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Original Author(s): Emilia O'Connor
Last updated: 7th December 2020
Revisions: 15

Original Author(s): Emilia O'Connor
Last updated: 7th December 2020
Revisions: 15

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Antibodies, or immunoglobulins, are Y-shaped glycoproteins produced by differentiated B-cells called plasma cells. They are present in bodily fluids, secretions and on the surface of specialised cells. Antibodies recognise and bind unique epitopes, which are molecular structures on the surface of their specific antigens.

In this article, we will consider antibody structure, function, classes and some clinical relevance.


Antibody molecules consist of two identical heavy chains and two identical light chains, which give the antibody two antigen-binding sites. The two heavy chains are connected by disulphide bonds, which also bind the heavy chains to the light chains. The heavy and light chains both consist of a series of amino-acid sequences, each corresponding to a protein domain. Each light chain has two domains (one variable and one constant), and each heavy chain has four domains (one variable and three constant).

There are five heavy chain types: μ (Mu), γ (Gamma), α (Alpha), ε (Epsilon) and δ (Delta), which classify IgM, IgG, IgA, IgE and IgD respectively.

There are two light chain types: κ (kappa) and λ (lambda). Each antibody can have either two κ or two λ chains but not one of each. The ratio of κ and λ is 2:1, but there are no functional differences between the types.

Each antibody contains two variable regions and one constant region.

The Fab regions (fragment antigen binding) contain the variable domains of the light and heavy chains. The variable domains make up the variable regions of the antibody. Variable regions give the antibody its antigen specificity, and therefore, differ between antibodies. Furthermore, each Fab region contains two constant domains; one from the heavy chain component and one from the light chain component.

The Fc region (fragment crystallisable), is made up of the remaining constant domains from the two heavy chains. The Fc region interacts with different immune cells and mediates various functions. For example, opsonisation (see below).

The constant region involves the constant domains from both the Fab and Fc parts. The heavy chain constant domains determine antibody class and are the same for all antibodies of the same class.

IgA and IgG antibodies also have hinge regions, which are flexible amino-acid chains in the central part of the heavy chains.

Illustrates the structure of antibodies.

Figure 1- A) the constant and variable domains of the heavy and light chains; B) Antibody Light chains and heavy chains ; C) Fab and Fc regions and functions; D) 3D illustration of antibody structure.


Antibodies are classified according to heavy chain type, which is encoded by a gene on chromosome 14. The different classes are IgG, IgA, IgM, IgD and IgE; in descending order of abundance in serum.


IgG is the most abundant antibody class. It is expressed on the surface of mature B-cells and in serum. There are four subclasses: IgG1, IgG2, IgG3 and IgG4; in order of serum concentration. IgG is the only antibody to cross the placenta and consequently, it transfers passive immunity from mother to foetus. Newborns, therefore, have high IgG concentrations in the first 3-6 months of life.


IgA is the most prevalent antibody in secretions, such as saliva and mucous. There are two subclasses, IgA1 and IgA2. IgA forms a dimer, where a joining chain connects 2 Y-shaped molecules, giving it four antigen-binding sites in total. IgA antibodies are resistant to enzymatic digestion and act principally as neutralising antibodies. They are secreted in breastmilk and so can protect a breastfed newborn from infections. They also protect mucosal surfaces from pathogenic invasion; examples include nose, lungs, and intestines


IgM antibodies are expressed on the surface of B-cells as monomers but secreted as pentameters. A pentameter has five antibodies connected by a joining chain, with ten antigen-binding sites in total. It is the first immunoglobulin produced during foetal development and the first produced by B-cells against a new infection. IgM has high avidity, meaning the antibody-antigen complex is strong, but low affinity, so the strength of a single epitope-antibody interaction is weak. Along with IgD, IgM is expressed by all naïve B-cells.

Figure 2 – IgM pentamer structure


IgD is present on the surface of B-cells. It has a role in B-cell and antibody production. Along with IgM, IgD is expressed by all naïve B-cells.


IgE is found mainly on mast cells but is present at low levels in the blood and extracellular fluid. IgE is associated with allergy, particularly type I hypersensitivity reactions such as atopic disease (e.g. asthma and dermatitis) and anaphylaxis. It triggers histamine release from mast cells and basophils. It is also involved in the body’s response to parasitic infections.


The Fc region binds different immune cell receptors (e.g. on phagocytes) and mediates various effector functions.


Antibodies (mainly IgG1 and IgG3) can act as opsonins by binding to the pathogen, which allows better recognition by phagocytes. Phagocytes then bind to the antibodies via their Fc receptors and initiate phagocytosis.

Illustrates opsonisation.

Figure 3- Pathogen opsonised by multiple antibodies; Phagocytes bind to these antibodies via their Fc receptors and initiate phagocytosis.


Antibodies can prevent pathogens accessing cells by blocking different parts of the bacterial or viral cell surface. Consequently, this neutralises certain viruses and bacterial toxins. Neutralising antibodies must have high affinity to be effective; IgG and IgA antibodies have the greatest effect.

Illustrates the process of neutralisation by antibodies.

Figure 4- 1A) Pathogens can bind to body cells directly and cause harm; 1B) Antibodies can bind to pathogens and prevent this process; 2A) Pathogens can release molecules, like toxins, which can cause harm; 2B) Antibodies can recognise these molecules and neutralise their effects.

Complement activation

The classical complement pathway can be activated by IgM or IgG antibodies when they bind microbial surfaces. This releases C3b, which acts as an opsonin, and other complement components which form membrane-attack complexes. These can punch holes in the pathogen plasma membrane and cause cell lysis.

Immune complexes

The binding of multiple antigens and antibodies together can form immune complexes. Complex formation limits the antigens’ diffusing ability. Ultimately, complexes will be targeted for phagocytosis.

Antibody-dependent cell-mediated cytotoxicity

Antibodies bind and opsonise target cells. Natural killer cells then recognise the Fc portion of the antibody and release cytotoxic granules (perforin and granzymes) into the target cell which trigger apoptosis, and interferon, which attracts phagocytes.

Clinical Relevance


Autoantibodies are antibodies that react with the body’s antigens when the immune system cannot distinguish between self and non-self. Autoantibodies are found in healthy people. However, they can lead to autoimmune disease in some individuals. Below are common examples of autoimmune disease.

Autoantibody Antibody target Disease
Rheumatoid factor (RF) Fc portion of IgG Rheumatoid arthritis
Anti-thyrotropin receptor antibodies (TRAbs) TSH receptor of thyroid Graves’ disease
Anti-tissue transglutaminase antibodies (anti-tTG) Tissue transglutaminase enzyme Coeliac disease

Monoclonal Antibodies

Monoclonal antibodies are man-made molecules designed to act as antibodies. In cancer treatment, monoclonal antibodies can bind to cancer-specific antigens and therefore, induce a specific immune response against cancer cells. An example of this, is trastuzumab (aka Herceptin), which is used to treat HER2 receptor-positive breast cancer. Monoclonal antibodies can also be used to treat autoimmune diseases.