Antibodies: Meaning, Structure and Mechanism

In this article we will discuss about:- 1. Meaning of Antibodies 2. Structure of Antibodies 3. Classes 4. Mechanism of Formation.

Meaning of Antibodies:

Antibodies, the magic bullets of the immune system, are glycoproteins formed in response to antigenic stimulation and counteract with antigens with great specificity.

The antibodies are found in the serum fraction of the blood and are also known as immunoglobulins (Ig). The chemical composition and structure of antibodies was revealed by G.M. Edelman and R.M. Porter who received in 1972 Nobel Prize in Physiology and Medicine for this contribution.

Structure of Antibodies:

Antibodies (immunoglobulins) have molecular weights ranging from 150,000 to 900,000 daltons. Electron microscopic viewing reveals that the antibody molecules resemble the letter “T” before they combine with antigens (Fig. 41.6A) while they resemble the letter “Y” after antigens combine with them (Fig. 41.6B).

It is considered that the antigen-antibody binding causes a rearrangement in the T-shape structure of the antibody molecule resulting in Y-shape thus providing more exposure to complement binding site of heavy-chain for further reactions.

An immunoglobulin (antibody) molecule is composed of four polypeptide chains (Fig. 41.7). Two of the four chains are identical to each other and are called heavy (H) chains because of greater number of amino acids (approximately 440 amino acids in each chain) and thus high molecular weight (approximately 50,000 daltons).

The remaining two chains, also identical to each other, are termed light (L) chains because of lesser number of amino acids, (approximately 440 amino acids in each chain) and thus low molecular weight (approximately 23,000 daltons). Each antibody molecule consists of a stem-part and two arms.

The stem-part of the antibody molecule is formed by approximately one-half of each heavy-chain, and the two chains are joined together by sulphur to sulphur (disulphide) bonds. Each arm of the antibody molecule consists of approximately one-half of a heavy-chain and one light-chain, again joined by a disulphide bond.

Both, light and heavy-chains also possess intrachain disulphide bonds that create “loops”, each loop called a domain. Each light-chain contains a single variable-domain (V_L) and a single constant-domain (C_L) whereas each heavy-chain contains a singly variable-domain (V_H) and three, sometimes, four constant-domains (C_H1, C_H2, C_H3 and in some cases C_H4).

The variable-domains form the variable (V) region while the constant-domains form the constant (C) region of each of the light and heavy-chains. Variable (V) regions of both the chains lie opposite to each other at the top of the two arms of the antibody molecule and represent the site where the antigen-antibody-binding takes place.

Remaining part of each of the chains represents the constant (C) region which varies in different class of antibodies with respect to its amino acid sequence, and thus determines the type of antigen-antibody reaction.

Classes of Antibodies:

All immunoglobulins (antibodies) physicochemical properties vary considerably because of variations in amino acid sequence in their heavy polypeptide chain. Therefore, according to their physicochemical properties, the immunoglobulins are subdivided into five different classes, namely, IgG, IgA, IgM, IgD, and IgE (Table 41.6).

Mechanism of Antibody Formation: Clonal Selection Theory:

These are the B-lymphocytes that produce antibodies in the body. Various theories have been proposed regarding the formation of antibodies, it is the clonal selection theory which has gained wide support. This theory states that there are a variety of B- lymphocytes present in the immune system.

These lymphocytes produce a small number of antibody molecules without any antigenic stimulation, and these antibody molecules integrate into the cytoplasmic membrane of their producer lymphocyte to serve as receptor site for specific antigen. When specific antigens enter the immune system, they interact only with complementary antibody- receptor site of B-lymphocyte.

In this way, such B-lymphocyte is “selected out” or “differentiated” by the union of specific antigen and its complementary antibody. This “selected out” or “differentiated” B-lymphocyte is stimulated to undergo multiplication leading to clones of plasma cells which synthesize and secrete a crop of antibodies complementary’ to the specific antigens that have entered the immune system.

In fact, the “selected out” or “differentiated” B-lymphocytes initiate multiplication forming two different cell populations: the primary B-lymphocytes and the secondary B-lymphocytes.

The primary, in response to antigenic stimulation, divide and transform into plasma cells which enter into the process of antibody formation, but the secondary B- lymphocytes do not. The latter circulate actively from blood to lymph and liver, and constitute memory cells.

These memory cells, however, transform into plasma cells when they are exposed to subsequent antigenic stimulation, perhaps years later, and enter into the process of antibody formation (Fig. 41.8A).

The B-lymphocytes get transformed into antibody-synthesizing mature plasma cells through a prolonged process (Fig. 41.8B). It has been revealed that a transformation period of about five days involving at-least eight successive cell generations is required for the formation of mature plasma cells from the B-lymphocyte cells.

With each cell generation, there is a progressive development of ribosomes and endoplasmic reticulum. By the fifth day, the RNA content of the plasma cell is very much increased and its entire protein synthesizing machinery is so activated that the endoplasmic reticulum cisternae are filled with antibody molecules, and the plasma cells rapidly secrete them.

It is estimated that about 90-95% of the total protein produced in plasma cells gives rise to antibodies, and about 10,000 antibody molecules are secreted per plasma cell per second. However, obviously thousands of plasma cells throughout the circulatory system are in operation for the production of antibodies at any given time.