Antibodies
Authors: Zouali Moncef 
Published: April 2016

Abstract

The immune system is able to generate a large repertoire of antibodies capable of recognising virtually all possible antigens present in the environment. An antibody is a Y‐shaped tetrameric protein characteristically composed of two heavy (H) and two light (L) polypeptide chains held together by covalent (disulfide) and noncovalent bonds. Each antibody chain is composed of a constant and a variable region, and its specificity is characterised by the uniqueness of its variable regions and the pairing of its H and L chains. At the three‐dimensional level, hypervariable regions of each chain converge to form a combining site that recognises antigenic determinants. Antibodies bind their nominal antigens with exquisite specificity and potentially neutralise their harmful effects, providing a first line of defence against pathogens. Rather than playing a protective role, certain antibodies may be responsible for undesirable functions, such as enhancing the infectious potential of pathogens or mediating hypersensitivity and autoimmune reactions.

Key Concepts

Each B lymphocyte is committed to the synthesis of one antibody specifically characterised by the uniqueness of its variable regions and the pairing of its heavy and light chains.

With antigen stimulation, B cells proliferate, differentiate and may recombine another constant exon, giving rise to IgG, IgA or IgE antibodies. This process, called isotype switching or class switching, enables an antibody of a given specificity to acquire a different constant region and, hence, to change its effector functions.

In humans, five classes of immunoglobulins, also called isotypes (IgG, IgM, IgA, IgD and IgE), differ in their physicochemical and serological properties and the amino acid sequence of their constant regions. There are four subclasses of IgGs (IgG1–IgG4) and two subclasses of IgAs (IgA1 and IgA2).

Secondary antibodies are dominated by IgG of higher affinity for the immunogen than the primary IgM. Persistence of memory lymphocytes for many years provides the organism with a potential long‐lasting protection against the invader and allows successful vaccination and prevention against pathogens.

An antibody is a Y‐shaped tetrameric protein characteristically composed of two heavy and two light polypeptide chains held together by covalent (disulfide) and noncovalent bonds. Each antibody chain is composed of a constant and a variable region.

At the three‐dimensional level, hypervariable regions of each chain converge to form a combining site that recognises antigenic determinants. Electrostatic forces between charged amino acid side chains, hydrogen bonds, van der Waals forces and hydrophobic forces, together with surface complementarity, impart antibody‐specific recognition.

The immune system is able to generate a large repertoire of antibodies able to recognise virtually all possible antigens present in pathogens and their products (bacteria, viruses and protozoal and metazoal parasites), and in the environment.

Antibodies secreted by B lymphocytes are responsible for the humoral immune response which plays a critical role in destruction of extracellular pathogens, prevention against the spread of intracellular infections and protection against toxins. The two structural portions of the antibody, that is the variable (Fab) and the constant (Fc) fragments, impart distinct biological functions.

Antibodies can contribute to elimination of undesirable cells by recruiting killer cells, a mechanism used to clear pathogen‐infected cells.

Rather than playing a protective role, antibodies may be responsible for undesirable functions, such as enhancing the infectious potential of certain pathogens or mediating hypersensitivity reactions.