IMMUNOGLOBULIN STRUCTURE AND FUNCTION March 19, 2009 10:00-11:00

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

IMMUNOGLOBULINS HAVE 4 POLYPEPTIDE CHAINS 2 Identical H(eavy) chains 2 Identical L(ight) chains

HEAVY AND LIGHT CHAINS HAVE VARIABLE AND CONSTANT REGIONS

ANTIBODY MOLECULES HAVE GLOBULAR REGIONS The globular regions are separated by a “flexible” hinge The globular regions contain globular domains

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

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

ANTIBODY MOLECULES CAN BE CLEAVED BY PROTEOLYTIC ENZYMES

ANTIGEN BINDING SITES ARE HYPERVARIABLE

ANTIBODIES BIND TO ANTIGENS IMMUNOGEN A molecule that elicits an immune response EPITOPE The part of an antigen to which an antibody binds

CARRIER HAPTEN HAPTEN-CARRIER NOT ALL ANTIGENS ARE IMMUNOGENIC Epitope

AN ANTIBODY BINDS EPITOPES ON A VIRAL PARTICLE

TWO TYPES OF EPITOPE

ANTIGEN BINDING SITES HAVE DIFFERENT SHAPES

MOST NATURAL ANTIGENS ARE MULTIVALENT

THE INTERACTION BETWEEN ANTIBODIES AND MULTIVALENT ANTIGENS LEADS TO COMPLEX FORMATION Trapped complexes cause inflammation

ANTIBODIES ARE CLINICAL TOOLS

PRODUCTION OF MONOCLONAL ANTIBODIES

RIA AND ELISA ARE USED TO MEASURE LEVELS OF SUBSTANCES IN SERUM Hormone levels Drug levels Viral levels

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

THERAPEUTIC MONOCLONAL ANTIBODIES Schwartz, NEJM 348;11 2003