Lecture on immunoglobulins

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Lecture on 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 1 2   + - albumin globulins Mobility Amountofprotein
  3. 3. Immunoglobulin Has Two Roles • Antigen Receptor – Recognition of and binding to antigens such as toxins, viruses, and exposed molecules on the surface of pathogenic organisms – V domain function • Effector Molecule – Elimination or inactivation of the foreign antigen or the cell that bears the antigen – C domain function
  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 The first 108 amino acids in light chains and first 118 amino acids in heavy chains constitute the variable region
  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
  9. 9. Immunoglobulin Fragments: Structure/Function Relationships • Fab – Ag binding – Valence = 1 – Specificty determined by VH and VL Papain Fc Fab • Fc – Effector functions
  10. 10. Immunoglobulin Fragments: Structure/Function Relationships • Fab – Ag binding • Fc – Effector functions • F(ab’)2 Pepsin Fc Peptides F(ab’)2
  11. 11. Human Immunoglobulin Classes Depending on the heavy chain make up, the immunoglobulins are differentiated into 5 major classes • IgG - Gamma heavy chains • IgM – Mu heavy chains • IgA - Alpha heavy chains • IgD - Delta heavy chains • IgE - Epsilon heavy chains
  12. 12. Human Immunoglobulin Subclasses • 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
  13. 13. Human Immunoglobulin Light Chain Types • Kappa • Lambda In human beings, 60% light chains are of Kappa variety and 40% are of Lamda type
  14. 14. Human Immunoglobulin Light Chain Subtypes • Lambda light chains – Lambda 1 – Lambda 2 – Lambda 3 – Lambda 4
  15. 15. IgG • Structure – Monomer (7S) IgG1, IgG2 and IgG4 IgG3
  16. 16. IgG  Predominant Ig of blood (75- 80%)  1 unit, smallest  Longest half-life  Antibody seen in secondary immnue response  Passive transfer  Crosses placental barrier – Rh iso-immunization  Agglutination  Opsonization  Complement Actn.
  17. 17. IgM • Structure – Pentamer (19S) – Extra domain (CH4) – J chain C4 J Chain
  18. 18. IgM  It can combine with 5 antigens simultaneously  3rd highest serum Ig  First Ig made by fetus and B cells  Major Ig of primary response  No hinge region  Natural antibodies are IgM in nature  It cannot cross the placenta  Agglutination, C’ act.
  19. 19. IgA • Structure – Serum - monomer – Secretions (sIgA) • Dimer (11S) • J chain • Secretory component J ChainSecretory Piece
  20. 20. Origin of Secretory Component of sIgA
  21. 21. IgA  Serum-monomer  2nd highest serum Ig  2 units  J chain  secretory component produced by epithelial cells  Major secretory Ig (Mucosal or Local Immunity) – Tears, saliva, gastric and pulmonary secretions  Prevents attachment & penetration of microorganisms  Does not fix complement (unless aggregated)
  22. 22. IgD • Structure – Monomer – Tail piece Tail Piece
  23. 23. IgD 1 unit 4th highest serum Ig Long hinge region. Found as membrane receptor on early B cells. Does not bind complement Not in all species.
  24. 24. IgE • Structure – Monomer – Extra domain (CH4) C4
  25. 25. IgE  1 unit  Least common serum Ig  Extra CH domain binds IgE specific receptors on basophils and mast cells.  Ag binding induces degranulation.  Parasitic immunity  Binds to Fc receptor on eosinophils  Type I Hypersensitivity  Allergy  Does not fix complement
  26. 26. IgE-Induced Degranulation of Mast Cells In Allergy
  27. 27. Clinical aspect • Paraproteinemias – Multiple myeloma – Bence-Jones proteinuria – Waldenstrom’s macroglobulinemia – Hyper gamma globulinemia
  28. 28. Multiple myeloma • When Ig secreting cells are transformed into malignant cells, one clone alone is enormously proliferated • This is seen in electrophoresis as the myeloma band or monoclonal band or M band • It is characterised by paraproteinemia, anemia, lytic bone lesions and proteinuria
  29. 29. • Bone marrow examination reveals large number of malignant plasma cells • Spontaneous pathological fracture of weight bearing bones, ribs and vertebrae may occur • X-ray shows punched out osteolytic lesions • Hypercalcemia and hypercalciuria • Raised beta-2 microglobin • Immunity is depressed • Prognosis is good
  30. 30. Bence-Jones proteinuria • Seen in 20% of patients with multiple myeloma • Monoclonal light chains are excreted in urine • They precipitate when heated between 45ºC and 60ºC; but redissolving at higher than 80ºC and lower than 45ºC • Bradshaw’s test

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