IMMUNOGLOBULINS

Dr. Vijay Marakala, MBBS, MD.BIOCHEMISTRY

IMS, MSU.

IMMUNOGLOBULINS

Introduction Structure Functions

Types Clinical importance

IMMUNOGLOBULINS [Ig]

Immunoglobulins are glycoprotein molecules that

are produced by plasma cells in response to an immunogen and which function as antibodies.

There are 5 classes of Immunoglobulins-

IgG, IgA, IgM, IgD and IgE

BASIC STRUCTURE OF Ig

Heavy and Light Chains

Disulfide bonds

Variable (V) and Constant (C) Regions

Hinge Region

Domains

Oligosaccharides

STRUCTURE OF Ig

Contain a minimum of two Light (L) & two

Heavy (H) Chains

Four chains are linked by

disulphide bonds

STRUCTURE OF Ig – L & V CHAINS

Light chain • may be either of two

types • Kappa or Lambda but

not both

Heavy chains • may be of five types• Alpha(α), gamma(γ),

delta(δ), mu(μ) and epsilon(ε)

Igs are named as per their heavy chain type as IgA, IgG, IgD, IgM and IgE

STRUCTURE OF Ig – V & C REGION

Most H chain contains 1VH and 3 constant domains –CH1, CH2

& CH3

L chain 1VL and 1 CL

Both chains contain variable (V) and constant (C) regions

STRUCTURE OF Ig - HINGE REGION • Each Ig molecule has

hinge region between CH-1 and CH-2

• Hinge region allows a better fit with the antigen surface

STRUCTURE OF Ig - DOMAINS

• Ig is folded into globular regions each of which contains an intra-chain disulfide bond. These regions are called DOMAINS.

STRUCTURE OF Ig – ANTIGEN BINDING SITE

• VL &VH form antigen binding site• Three variable amino

acid sequences at the amino terminal end called HPERVARIABLE REGION [CDR]• Specificity of antibodies

is due to hypervariable region

STRUCTURE OF Ig – Fab &Fc• Enzyme papain

digestion splits the Ig into two fragments• Fab-fragment for

antigen binding• Fc – crystallisable

fragment or fragment for complement binding

STRUCTURE OF Ig - Oligosaccharides• Carbohydrates are

attached to the CH2 domain in most immunoglobulins.• However, in some cases

carbohydrates may also be attached at other locations.

IgG [HEAVY CHAIN γ]• Monomer• Major class of Ig in serum -70% of total• Main antibody in the secondary response• Constitutes important defence against bacteria and

viruses• Only antibody that crosses the placenta• Maternal antibody that protects the foetus

IgA [HEAVY CHAIN α]• Monomer or dimer• IgA occurs in two forms

Secretory IgA and [Dimer]Serum IgA [Monomer]

• Second most abundant class – 20% of serum Ig• Major component of colostrum• Also present in saliva, tears and respiratory, intestinal

and genital secretions• Protects mucous membrane from antigenic attack

IgM [HEAVY CHAIN μ]• Monomer or pentamer• 8-10% of normal serum

immunoglobulins• Produced early in the

primary response to an antigen• Activate complement,

promotes phagocytosis and causes lysis of antigenic cells (bacteria)

IgD [HEAVY CHAIN δ]• Monomer• Less than 1% of serum

Ig• No known antibody

function• May function as an

antigen receptor• IgD is labile molecule

IgE [HEAVY CHAIN ε]

• IgE exists as a monomer.• Trace amount in serum

0.004%• Involved in allergic

reactions

• Binds very tightly basophils and mast cells

CLINICAL IMPORTANCE OF IMMUNOGLOBULIN

Multiple myelomaLiver diseaseRheumatoid arthritis

AgammaglobulinemiaHIVNephrotic syndrome