免疫球蛋白

Ab is produced by B cells in the response to a stimulation of Ag. Ab possesses a high degree of specificity and affinity
• Immunoglobulin (Ig):
It refers to all globulins that possess the activity of Ab or show a similar structure to Ab
• • • Appear in the early stage after infection Be produced during fetus The first mIg of the B cells, act as the antigen receptors(BCR)
Fragments: Function:
2Fab:fragment antigen-binding Fc:fragment crystallizable

Fab: recognize and bind Ag Fc: (1) fix complement (2) crossing the placenta (3) bind to FcR in different cells
•
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
2. Domains of Ig
• L chain(2) : VL, CL • H chain(4~5): VH, CH1, CH2, CH3 CH4(in IgM,IgE) hinge region
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
IgA源自文库
Ⅱ. Domains of Ig
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
IgM)
Secretory piece( SP):
. Produced by mucosa epithelial cells . Secretory IgA (sIgA) . Functions: protect sIgA, resist proteolysis in extra secretory liquid.
Section Ⅳ Biological Activity of Ab
SectionⅤ Immunogenicity of Ig Section Ⅵ Artificial Ab
Antibody (Ab):
Concepts
Glycoprotein molecules that are produced by plasma cells and can combine with the corresponding Ag specifically are called Ab.
“N”
“N” “C”
terminal end terminal end
“C”
L chains attach to H chains from “N” end
2. classes and types of Ig
(1) According to the differences of H chains
(amino acid composition, sequence)
Other structures of Ig
• Joining chain(J) Secretory piece(SP)
Joining chain(J ) :


Produced by plasma cells
pentamer or polymer(IgA,
Functions:linker, to compose dimer、
Ig
Ⅰ. Basic structure

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.
1. H and L chain:
. Heavy chains (H):
450 ~ 550 aa, 50 ~ 75 KD
. Light chains (L):
214 aa, 25 KD
Two terminal ends for each peptide chain
(2) Variable region ( V )
• • CH: CL:
(2) Variable region ( V ):
Hypervariable region(HVR)
There are three highly diversity stretches within the V egion, they are called HVR.
:
20:1 (in mice); 2:1 (in human)
3. Two regions of each peptide chain
(1) Constant region (C) (2) Variable region (V) (3) Hinge region
3. Two regions of each peptide chain
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
Idiotype of Ig
Igs produced by different B cells possess unique structure respectively in hypervariable region (HVR), the unique structure of Ig is called idiotype or idiotypic determinant
Chapter 5 Immunoglobulin
Contents
Introduction SectionⅠ Molecular Structure of Ig SectionⅡ Characteristics and Functions of the 5 Classes of Ig Section Ⅲ Fc Receptors for Ab Molecules
• Therefore, All Abs are Igs, but not all Igs
possess the functions of Abs
Other Concepts
γ - Globulin Antiserum Humoral Immunity sIg and mIg(BCR)
SectionⅠ Molecular Structure of
(1) Constant region ( C )
• • CH: CL: 3/4 or 4/5 (,) of H chain from the c end 1/2 of L chain from the c end 1/4 or 1/5 (,) of H chain from the N end 1/2 of L chain from the N end
Ⅲ. Hydrolytic fragments of Ig
Ig can be digested by papain and pepsin • Position • Fragments • Function
1. Digested by papain
• Position:
near the S-S bonds of H inter-chains fromthe N end
In fact: HVR CDR Idiotype are in the same sites of Ig
(3) Hinge region:
• Flexible and suitable for CDR of Ig binding to antigenic determinants. • Sensitive to proteolytic enzyme • IgM, IgE
Ⅰ. IgG
1. Highest concentration in serum (75% of total Ig)
2. Four subclasses: IgG1, IgG2, IgG3,
IgG4
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
• Take part in type Ⅱ and Ⅲ
hypersensitivity
Ⅱ. IgM
1. Highest MW：pentamer（90 KD）,10 valences
2. Half-life is shorter(4~5 days) 3. The first Ig to be synthesized
Igs can be divided into 5 classes • • Five classes of H Chain: Five classes of Igs: IgG IgA IgM IgD IgE IgG1~ IgG4 IgA1, IgA2 subclasses
(2) According to the differences of L chains: Two types of L chain: , 1~ 4
Significance
Elucidating the relationships
between the structure and function of Igs
Decrease the immunogenicity of Ig for clinical treatment
SectionⅡ Characteristics and Functions of the 5 Classes of Igs

Framework region(FR): FR1-FR4
Ag-binding sites
Complementarity determining regions(CDR)
(2) Variable region (V)
Complementarity determining regions(CDR) L: CDR1, CDR2, CDR3 H: CDR1, CDR2, CDR3