Immunoglobulins: Structure and Function
Immunoglobulins:Structure and Function <ul><li>Definition:  Glycoprotein molecules that are produced by plasma cells in re...
General Functions of Immunoglobulins <ul><li>Effector functions  </li></ul><ul><ul><li>Fixation of complement </li></ul></...
Basic Immunoglobulin Structure <ul><li>Immunoglobulins - heterogeneous </li></ul><ul><li>Myeloma proteins - homogeneous im...
Immunoglobulin Structure <ul><li>Heavy & Light Chains </li></ul><ul><li>Disulfide bonds </li></ul><ul><ul><li>Inter-chain ...
Immunoglobulin Structure <ul><li>Variable & Constant Regions </li></ul><ul><ul><li>V L  & C L </li></ul></ul><ul><ul><li>V...
Immunoglobulin Structure <ul><li>Domains </li></ul><ul><ul><li>V L  & C L </li></ul></ul><ul><ul><li>V H  & C H1  - C H3  ...
IgG molecule Used with permission from:  Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University...
Structure of the Variable Region <ul><li>Hypervariable (HVR) or complimentarity determining regions (CDR) </li></ul><ul><l...
Immunoglobulin Fragments: Structure/Function Relationships <ul><li>Fab </li></ul><ul><ul><li>Ag binding </li></ul></ul><ul...
Immunoglobulin Fragments: Structure/Function Relationships Ag  Binding Complement Binding Site Placental Transfer Binding ...
Immunoglobulin Fragments: Structure/Function Relationships <ul><li>Fab </li></ul><ul><ul><li>Ag binding </li></ul></ul><ul...
Human Immunoglobulin Classes <ul><li>IgG - Gamma (  ) heavy chains </li></ul><ul><li>IgM - Mu (  ) heavy chains </li></u...
Human Immunoglobulin Subclasses <ul><li>IgG Subclasses </li></ul><ul><ul><li>IgG1 - Gamma 1 (  1) heavy chains </li></ul>...
Human Immunoglobulin Light Chain Types <ul><li>Kappa (  ) </li></ul><ul><li>Lambda (  ) </li></ul>
Human Immunoglobulin Light Chain Subtypes <ul><li>Lambda light chains </li></ul><ul><ul><li>Lambda 1 (  1) </li></ul></ul...
Immunoglobulins <ul><li>Nomenclature </li></ul><ul><ul><li>IgM (kappa) </li></ul></ul><ul><ul><li>IgA1(lambda 2) </li></ul...
IgG <ul><li>Structure </li></ul><ul><ul><li>Monomer (7S) </li></ul></ul>IgG1, IgG2 and IgG4 IgG3
IgG <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>Major serum Ig </li></ul></ul><ul><ul><li>Major I...
IgM <ul><li>Structure </li></ul><ul><ul><li>Pentamer (19S) </li></ul></ul><ul><ul><li>Extra domain (C H4 ) </li></ul></ul>...
IgM <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>3rd highest serum Ig </li></ul></ul><ul><ul><li>F...
Fixation of C1 by IgG and IgM Abs No activation Activation C1r C1s C1q C1r C1s C1q
IgM <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>3rd highest serum Ig </li></ul></ul><ul><ul><li>F...
B Cell Antigen Receptor (BcR) Ig-  Ig-  Ig-  Ig- 
IgA <ul><li>Structure </li></ul><ul><ul><li>Serum - monomer </li></ul></ul><ul><ul><li>Secretions (sIgA) </li></ul></ul><u...
Origin of Secretory Component of sIgA Y Y Y Y Y Y
IgA <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>2nd highest serum Ig </li></ul></ul><ul><ul><li>M...
IgD <ul><li>Structure </li></ul><ul><ul><li>Monomer </li></ul></ul><ul><ul><li>Tail piece </li></ul></ul>Tail Piece
IgD <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>4th highest serum Ig </li></ul></ul><ul><ul><li>B...
IgE <ul><li>Structure </li></ul><ul><ul><li>Monomer </li></ul></ul><ul><ul><li>Extra domain (C H4 ) </li></ul></ul>C  4
IgE <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>Least common serum Ig </li></ul></ul><ul><ul><ul>...
