特点，描绘了对比鲜明的晦明变化图及四季风光图，写出了其中的“乐亦无穷”。第二段是第一段“山水之乐”的具体化。3第三段同样是写“