首页生物学分子生物学分子生物学基因Gene 25 第二十四章 免疫多样性(Immune diversity).ppt

25 第二十四章 免疫多样性(Immune diversity).ppt

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本课件为《分子生物学》第24章免疫多样性(Immune diversity),依据 Gene VII 教材编排,沿The major等小节推进,讲解本章核心概念与分子机制,配逐页图示与文字版。

Chapter 24 cover slide: Immune diversity; sections include The major, Introduction, Clonal selection
Lecture slide on The major histocompatibility: 24.1 Introduction
Term-definition slide on Introduction, explaining Antigen, Superfamily, T cells
查看本课件的文字版(共 53 页,供检索与复制)

第1页:Chapter 24 Immune diversity

Chapter 24 Immune diversity

第2页:24.1 Introduction

  • 24.1 Introduction
  • 24.2 Clonal selection amplifies lymphocytes that respond to individual antigens
  • 24.3 Immunoglobulin genes are assembled from their parts in lymphocytes
  • 24.4 Light chains are assembled by a single recombination
  • 24.5 Heavy chains are assembled by two recomb in at ions
  • 24.6 Recombination generates extensive diversity
  • 24.7 Avian immunoglobulins are assembled from pseudogenes
  • 24.8 Immune recombination uses two types of consensus sequence
  • 24.9 Recombination generates deletions or inversions
  • 24.10 The RAG proteins catalyze breakage and reunion
  • 24.11 Allelic exclusion is triggered by productive rearrangement
  • 24.12 DNA recombination causes class switching
  • 24.13 Early heavy chain expression can be changed by RNA processing
  • 24.14 Somatic mutation generates additional diversity
  • 24.15 B cell development and memory
  • 24.16 T-cell receptors are related to immunoglobulins

第3页:Key terms: Antigen, Superfamily, T cells

Antigen
Antigen is any molecule whose entry into an organism provokes synthesis of an antibody (immunoglobulin).
Superfamily
Superfamily is a set of genes all related by presumed descent from a common ancestor, but now showing considerable vari at ion.
T cells
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.

第4页:Humoral immunity is conferred by the binding

Figure 24.1 Humoral immunity is conferred by the binding of 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.

第5页:In cell-mediated immunity, killer T cells use

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.

第6页:Hapten is a small molecule

Hapten is a small molecule that acts as an antigen when conjugated to a protein.

第7页:The pool of immature lymphocytes contains B cells

Figure 24.3 The pool of immature lymphocytes contains B cells and T cells making antibodies and receptors with a variety of specificities. Reaction with an antigen leads to clonal expansi on of the lymphocyte with the antibody (B cell) or receptor (T cell) that can recognize the antigen.

第8页:Key terms: C genes, V gene

C genes
C genes code for the constant regions of immunoglobulin protein chains.
V gene
V gene is sequence coding for the major part of the variable (N-terminal) region of an immunoglobulin chain.

第9页:Heavy and light chains combine to generate

Figure 24.4 Heavy and light chains combine to generate an immunoglobulin with several discrete domains.

第10页:Heavy and light chains combine to generate

Figure 24.4 Heavy and light chains combine to generate an immunoglobulin with several discrete domains.

说明:本页源文与上一页完全相同,疑为课件连续两页沿用同一页内容,已按原文保留。

第11页:Table 24.1 Each immunoglobulin family consists

Table 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 Genes Man Mouse Man Mouse Lambda<3002>64 Kappa<300~100011 Heavy~300>100098.

说明:原页为数据表,源文抽取后列标题与数值粘连,无法安全切分为表格,此处保留原文文字,建议对照原课件图片补充表格内容。

第12页:The lambda C gene segment is preceded by a J

Figure 24.5 The lambda C gene segment is preceded by a J segment, so that V-J recombination generates a functional lambda light-cha in gene.

第13页:The kappa C gene segment is preceded by multiple

Figure 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 processing.

第14页:Heavy genes are assembled by sequential joining

Figure 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.

第15页:The lambda family consists of V gene segments

Figure 24.8 The lambda family consists of V gene segments linked to a small number of J-C gene segments.

第16页:The human and mouse kappa families consist of V

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.

第17页:A single gene cluster in man contains all

Figure 24.10 A single gene cluster in man contains all the information for heavy-chain gene assembly.

第18页:The chicken lambda light locus has 25 V

Figure 24.11 The chicken lambda light locus has 25 V pseudogenes upstream of the single functional V-J-C region. But sequences derived from the pseudogenes are found in active rearranged V-J-C genes.

