页数:53页文件大小:1.00 MB来源: 分子生物学基因Geneppt课件
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 Immune diversity
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.
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.
Hapten is a small molecule that acts as an antigen when conjugated to a protein.
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.
Figure 24.4 Heavy and light chains combine to generate an immunoglobulin with several discrete domains.
Figure 24.4 Heavy and light chains combine to generate an immunoglobulin with several discrete domains.
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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.
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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.
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.
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.
Figure 24.8 The lambda family consists of V gene segments linked to a small number of J-C gene segments.
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.
Figure 24.10 A single gene cluster in man contains all the information for heavy-chain gene assembly.
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.
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.
Figure 24.13 Breakage and reunion at consensus sequences generates immunoglobulin genes.
Figure 24.14 Processing of coding ends introduces variability at the junction.
Figure 15.8 Reciprocal recombination between direct repeats excises the material between them; each product of recombination has one copy of the direct repeat.
Figure 15.9 Reciprocal recombination between inverted repeats inverts the region between them.
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.
Allelic exclusion describes the expression in any particular lymphocyte of only one allele coding for the expressed immunoglobulin.
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.
Class switching is a change in the expression of the C region of an immunoglobulin heavy chain during lymphocyte differenti at ion.
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.
Figure 24.10 A single gene cluster in man contains all the information for heavy-chain gene assembly.
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.
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.
Figure 24.19 The 3end controls the use of splicing junctions so that alternative forms of the heavy gene are expressed.
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.
Figure 24.21 B cell development proceeds through sequential stages.
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.
Figure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer (H2L2) linked to two copies of the signal-transducing heterodimer (Igab).
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.
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.
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.
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.
Figure 24.14 Processing of coding ends introduces variability at the junction.
Figure 24.13 Breakage and reunion at consensus sequences generates immunoglobulin genes.
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.
Figure 24.27 T cell development proceeds through sequential stages.
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.
Figure 24.22 The B cell antigen receptor consists of an immunoglobulin tetramer (H2L2) linked to two copies of the signal-transducing heterodimer (Igab).
Trans plant at ion antigen is protein coded by a major histocompatibility locus, present on all mammalian cells, involved in interactions between lymphocytes.
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.
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.
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.
Figure 24.32 Each class of MHC genes has a characteristic organization, in which exons represent individual protein domains.
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