Antibody (Ab): Introduction, Structure, Theory of Production, Classes

Antibody (Ab): Introduction, Structure, Theory of Production, Classes and Properties

Introduction of Antibody (Ab)

The antibody (Ab) is also called immunoglobulin (Ig). Immunoglobulin is a glycoprotein that is made in response to an antigen and can recognize and bind to the antigen that caused its production. It protects us from microbial infection. They are gamma globulin and synthesized by plasma cells. They constitute 25-30 % of total serum proteins. Antibodies are present in serum, tissue fluids, and mucosal surfaces and on the surface of B-cells where they act as antigen receptors. Antibody initiates new complement pathways and also activities phagocytic cells.

Antibody (Ab) Producing Apparatus

Following are the antibody-producing apparatus-

Thymus gland
Lymphocytes
Lymph nodes
Spleen
Bone marrow
Plasma cell

Theory of Antibody (Ab) Production

Direct Template Theory of Pauling

Landsteiner and others observed that antibody formation is a modification of protein synthesis, which is brought about by the presence of antigen or introduction of an antigen. It is assumed that when an antigen enters the body, it is taken up by the phagocytic cells and in these cells, antigen serves the purpose of mold or template ( die or cast) on which impression the corresponding appropriate immunoglobulin synthesis occurs.

Indirect Template Theory

Burnet and Fenner’s theory: Antibody-producing apparatus can recognize self and non – self-antigen.

Selective Theory

Ehrlich’s Selective Theory

Ehrlich (1900): Immunogens act selectively with specific biosynthetic units or subunits of the cells then to make a greater amount of antibody molecules where they were already enrolled to make some amount of antibodies advance immunization. Antigen selects the lymphocyte, which makes the antibodies.

Antigen→ Lymphocyte

↓

Activation of Lymphocyte

↓

Lymphocyte transformed into

plasma cell

↓

Plasma cell starts producing antibodies

↓

Antibodies react in a specific and observable manner.

Clonal Selection Theory

The cell selected by antigen undergoes much division during the clonal proliferation and the progeny matures to give an expanded population of antibody-forming cells.

Cell-Mediated Immunity or Cellular Immunity

The cell itself takes part to destroys organisms. It mainly depends on the specifically developed T cells by certain antigens. Cell-mediated immunity (CMI) protects against intracellular organisms. Lymphokines producing T- cells help macrophages to kill intracellular parasites. Natural killer (NK) cells kill virally infected cells.

Humoral Immunity

Antibodies take part in fighting against microorganisms. It depends on the active production of antibodies against antigens by plasma cells so that the antibodies will combine specifically with the corresponding antigens and finally modify their activity.

Structure of Immunoglobulin

Composed of 4 polypeptide chains- 2 identical light chains (25 kDa each) and 2 identical heavy chains (50-73 kDa each)
Linked by disulfide bonds
Light chains similar in all immunoglobulins
Light chains occur in 2 varieties:-kappa (k) and lambda( λ )
Kappa chains are more frequently found.
Heavy chains:- gamma, alpha, mu, delta and epsilon.
One Ig contains one type of light chain and one type of heavy chain.
Fc (Fragment Crystallizable ) -fixes complement
Fab( Fragment, antigen-binding) binds antigen.
Fab terminal has amino and Fc terminal have-COOH group.
L and H chain consists of 2 parts-V (variable) region at amino-terminal and C (constant) region at carboxyl-terminal.
Hypervariable region: binds epitope also called complement determining region (CDR).

H and L Chains

The chains of higher molecular weight are designed – H chains and those of lower molecular weight light (L) chains.

V and C Region

Each polypeptide 4 chain contains an amino acid terminal portion- the variable (V) region and the carbohydrate portion – the constant region.

Domains

A segment of the H and L chains that are folded 3 dimensionally and stabilize with a disulfide bond is called domains.

Antigen Binding Site

The part of the antibody molecule which binds antigen is formed by only small numbers of amino acids in the V region of the H and L chain.

Fab and Fc Fragment

Digestion of an IgG molecule by the enzyme – papain produces 2 Fab ( antigen binding) fragments and one Fc ( Fraction crystalizable) fragment.

L- Chain Types

L- chains are divided into kappa (k) and lambda types on the basis of antigenic determinants.

