Immunoglobulins: Structure and Function
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1 Immunoglobulins: Structure and Function
2 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 α 1 α 2 β γ Mobility Immune serum Ag adsorbed serum
3 Ag binding General Functions of Immunoglobulins Can result in protection Valence Effector functions Fixation of complement Binding to various cells (Usually require Ag binding)
4 Basic Immunoglobulin Structure Immunoglobulins - heterogeneous Myeloma proteins - homogeneous immunoglobulins
5 Immunoglobulin Structure Heavy & Light Chains Disulfide bonds Inter-chain Intra-chain V L C L Disulfide bond Carbohydrate C H1 C H2 C H3 V H Hinge Region
6 Immunoglobulin Structure Disulfide bond Variable & Constant Regions Carbohydrate V L & C L C L V H & C H Hinge Region V H C H1 Hinge Region C H2 C H3 V L
7 Immunoglobulin Structure Domains Disulfide bond V L & C L Carbohydrate V H & C H1 -C H3 (or C H4 ) Oligosaccharides V L C L C H1 C H2 C H3 V H Hinge Region
8 IgG molecule Used with permission from: Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University, Cambridge, England
9 Structure of the Variable Region Hypervariable (HVR) or complimentarity determining regions (CDR) HVR3 Variability Index HVR1 HVR2 FR1 FR2 FR3 FR4 0 Framework regions Amino acid residue
10 Immunoglobulin Fragments: Structure/Function Relationships Fab Fc Ag binding Valence = 1 Specificity determined by V H and V L Effector functions Fab Papain Fc
11 Immunoglobulin Fragments: Structure/Function Relationships Ag Binding Binding to Fc Receptors Complement Binding Site Placental Transfer
12 Immunoglobulin Fragments: Structure/Function Relationships Fab Fc Ag binding Effector functions Pepsin F(ab ) 2 Fc Peptides F(ab ) 2
13 Human Immunoglobulin Classes IgG-Gamma(γ) heavy chains IgM - Mu (µ) heavy chains IgA - Alpha (α) heavy chains IgD - Delta (δ) heavy chains IgE - Epsilon (ε) heavy chains
14 Human Immunoglobulin Subclasses IgG Subclasses IgG1 - Gamma 1 (γ1) heavy chains IgG2 - Gamma 2 (γ2) heavy chains IgG3 - Gamma 3 (γ3) heavy chains IgG4 - Gamma 4 (γ4) heavy chains IgA subclasses IgA1 - Alpha 1 (α1) heavy chains IgA2 - Alpha 2 (α2) heavy chains
15 Kappa(κ) Lambda (λ) Human Immunoglobulin Light Chain Types
16 Human Immunoglobulin Light Chain Subtypes Lambda light chains Lambda 1 (λ1) Lambda 2 (λ2) Lambda 3 (λ3) Lambda 4 (λ4)
17 Immunoglobulins Nomenclature IgM (kappa) IgA1(lambda 2) IgG Heterogeneity
18 IgG Structure Monomer (7S) IgG1, IgG2 and IgG4 IgG3
19 IgG Structure Properties Major serum Ig (systemic immunity) Major Ig in extravascular spaces Placental transfer Does not require Ag binding (± IgG2) Fixes complement (± IgG4) Binds to Fc receptors (± IgG2, IgG4) Phagocytes - opsonization K cells -ADCC
20 IgM Structure Pentamer (19S) Extra domain (C H4 ) J chain J Chain Cµ4
21 Structure Properties 3rd highest serum Ig IgM First Ig made by fetus and B cells Fixes complement
22 Fixation of C1 by IgG and IgM Abs C1r C1s C1q C1r C1s C1q No activation Activation
23 IgM Structure Properties 3rd highest serum Ig First Ig made by fetus and B cells Fixes complement Agglutinating Ig Binds to Fc receptors B cell surface Ig Tail Piece
24 B Cell Antigen Receptor (BcR) Ig-α Ig-β Ig-α Ig-β
25 IgA Structure Serum - monomer Secretions (siga) Dimer (11S) J chain Secretory component Secretory Piece J Chain
26 Origin of Secretory Component of siga
27 IgA Structure Properties 2nd highest serum Ig Major secretory Ig (Mucosal or Local Immunity) Tears, saliva, gastric and pulmonary secretions Does not fix complement (unless aggregated) Binds to Fc receptors on some cells
28 IgD Structure Monomer Tail piece Tail Piece
29 IgD Structure Properties 4th highest serum Ig B cell surface Ig Does not bind complement
30 IgE Structure Monomer Extra domain (C H4 ) Cε4
31 IgE Structure Properties Least common serum Ig Binds to basophils and mast cells (Does not require Ag binding) Allergic reactions Parasitic infections (Helminths) Binds to Fc receptor on eosinophils Does not fix complement
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