ANTIBODY AND ANTIGEN

Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).

Specific genes for antibodies direct the construction of antigen specific regions of the antibody molecule. Such antigen-specific regions are located at the extremes of the Y-shaped immunglobulin-molecule.

Once the immune system has created an antibody for an antigen whose attack it has survived, it continues to produce antibodies for subsequent attacks from that antigen. This long-term memory of the immune system provides the basis for the practice of vaccination against disease. The immune system, with its production of antibodies, has the ability to recognize, remember, and destroy well over a million different antigens.

There are several types of simple proteins known as globulins in the blood: alpha, beta, and gamma. Antibodies are gamma globulins produced by B lymphocytes when antigens enter the body. The gamma globulins are referred to as immunoglobulins. In medical literature they appear in the abbreviated form as Ig. Each antigen stimulates the production of a specific antibody (Ig).

Antibodies are all in a Y-shape with differences in the upper branch of the Y. These structural differences of amino acids in each of the antibodies enable the individual antibody to recognize an antigen. An antigen has on its surface a combining site that the antibody recognizes from the combining sites on the arms of its Y-shaped structure. In response to the antigen that has called it forth, the antibody wraps its two combining sites like a "lock" around the "key" of the antigen combining sites to destroy it.

An antibody's mode of action varies with different types of antigens. With its two-armed Y-shaped structure, the antibody can attack two antigens at the same time with each arm. If the antigen is a toxin produced by pathogenic bacteria that cause an infection like diphtheria or tetanus, the binding process of the antibody will nullify the antigen's toxin. When an antibody surrounds a virus, such as one that causes influenza, it prevents it from entering other body cells. Another mode of action by the antibodies is to call forth the assistance of a group of immune agents that operate in what is known as the plasma complement system. First, the antibodies will coat infectious bacteria and then white blood cells will complete the job by engulfing the bacteria, destroying them, and then removing them from the body.

There are five different antibody types, each one having a different Y-shaped configuration and function. They are the Ig G, A, M, D, and E antibodies.

IgG is the most common type of antibody. It is the chief Ig against microbes. It acts by coating the microbe to hasten its removal by other immune system cells. It gives lifetime or long-standing immunity against infectious diseases. It is highly mobile, passing out of the blood stream and between cells, going from organs to the skin where it neutralizes surface bacteria and other invading microorganisms. This mobility allows the antibody to pass through the placenta of the mother to her fetus, thus conferring a temporary defense to the unborn child.

After birth, IgG is passed along to the child through the mother's milk, assuming that she nurses the baby. But some of the Ig will still be retained in the baby from the placental transmission until it has time to develop its own antibodies. Placental transfer of antibodies does not occur in horses, pigs, cows, and sheep. They pass their antibodies to their offspring only through their milk.

This antibody is found in body fluids such as tears, saliva, and other bodily secretions. It is an antibody that provides a first line of defense against invading pathogens and allergens, and is the body's major defense against viruses. It is found in large quantities in the bloodstream and protects other wet surfaces of the body. While they have basic similarities, each IgA is further differentiated to deal with the specific types of invaders that are present at different openings of the body.

Since this is the largest of the antibodies, it is effective against larger microorganisms. Because of its large size (it combines five Y-shaped units), it remains in the bloodstream where it provides an early and diffuse protection against invading antigens, while the more specific and effective IgG antibodies are being produced by the plasma cells.

The ratio of IgM and IgG cells can indicate the various stages of a disease. In an early stage of a disease there are more IgM antibodies. The presence of a greater number of IgG antibodies would indicate a later stage of the disease. IgM antibodies usually form clusters that are in the shape of a star.

This antibody appears to act in conjunction with B and T-cells to help them in location of antigens. Research continues on establishing more precise functions of this antibody.

The antibody responsible for allergic reactions, IgE acts by attaching to cells in the skin called mast cells and basophil cells (mast cells that circulate in the body). In the presence of environmental antigens like pollens, foods, chemicals, and drugs, IgE releases histamines from the mast cells. The histamines cause the nasal inflammation (swollen tissues, running nose, sneezing) and the other discomforts of hay fever or other types of allergic responses, such as hives, asthma, and in rare cases, anaphylactic shock (a life-threatening condition brought on by an allergy to a drug or insect bite). An explanation for the role of IgE in allergy is that it was an antibody that was useful to early man to prepare the immune system to fight parasites. This function is presently overextended in reacting to environmental antigens.

The presence of antibodies can be detected whenever antigens such as bacteria or red blood cells are found to agglutinate (clump together), or where they precipitate out of solution, or where there has been a stimulation of the plasma complement system. Antibodies are also used in laboratory tests for blood typing when transfusions are needed and in a number of different types of clinical tests, such as the Wassermann test for syphilis and tests for typhoid fever and infectious mononucleosis.

