1、Chapter 24Immune 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 recombinati

2、ons24.6 Recombination 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

3、 triggered 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 Th

4、e major histocompatibility 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 variati

5、on.T cells are 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 fo

6、rm antigen-antibody 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

7、 on the surface of 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 c

8、ells making antibodies 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 g

9、enes code for the constant 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 genera

10、te an immunoglobulin with 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 lymphocytesTabl

11、e 24.1 Each immunoglobulin 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 reco

12、mbination generates a functional 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

13、C gene segment during RNA processing.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 ar

14、e assembled from their parts in 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

15、a single C gene segment.24.4 The 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 f

16、unctional V-J-C region. But sequences 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

17、 bp between its components; the other 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

18、 and rearrangementsFigure 24.14 Processing 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 recom

19、bination has one copy of the direct 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 rea

20、rrangementsFigure 24.15 A V gene promoter 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

21、 the expression in any particular lymphocyte 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

22、, and results in allelic exclusion.24.6 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

23、 type and function is determined by the 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 cl

24、ass switchingFigure 24.18 Class switching 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 o

25、f free antibodies to antigens to form antigen-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 alternativ

26、e forms of the heavy gene are expressed.24.7 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 there

27、fore affecting only its daughter cells; it is 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

28、 antigen provokes both the primary response and 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 2

29、4.16 A successful rearrangement to produce an active light or heavy chain suppresses further rearrangements of the same type, and results in allelic exclusion.24.9 B cell development and memoryFigure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer (H2L2) linked to two copies

30、 of the signal-transducing heterodimer (Igab).24.9 B 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 ar

31、e recognized together.24.10 T-cell receptors are related 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

32、related to immunoglobulinsFigure 24.24 The human TCRa locus 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 rel

33、ated to immunoglobulinsFigure 24.25 The TCRb locus contains 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 rec

34、eptors are related to immunoglobulinsFigure 24.13 Breakage and 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),

35、lying upstream of the J-C loci.24.10 T-cell receptors are related 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 co

36、mplex. The variable regions of the TCR are exposed on the cell surface. 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 t

37、wo copies of the signal-transducing heterodimer (Igab).24.10 T-cell 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 lo

38、cus codes for many genes of the immune system Figure 24.29 The histocompatibility 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 histocomp

39、atibility locus codes for many genes of the immune system Figure 24.30 The 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 m

40、ajor histocompatibility locus codes for many genes of the immune system Figure 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).

41、 Class II antigens consist of two (a and b) polypeptides, each with two domains (a1 & a2, b1 & 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 exon

42、s represent individual protein domains24.11 The major histocompatibility locus codes for many genes 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

43、 containing two identical light chains and two identical heavy chains. Each type of chain is coded 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醉翁亭記 1反復(fù)朗讀并背誦課文，培養(yǎng)文

44、言語感。2結(jié)合注釋疏通文義，了解文本內(nèi)容，掌握文本寫作思路。3把握文章的藝術(shù)特色，理解虛詞在文中的作用。4體會作者的思想感情，理解作者的政治理想。一、導(dǎo)入新課范仲淹因參與改革被貶，于慶歷六年寫下岳陽樓記，寄托自己“先天下之憂而憂，后天下之樂而樂”的政治理想。實際上，這次改革，受到貶謫的除了范仲淹和滕子京之外，還有范仲淹改革的另一位支持者北宋大文學(xué)家、史學(xué)家歐陽修。他于慶歷五年被貶謫到滁州，也就是今天的安徽省滁州市。也是在此期間，歐陽修在滁州留下了不遜于岳陽樓記的千古名篇醉翁亭記。接下來就讓我們一起來學(xué)習這篇課文吧！【教學(xué)提示】結(jié)合前文教學(xué)，有利于學(xué)生把握本文寫作背景，進而加深學(xué)生對作品含義的理

45、解。二、教學(xué)新課目標導(dǎo)學(xué)一：認識作者，了解作品背景作者簡介：歐陽修(10071072)，字永叔，自號醉翁，晚年又號“六一居士”。吉州永豐(今屬江西)人，因吉州原屬廬陵郡，因此他又以“廬陵歐陽修”自居。謚號文忠，世稱歐陽文忠公。北宋政治家、文學(xué)家、史學(xué)家，與韓愈、柳宗元、王安石、蘇洵、蘇軾、蘇轍、曾鞏合稱“唐宋八大家”。后人又將其與韓愈、柳宗元和蘇軾合稱“千古文章四大家”。關(guān)于“醉翁”與“六一居士”：初謫滁山，自號醉翁。既老而衰且病，將退休于潁水之上，則又更號六一居士?？陀袉栐唬骸傲缓沃^也？”居士曰：“吾家藏書一萬卷，集錄三代以來金石遺文一千卷，有琴一張，有棋一局，而常置酒一壺?！笨驮唬骸笆菫?/p>

