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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