Immunoglobulins 2001

7,869 views

Published on

  • Be the first to comment

Immunoglobulins 2001

  1. 1. Immunoglobulins:Structure and Function
  2. 2. Immunoglobulins:Structure andFunction Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies + - Amount of protein albumin globulins 1 2   Immune serum Ag adsorbed serum Mobility
  3. 3. General Functions ofImmunoglobulins• Ag binding – Can result in protection – Valency Effector functions  Fixation of (Usually require Ag binding) complement  Binding to various cells
  4. 4. Basic Immunoglobulin Structure Immunoglobulins - heterogeneous Myeloma proteins - homogeneous immunoglobulins
  5. 5. Immunoglobulin Structure Disulfide bond Heavy & Light Chains Carbohydrate Disulfide bonds  Inter-chain CL VL  Intra-chain CH2 CH3 CH1 Hinge Region VH
  6. 6. Immunoglobulin Structure Disulfide bond Variable & Carbohydrate Constant Regions CL VL  VL & CL CH2 CH3  VH & CH CH1 Hinge Region VH Hinge Region
  7. 7. Immunoglobulin Structure Disulfide bond Domains  VL & C L Carbohydrate  VH & CH1 - CH3 (or CL CH4) VL CH2 CH3 Oligosaccharides CH1 Hinge Region VH
  8. 8. IgG moleculeUsed with permission from: Dr. Mike Clark, ImmunologyDivision, Department of Pathology Cambridge University,Cambridge, England
  9. 9. Structure of the Variable Region Hypervariable (HVR) or complimentarity determining regions (CDR) HVR3 150Variability Index 100 HVR2 HVR1 50 FR1 FR2 FR3 FR4 0 25 50 75 100 Amino acid residue Framework regions
  10. 10. Immunoglobulin Fragments:Structure/Function Relationships Fab Papain  Ag binding  Valence = 1  Specificty determined by VH and VL Fc  Effector functions Fc Fab
  11. 11. Immunoglobulin Fragments:Structure/Function RelationshipsAg Binding Complement Binding Site Binding to Fc Receptors Placental Transfer
  12. 12. Immunoglobulin Fragments:Structure/Function Relationships Fab Pepsin  Ag binding Fc  Effector functions F(ab’)2 Fc Peptides F(ab’)2
  13. 13. Human ImmunoglobulinClasses IgG - Gamma heavy chains IgM - Mu heavy chains IgA - Alpha heavy chains IgD - Delta heavy chains IgE - Epsilon heavy chains
  14. 14. Human ImmunoglobulinSubclasses IgG Subclasses  IgG1 - Gamma 1 heavy chains  IgG2 - Gamma 2 heavy chains  IgG3 - Gamma 3 heavy chains  IgG4 - Gamma 4 heavy chains IgA subclasses  IgA1 - Alpha 1 heavy chains  IgA2 - Alpha 2 heavy chains
  15. 15. Human ImmunoglobulinLight Chain Types Kappa () Lambda ()
  16. 16. Human ImmunoglobulinLight Chain Subtypes Lambda light chains  Lambda 1  Lambda 2  Lambda 3  Lambda 4
  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  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 J Chain Structure  Pentamer (19S)  Extra domain (CH4)  J chain C4
  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 C1 s C1q C1r C1 s C1q No activation Activation
  23. 23. IgM  Structure  Properties  3rd highest serum Ig  First Ig made by fetus and B cells  Fixes complement  Agglutinating Ig  Binds to Fc receptors Tail Piece  B cell surface Ig
  24. 24. B Cell Antigen Receptor (BcR) Ig- Ig- Ig- Ig-
  25. 25. IgA Structure  Serum - monomer  Secretions Secretory J (sIgA) Piece Chain  Dimer (11S)  J chain  Secretory component
  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) C4
  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

×