immunoglobulin immunology. immunoglobulin 1. introduction 2. the basic structure of immunoglobulins...

Immunoglobulin

IMMUNOLOGY

immunoglobulin

1. Introduction

2. the basic structure of immunoglobulins

3. Fuction of immunoglobulins

4. the structures and properties of

immunoglobulin classes

5. Monoclonal antibody

IntroductionImmunoglobulins (Ig) - Glycoprotein molecules which are produced by

plasma cells in response to an immunogen and which function as antibodies. The immunoglobulins derive their name from the finding that when antibody-containing serum is place in an electrical field the antibodies, which were responsible for immunity, migrated with the globular proteins

- secreted Ig(sIg) ; membrane Ig(mIg)

immunoglobulin

Introduction

immunoglobulin

IntroductionAntibody(Ab) - Serum protein formed in response to

immunization; antibodies are generally defined in terms of their specific binding to the immunizing antigen.

immunoglobulin

basic structure of the immunoglobulinsimmunoglobulin

basic structure of the immunoglobulins1.Heavy Chain and Light Chain

heavy chain (H chain)

50-75Kd 450-550aa

isotype:IgM,IgD,IgA,IgE,IgG

H chain: μ δ α ε γ

light chain (L chain)

25Kd 214aa

classes of L chain: κ λ

immunoglobulin

basic structure of the immunoglobulins2.variable region and constant region

variable region(V region)

Light Chain - VL (110 aa)

Heavy Chain - VH (110 aa)

HRV(hypervariable region)

CDR(complementarity-determining region)

FR(framework region)

immunoglobulin

immunoglobulin

basic structure of the immunoglobulins

CDR binds with epitope of antigen

basic structure of the immunoglobulins2.variable region and constant region

constant region(C region)

Light Chain - CL (110 aa)

Heavy Chain - CH (330-440 aa)

CH1, CH2, CH3,( CH4)

immunoglobulin

basic structure of the immunoglobulins3. Hinge Region - between the CH1 and CH2 region of the H chain - be made of cysteine and proline residues cysteine:be involved in formation of interchain disulfide bonds proline residues:prevent folding in a globular structure - flexibility: allow the two Fab arms to open; close to accommodate binding to epitope; be cleaved by proteases.- IgM and IgE have no hinge region

immunoglobulin

Domains of immunoglobulinDomains - 3D images of the immunoglobulin molecule shows

that it is not straight as depicted in Figure. Rather, it is folded into globular regions each of which contains an intra-chain disulfide bond. These regions are called domains.

1. Light Chain Domains - VL and CL

2. Heavy Chain Domains - VH, CH1,CH2, CH3 (or CH4)

immunoglobulin

Domains of immunoglobulinimmunoglobulin

immunoglobulin

Domains of the Ig

immunoglobulin

Immunoglobulin fragmentsimmunoglobulin

J chain and SP Joining chain

-J chain

a ploypeptide chain

Join the units together

immunoglobulin

J chain and SP Secretory piece

-SP,SC

immunoglobulin

Function of immunoglobulinsimmunoglobulin

Functions of V regions - recognition and binding to antigen - HVR (CDR) - neutralization of toxins;

immobilization of microorganisms; neutralization

of viral activity

Function of C regions (Fc portion)

1. Activation of complement: IgM, IgG1,3; IgA2. Binding to Fc receptor of cellopsonization, enhancement of Ag

uptake by DC and M ADCC Participation in type I hypersensitivity3. Passage through the placenta (IgG) and mucosa (sIgA)

immunoglobulin

immunoglobulin

Opsonization of antibody

immunoglobulin

Antibody-dependent cell-mediated cytotoxicity (ADCC)

IgGimmunoglobulin

a) IgG is the major Ig in serum - 75% of serum Ig

b) IgG is the major Ig in extra vascular spaces

c) Fixes complement - Not all subclasses fix equally

well; IgG4 does not fix complement

d) Binding to cells - Macrophages, monocytes, PMN's and some lymphocytes have Fc receptors for the Fc region of IgG.

IgMimmunoglobulin

a) IgM is the 3rd most common serum Ig.

b) IgM is the first Ig to be made by the fetus and the first Ig to be made by a virgin B cells when it is stimulated by antigen.

c) As a consequence of its pentameric structure, IgM is a good complement fixing Ig. Thus, IgM antibodies are very efficient in leading to the lysis of microorganisms

d) As a consequence of its structure, IgM is also a good agglutinating Ig .

e) IgM binds to some cells via Fc receptors.

IgAimmunoglobulina) IgA is the 2nd most common serum

Ig.b) IgA is the major class of Ig in secretions – tears, saliva, colostrum, mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity.c) Normally IgA does not fix complement, unless aggregated.d) IgA can binding to some cells - PMN's and some lymphocytes.

immunoglobulin

IgA

IgDimmunoglobulina) IgD is found in low levels in serum;

its role in serum uncertain.b) IgD is primarily found on B cell surfaces where it functions as a receptor for antigen. IgD on the surface of B cells has extra amino acids at C-terminal end for anchoring to the membrane. It also associates with the Ig-alpha and Ig-beta chains.c) IgD does not bind complement.

IgEimmunoglobulin

a) IgE is the least common serum Ig

since it binds very tightly to Fc receptors on basophils and mast cells even before interacting with antigen.

b) Involved in allergic reactions

c) IgE also plays a role in parasitic

helminth diseases

d) IgE does not fix complement

immunoglobulin

Monoclonal antibody