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IMMUNOGLOBULIN STRUCTURE AND FUNCTION
March 19, 2009 10:00-11:00
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IMMUNOGLOBULIN AND HUMORAL IMMUNITY
Two functions: 1)mIg Is the B cell antigen recognition receptor 2) secreted Ig is the effector protein for adaptive humoral immune responses
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IMMUNOGLOBULINS HAVE 4 POLYPEPTIDE CHAINS
2 Identical H(eavy) chains 2 Identical L(ight) chains
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HEAVY AND LIGHT CHAINS HAVE VARIABLE AND CONSTANT REGIONS
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ANTIBODY MOLECULES HAVE GLOBULAR REGIONS
The globular regions are separated by a “flexible” hinge The globular regions contain globular domains
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THE STRUCTURE OF THE DOMAINS PROVIDES STABILITY
Domains are approximately 110 amino acids Amino acids are aligned in b sheets V and C are slightly different
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THE DIFFERENT CLASSES OF ANTIBODY
There are two types of L chain: k and l There are 5 types of H chain: g, m, d, a, e A complete antibody molecule has 2 identical light chains and 2 identical heavy chains
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ANTIBODY MOLECULES CAN BE CLEAVED BY PROTEOLYTIC ENZYMES
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ANTIGEN BINDING SITES ARE HYPERVARIABLE
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ANTIBODIES BIND TO ANTIGENS
IMMUNOGEN A molecule that elicits an immune response EPITOPE The part of an antigen to which an antibody binds
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CARRIER HAPTEN HAPTEN-CARRIER NOT ALL ANTIGENS ARE IMMUNOGENIC Epitope
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AN ANTIBODY BINDS EPITOPES ON A VIRAL PARTICLE
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TWO TYPES OF EPITOPE
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ANTIGEN BINDING SITES HAVE DIFFERENT SHAPES
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MOST NATURAL ANTIGENS ARE MULTIVALENT
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THE INTERACTION BETWEEN ANTIBODIES AND MULTIVALENT
ANTIGENS LEADS TO COMPLEX FORMATION Trapped complexes cause inflammation
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ANTIBODIES ARE CLINICAL TOOLS
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PRODUCTION OF MONOCLONAL ANTIBODIES
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RIA AND ELISA ARE USED TO MEASURE LEVELS OF SUBSTANCES
IN SERUM Hormone levels Drug levels Viral levels
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APPLICATIONS DIAGNOSTIC Measuring protein levels: ELISA Identification and Characterization of Antigens: Immunoprecipitation and Western Blots Characterization of Cells and Cell Separation: Fluorescent labeling and Flow Cytometry Localization of antigen in tissue: Immunohistochemistry THERAPEUTIC Treatment of inflammatory disease with anti-cytokine Treatment of cancer with toxin conjugated antibodies Passive immunization
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THERAPEUTIC MONOCLONAL ANTIBODIES
Schwartz, NEJM 348;
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