Immunoglobulins 151229080943

IMMUNOGLOBULINS

Dr. Gangadhar ChatterjeeMBBS, MD.

BIOCHEMISTRY

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 & H 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 HYPERVARIABLE REGION [CDR]• Specificity of antibodies

is due to hypervariable region

Digestion with proteolytic enzymes

Papain enzyme • Peptide bonds in the hinge

region are broken • Produces 3 fragments • 2 identical fragments called

Fab fragments –antigen binding activity. • Other fragment called Fc

fragment (Fraction crystallizable)

Pepsin digestion •Produce a single fragment composed of two Fab like subunits F(ab)2 binds antigen•Fc fragment is not recovered- digested to small numerous peptides.

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.

DNA rearrangements in the generation of immunoglobulins.

Arrangement of DNA: The process by which immunoglobulins (antibodies) are produced by B lymphocytes involves permanent rearrangements of the DNA in these cells. The immunoglobulins (for example, IgG) consist of two light and two heavy chains, with each chain containing regions of variable and constant amino acid sequence.

The variable region is the result of somatic recombination of segments within both the light- and the heavy-chain genes. During B-lymphocyte development, single variable (V),diversity (D), and joining (J) gene segments are brought together through gene rearrangement to form a unique variable region. This process allows the generation of 109–1011 different immunoglobulins from a single gene, providing the diversityneeded for the recognition of an enormous number of antigens.

Properties and biological activities of ImmunoglobulinsIg G Ig A Ig M Ig D Ig E

1. Structure Monomer Monomer in serumDimer in secretion

Pentamer Monomer

Monomer

2. Heavy chainCH domain

Gamma Three

Alfa Three

Mu Four

Delta Three

EpsilonFour

3. Mol. Wt. 1,50,000 1,60,000 9,00,000 1,80,000 1,90,000

4. Serum concentration (mg/ml) 12 2 1.2 0.03 0.00004

5. Present on membrane of mature B cell

_ _ + + _

5. IntravascularDistribution (%)

45 42 80 75 50

6. Crosses placenta + - - - -

7. Present in milk + + - - -

8. Selective secretion by seromucous glands

- + - - -

9. Activation of complement Classical Alternate

+-

-+

+-

--

--

10 Binds to FC receptor of phagocytes + - - - -

11 Induces mast cell degranulation - - - - +

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