46、五一爾，奈何？”居士曰：“以吾一翁，老于此五物之間，豈不為六一乎？”寫作背景：宋仁宗慶歷五年(1045年)，參知政事范仲淹等人遭讒離職，歐陽修上書替他們分辯，被貶到滁州做了兩年知州。到任以后，他內(nèi)心抑郁，但還能發(fā)揮“寬簡而不擾”的作風，取得了某些政績。醉翁亭記就是在這個時期寫就的。目標導(dǎo)學(xué)二：朗讀文章，通文順字1初讀文章，結(jié)合工具書梳理文章字詞。2朗讀文章，劃分文章節(jié)奏，標出節(jié)奏劃分有疑難的語句。節(jié)奏劃分示例環(huán)滁/皆山也。其/西南諸峰，林壑/尤美，望之/蔚然而深秀者，瑯琊也。山行/六七里，漸聞/水聲潺潺，而瀉出于/兩峰之間者，釀泉也。峰回/路轉(zhuǎn)，有亭/翼然臨于泉上者，醉翁亭也。作亭者/誰？山之

47、僧/曰/智仙也。名之者/誰？太守/自謂也。太守與客來飲/于此，飲少/輒醉，而/年又最高，故/自號曰/醉翁也。醉翁之意/不在酒，在乎/山水之間也。山水之樂，得之心/而寓之酒也。節(jié)奏劃分思考“山行/六七里”為什么不能劃分為“山/行六七里”？明確：“山行”意指“沿著山路走”，“山行”是個狀中短語，不能將其割裂?！巴?蔚然而深秀者”為什么不能劃分為“望之蔚然/而深秀者”？明確：“蔚然而深秀”是兩個并列的詞，不宜割裂，“望之”是總起詞語，故應(yīng)從其后斷句?！窘虒W(xué)提示】引導(dǎo)學(xué)生在反復(fù)朗讀的過程中劃分朗讀節(jié)奏，在劃分節(jié)奏的過程中感知文意。對于部分結(jié)構(gòu)復(fù)雜的句子，教師可做適當?shù)闹v解引導(dǎo)。目標導(dǎo)學(xué)三：結(jié)合注釋，

48、翻譯訓(xùn)練1學(xué)生結(jié)合課下注釋和工具書自行疏通文義，并畫出不解之處。【教學(xué)提示】節(jié)奏劃分與明確文意相輔相成，若能以節(jié)奏劃分引導(dǎo)學(xué)生明確文意最好；若學(xué)生理解有限，亦可在解讀文意后把握節(jié)奏劃分。2以四人小組為單位，組內(nèi)互助解疑，并嘗試用“直譯”與“意譯”兩種方法譯讀文章。3教師選擇疑難句或值得翻譯的句子，請學(xué)生用兩種翻譯方法進行翻譯。翻譯示例：若夫日出而林霏開，云歸而巖穴暝，晦明變化者，山間之朝暮也。野芳發(fā)而幽香，佳木秀而繁陰，風霜高潔，水落而石出者，山間之四時也。直譯法：那太陽一出來，樹林里的霧氣散開，云霧聚攏，山谷就顯得昏暗了，朝則自暗而明，暮則自明而暗，或暗或明，變化不一，這是山間早晚的景色。野

49、花開放，有一股清幽的香味，好的樹木枝葉繁茂，形成濃郁的綠蔭。天高氣爽，霜色潔白，泉水淺了，石底露出水面，這是山中四季的景色。意譯法：太陽升起，山林里霧氣開始消散，煙云聚攏，山谷又開始顯得昏暗，清晨自暗而明，薄暮又自明而暗，如此暗明變化的，就是山中的朝暮。春天野花綻開并散發(fā)出陣陣幽香，夏日佳樹繁茂并形成一片濃蔭，秋天風高氣爽，霜色潔白，冬日水枯而石底上露，如此，就是山中的四季?！窘虒W(xué)提示】翻譯有直譯與意譯兩種方式，直譯鍛煉學(xué)生用語的準確性，但可能會降低譯文的美感；意譯可加強譯文的美感，培養(yǎng)學(xué)生的翻譯興趣，但可能會降低譯文的準確性。因此，需兩種翻譯方式都做必要引導(dǎo)。全文直譯內(nèi)容見我的積累本。目標導(dǎo)學(xué)四：解讀文段，把握文本內(nèi)容1賞析第一段，說說本文是如何引出“醉翁亭”的位置的，作者在此運用了怎樣的藝術(shù)手法。明確：首先以“環(huán)滁皆山也”五字領(lǐng)起，將滁州的地理環(huán)境一筆勾出，點出醉翁亭坐落在群山之中，并縱觀滁州全貌，鳥瞰群山環(huán)抱之景。接著作者將“鏡頭”全景移向局部，先寫“西南諸峰，林壑尤美”，醉翁亭坐落在有最美的林壑的西南諸峰之中，視