Transcript Document
Immunoglobulins: Structure and Function Immunoglobulins:Structure and Function Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies + Amount of protein albumin globulins 1 2 Immune serum Ag adsorbed serum Mobility General Functions of Immunoglobulins Ag binding Can result in protection Valency Effector functions Fixation of complement Binding to various cells Usually requires Ag binding Basic Immunoglobulin Structure Immunoglobulins - heterogeneous Myeloma proteins - homogeneous immunoglobulins Immunoglobulin Structure Disulfide bond Heavy & Light Chains Disulfide bonds Carbohydrate CL VL Inter-chain Intra-chain CH2 CH1 VH Hinge Region CH3 Immunoglobulins (Ig) are glycoproteins made up of light (L) and heavy(H) polypeptide chains. The simplest antibody molecule has a Y shape and consists of four polypeptide chains:two H chains and two L chains. The four chains are linked by disulfide bonds. Immunoglobulin Structure Disulfide bond Variable & Constant Regions VL & CL VH & CH Hinge Region Carbohydrate CL VL CH2 CH1 VH Hinge Region CH3 H chains are distinct for each Of the five Ig classes or isotypes and are designated γ α μδ ε for the respective classes of Ig, namely IgG IgD IgE. IgA IgM Human Immunoglobulin Classes IgG - Gamma () heavy chains IgM - Mu () heavy chains IgA - Alpha () heavy chains IgD - Delta () heavy chains IgE - Epsilon () heavy chains L chains are one of two types Designated κ and λ and only one type is found in Ig. Human Immunoglobulin Light Chain Types Kappa () Lambda () L and H chains are subdivided into variable and constant regions.The regions are composed of three-dimensionally folded, repeating segments called domains. An L chain consists of one variable (VL) and one constant (CL) domain.Most H chains consist of one variable (VH) and three constant(CH) domains.(IgG and IgA have three CH domains,whereas IgM and IgE have four.) Immunoglobulin Structure Disulfide bond Domains VL & CL VH & CH1 - CH3 (or CH4) Oligosaccharides Carbohydrate CL VL CH2 CH1 VH Hinge Region CH3 The various regions are responsible for antigenbinding ,whereas the constant regions are responsible biologic functions eg, for various complement activation and binding to cell surface receptors. The variable regions of both L and H chains have three extremely variable (“hypervariable”) amino acid sequence at the amino- terminal end that form the antigenbinding site. Structure of the Variable Region Hypervariable (HVR) or complimentarity determining regions (CDR) Framework regions Variability Index HVR3 150 100 HVR2 HVR1 50 FR2 FR1 0 25 FR3 75 50 Amino acid residue FR4 100 Immunoglobulin Fragments: Structure/Function Relationships Fab Fc Papain Ag binding Valence = 1 Specificty determined by VH and VL Fc Effector functions Fab Immunoglobulin Fragments: Structure/Function Relationships Ag Binding Complement Binding Site Binding to Fc Receptors Placental Transfer Immunoglobulin Fragments: Structure/Function Relationships Pepsin Fab Fc Ag binding Effector functions F(ab’)2 Fc Peptides F(ab’)2 IgG Structure Monomer (7S) IgG1, IgG2 and IgG4 IgG3 IgG Structure Properties Major serum Ig Major Ig in extravascular spaces The only antibody to cross the placental Fixes complement Binds to Fc receptors Phagocytes - opsonization NK cells – ADCC Binds to SPA IgM Structure Pentamer (19S) composed 5 H2L2 units plus one molecule of J chain Extra domain (CH4) J chain J Chain C4 Fixation of C1 by IgG and IgM Abs No activation Activation IgM Structure Properties 3rd highest serum Ig First Ig made by fetus and B cells Produced early in the primary response The most efficient Ig Fixes complement Agglutinating Ig Binds to Fc receptors B cell surface Ig Tail Piece B Cell Antigen Receptor (BcR) Ig- Ig- Ig- Ig- IgA Structure Serum - monomer Secretions (sIgA) Dimer (11S), sIgA molecule consists of two H2L2 units plus one molecule each of J chain and secretory component(SC or SP) Secretory Piece J Chain •Origin of sIgA: The SP is a polypeptide synthesized by epithelial cells that provides for IgA passage to the mucosal surface. It also protests IgA from being degraded in the intestinal tract. IgA Properties 2nd highest serum Ig Major secretory Ig ( saliva, tears, respiratory, intestinal, and genital tract secretions.) Does not fix complement unless aggregated Binds to Fc receptors on some cells IgD Structure Monomer Tail piece Tail Piece IgD Structure Properties 4th highest serum Ig B cell surface Ig Does not bind complement IgE Structure Monomer Extra domain (CH4) C4 IgE Structure Properties Least common serum Ig Allergic reactions Parasitic infections Does not fix complement