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Immunogenetics Genetic Changes that Provide for Homology and Diversity Among Immune System Proteins
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Immune System Cells and Receptors
T cell receptor Stimulate an immune response Antibody Immune System Cells and Receptors
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Communication Among Immune System Cells
1. Macrophage engulfs invader 2. Macrophage displays “processed” antigen on MHC molecule 7. Division gives rise to memory B cells and plasma cells 6. Activated Helper T cell stimulates division of selected B lymphocyte 4. Helper T Cell binds to Macrophage 3. Invader binds to B lymphocyte that carries antibody matching the antigen 5. Macrophage releases cytokines to activate Helper T cell
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Clonal Selection of B cells
Each B lymphocyte has a unique antibody on its surface B lymphocyte with antibody matching the antigen is stimulated to divide
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B cell-bound antibodies recognize antigens on a bacterial or viral invader.
Circulating antibodies mark the invader for destruction.
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Antibody Structure Antibody has 2 heavy chains and 2 light chains.
Each chain has variable (V) and constant (C) region joined by a J region. Variable regions bind to antigen. Constant regions bind to cells or other antibodies.
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Structure and Expression of Light Chain Genes
Somatic recombination brings one V and one J segment together RNA Processing leads to one VJC combination
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Structure and Expression of Heavy Chain Genes
6J Somatic recombination brings one V, D and J segment together near a C segment RNA Processing leads to one VDJC combination
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Somatic Recombination
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Generating Antibody Diversity
Germ Line Diversity Multiple V, D, J Segments Combinatorial Joining Large number of V, D, J combinations by somatic recombination Junctional Diversity Mutations produced at the junctions between gene segments by exonuclease and terminal transferase activities Somatic Hypermutation V genes undergo an increased mutation rate as immune cells divide throughout the response period Joining Light & Heavy Chains Combining different light and heavy chains increases the number of unique antibodies formed
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How did the arrangement of antibody genes arise?
Changes in gene number and organization are due to Duplication Diversification Selection
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Levels of Duplication Individual Genes Multigene Families
Gene Superfamily
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Action of Natural Selection
Natural selection acts on the genetic variability caused by mutation If the Mutation is The gene will be Neutral Unselected (Remain or Disappear as a result of genetic drift) Deleterious Eliminated Advantageous Fixed
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Three Multigene Families Encode Antibodies
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Immune System Receptors Belong to the Immunoglobulin Gene Superfamily
A Gene Superfamily is a large set of related genes that is divisible into smaller sets or families Genes in each family are more closely related to each other than to genes in other families Multigene families within this Superfamily Antibody Genes T cell receptor genes MHC protein genes
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Immunoglobulin Superfamily Genes Share a Common Homology Unit
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