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Immunoglobulins 2001

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Immunoglobulins 2001

  1. 1. Immunoglobulins: Structure and Function
  2. 2. Immunoglobulins:Structure and Function <ul><li>Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies </li></ul>Immune serum Ag adsorbed serum  1  2   + - albumin globulins Mobility Amount of protein
  3. 3. General Functions of Immunoglobulins <ul><li>Effector functions </li></ul><ul><ul><li>Fixation of complement </li></ul></ul><ul><ul><li>Binding to various cells </li></ul></ul>(Usually require Ag binding) <ul><li>Ag binding </li></ul><ul><ul><li>Can result in protection </li></ul></ul><ul><ul><li>Valency </li></ul></ul>
  4. 4. Basic Immunoglobulin Structure <ul><li>Immunoglobulins - heterogeneous </li></ul><ul><li>Myeloma proteins - homogeneous immunoglobulins </li></ul>
  5. 5. Immunoglobulin Structure <ul><li>Heavy & Light Chains </li></ul><ul><li>Disulfide bonds </li></ul><ul><ul><li>Inter-chain </li></ul></ul><ul><ul><li>Intra-chain </li></ul></ul>C H1 V L C L V H C H2 C H3 Hinge Region Carbohydrate Disulfide bond
  6. 6. Immunoglobulin Structure <ul><li>Variable & Constant Regions </li></ul><ul><ul><li>V L & C L </li></ul></ul><ul><ul><li>V H & C H </li></ul></ul><ul><li>Hinge Region </li></ul>C H1 V L C L V H C H2 C H3 Hinge Region Carbohydrate Disulfide bond
  7. 7. Immunoglobulin Structure <ul><li>Domains </li></ul><ul><ul><li>V L & C L </li></ul></ul><ul><ul><li>V H & C H1 - C H3 (or C H4 ) </li></ul></ul><ul><li>Oligosaccharides </li></ul>C H1 V L C L V H C H2 C H3 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 <ul><li>Hypervariable (HVR) or complimentarity determining regions (CDR) </li></ul><ul><li>Framework regions </li></ul>HVR3 FR1 FR2 FR3 FR4 HVR1 HVR2 Variability Index 25 75 50 100 Amino acid residue 150 100 50 0
  10. 10. Immunoglobulin Fragments: Structure/Function Relationships <ul><li>Fab </li></ul><ul><ul><li>Ag binding </li></ul></ul><ul><ul><li>Valence = 1 </li></ul></ul><ul><ul><li>Specificty determined by V H and V L </li></ul></ul><ul><li>Fc </li></ul><ul><ul><li>Effector functions </li></ul></ul>Papain Fc Fab
  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 <ul><li>Fab </li></ul><ul><ul><li>Ag binding </li></ul></ul><ul><li>Fc </li></ul><ul><ul><li>Effector functions </li></ul></ul><ul><li>F(ab’) 2 </li></ul>Pepsin Fc Peptides F(ab’) 2
  13. 13. Human Immunoglobulin Classes <ul><li>IgG - Gamma (  ) heavy chains </li></ul><ul><li>IgM - Mu (  ) heavy chains </li></ul><ul><li>IgA - Alpha (  ) heavy chains </li></ul><ul><li>IgD - Delta (  ) heavy chains </li></ul><ul><li>IgE - Epsilon (  ) heavy chains </li></ul>
  14. 14. Human Immunoglobulin Subclasses <ul><li>IgG Subclasses </li></ul><ul><ul><li>IgG1 - Gamma 1 (  1) heavy chains </li></ul></ul><ul><ul><li>IgG2 - Gamma 2 (  2) heavy chains </li></ul></ul><ul><ul><li>IgG3 - Gamma 3 (  3) heavy chains </li></ul></ul><ul><ul><li>IgG4 - Gamma 4 (  4) heavy chains </li></ul></ul><ul><li>IgA subclasses </li></ul><ul><ul><li>IgA1 - Alpha 1 (  1) heavy chains </li></ul></ul><ul><ul><li>IgA2 - Alpha 2 (  2) heavy chains </li></ul></ul>
  15. 15. Human Immunoglobulin Light Chain Types <ul><li>Kappa (  ) </li></ul><ul><li>Lambda (  ) </li></ul>
  16. 16. Human Immunoglobulin Light Chain Subtypes <ul><li>Lambda light chains </li></ul><ul><ul><li>Lambda 1 (  1) </li></ul></ul><ul><ul><li>Lambda 2 (  2) </li></ul></ul><ul><ul><li>Lambda 3 (  3) </li></ul></ul><ul><ul><li>Lambda 4 (  4) </li></ul></ul>
