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Immunoglobulins Structure and Function

Immunoglobulins Structure and Function. By Eisa Salehi PhD Department of Immunology. -. +. albumin. Amount of protein. globulins. γ. β. α 1. α 2. Immune serum. Ag adsorbed serum. Mobility. Immunoglobulins:Structure and Function.

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Immunoglobulins Structure and Function

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  1. ImmunoglobulinsStructure and Function By Eisa Salehi PhD Department of Immunology

  2. - + albumin Amount of protein globulins γ β α1 α2 Immune serum Ag adsorbed serum Mobility Immunoglobulins:Structure and Function • Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

  3. Basic Immunoglobulin Structure • Immunoglobulins - heterogeneous • Myeloma proteins - homogeneous immunoglobulins • Immunoglobulin vs. Antibody

  4. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Heavy & Light Chains • Disulfide bonds • Inter-chain • Intra-chain

  5. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Variable & Constant Regions • VL & CL • VH & CH • Hinge Region

  6. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Domains • VL & CL • VH & CH1 - CH3 (or CH4) • Oligosaccharides

  7. Papain Fc Fab Immunoglobulin Fragments: Structure/Function Relationships • Fab • Ag binding • Valence = 1 • Specificty determined by VH and VL • Fc • Effector functions

  8. Pepsin Fc Peptides F(ab’)2 Immunoglobulin Fragments: Structure/Function Relationships • Fab • Ag binding • Fc • Effector functions • F(ab’)2

  9. Ag Binding Complement Binding Site Binding to Fc Receptors Placental Transfer Immunoglobulin Fragments: Structure/Function Relationships

  10. Structure of the Variable Region • Hypervariable (HVR) or complimentarity determining regions (CDR) • Framework regions

  11. 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

  12. 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

  13. Human ImmunoglobulinLight Chain Types • Kappa (κ) • Lambda (λ)

  14. Human Immunoglobulin Light Chain Subtypes • Lambda light chains • Lambda 1 (λ1) • Lambda 2 (λ 2) • Lambda 3 (λ 3) • Lambda 4 (λ 4)

  15. IgG moleculeچكش صخره ها را تراش نمي دهد بلكه آب با طراوات و رقص و آوازش بدان شكل مي دهد

  16. IgG1, IgG2 and IgG4 IgG3 IgG • Structure • Monomer (7S)

  17. 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

  18. J Chain Cμ4 IgM • Structure • Pentamer (19S) • Extra domain (CH4) • J chain

  19. IgM • Structure • Properties • 3rd highest serum Ig • First Ig made by fetus and B cells • Fixes complement

  20. C1r C1r C1s C1s C1q C1q Fixation of C1 by IgG and IgM Abs No activation Activation

  21. Tail Piece 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

  22. Ig-β Ig- α Ig- β Ig- α B Cell Antigen Receptor (BcR)

  23. Secretory Piece J Chain IgA • Structure • Serum - monomer • Secretions (sIgA) • Dimer (11S) • J chain • Secretory component

  24. Y Y Y Y Y Y Origin of Secretory Component of sIgA

  25. 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

  26. Tail Piece IgD • Structure • Monomer • Tail piece

  27. IgD • Structure • Properties • 4th highest serum Ig • B cell surface Ig • Does not bind complement

  28. Cε4 IgE • Structure • Monomer • Extra domain (CH4)

  29. 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

  30. Immunoglobulin:Isotypes, Allotypes and Idiotypes

  31. Immunoglobulin Isotypes Human IgM Reacts with IgM, IgG, IgA, IgD, IgE ?? antiserum React with IgG, IgA, IgD and IgE ?? Absorbed antiserum Reacts only with IgM Recognizes determinants specific for μ heavy chains (isotypes) ??

  32. Immunoglobulin Isotypes • Definition - Antigenic determinants that characterize the classes and subclasses of heavy chains and types and subtypes of light chains

  33. IgG1 (kappa) حسن IgM (kappa) حسن Immunoglobulin Isotypes • Occurrence • Importance • Ig levels • B cell tumors • Immunodeficiencies • Definition • Location

  34. IgG1 (kappa) حسن IgG1 (kappa) نقی Immunoglobulin Allotypes • Definition - Antigenic determinants specified • by allelic forms of the Ig genes • Source of anti-allotypic Abs • Location • Occurrence

  35. Human Immunoglobulin Allotypes • Nomenclature • G1m(3) • Km(1)

  36. 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

  37. Human Immunoglobulin Allotypes • Genetics (pseudoalleles) • Co-dominant G1m(17) G1m(1) 214 355-358

  38. Immunoglobulin Allotypes • Definition • Location • Occurrence • Importance • Monitoring bone marrow grafts • Forensic medicine • Paternity testing

  39. Immunoglobulin Idiotypes • Definition - Unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity

  40. Immunoglobulin Idiotypes Strain A Mouse Anti-DNP Ab DNP-BSA Ab against combining site of anti-DNP Ab Strain A Mouse Purified anti-DNP Ab Antigenic determinants created by the HVR = Idiotypes

  41. Immunoglobulin Idiotypes • Definition • Location IgG1 (kappa) نقی anti-A IgG1 (kappa) نقی anti-B

  42. Immunoglobulin Idiotypes • Definition • Location • Importance • V region marker • Regulation of immune responses

  43. Regulation by Id/anti-Id + + Ag Id anti-Id anti-anti-Id - -

  44. Immunoglobulin Idiotypes • Definition • Location • Importance • V region marker • Regulation of immune responses • Vaccines

  45. + + Ag Id anti-Id Ag Id anti-Id - Anti-Idiotype Vaccines

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