第19页:Consensus sequences are present in inverted

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 other has 23 bp spacing.

第20页:Breakage and reunion at consensus sequences

Figure 24.13 Breakage and reunion at consensus sequences generates immunoglobulin genes.

第21页:Processing of coding ends introduces variability

Figure 24.14 Processing of coding ends introduces variability at the junction.

第22页:Reciprocal recombination between direct repeats

Figure 15.8 Reciprocal recombination between direct repeats excises the material between them; each product of recombination has one copy of the direct repeat.

第23页:Reciprocal recombination between inverted repeats

Figure 15.9 Reciprocal recombination between inverted repeats inverts the region between them.

第24页:A V gene promoter is inactive until recombination

Figure 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.

第25页:Allelic exclusion describes the expression in any

Allelic exclusion describes the expression in any particular lymphocyte of only one allele coding for the expressed immunoglobulin.

第26页:A successful rearrangement to produce an active

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.

第27页:Class switching is a change in the expression

Class switching is a change in the expression of the C region of an immunoglobulin heavy chain during lymphocyte differenti at ion.

第28页:Immunoglobulin type and function is determined

Figure 24.17 Immunoglobulin type and function is determined by the heavy chain. J is a joining protein in IgM; all other Ig types exist as tetramers.

第29页:A single gene cluster in man contains all

Figure 24.10 A single gene cluster in man contains all the information for heavy-chain gene assembly.

第30页:Class switching of heavy genes may occur

Figure 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.

第31页:Humoral immunity is conferred by the binding

Figure 24.1 Humoral immunity is conferred by the binding of 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.

第32页:The 3end controls the use of splicing junctions

Figure 24.19 The 3end controls the use of splicing junctions so that alternative forms of the heavy gene are expressed.

第33页:Key terms: Hybridoma, Somatic mutation

Hybridoma
Hybridoma is a cell line produced by fusing a myeloma with a lymphocyte; it continues indefinitely to express the immunoglobulins of both parents.
Somatic mutation
Somatic mutation is a mutation occur ring in a somatic cell, and therefore affecting only its daughter cells; it is not inherited by descendants of the organism.

第34页:B cell differenti at ion is responsible

Figure 24.20 B cell differenti at ion 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 storage of memory cells. Subsequent exposure to antigen provokes the secondary response of the memory cells.

第35页:B cell development proceeds through sequential

Figure 24.21 B cell development proceeds through sequential stages.

第36页:A successful rearrangement to produce an active

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.

第37页:The B cell antigen receptor consists of

Figure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer (H2L2) linked to two copies of the signal-transducing heterodimer (Igab).

第38页:The gd receptor is synthesized early in T-cell

Figure 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.

第39页:In cell-mediated immunity, killer T cells use

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.

第40页:The human TCRa locus has interspersed a and d

Figure 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.

第41页:The TCRb locus contains many V gene segments

Figure 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.

第42页:Processing of coding ends introduces variability

Figure 24.14 Processing of coding ends introduces variability at the junction.

第43页:Breakage and reunion at consensus sequences

Figure 24.13 Breakage and reunion at consensus sequences generates immunoglobulin genes.

第44页:The TCRg locus contains a small number

Figure 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.

第45页:T cell development proceeds through sequential

Figure 24.27 T cell development proceeds through sequential stages.

第46页:The two chains of the T-cell receptor associate

Figure 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 surface. The cytoplasmic domains of the z chains of CD3 provide the effector function.

第47页:The B cell antigen receptor consists of

Figure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer (H2L2) linked to two copies of the signal-transducing heterodimer (Igab).

第48页:Trans plant at ion antigen is protein coded by

Trans plant at ion antigen is protein coded by a major histocompatibility locus, present on all mammalian cells, involved in interactions between lymphocytes.

第49页:The histocompatibility locus of the mouse

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.

第50页:The human major histocompatibility locus codes

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.

第51页:Class I and class II histocompatibility antigens

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 microglobul in (b2 m). Class II antigens consist of two (a and b) polypeptides, each with two domains (a1 & a2, b1 & b2) with a similar overall structure.

第52页:Each class of MHC genes has a characteristic

Figure 24.32 Each class of MHC genes has a characteristic organization, in which exons represent individual protein domains.

第53页:Key terms: Immunoglobulins and T-cell receptors

Immunoglobulins and T-cell receptors
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 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
Allelic exclusion ensures that a given lymphocyte synthesizes only a single Ig or TCR.

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