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Immunoglobulins Structure and Function By Eisa Salehi PhD Department of Immunology
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Immunoglobulins:Structure and Function Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies Immune serum Ag adsorbed serum α1α1 α2α2 β γ + - albumin globulins Mobility Amount of protein
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Basic Immunoglobulin Structure Immunoglobulins - heterogeneous Myeloma proteins - homogeneous immunoglobulins Immunoglobulin vs. Antibody
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Immunoglobulin Structure Heavy & Light Chains Disulfide bonds Inter-chain Intra-chain C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond
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Immunoglobulin Structure Variable & Constant Regions V L & C L V H & C H Hinge Region C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond
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Immunoglobulin Structure Domains V L & C L V H & C H1 - C H3 (or C H4 ) Oligosaccharides C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond
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Immunoglobulin Fragments: Structure/Function Relationships Fab Ag binding Valence = 1 Specificty determined by V H and V L Papain Fc Fab Fc Effector functions
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Immunoglobulin Fragments: Structure/Function Relationships Fab Ag binding Fc Effector functions F(ab’) 2 Pepsin Fc Peptides F(ab’) 2
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Immunoglobulin Fragments: Structure/Function Relationships Ag Binding Complement Binding Site Placental Transfer Binding to Fc Receptors
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Structure of the Variable Region Hypervariable (HVR) or complimentarity determining regions (CDR) Framework regions
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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
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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 (α 2) heavy chains
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Human Immunoglobulin Light Chain Types Kappa ( κ ) Lambda (λ)
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Human Immunoglobulin Light Chain Subtypes Lambda light chains Lambda 1 (λ1) Lambda 2 (λ 2) Lambda 3 (λ 3) Lambda 4 (λ 4)
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IgG molecule چكش صخره ها را تراش نمي دهد بلكه آب با طراوات و رقص و آوازش بدان شكل مي دهد
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IgG Structure Monomer (7S) IgG1, IgG2 and IgG4IgG3
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IgG Structure Properties Major serum Ig 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
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IgM Structure Pentamer (19S) Extra domain (C H4 ) J chain Cμ4Cμ4 J Chain
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IgM Structure Properties 3rd highest serum Ig First Ig made by fetus and B cells Fixes complement
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Fixation of C1 by IgG and IgM Abs C1r C1s C1q C1r C1s C1q No activationActivation
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IgM Structure Properties 3rd highest serum Ig First Ig made by fetus and B cells Fixes complement Tail Piece Agglutinating Ig Binds to Fc receptors B cell surface Ig
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B Cell Antigen Receptor (BcR) Ig- α Ig- β
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IgA Structure Serum - monomer Secretions (sIgA) Dimer (11S) J chain Secretory component J ChainSecretory Piece
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Origin of Secretory Component of sIgA
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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
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IgD Structure Monomer Tail piece Tail Piece
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IgD Structure Properties 4th highest serum Ig B cell surface Ig Does not bind complement
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IgE Structure Monomer Extra domain (C H4 ) Cε4Cε4
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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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Immunoglobulin: Isotypes, Allotypes and Idiotypes
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Human IgM antiserum Reacts with IgM, IgG, IgA, IgD, IgE React with IgG, IgA, IgD and IgE Absorbed antiserum Reacts only with IgM Recognizes determinants specific for μ heavy chains (isotypes) Immunoglobulin Isotypes ??
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Immunoglobulin Isotypes Definition - Antigenic determinants that characterize the classes and subclasses of heavy chains and types and subtypes of light chains
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Immunoglobulin Isotypes Occurrence Importance Ig levels B cell tumors Immunodeficiencies Definition Location IgM (kappa) حسن IgG1 (kappa) حسن
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Immunoglobulin Allotypes Definition - Antigenic determinants specified by allelic forms of the Ig genes Location Occurrence – Source of anti-allotypic Abs IgG1 (kappa) نقی IgG1 (kappa) حسن
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Human Immunoglobulin Allotypes Nomenclature – G1m(3) – Km(1)
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Human Immunoglobulin Allotypes Genetics (alleles) – Co-dominant autosomal genes Km(1)/Km(3) X Km(1)/Km(1) Km(1)/Km(1) and Km(1)/Km(3) – Allelic exclusion
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Genetics (pseudoalleles) Co-dominant G1m(17)G1m(1) 214355-358 Human Immunoglobulin Allotypes
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Immunoglobulin Allotypes Definition Location Occurrence Importance Monitoring bone marrow grafts Forensic medicine Paternity testing
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Immunoglobulin Idiotypes Definition - Unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity
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DNP-BSA Strain A Mouse Anti-DNP Ab Purified anti-DNP Ab Strain A Mouse Ab against combining site of anti-DNP Ab Immunoglobulin Idiotypes Antigenic determinants created by the HVR = Idiotypes
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Immunoglobulin Idiotypes Definition Location IgG1 (kappa) نقی anti-B IgG1 (kappa) نقی anti-A
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Immunoglobulin Idiotypes Definition Location Importance V region marker Regulation of immune responses
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AgIdanti-Id + - anti-anti-Id + - Regulation by Id/anti-Id
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Immunoglobulin Idiotypes Definition Location Importance V region marker Regulation of immune responses Vaccines
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AgIdanti-Id + - Anti-Idiotype Vaccines AgIdanti-Id +
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Immunoglobulin Idiotypes Definition Location Importance V region marker Regulation of immune responses Vaccines Treatment of B cell tumors (T cell)
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Immunoglobulin Superfamily
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General Functions of Immunoglobulins Effector functions Fixation of complement Binding to various cells (Usually require Ag binding) Ag binding –Can result in protection –Valency
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General Functions of Immunoglobulins
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آنچه سبب غرق شدن مي گردد فرو رفتن در آب نيست بلكه ماندن زير آب است
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