  17. 17. Immunoglobulins <ul><li>Nomenclature </li></ul><ul><ul><li>IgM (kappa) </li></ul></ul><ul><ul><li>IgA1(lambda 2) </li></ul></ul><ul><ul><li>IgG </li></ul></ul><ul><li>Heterogeneity </li></ul>
  18. 18. IgG <ul><li>Structure </li></ul><ul><ul><li>Monomer (7S) </li></ul></ul>IgG1, IgG2 and IgG4 IgG3
  19. 19. IgG <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>Major serum Ig </li></ul></ul><ul><ul><li>Major Ig in extravascular spaces </li></ul></ul><ul><ul><li>Placental transfer – Does not require Ag binding (  IgG2) </li></ul></ul><ul><ul><li>Fixes complement (  IgG4) </li></ul></ul><ul><ul><li>Binds to Fc receptors (  IgG2, IgG4) </li></ul></ul><ul><ul><ul><li>Phagocytes - opsonization </li></ul></ul></ul><ul><ul><ul><li>K cells - ADCC </li></ul></ul></ul>
  20. 20. IgM <ul><li>Structure </li></ul><ul><ul><li>Pentamer (19S) </li></ul></ul><ul><ul><li>Extra domain (C H4 ) </li></ul></ul><ul><ul><li>J chain </li></ul></ul>C  4 J Chain
  21. 21. IgM <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>3rd highest serum Ig </li></ul></ul><ul><ul><li>First Ig made by fetus and B cells </li></ul></ul><ul><ul><li>Fixes complement </li></ul></ul>
  22. 22. Fixation of C1 by IgG and IgM Abs No activation Activation C1r C1s C1q C1r C1s C1q
  23. 23. IgM <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>3rd highest serum Ig </li></ul></ul><ul><ul><li>First Ig made by fetus and B cells </li></ul></ul><ul><ul><li>Fixes complement </li></ul></ul><ul><ul><li>Agglutinating Ig </li></ul></ul><ul><ul><li>Binds to Fc receptors </li></ul></ul><ul><ul><li>B cell surface Ig </li></ul></ul>Tail Piece
  24. 24. B Cell Antigen Receptor (BcR) Ig-  Ig-  Ig-  Ig- 
  25. 25. IgA <ul><li>Structure </li></ul><ul><ul><li>Serum - monomer </li></ul></ul><ul><ul><li>Secretions (sIgA) </li></ul></ul><ul><ul><ul><li>Dimer (11S) </li></ul></ul></ul><ul><ul><ul><li>J chain </li></ul></ul></ul><ul><ul><ul><li>Secretory component </li></ul></ul></ul>J Chain Secretory Piece
  26. 26. Origin of Secretory Component of sIgA Y Y Y Y Y Y
  27. 27. IgA <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>2nd highest serum Ig </li></ul></ul><ul><ul><li>Major secretory Ig (Mucosal or Local Immunity) </li></ul></ul><ul><ul><ul><li>Tears, saliva, gastric and pulmonary secretions </li></ul></ul></ul><ul><ul><li>Does not fix complement (unless aggregated) </li></ul></ul><ul><ul><li>Binds to Fc receptors on some cells </li></ul></ul>
  28. 28. IgD <ul><li>Structure </li></ul><ul><ul><li>Monomer </li></ul></ul><ul><ul><li>Tail piece </li></ul></ul>Tail Piece
  29. 29. IgD <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>4th highest serum Ig </li></ul></ul><ul><ul><li>B cell surface Ig </li></ul></ul><ul><ul><li>Does not bind complement </li></ul></ul>
  30. 30. IgE <ul><li>Structure </li></ul><ul><ul><li>Monomer </li></ul></ul><ul><ul><li>Extra domain (C H4 ) </li></ul></ul>C  4
  31. 31. IgE <ul><li>Structure </li></ul><ul><li>Properties </li></ul><ul><ul><li>Least common serum Ig </li></ul></ul><ul><ul><ul><li>Binds to basophils and mast cells (Does not require Ag binding) </li></ul></ul></ul><ul><ul><li>Allergic reactions </li></ul></ul><ul><ul><li>Parasitic infections (Helminths) </li></ul></ul><ul><ul><ul><li>Binds to Fc receptor on eosinophils </li></ul></ul></ul><ul><ul><li>Does not fix complement </li></ul></ul>
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