1 / 90

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.

lars
Télécharger la présentation

Chapter 5 Immunoglobulin

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related