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Immunoglobulins: Structure and Function

Immunoglobulins: Structure and Function. -. +. 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. Immunoglobulins:Structure and Function

  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. General Functions of Immunoglobulins • Ag binding • 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. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Heavy & Light Chains • Disulfide bonds • Inter-chain • Intra-chain

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

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

  8. IgG molecule Used with permission from: Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University, Cambridge, England

  9. HVR3 150 Variability Index 100 HVR2 HVR1 50 FR2 FR1 FR4 FR3 0 25 75 100 50 Amino acid residue Structure of the Variable Region • Hypervariable (HVR) or complimentarity determining regions (CDR) • Framework regions

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

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

  12. Pepsin Fc Peptides F(ab’)2 Immunoglobulin Fragments: Structure/Function Relationships • Fab • Ag binding • Fc • Effector functions • 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. Human ImmunoglobulinLight Chain Types • Kappa (κ) • Lambda (λ)

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

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

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

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

  23. 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

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

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

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

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

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

  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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