Immunoglobulins

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Immunoglobulin
Antibody Structure and Function
Serology

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Immunoglobulins

  1. 1. Immunoglobulins: Structure and Function
  2. 2. 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 α1 α2 β γ + - albumin globulins Mobility Amountofprotein
  3. 3. General Functions of Immunoglobulins • Effector functions – Fixation of complement – Binding to various cells (Usually require Ag binding) • Ag binding – Can result in protection – Valence
  4. 4. Basic Immunoglobulin Structure • Immunoglobulins - heterogeneous • Myeloma proteins - homogeneous immunoglobulins
  5. 5. Immunoglobulin Structure • Heavy & Light Chains • Disulfide bonds – Inter-chain – Intra-chain CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
  6. 6. Immunoglobulin Structure • Variable & Constant Regions – VL & CL – VH & CH • Hinge Region CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
  7. 7. Immunoglobulin Structure • Domains – VL & CL – VH & CH1 - CH3 (or CH4) • Oligosaccharides CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
  8. 8. IgG molecule Used with permission from: Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University, Cambridge, England
  9. 9. Structure of the Variable Region • Hypervariable (HVR) or complimentarity determining regions (CDR) HVR3 FR1 FR2 FR3 FR4 HVR1 HVR2 VariabilityIndex 25 7550 100 Amino acid residue 150 100 50 0 • Framework regions
  10. 10. Immunoglobulin Fragments: Structure/Function Relationships • Fab – Ag binding – Valence = 1 – Specificity determined by VH and VL Papain Fc Fab • Fc – Effector functions
  11. 11. Immunoglobulin Fragments: Structure/Function Relationships Ag Binding Complement Binding Site Placental Transfer Binding to Fc Receptors
  12. 12. Immunoglobulin Fragments: Structure/Function Relationships • Fab – Ag binding • Fc – Effector functions • F(ab’)2 Pepsin Fc Peptides F(ab’)2
  13. 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. 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. 15. Human Immunoglobulin Light Chain Types • Kappa (κ) • Lambda (λ)
  16. 16. Human Immunoglobulin Light Chain Subtypes • Lambda light chains – Lambda 1 (λ1) – Lambda 2 (λ2) – Lambda 3 (λ3) – Lambda 4 (λ4)
  17. 17. Immunoglobulins • Nomenclature – IgM (kappa) – IgA1(lambda 2) – IgG • Heterogeneity
  18. 18. IgG • Structure – Monomer (7S) IgG1, IgG2 and IgG4 IgG3
  19. 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. 20. IgM • Structure – Pentamer (19S) – Extra domain (CH4) – J chain Cµ4 J Chain
  21. 21. IgM • Structure • Properties – 3rd highest serum Ig – First Ig made by fetus and B cells – Fixes complement
  22. 22. Fixation of C1 by IgG and IgM Abs C1r C1s C1q C1r C1s C1q No activation Activation
  23. 23. 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
  24. 24. B Cell Antigen Receptor (BcR) Ig-αIg-β Ig-βIg-α
  25. 25. IgA • Structure – Serum - monomer – Secretions (sIgA) • Dimer (11S) • J chain • Secretory component J ChainSecretory Piece
  26. 26. Origin of Secretory Component of sIgA
  27. 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. 28. IgD • Structure – Monomer – Tail piece Tail Piece
  29. 29. IgD • Structure • Properties – 4th highest serum Ig – B cell surface Ig – Does not bind complement
  30. 30. IgE • Structure – Monomer – Extra domain (CH4) Cε4
  31. 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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