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UMass Amherst MICROBIO 310 - Antibodies and Immunity

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Microbio 310 1st Edition Lecture 27 Outline of Last Lecture I. 29.1 Innate Response Mechanisms II. 29.2 Adaptive Response Mechanisms III. 29.3 Immunogens and Antigens IV. 29.4 Antigen Presentation to T Cells V. 29.5 T-Cytotoxic Cells and Natural Killer Cells VI. 29.6 T-Helper Cells Outline of Current Lecture I. 29.7 AntibodiesII. 29.8 Antibody ProductionIII. 29.9 Antibodies, Complement, and Pathogen DestructionIV. 30.1 Innate Immunity and Pattern RecognitionV. 30.2 Adaptive Immunity and the Immunoglobulin SuperfamilyVI. 30.3 MHC Protein StructureVII. 30.4 MHC Polymorphism and Antigen BindingVIII. 30.5 Antibody Proteins and Antigen BindingCurrent Lecture29.7 AntibodiesThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Antibodies or immunoglobulins (Ig) are protein molecules that interact specifically with antigenic determinants- Found in serum, milk, and gastric secretions - 5 major classes (IgG, IgA, IgM, IgD, and IgE)• IgG is the most common antibody circulating in the body– 4 polypeptide chains (2 heavy and 2 light chains)– Antigen-binding site results from interaction between heavy and light chains – Billions of different antigen-binding sites• IgM is usually an aggregate of five immunoglobulin molecules attached by at least one J (joining) chain; can bind multiple antigens– First antibody to appear after immunization; strong complement factor• Dimers of IgA are present in body fluids such as saliva, tears, breast milk colostrum, and mucosal secretions • IgE is found in serum and functions as an antibody that binds to eosinophils; involved in allergic reactions and parasite immunity• IgD is present in serum and has no known function29.8 Antibody Production• Each person can produce billions of different antibodies and TCRs– Each receptor can interact with an antigen in our environment– This diversity is created by a mechanism exclusive to T and B cells• Somatic recombination is this mechanism: during development of B cells in the bone marrow, both heavy-chain and light-chain genes rearrange. The genes are recombined—individual gene pieces are mixed and matched in various combinations—by gene splicing and rearrangements in the differentiating B cells.• Antibody production begins with antigen exposure and culminates in the production and secretion of an antigen-specific antibody– Antigen-stimulated B cells multiply and differentiate to form antibody-secreting plasmacells and memory cells (primary antibody response)– Memory B cells generated may live for years and quickly transform into antibody-secreting cells (secondary antibody response)—higher antibody production than primaryantibody response29.9 Antibodies, Complement, and Pathogen Destruction• Complement is composed of a group of sequentially interacting proteins– Create membrane attack complex (MAC) that puts holes in bacterial membranes– Important roles in innate and adaptive immunity– Cause lysis of pathogens or mark them for recognition by phagocytes (will kill ANY bacteria)– Individual proteins of complement are called C1, C2, C3, etc.– These proteins react in a defined sequence– Complement lyses many gram-negative bacteria– Classical complement activation: involves antigen-antibody interaction– Mannose-binding lectin (MBL) pathway activation: MBL binds to mannose on the bacterial membrane– Alternative pathway activation: C3 binding leads to C3b production30.1 Innate Immunity and Pattern Recognition• Pathogen-associated molecular patterns (PAMPs)– Structural components common to a particular group of infectious agents– Include polysaccharides, lipids, proteins, and nucleic acids• Pattern recognition receptors (PRRs)– Soluble and membrane-bound host proteins that interact with PAMPs– Found on surfaces of macrophages, monocytes, neutrophils, and dendritic cells– PRRs were first recognized in the fruit fly and were called Toll receptors– Toll-like receptors (TLRs)• Structural, functional, and evolutionary homologs of the Toll receptors• Cytoplasmic membranes are a barrier to PAMPs– Cells must respond to the danger without allowing the PAMPs into the cell– Use signal transduction to initiate transcription and translation of host-response proteins• For example, binding of LPS (lipopolysaccharide, outer membrane of gram negative bacteria) to TLR-430.2 Adaptive Immunity & Immunoglobulin Superfamily• Immunoglobulin gene superfamily– Consists of a large number of genes and their products that share structural, evolutionary, and functional features with immunoglobulin genes and proteins– Includes antigen-binding proteins in the adaptive immune response• Immunoglobulins (Igs or antibodies)• T cell receptors (TCRs)• Major histocompatibility complex (MHC)• Structure and Evolution of Antigen-Binding Proteins– Ig, TCR, and MHC proteins• Share structural features• Consist of a number of domains – Constant and variable domains• Signal transduction is also the activation mechanism for phagocytes and lymphocytes in adaptive immunity– Antigen receptors associate with adaptor molecules that have immune-based tyrosine-activation motifs (ITAMs)30.3 MHC Protein Structure• MHC proteins– Major antigen barriers for tissue transplantation– Referred to as the human leukocyte antigen (HLA) complex– In normal cells the MHC proteins contain “self peptides”– In a cell infected with virus, the host cell’s MHC expresses some viral peptides• The cell is then targeted for destruction by T cells• Two structural classes:– Class I MHC proteins• Consist of two polypeptides• Membrane-integrated alpha chain• Noncovalently associated beta-2 microglobulin– Class II MHC proteins• Consist of two noncovalently linked, membrane-integrated polypeptides30.4 MHC Polymorphism and Antigen Binding• There are at least three human MHC class I genes:– HLA-A– HLA-B– HLA-C• All are highly polymorphic (multiple alleles at a specific gene locus)– As antigen binding pocket changes in shape and charge they can bind different antigens; important because they must bind all potential antigens• MHC class II proteins are also highly polymorphic• MHC genes are expressed codominantly (equally) in an individual30.5 Antibody Proteins and Antigen Binding• Antibodies, or immunoglobulins (Igs)– Are either soluble proteins


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