医学免疫学英文版课件：Chapter 5 Antibody

1、MEDICAL IMMUNOLOGYChapter 5 Antibody/ImmunoglobulinContentsIntroductionSection Molecular Structure of AbSection Biological Activity of Abs Section Characteristics and Functions of the 5 Classes of AbsSection Immunogenicity of AbSection Artificial AbAntibody (Ab): Glycoproteins that are produced by p

2、lasma cells and can combine with the corresponding Ag specifically.Ab is produced by B cells in the response to Ag stimulation.Ab possesses a high degree of specificity and affinity to corresponding Ag. (Kd 10-7-10-11) Humoral Immunity Blood/Antiserum secreted immunoglobulin (sIg) membrane immunoglo

3、bulin (mIg)-BCRImmunoglobulin (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 AbsSection Molecular Structure of Ab four polypeptide chains Heavy chain: Light chain: , . Basic struc

4、tureIg is composed of four polypeptide chains joined by S-S bonds. It shows “Y” shape.1. H and L chain:. Heavy chains (H): 450 550 aa, 55 75 KD. Light chains (L): 214 aa, 25 KD(1) According to the differences of H chains (amino acid composition, sequence) Igs can be divided into 5 classes subclasses

5、 Five classes of H Chain: Five classes of Igs: IgG IgA IgM IgD IgEIgG1 IgG4IgA1, IgA2 (2) According to the differences of L chains Two types of L chain: , : 2:1 (in human) : 20:1 (in mice) 1 4 (subtypes)(1) Variable region ( V )VH: 1/4 or 1/5 (, ) of H chain from the N end VL: 1/2 of L chain from th

6、e N end (2) 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) and Constant region (C) (1) Variable region ( V )Hypervariable region (HVR) Vl: 2434, 5056, 8797 Vh: 3135, 5065, 95102 Antigen-binding site Complementarity-determin

7、ing regions (CDR)Framework region (FR): FR1-FR4 Stabilize the CDR structure and facilitate the interaction between Abs and Ags(2) Constant region ( C )and: similar length of CLDifferent type of Abs has different length of CH IgG、IgA、IgD: CH1、CH2、CH3 IgM、IgE: CH1、CH2、CH3、CH4(1) Hinge region Between C

8、H1 and CH2Flexible and suitable for CDR of Ig binding to antigenic determinants.Complement activation: CH2 complement binding site IgM, IgE: no hinge region3. Other structures of Ig(2) Joining chain (J) Produced by plasma cells, rich in cysteinsFunctions: linker to compose dimer or polymer(3) Secret

9、ory piece ( SP) Produced by mucosal epithelial cells Secretory IgA (sIgA) Functions: transportation of sIgA and protect sIgA from proteolysisIgADomains of Ig L chain (2) : VL, CLH chain (45): VH, CH1, CH2, CH3 CH4 (in IgM, IgE) Polypeptide chains composed of 110aa are folded into a globular structur

10、e by intra-chain s-s bond, which is called a domain Function of each domains VH, VL antigen-binding siteIgG CH2/IgM CH3 complement activation: C1q binding-siteIgG CH2 permeate placenta (IgG) CH3/CH4: binding of Fc receptor IgG CH3: macrophage/phagocytosis IgE CH3: mast cell/type I hypersensitivity.

11、Fragmentation of Ig by proteolytic cleavagepapain (木瓜蛋白酶)pepsin (胃蛋白酶)1. Digested by papainPosition near the S-S bonds of H inter-chains from the N end Fragments 2 Fab: fragment of antigen-binding Fc: fragment crystallizable Function: Fab: recognize and bind Ag Fc: (1) complement activation (2) cros

12、sing the placenta (3) bind to FcR in different cells Position: near the S-S bond of H inter-chains from the C end 2. Digested by pepsinFragments and function : F(ab)2: binding antigen (2 valence) pFc: no function Significance Elucidating the relationships between the structure and function of Igs De

13、crease the immunogenicity of Ig for clinical treatmentSection Biological Activity of Abs1. Recognition and binding of Ags 2. Complement activationIgM, IgG13: classical pathwayIgA, IgG4, IgE: alternative pathway3. Binding to Fc receptorIgG-FcR: FcR(CD64)-phagocyte FcR(CD32)-immune complex FcR(CD16)-N

14、K,macrophage,T cellIgE-FcR: FcR- mast cell, basophil FcR- macrophage, B cellIgA-FcR(CD89)-phagocyte, neutrophil(1) Opsonization (IgG, IgM) Enhance the phagocytosis of M (2) ADCC ( antibody-dependent cell-mediated cytotoxicity)(3) Hypersensitivity type - mast cell, basophil (FcR) FceRIdegranulation I

15、gEallergeninflammation4. Selective transportation Planceta transfer (IgG)Mucosa transfer (sIgA) Section Characteristics and Functions of the 5 Classes of Abs. IgG 1. Highest concentration in serum(75% of total Ig) 2. Four subclasses: IgG1, IgG2, IgG3, IgG43. Unique Ig that can pass through placenta4

16、. 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 35 years old 6. Functions of IgG:Against bacteria and virus, neutralize toxin especially in secondary immune responseCombine with the Fc receptor (FcR)Activate complementTake part i

17、n type and hypersensitivity. IgM 1. Highest MW：pentamer（90 KD, 10 valences) 2. Half-life is shorter (45 days)3. The first Ig to be synthesizedAppear in the early stage after infection Be produced during fetusThe first mIg of the B cells, act as the antigen receptors (BCR), immature B cells with only

18、 mIgM4. Functions:IgM is more effective in binding Ag and activating C, and play an important role in anti-infectionNatural Ab for blood-type antigenmIgM acts as BCR Auto-antibody: rheumatoid factor (RF)Take part in type and hypersensitivity1. Two types Serum type ：monomer Secretary type (sIgA): dim

19、er2. Two subclasses：IgA1，IgA2 . IgA3. To be produced at 4 months after birth4. Exist in almost all body fluid 5. Local mucosal immunity Immune barrier Neutralize virus/toxin Transfer from milk to new-born, passive immunity Activate C by alternative pathway Take part in type hypersensitivity . IgD1.

20、The concentration in serum is low and sensitive to proteinase2. Act as the antigen receptor on B cells (mIgD): Marker of the maturation of B cells Immature B cell: mIgM only Mature (nave) B cell: mIgM and mIgD Activated or memory B cell: mIgM only . IgE1. Concentration of IgE in serum is the lowest in normal individual, but is very high in some patients.2. Produced by plasma cells in MALT3. Cell-binding Ig and take part in typepersensitivity FcR: mast cell, basophilSection Immunogenicity of Ig