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Chapter 5 Immunoglobulin

Chapter 5 Immunoglobulin. Contents. Introduction Section Ⅰ Molecular Structure of Ig SectionⅡ Characteristics and Functions of the 5 Classes of Ig SectionⅢ Fc Receptors for Ab Molecules SectionⅣ Biological Activity of Ab SectionⅤ Immunogenicity of Ig SectionⅥ Artificial Ab. Concepts.

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Chapter 5 Immunoglobulin

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  1. Chapter 5Immunoglobulin

  2. Contents • Introduction • SectionⅠ Molecular Structure of Ig • SectionⅡ Characteristics and Functions of the 5 Classes of Ig • SectionⅢ Fc Receptors for Ab Molecules • SectionⅣ Biological Activity of Ab • SectionⅤ Immunogenicity of Ig • SectionⅥ Artificial Ab

  3. Concepts Antibody (Ab): Glycoprotein molecules that are produced by plasma cells and can combine with the corresponding Ag specifically are called Ab. Ab is produced by B cells in the response to a stimulation of Ag. Ab possesses a high degree of specificity and affinity

  4. Immunoglobulin(Ig): It refers to all globulins that possess the activity of Ab or show a similar structure to Ab • Therefore, All Abs are Igs, but not all Igs possess the functions of Abs

  5. Other Concepts • - Globulin Antiserum Humoral Immunity sIg and mIg(BCR)

  6. SectionⅠMolecular Structure of Ig

  7. Ⅰ.Basic structure (four polypeptide chains) • Ig is composed of four polypeptide chains joined by S-S bonds. inter-chain disulfide bonds (S-S) intra-chain disulfide bonds (S-S) • It shows “T” or “Y” shape.

  8. 1. H and L chain: .Heavy chains (H): 450 ~ 550 aa, 50 ~ 75 KD .Light chains (L): 214 aa, 25 KD

  9. Two terminal ends for each peptide chain “N” terminal end “C” terminal end L chains attach to H chains from “N” end “N” “C”

  10. 2. classes and types of Ig (1) According to the differences of H chains (amino acid composition, sequence) Igs can be divided into 5 classes • Five classes of H Chain:  • Five classes of Igs: IgG IgA IgM IgD IgE subclasses IgG1~IgG4 IgA1, IgA2

  11. (2) According to the differences of L chains • Two types of L chain: ,   : 20:1 (in mice); 2:1 (in human) subtypes 1~4

  12. 3.Two regions of each peptide chain (1) Constantregion (C) (2) Variableregion (V) (3)Hinge region

  13. 3. Two regions of each peptidechain (1) Constant region ( C ) • CH: 3/4 or 4/5 (,)of H chain from the c end • CL: 1/2 of L chain from the c end (2) Variable region ( V ) • CH: 1/4 or 1/5 (,)of H chain from the N end • CL: 1/2 of L chain from the N end

  14. (2) Variable region ( V ): • Hypervariable region(HVR) There are three highly diversity stretches within the V egion, they are called HVR. • Framework region(FR): FR1-FR4

  15. Ag-binding sites

  16. Complementarity determining regions(CDR)

  17. (2) Variable region (V) Complementarity determining regions(CDR) L: CDR1, CDR2, CDR3 H: CDR1, CDR2, CDR3

  18. Idiotype of Ig Igs produced by different B cells possess unique structure respectivelyin hypervariable region (HVR), the unique structure of Ig is called idiotype or idiotypic determinant

  19. In fact: HVR CDR Idiotype are in the same sites of Ig

  20. (3) Hinge region: • Flexible and suitable for CDR of Ig binding to antigenic determinants. • Sensitive to proteolytic enzyme • IgM, IgE

  21. Other structures of Ig • Joining chain(J) • Secretory piece(SP)

  22. Joining chain(J ) : • Produced by plasma cells • Functions:linker, to compose dimer、pentamer or polymer(IgA, IgM)

  23. Secretory piece( SP): .Produced by mucosa epithelial cells . Secretory IgA (sIgA) . Functions: protect sIgA, resist proteolysis in extra secretory liquid. IgA

  24. Ⅱ. Domains of Ig

  25. 1. Domain : Polypeptide chains of Ig are folded into a globular structure by intra chain s-s bond within each 110aa region which is called a domain

  26. 2.Domains of Ig • L chain(2) : VL, CL • H chain(4~5): VH, CH1, CH2, CH3 CH4(in IgM,IgE) hinge region

  27. 3. Function of each domain • VH, VL: antigen-binding site • CH1, CL: allogeneic marker • CH2/CH3: complement-fixing site, permeate placenta(IgG) • CH3/CH4: cell-binding site • Hinge region : flexible and suitable for CDR of Ig binding to antigenic determinants

  28. Ⅲ. Hydrolytic fragments of Ig Ig can be digested by papain and pepsin • Position • Fragments • Function

  29. 1. Digested by papain • Position: near the S-S bonds of H inter-chains fromthe N end • Fragments: 2Fab:fragment antigen-binding Fc:fragment crystallizable • Function: Fab: recognize and bind Ag Fc: (1) fix complement (2) crossing the placenta (3) bind to FcR in different cells

  30. Ag:Ab ratio

  31. 2.Digested by pepsin • Position: near the S-S bond of H inter-chains from the C end • Fragments and function : F(ab′)2: bind antigen(2 valence) pFc′: no function

  32. Significance • Elucidating the relationships between the structure and function of Igs • Decrease the immunogenicity of Ig for clinical treatment

  33. SectionⅡ Characteristics and Functions of the 5 Classes of Igs

  34. Ⅰ.IgG 1. Highest concentration in serum(75% of total Ig)

  35. 2. Four subclasses: IgG1, IgG2, IgG3, IgG4

  36. 3. Unique Ig that can pass through placenta 4. Half-life is longer( 16-24 days ) 5. Starts to be produced at 2-3 month after birth and reach the level of adult at 5 years old

  37. 6. Functions of IgG: • Against bacteria and virus,neutralize toxin • Combine with the Fc receptor(FcγR) • Activate complement • Combine with SPA • Some belong to the auto-antibodies • Take part in type Ⅱ and Ⅲ hypersensitivity

  38. 1. Highest MW：pentamer（90 KD）,10 valences Ⅱ. IgM

  39. 2. Half-life is shorter(4~5 days) 3. The first Ig to be synthesized • Appear in the early stage after infection • Be produced during fetus • The first mIg of the B cells, act as the antigen receptors(BCR)

  40. 4. Functions: • IgM is more effective in binding Ag and activating C, and play an important role in anti-infection • Natural Ab for blood-type antigen • Auto-antibody: rheumatoid factor(RF) • Take part in type Ⅱ and Ⅲ hypersensitivity

  41. Ⅲ. IgA 1. Two types Serum type：monomer Secretary type（sIgA）: dimer，trimer or polymer 2. Two subclasses：IgA1，IgA2

  42. 3. To be produced at 4 months after birth 4. Exist in almost all body fluid

  43. 6. Local mucosalimmunity • Immune barrier • Neutralize virus/toxin • Rich in colostrum • Activate C by alternative pathway • Take part in type Ⅲ hypersensitivity

  44. Ⅳ. IgD 1. The concentrationin serum is low and sensitive to proteinase 2. Act as the antigen receptor on B cells (mIgD): Regulate the differentiation of B cells

  45. Ⅴ.IgE 1.Concerntration of IgE in serum is the lowest in normal individual, but is very high in some patients. 2.Related to typeⅠpersensitivity FcεRⅠ: mast cell, basophil

  46. SectionⅢ Fc Receptors for Ab Molecules

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