S- Value

The sedimentation coefficient of protein was measured by the technique Svedberg. Normally, the larger the S- value, the higher the molecular weight

Hinge Region

The area of -H- in the C- region between the first and second -C- region domains (CH1 and CH2) is the hinge region. It is more flexible and is more exposed to enzymes and chemicals. Thus the papain acts here to produce Fab and Fc fragments. On the other hand, when pepsin acts, it results in two Fab fragments held together in position, formulated as ( Fab)2 while the Fc portion is digested into smaller fragments. The domains in – H- chains are designated- VH, CH2, CH3, CH4, and those in L- chain are designed VL and CL

Polymers

Immunoglobulins composed of more than a single basic monomeric unit is called- Polymers. e.g. IgG- dimer ( 2 units), trimer (3 units), IgM- pentamers ( 5 units).

J- Chain

The joining (J) chain is a small polypeptide, conveyed by mucosal and glandular plasma cells, that regulates the polymer formation of immunoglobulin (Ig)A and IgM. It is normally found in polymeric immunoglobulins.

Classes of Antibody (Ab)

There are 5 classes of immunoglobulins. These are IgG- (gamma), Ig A- (alpha), Ig M- (mu), Ig D- (delta), Ig E – (epsilon). They are defined by the antigenic differences in the C region of H- chain.

Immunoglobulin Mu (IgM)

Properties of IgM are as follows-

Pentamer
10 antigen-binding sites
Mainly found in serum
Offers protection against bacteria
Appears early in response to acute infection
Can not cross the placenta ( presence of IgM in fetus blood indicates intrauterine infection)
Its molecular weight is 960000 Da sand so it is also called a millionaire molecule.
It is the most efficient antibody that takes part in agglutination, complement fixation test (CFT), and cytolytic reaction.

Immunoglobulin Gamma (IgG)

Properties of IgG are given below-

Major immunoglobulin ( 80% of total) and consists of 2L and 2H chains. It has 4 subclasses ( IgG1, IgG2, IgG3, IgG4)
Appears late, usually after 2 weeks of infection, and persists longer (IgM appears early and persists shorter.)
Takes part in precipitation, complement fixation, and neutralization of toxins and viruses.
IgG attached to the bacteria attracts phagocytic cells.
Almost equal distribution of both intravascular and extravascular spaces.
The only immunoglobulin can pass through the placental barrier.
It has the longest half period.

Immunoglobulin Alpha (IgA)

IgA properties are as follows-

Principal immunoglobin that appears in the serum mucus secretion. It occurs in 3 forms: serum IgA and Secretory IgA.
Protect exposed mucus membrane from microorganism
IgA in the secretion in the dimer ( Mol.wt.4 hundred thousand) while serum IgA is monomeric( Mol. Wt. 160000)
IgA is largely synthesized locally by plasma cells. Only a little amount may be derived from the serum.

Immunoglobulin Epsilon (IgE)

Properties of IgE-

It was discovered by Ishizaka ( 1966), is called cytophilic antibody
Inactivated by heat at 56°C in 1 hr.
Produced in very small amount plasma cells lining on the respiratory and intestinal tract.
It has affinity on the tissue surface and basophils.
It medicates type-1 hypersensitivity reaction.
It attaches itself to the cells by Fc fragment.
Increased IgE level is seen in a patient with intestinal parasitic infestation.
In contact with IgE with antigen( allergen), mast cells are degranulated with the release of vasoactive amines ( histamine)

Immunoglobulin Delta (IgD)

Properties are as follows-

Mainly intravascular distribution
IgD was first discovered by Rose and Fahey in 1965 in myeloma cells.
It is present on the membrane of unstimulated -B – lymphocytes that serves recognition receptor for antigen.

Keynotes on Antibody (Ab)

All antibodies are immunoglobulins but not all immunoglobulins are antibodies e.g. cryoglobulin is immunoglobulin but not antibody.
The antibody of acute infection is IgM while in chronic (past) infection is IgG.
The antibody of allergy and parasitic infection is IgE.
The antibody which can cross the placenta is IgG.
Due to its pentameric structure, IgM is a powerful agglutinating and precipitating antibody, and a strong complement fixing immunoglobulin too.

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