Chapter 3 Ig

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Slide 1: 

Medical Immunology Sun Wensheng Immunology Institute Medical School Shandong University 2005

Chapter 6 Antibody : 

Chapter 6 Antibody

Definition : 

Definition Antibody (Ab) : Ab is one kind of globulin that can combine with a corresponding Ag specifically. Ab is produced by B cells in the response to a stimulation of Ag. .

Slide 4: 

Immunoglobulin( Ig): All glubulins that posses the activation of Ab or show a similar structure to Ab Therefore, All Abs are Igs, but not all Igs possess the functions of Abs

Other Concepter : 

Other Concepter - Globulin Antiserum Humoral Immunity

I. Molecular Structure of Ig : 

I. Molecular Structure of Ig

(I). Basic structure : 

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

1.H and L chain: : 

1.H and L chain: . heavy chains (H): 450 ~550aa, 50—75KD . light chains (L) 214 aa, 25KD

Slide 9: 

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

2. classes and types of Ig : 

2. classes and types of Ig 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 Ig : IgG, IgA, IgM, IgD, IgE

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Two types of L chain : ?, ? ? : ? 20:1 (in mice) 2:1 (in human)

: 

Constant region ( C ) CH: 3/4 or 4/5 of H chain CL: 1/2 of L chain 3. Two regions of each peptide

2) Variable region (V): : 

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

: 


complementary determinat regions(CDR) : 

complementary determinat regions(CDR)

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Ag-binding sites L: CDR1, CDR2, CDR3 H: CDR1, CDR2,CDR3

Idiotype of Ig : 

Idiotype of Ig Igs produced by different B cells possess unique structure in hypervariable region(HVR) . The unique strcture of Ig is called idiotype of Ig

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Infact: HV R CDR idiotype are the same sites of Ig

Other structures of Ig : 

Other structures of Ig Joining chain(J ) Secretory piece( SP):

Joining chain(J ) : : 

Joining chain(J ) : produced by plasma cells Functions: linker to compose dimer ?pentamer or polymer( Ig A, IgM)

Secretory piece( SP): : 

Secretory piece( SP): . produced by mucosa epithelial cells . exist in secretory IgA (SIg A) . Functions: protect SIgA, resist proteolysis in extra secretory liquid.

Secretory piece( SP): : 

Secretory piece( SP):

(II). Domains of Ig : 

(II). Domains of Ig

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.1. Domain : Polypeptide chains of Ig are folded by intra chain s-s bind into globular shape in each 110aa regions which is called a domain

2.   Domains of Ig : 

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

3.function of each domain : 

3.function of each domain VH , VL: antigen-binding site CH1, CL: allogeneic marker CH2: complement-fixing site CH3/CH4: cell-binding site hinge region : flexible and suitable for CDR of Ig combing with antigenic determinants.

(III). Hydrolysis fragments of Ig and their functions : 

(III). Hydrolysis fragments of Ig and their functions Digested by papain pepsin .position .Fragments: .Function:

: 


1)Digested by papain : 

1)Digested by papain Position : near the S-S bonds of H inter-chains,from the N end fragments: 2Fab ,Fc Function: Fab fragment of Ag binding Fc 1)fixing complement 2)crossing the placenta 3) fixing different cell

: 

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 values) pFc’ no function

Significance : 

Significance ·  elucidating the relationships between the structure and function of Igs Decrease the immunogenicity of Ig for clinical treatment

Slide 36: 

II. 5 classes of Ig and their functions

( I ) IgG : 

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

: 

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

Slide 39: 

3.Unique Ig that can pass through placenta. 4.half-life is longer( 20-23 days ) 5. starts to be produced at 2-3 month after birth and reach the level of adult at 5 years old

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6.Functions of IgG: against bacteria and virus,neutralize toxin some belong to the auto-antibodies: eg. long active thyriod stimulator (LATS) combine with the Fc receptor(Fc?R)

(II). IgA : 

(II). IgA 1.Two types serum type :monomer secretary type(SIgA): dimer,trimer or polymer 2.two subclasses:IgA1,IgA2

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3.to be produced at 4 month after birth 4.exist in almost all humoral 5.activate the complement by alternative pathway

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6.local immunity of mucosa Immune barrier rich in colostrum neutralize virus/toxin

(III) IgM : 

(III) IgM

: 

1.highest MW:pentamer(90KD) Valences:10 valences in theory 2.half-life is shorter(4~5 days) 3.the first Ig to be synthesized be produced during fetus appear in the early stage after infection the first mIg of the B cells,act as the antigen receptors(BCR)

4.Function: : 

4.Function: IgM is more effect in anti-nfection anti-bacterium natural Ab for blood-type antigen auto-antibody :reumatiod factor(RF)

(IV). IgD : 

(IV). IgD 1.concerntration in serum is low and sensitive to proteinase 2.act as the antigen receptor on B cells(mIgD): regulate differentiation of B cells

(V). IgE : 

(V). IgE 1.concerntration in serum is lowest in normal individual, but is very high in some patients 2.related to type I persensitivity

Slide 51: 

????,???!!!

III . Biological efforts of Ab : 

III . Biological efforts of Ab 1.bind to antigen specifically 2.fix complement 3.bind to Fc receptor on some cells Fc?R Fc?R go

Slide 53: 

1)Opsonization(IgG,IgM) enhance of the phagocytosis of MF back

2)ADCC( antibody dependent cell mediated cytoxicity) : 

2)ADCC( antibody dependent cell mediated cytoxicity) back

Slide 55: 

placenta-crossing site (IgG) hypersensitivity type I (IgE) -mast cell - basophils

3)hypersensitivity type I---- mast cell and basophils : 

3)hypersensitivity type I---- mast cell and basophils back

III. Biological efforts of Ab : 

III. Biological efforts of Ab 1.bind to antigen specifically 2.fix complement 3.bind to Fc receptor on some cells 4. transfer selectively : .planceta transfer (IgG) .mucus transfer (SIgA) 5. Related with the pathological (hypersenstivity ,autoimmue disease ) 6. bear antigenicity go

6. bear antigenicity : 

6. bear antigenicity isotype allotype idiotype

IV. Preparation of Ab : 

IV. Preparation of Ab Polyclonal Ab Monoclonal Ab Gene engineering Ab

1.Polyclonal Ab : 

1.Polyclonal Ab a mixture Ab with different specificities and affinities generated in a natural response or artificial immunization

2. Monoclonal Ab (mAb) : 

2. Monoclonal Ab (mAb) Ab produced by single clone (or one hybridomas clone ) and having a single specificity

mAb / McAb : 

mAb / McAb Prepared by hybridomas technique: Immunized spleen cells(B) hybride with myeloma cells hybridoma

3.Gene engineering Ab : 

3.Gene engineering Ab Abs prepared by the method of gene recombination chimeric Ab: human Fc biand with mice Fab recombinant single chain Ab: VH-linker-VL

To my students: Why not the best : 

To my students: Why not the best