1. Immunoglobulins Structure and Function By Eisa Salehi PhD Department of Immunology

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 α1α1 α2α2 β γ + - albumin globulins Mobility Amount of protein

3. Basic Immunoglobulin Structure Immunoglobulins - heterogeneous Myeloma proteins - homogeneous immunoglobulins Immunoglobulin vs. Antibody

4. Immunoglobulin Structure Heavy & Light Chains Disulfide bonds Inter-chain Intra-chain C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond

5. Immunoglobulin Structure Variable & Constant Regions V L & C L V H & C H Hinge Region C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond

6. Immunoglobulin Structure Domains V L & C L V H & C H1 - C H3 (or C H4 ) Oligosaccharides C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond

7. Immunoglobulin Fragments: Structure/Function Relationships Fab Ag binding Valence = 1 Specificty determined by V H and V L Papain Fc Fab Fc Effector functions

8. Immunoglobulin Fragments: Structure/Function Relationships Fab Ag binding Fc Effector functions F(ab’) 2 Pepsin Fc Peptides F(ab’) 2

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

10. Structure of the Variable Region Hypervariable (HVR) or complimentarity determining regions (CDR) Framework regions

11. 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

12. 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 (α 2) heavy chains

13. Human Immunoglobulin Light Chain Types Kappa ( κ ) Lambda (λ)

14. Human Immunoglobulin Light Chain Subtypes Lambda light chains Lambda 1 (λ1) Lambda 2 (λ 2) Lambda 3 (λ 3) Lambda 4 (λ 4)

16. IgG molecule چكش صخره ها را تراش نمي دهد بلكه آب با طراوات و رقص و آوازش بدان شكل مي دهد

17. IgG Structure Monomer (7S) IgG1, IgG2 and IgG4IgG3

18. 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

19. IgM Structure Pentamer (19S) Extra domain (C H4 ) J chain Cμ4Cμ4 J Chain

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

21. Fixation of C1 by IgG and IgM Abs C1r C1s C1q C1r C1s C1q No activationActivation

22. 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

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

24. IgA Structure Serum - monomer Secretions (sIgA) Dimer (11S) J chain Secretory component J ChainSecretory Piece

25. Origin of Secretory Component of sIgA

26. 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

27. IgD Structure Monomer Tail piece Tail Piece

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

29. IgE Structure Monomer Extra domain (C H4 ) Cε4Cε4

30. 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

34. Immunoglobulin: Isotypes, Allotypes and Idiotypes

35. Human IgM antiserum Reacts with IgM, IgG, IgA, IgD, IgE React with IgG, IgA, IgD and IgE Absorbed antiserum Reacts only with IgM Recognizes determinants specific for μ heavy chains (isotypes) Immunoglobulin Isotypes ??

36. Immunoglobulin Isotypes Definition - Antigenic determinants that characterize the classes and subclasses of heavy chains and types and subtypes of light chains

37. Immunoglobulin Isotypes Occurrence Importance Ig levels B cell tumors Immunodeficiencies Definition Location IgM (kappa) حسن IgG1 (kappa) حسن

38. Immunoglobulin Allotypes Definition - Antigenic determinants specified by allelic forms of the Ig genes Location Occurrence – Source of anti-allotypic Abs IgG1 (kappa) نقی IgG1 (kappa) حسن

39. Human Immunoglobulin Allotypes Nomenclature – G1m(3) – Km(1)

40. Human Immunoglobulin Allotypes Genetics (alleles) – Co-dominant autosomal genes Km(1)/Km(3) X Km(1)/Km(1) Km(1)/Km(1) and Km(1)/Km(3) – Allelic exclusion

41. Genetics (pseudoalleles) Co-dominant G1m(17)G1m(1) 214355-358 Human Immunoglobulin Allotypes

42. Immunoglobulin Allotypes Definition Location Occurrence Importance Monitoring bone marrow grafts Forensic medicine Paternity testing

43. Immunoglobulin Idiotypes Definition - Unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity

44. DNP-BSA Strain A Mouse Anti-DNP Ab Purified anti-DNP Ab Strain A Mouse Ab against combining site of anti-DNP Ab Immunoglobulin Idiotypes Antigenic determinants created by the HVR = Idiotypes

45. Immunoglobulin Idiotypes Definition Location IgG1 (kappa) نقی anti-B IgG1 (kappa) نقی anti-A

46. Immunoglobulin Idiotypes Definition Location Importance V region marker Regulation of immune responses

47. AgIdanti-Id + - anti-anti-Id + - Regulation by Id/anti-Id

49. Immunoglobulin Idiotypes Definition Location Importance V region marker Regulation of immune responses Vaccines

50. AgIdanti-Id + - Anti-Idiotype Vaccines AgIdanti-Id +

51. Immunoglobulin Idiotypes Definition Location Importance V region marker Regulation of immune responses Vaccines Treatment of B cell tumors (T cell)

53. Immunoglobulin Superfamily

56. General Functions of Immunoglobulins Effector functions Fixation of complement Binding to various cells (Usually require Ag binding) Ag binding –Can result in protection –Valency

57. General Functions of Immunoglobulins

62. آنچه سبب غرق شدن مي گردد فرو رفتن در آب نيست بلكه ماندن زير آب است