Antibodies

Key Terms

• Antibody: A molecule of the immune system produced by B cells and targeted toward eliminating a specific antigen
• Antigen: Foreign material that stimulates the host organism to produce antibodies specific to that material
• Autoantibody: An antibody that binds to a protein that is a normal part of the human body from which it originates (as opposed to part of a bacteria, virus, or another human being)
• Heavy chain: The larger subunits of an antibody
• Immune system: The cells and organs of the body that fight infection; destruction of these cells leaves the body vulnerable to numerous diseases
• Immunoglobulin (Ig): A protein activated by the immune system
• Isotypes: The different classes of antibodies
• Light chain: The smaller subunits of an antibody
• Lymphocytes: White blood cells that specifically target a foreign organism for destruction; the two classes of lymphocytes are B cells, which produce antibodies, and T cells, which kill infected cells
• ALSO KNOWN AS: Gammaglobulins, immunoglobulins

Definition

Antibodies are proteins produced by the B lymphocyte white blood cells of the immune system of human and nonhuman animals in response to the introduction of foreign material such as viruses, bacteria, or parasites and their molecules. A particular B lymphocyte, or B cell, and its progeny cells (clones) produce a singular antibody molecule that binds specifically to a structural determinant on a specific foreign molecule (antigen). A given antigen may elicit different antibodies from a number of genetically distinct B lymphocytes, each of which produces a single type of antibody that binds to a select part of the foreign molecule. Such diverse antibody production is called polyclonal response, and the products are called polyclonal antibodies.

The antibody synthesized by a particular B lymphocyte and its clones is called a monoclonal antibody. Production of such antibodies is extremely useful and widely applied in medicine and science.

The basic unit of an antibody molecule is a structure comprising four polypeptides: two identical “heavy” chains and two identical “light” chains. Five classes of heavy chain lead to five classes of antibodies: IgG, IgD, IgE, IgA, and IgM (the letters Ig mean “immunoglobulin”).

Proteins in the antibody classes IgG, IgD, and IgE, and serum IgA, have the four-polypeptide-chain structure. IgA molecules in external secretions of the body have two or more of the basic four-polypeptide antibody unit in combination with J-chain and secretory component polypeptides. IgM consists of five of the basic four-polypeptide antibody units in combination with a J-chain polypeptide.

The basic four-chain unit of antibodies is further subdivided by proteolytic fragmentation into regions (domains) called Fab and Fc. The Fab region consists of the N-terminal parts of a heavy and light chain and binds to antigens; thus, each four-chain unit of antibodies contains two binding sites for antigens. The Fc region consists of the C-terminal parts of two heavy chains and modulates interactions of antibodies with other molecular and cellular components of the immune system. The Fc regions of different antibody classes differ in the effects that they mediate. Upon binding an antigen—for example, on a bacteria or virus—the Fc regions of IgG and IgM undergo a change in shape and activate another group of proteins that belong to the complement system. Other antibody classes do not do this. The different complement proteins are deposited on the surface of the microorganisms to which the IgG or IgM antibodies are bound with certain consequences. White blood cells such as macrophages and neutrophils can bind to complement proteins; through this attachment, the white blood cells engulf the foreign bodies and destroy them in a process called phagocytosis. Other complement proteins create holes in bacteria, which leads to their death.

White blood cells also use some of their cell-surface proteins, called Fc-gamma receptors, to bind to IgG antibodies that are attached to foreign infectious bodies. This also leads to phagocytosis, or the release of killing molecules from the white blood cells.

The Fc region of IgG is essential to the transplacental transfer of passive immunity from a pregnant female to her fetus. Placental Fc-gamma receptors bind the IgG molecules to allow their uptake and subsequent transfer across placental cells to fetal blood, thus providing months of antibody-mediated immunity to the newborn. In hoofed animals such as cows, goats, and sheep, immunoglobulins are transferred from a special form of mother’s milk called colostrum across the calf’s small intestine. This form of antibody transport does not occur in humans. However, IgA antibodies in human milk are believed to be beneficial in reducing the chance of intestinal infections in infants.

Viral and Microbial Diseases

Vaccines or immune responses to natural viral infection may elicit the production of antibodies that neutralize the infective agent. Such antibodies are important in the cases of influenza, hepatitis B, human papillomavirus, respiratory syncytial virus, measles, mumps, vaccinia, varicella-zoster viruses, and poliovirus. In the case of dengue virus infection, antibodies can prevent infection with a previously encountered strain, or they may exacerbate the effects of infection if the infection occurs with a different strain of the virus.

Antibodies also feature prominently in immunity or therapy directed against bacterial infection. Tetanus treatment includes the use of passive immunization with human antitetanus antibodies, which neutralize the toxin produced by the bacterium Clostridium tetani. Widespread childhood vaccinations include those against bacteria causing diphtheria, tetanus, and pertussis (DTP).

Methods and Diagnostics

Antibodies are used in various techniques for research studies of infectious diseases. These techniques include enzyme-linked immunoabsorbent assay (ELISA), immunofluorescence, Western blotting, immunoprecipitation, and flow cytometry. Antibodies research also assists in the creation of vaccines.

One newer research avenue aims to isolate B lymphocytes that make protective antibodies to influenza from vaccinated people. The antibodies would be used to provide passive immunity to influenza. Another promising avenue of research is the discovery of a new antibody, SC27, which researchers argue can neutralize all known variants of SARS-CoV-2. This virus was the cause of the devastating COVID-19 pandemic of 2020.

Impact

Antibody technology is prevalent in diagnostic testing for infectious diseases and is widely applied in biomedical research at a global level. Antibodies are used not only in research involving humans but also in animal diagnostic tests, both for farm animals and for household pets. Many companies around the world produce monoclonal and polyclonal antibodies from various animals, including mice, rats, rabbits, sheep, goats, donkeys, camels, sharks, chickens, ducks, and guinea pigs. Other companies produce instruments such as microplate readers, flow cytometers, fluorescence microscopes, electrophoresis equipment, and microarray readers, all of which are used in techniques involving antibodies.

Bibliography

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Coico, Richard, and Geoffrey Sunshine. Immunology: A Short Course. 7th ed., Wiley, 2015.

"Newly Discovered Antibody Protects Against All COVID-19 Variants." The University of Texas at Austin, 3 Sept. 2024, cockrell.utexas.edu/news/archive/10052-newly-discovered-antibody-protects-against-all-covid-19-variants-2. Accessed 31 Oct. 2024.

Parham, Peter. The Immune System. 4th ed., Garland, 2015.

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