Antibody Molecules: Structure and Function by Benjamin/Cumming - University - Medical Sciences

Antibody Molecules: Structure and Function Lecture Objectives „ What Antibodies are „ The structure and function of Abs „ Mechanism of Function of Abs in immunity What are Antibodies? ‹ Proteins that recognize and bind to a particular antigen with very high specificity. ‹ Made in response to exposure to the antigen. ‹ One virus or microbe may have several antigenic determinant sites, to which different antibodies may bind. ‹ Each antibody has at least two identical sites that bind antigen: Antigen binding sites. ‹ Valence of an antibody: Number of antigen binding sites. Most are bivalent. ‹ Belong to a group of serum proteins called immunoglobulins (Igs). Antibodies and their Characteristics Antibodies are Produced by B Lymphocytes STRUCTURE AND FUNCTION OF Abs Antibodies „ = Immunoglobulins or γ globulins „ Structure „ 12 domains (~110 aa) „ Heavy chains & light chains „ Fab region „ Variable region „ Fc region „ Constant region Y shaped glycoproteins γ Globulin „ Name based on electrophoretic activity „ Abs constitute 20% of plasma proteins Antibody Structure „ Product of B cell activation (plasma cell) „ Made up of four polypeptides „ Connected by disulfide bonds „ Antigen binding fragment (Fabs) „ Crystallizable fragment (Fc) „ Fc and Fab joined by a hinge region „ Various Classes based on Fc Fab „ Variable (N-terminal of the heavy and light chains) „ Binds to the antigenic determinant „ Swiveling enables more efficiency „ Held together by disulfide bonds Fc „ Constant (C-terminal of heavy chain) „ Binds to macrophages „ Anchors Ig to lymphocyte „ Also held together by disulfide bonds „ Responsible for class identification Immunoglobulin Classes „ Isotypes – based on the Fc fragment or heavy chain „ 5 Immunoglobulin (Ig) classes „ IgG (γ chain, primary, memory, most abundant) „ IgM (μ chain, pentavalent, complement fix) „ IgA (α chain, local immunity, secretory IgA) „ IgD (δ chain, receptor for Ag on B-cells) „ IgE (ε chain, allergic reactions, react with basophils) IgG ‹ Structure: Monomer ‹ Percentage serum antibodies: 80% ‹ Location: Blood, lymph, intestine ‹ Half-life in serum: 23 days ‹ Complement Fixation: Yes ‹ Placental Transfer: Yes ‹ Known Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn. Immunoglobulin Classes IgM ‹ Structure: Pentamer-equivalent to 10 binding sites ‹ Percentage serum antibodies: 5-10% ‹ Location: Blood, lymph, B cell surface (monomer) ‹ Half-life in serum: 5 days ‹ Complement Fixation: Yes ‹ Placental Transfer: No ‹ Known Functions: First antibodies produced during an infection. Avid binding-٨binding sites. Effective against microbes and agglutinating antigens. Immunoglobulin Classes IgA ‹ Structure: Dimer ‹ Percentage serum antibodies: 10-15% ‹ Location: Secretions (tears, saliva, intestine, milk), lung, genitourinary tract, blood and lymph. ‹ Half-life in serum: 6 days ‹ Complement Fixation: No ‹ Placental Transfer: No ‹ Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract. Immunoglobulin Classes IgD ‹ Structure: Monomer ‹ Percentage serum antibodies: 0.2% ‹ Location: B-cell surface, blood, and lymph ‹ Half-life in serum: 3 days ‹ Complement Fixation: No ‹ Placental Transfer: No ‹ Known Functions: In serum function is unknown. On B cell surface, initiate immune response. Immunoglobulin Classes IgE ‹ Structure: Monomer ‹ Percentage serum antibodies: 0.002% ‹ Location: Bound to mast cells and basophils throughout body. Blood. ‹ Half-life in serum: 2 days ‹ Complement Fixation: No ‹ Placental Transfer: No ‹ Known Functions: Allergic reactions. Possibly lysis of worms. Immunoglobulin Classes Immunoglobulin Sub-classes „ IgG „ a) IgG1 - Gamma 1 (γ1) heavy chains „ b) IgG2 - Gamma 2 (γ2) heavy chains „ c) IgG3 - Gamma 3 (γ3) heavy chains „ d) IgG4 - Gamma 4 (γ4) heavy chains „ IgA „ a) IgA1 - Alpha 1 (α1) heavy chains „ b) IgA2 - Alpha 2 (α2) heavy chains Class switching „ Class switching the process by which B cell undergoes V-C gene rearrangement to express a new heavy chain isotype without altering the specificity (V-region ) of the antibody produced. „ B cells develop from stem cells in the bone marrow of adults (liver of fetuses). „ After maturation B cells migrate to lymphoid organs (lymph node or spleen). „ Clonal Selection: When a …