Antibodies Elizabeth Newman

Elizabeth Newman

FYS Final Paper 2

Dr. Macosko

27 March 2006

Antibodies and the Detection of Viruses

In 2006, 4.3 million people were diagnosed with the human immunodeficiency virus (HIV). Also in 2006, 2.3 million children were living with HIV. Most cases of AIDS go undiagnosed, especially in underdeveloped countries stricken by poverty and lack of education. In the United States, individuals are often too embarrassed and too afraid to be tested for the HIV virus. Recently, researchers and scientists have developed an oral test that is both cheap and can be taken in the privacy of your home. This test is called Orasure. Orasure works by detecting the HIV antibodies present in the saliva of an infected person. An antibody, or immunoglobin, is a protein that binds to a specific antigen that must be eliminated by the immune system. Therefore, diagnostic test can be created to detect antibodies that are specific to certain diseases and viruses due to the structure of antibodies that allows for specificity. Antibodies play a vital role in immune responses by activating the Complement System. The Complement System is a series of thirty proenzymes that trigger immune responses through the complement cascade. The Complement System is activated when an antibody binds to a specific antigen. Due to the structure of antibodies, antibodies have the unique ability to distinguish between many different antigens. Because of the antibodies’ specificity, antibodies are used in medicine in order to detect specific diseases, such as HIV.

The structure of antibodies allows for their specificity and the diagnosis of viruses. Antibodies are composed of four polypeptides: two heavy chains and two light chains. These two chains form a “y” shape. The amino acid sequence located at the tips of the antibody is the region that distinguishes one antibody from another and gives the antibody its specificity. The tip of the antibody is called the variable region. The antibody will only bind to an antigen with the corresponding amino acid sequence. There are 110-130 amino acids that make different combinations at the variable region of the antibody. Also, there are constant regions on the antibody. The constant regions are responsible for the biologic functions of the antibodies. The unique combinations of amino acids at the variable region are used in the classification of antibodies.

This diagram shows the y-shape structure of the antibody and the variable region of the antibody.

The heavy chains and the light chains have different functions. The light chains of the antibodies are divided into two domains. The domains consist of about 110 amino acids. The two domains are called the N-terminal and the C-terminal. The N-terminal is highly variable and is called the V_L region (very light). On the contrary, the C-terminal remains constant and is called the C_L region (constant light). The heavy chains are larger than the light chains, but their structures are very similar. The heavy chains have a N-terminal that is composed of 110 amino acids that vary in sequence from one another. The N-terminal is called the V_H region (variable heavy). There is also a C_H region that remains constant (constant heavy). Therefore, these chains allow for the variability of antibodies that is essential for antigen binding.

Antibodies are divided into five classes according the combinations of amino acids at the variable region. The variable region is divided into two different subunits: the hypervariable region and the framework region. The hypervariable region binds to the surface of the antigen and consists of many different amino acids. The framework regions form beta sheet structures that act as structural supports when the hypervariable region binds to an antigen.

The functional fragments of antibodies each play a different role during the process of binding to an antigen. The Fab fragment of the antibody contains the antigen binding sites. The Fab fragment is located on the heavy chain and is created through papain synthesis. The Fc fragment is the constant region that is created through papain digestion and consists of a dimmer of the heavy chain. The Fc fragment controls the effecter functions of the antibody. The F(ab’)₂ fragment binds to the antigen, but is not involved in effecter functions. It is created through pepsin digestion and consists of the light chain. The F(ab’)₂ is dimeric due to the interchain disulfide bridge that binds two hydrogen atoms. The F(ab)’ fragment is a monomer that forms through the reduction of the disulfide bonds that bridge the hydrogen atoms of the F(ab’)_2. The Fd fragment is created through the reduction of the Fab fragment. Thus, each fragment is essential in the specificity of the antibody because each fragment plays a vital role in the binding of the antibody to the specific antigen.

This diagram shows the Fc and Fab regions of the antibody and the disulfide bridge that holds the antibody in its “y” shaped structure. Also, the light and heavy chains are shown.

There are five classes of antibodies: IgM (pentamer), IgG (monomer), IgA (dimmer), IgE (monomer), and IgD (monomer). IgM antibodies are produced directly after the recognition of the antigen. Eventually, the concentration of IgM in the blood will decrease as the immune response continues. IgM has a total of five or six Fc sites for antigen binding. IgG can be found in blood and in tissue fluids. IgG proteins pass through the placenta and allow for passive immunity in a fetus. IgG is less effective in the complement system because it is a monomer and has less Fc sites open for binding to the antigen. IgA antibodies are localized antibodies found in tears, saliva, and breast milk. IgA provides immunity for an infant. IgA consists of a J chain and a secretary component. IgE cause the release of chemicals that cause allergic reactions.

Furthermore, when an antibody binds to an antigen, several different mechanisms may occur. When viral neutralization occurs, the antibody blocks the virus’s ability to affect the host cell. Opsoniztion occurs when an antibody coats the surface of a bacterial cell surface which increases phagocytosis. Therefore, the specificity of the antibodies allows the antibodies to serve many unique functions.

As said before, antibodies have become very important in the diagnosis of many diseases. For instance, HIV diagnostic tests recognize the HIV antibodies in a person’s blood. Recently, a HIV test, called Orasure, was developed to be used at home, giving people privacy and comfort. Orasure collects HIV antibodies from the saliva. Through the antibodies in the saliva, Orasure can determine the presence of the HIV antibodies. In order to use this test, an individual simply swipes the side of his or her cheek and the test is completed in the matter of seconds. Because of this test, many people who were once afraid to be tested for HIV, will take the test. Furthermore, since these tests are easy to take and give definite results, they could be administered easily in underdeveloped countries. Thus, antibodies and the technology reliant on antibodies are very important in the world of medicine.

Overall, the structure of antibodies allows for specificity and allows for the antibody to differentiate between different antigens. The many different fragments of the antibodies perform specific functions, but work together in order to trigger an immune response. Antibodies are very important in current research to detect certain diseases such as HIV. If researchers learn more about the specificity of antibodies, more tests can be made to diagnosis a large range of different diseases. Furthermore, recent technological advances allow scientists to create diagnostic tests that are more convenient for the patient, such as Oraure. Orasure will ensure the privacy of a patient and be very helping in underdeveloped countries. Orasure is especially important because if more people are comfortable taking the test, the spreading of the HIV virus will greatly decrease. Thus, a disease that causes about 84,000 deaths each year can be better controlled. Overall, without the specificity of antibodies, the HIV virus could not be detected, and the virus would spread at a faster rate and those infected with the virus would never be treated.