Definition :
Antibodies are immunoglobulins which are produced in the body in response to the antigen Are Foreign bodies.
Thus all antibodies are immunoglobulins but all immunoglobulins are not antibodies.
Location and formation :
The antibodies May be bound to a cell membrane or they May remain free.
Antibodies are produced by B lymphocytes and plasma cells.
In fact B lymphocytes get transformed into plasma cell .
The mature plasma cell produced antibodies at an extremely rapid rate — about 2000 molecules per second .
Antibodies direct the antibody mediated immunity ( = humoral immunity, )
Types of Antibodies :
There are five types of antibodies viz:
- Ig A (Ig alpha)
- Ig D (Ig delta)
- Ig E (Ig epsilon)
- Ig G (Ig gamma)
- Ig M (Ig mu)
Among tye antibodies , IgG forms 80 % of the antibodies in the body.
Antibody Structure :
Ig G has been studied extensively and serves as a model of basic structural unit of all Igs.
An antibody molecule consists of the following parts.
(I) Heavy and Light Chains
An antibody molecule is made up of 4 peptide chains , two small called light chain and two longer called heavy chain.
Hence an antibody is represented as H2L2.
The heavy chain has larger number of aminoacids while light chain has smaller number of amino acids.
Heavy and light chains May chains May be either lambda or Kappa type.
(ii) Constant and Variable Regions
There are two different regions the constant region and variable region in each chain of the antibody.
(iii) Disulfide Bonds and Hinge Region
A disulfide bond joins a light chain with a heavy chain.
Two disulfide bonds also link the two heavy chains.
This part of the antibody displays considerable flexibility ad is called the hinge region. Because the antibody “arms” can move somewhat as the hinge regions bends, an antibody can assume a Y shaped molecule.
(iv) Fragment Antigen Binding (Fab) and Fragment Crystallizable (Fc).
Two identical fragments of Y shaped molecule posses the antigen binding sites and are thus named fragment antigen binding (Fab).
The antigen binding sites bind to the specific antigens in a lock and key pattern, forming an antigen antibody complex.
The third fragment which lacks the ability to bind to antigen and can be crystallized, is , therefore known as fragment crystallizable (Fc).
The stem of. The Y shaped antibody monomer is called the Fc region, so named because when antibody structure was first being identified , it was a fragment (F) that crystallized © in cold storage.
Characteristics and Functions of Immunoglobulins
Antibodies show that following Characteristics and. Perform different functions.
(I) IgA
It is the second most abundant class, constituting about 10 to 15 percent of antibodies of serum.
It is mainly found in Sweat ‚Tears ‚saliva ‚mucus colostrum (first milk secreted by a mother) and gastrointestinal secretions.
Smaller quantities are present in blood and lymph.
Ig A Has an extra polypeptide called change joining chain and extra protein known as secretory component. Levels decrease during stress, lowering resistance to infection . provides localised protection in external secretions ( tears, intestinal secretions etc) against bacteria and viruses .
When IgA is excreted through faeces, it is called Coproantibody.
(ii) Ig D
It is mainly found on the surface of B cells as antigen receptors, where it activates B cells for antigen recognition. It is about 0.2 % of all antibodies in the blood.
(iii) Ig E
It is less than 0.1 % of all antibodies in the blood ; Located on mast cell and basophils releasing histamine from mast cells and basophils.
it is involved in allergic and hypersensitivity reaction; provides protection against worms.This immunoglobulins was discovered in 1966 by Ishizaka. It exhibits unique properties such as hard heat liability (in activated at 56°C in one hour).
IgE mediates Type 1 hypersensitivity (anaphylaxis). Prausnitz and Kustner demonstrated transmission of IgE mediates type I hypersensitivity. It is called Prausnitz Kustner (PK). Thus IgE acts as mediator in all allergic reaction.
(iv) Ig G
The most abundant class of IG in the body constituting approximately 80% of total Igs.
It is found in the blood , lymph and intestine . it protects against bacteria and viruses by enhancing phagocytosis, neutralizing toxins and complement activation.
It is the only class of antibody to cross the placenta from mother to foetus thereby conferring considerable immune protection. In newborns.
(v) Ig M
IGM is about 5 to 10% off all antibodies in the blood. It is also found in lymph . it is the largest Ig which secreted first by the plasma cells.
it is named because it is a macro globulin at least five times larger than IgG.
IgM is the oldest immunoglobulins class. It is activates rhe B cells . it is also the earliest immunoglobulins to be synthesized by the foetus ,
IgM has J chain and its each dimer contains polypetide called a secretory component .
It cannot cross the placental barrier. IgM is 500 — 1000 times more effective than IgG in Opsonisation (to be described ahead) , in bacterial action and in agglutination. But in neutralization of Toxins and viruses , it is less active than IgG. It helps in Complement activation.
Monoclonal Antibodies ( MAbs)
Production.
- A mouse is injected with the specific antigen that will induce antibodies against the antigen the antigen.
- The spleen of the mouse is removed and a suspension is made . the suspension include B cells that produces antibodies against the injected antigen.
- The spleen cells are then mixed with myeloma cells (cancer cells ) that are capable of continuous growth in culture but have lost the ability to produce antibodies. Some of the antibody producing spleen cells and myeloma cells fuse to form hybrid cells . These hybrid cells are now capable of growing continuosly in culture while producing antibodies.
- The mixture of cells is placed in a selective medium. That allows only hybrid cells to grow.
- Hybrid cells proliferate into clones called hybridomas. The hybridomas are screened for production of the desired antibody.
- The selected hybridomas are then cultured to produce large quantities of monoclonal antibodies (MAbs) because they come from a single clone of identical cells.
The method of production of Monoclonal antibodies (MAbs) was described by Jerne, Kohler and Milstein in 1975 for which they were awarded Nobel prize for Medicine in 1984.
Uses :
They recognize several bacterial pathogens, diagnosis of pregnancy, allergies and disease such as hepatitis, rabies and some sexually transmitted diseases.
MAbs have also been used to detect cancer at an early stage and to know the extent of metastasis.
MAbs are also being used since 1986 to minimize rejection of kidney transplant .
For these purpose MAbs are prepared that react with the T cell that are responsible for rejection of the transplanted tissue. The MAbs suppress the T cell activity. They May also be used to treat autoimmune diseases.