By definition, anything that makes the immune system respond to produce antibodies is an antigen. Antigens are living foreign bodies such as viruses, bacteria, and fungi that cause disease and infection. Or they can be dust, chemicals, pollen grains, or food proteins that cause allergic reactions.

Antigens that cause allergic reactions are called allergens. A large percentage of any population, in varying degrees, is allergic to animals, fabrics, drugs, foods, and products for the home and industry. Not all antigens are foreign bodies. They may be produced in the body itself. For example, cancer cells are antigens that the body produces. In an attempt to differentiate its "self" from foreign substances, the immune system will reject an organ transplant that is trying to maintain the body or a blood transfusion that is not of the same blood type as itself.

There are some substances such as nylon, plastic, or Teflon that rarely display antigenic properties. For that reason, nonantigenic substances are used for artificial blood vessels, component parts in heart pacemakers, and needles for hypodermic syringes. These substances seldom trigger an immune system response, but there are other substances that are highly antigenic and will almost certainly cause an immune system reaction. Practically everyone reacts to certain chemicals, for example, the resin from the poison ivy plant, the venoms from insect and reptile bites, solvents, formalin, and asbestos. Viral and bacterial infections also generally trigger an antibody response from the immune system. For most people penicillin is not antigenic, but for some there can be an immunological response that ranges from severe skin rashes to death.

Another type of antigen is found in the tissue cells of organ transplants. If, for example, a kidney is transplanted, the surface cells of the kidney contain antigens that the new host body will begin to reject. These are called human leukocyte antigens (HLA), and there are four major types of HLA subdivided into further groups. In order to avoid organ rejection, tissue samples are taken to see how well the new organ tissues match for HLA compatibility with the recipient's body. Drugs will also be used to suppress and control the production of helper/suppressor T-cells and the amount of antibodies.

Red blood cells with the ABO antigens pose a problem when the need for blood transfusions arises. Before a transfusion, the blood is tested for type so that a compatible type is used. Type A blood has one kind of antigen and type B another. A person with type AB blood has both the A and B antigen. Type O blood has no antigens. A person with type A blood would require either type A or O for a successful transfusion. Type B and AB would be rejected. Type B blood would be compatible with a B donor or an O donor. Since O has no antigens, it is considered to be the universal donor. Type AB is the universal recipient because its antibodies can accept A, B, AB, or O. One way of getting around the problem of blood types in transfusion came about as a result of World War II. The great need for blood transfusions led to the development of blood plasma, blood in which the red and white cells are removed. Without the red blood cells, blood could be quickly administered to a wounded soldier without the delay of checking for the blood antigen type.

Another antigenic blood condition can affect the life of newborn babies. Rhesus disease (also called erythroblastosis fetalis) is a blood disease caused by the incompatibility of Rh factors between a fetus and a mother's red blood cells. When an Rh negative mother gives birth to an Rh positive baby, any transfer of the baby's blood to the mother will result in the production of antibodies against Rh positive red blood cells. At her next pregnancy the mother will then pass those antibodies against Rh positive blood to the fetus. If this fetus is Rh positive, it will suffer from Rh disease. Tests for Rh blood factors are routinely administered during pregnancy.

Western medicine's interest in the practice of vaccination began in the eighteenth century. This practice probably originated with the ancient Chinese and was adopted by Turkish doctors. A British aristocrat, Lady Mary Wortley Montagu (1689–1762), discovered a crude form of vaccination taking place in a lower-class section of the city of Constantinople while she was traveling through Turkey. She described her experience in a letter to a friend. Children who were injected with pus from a smallpox victim did not die from the disease but built up immunity to it. Rejected in England by most doctors who thought the practice was barbarous, smallpox vaccination was adopted by a few English physicians of the period. They demonstrated a high rate of effectiveness in smallpox prevention.

By the end of the eighteenth century, Edward Jenner (1749–1823) improved the effectiveness of vaccination by injecting a subject with cowpox, then later injecting the same subject with smallpox. The experiment showed that immunity against a disease could be achieved by using a vaccine that did not contain the specific pathogen for the disease. In the nineteenth century, Louis Pasteur (1822–1895) proposed the germ theory of disease. He went on to develop a rabies vaccine that was made from the spinal cords of rabid rabbits. Through a series of injections starting from the weakest strain of the disease, Pasteur was able, after 13 injections, to prevent the death of a child who had been bitten by a rabid dog.

There is now greater understanding of the principles of vaccines and the immunizations they bring because of our knowledge of the role played by antibodies and antigens within the immune system. Vaccination provides active immunity because our immune systems have had the time to recognize the invading germ and then to begin production of specific antibodies for the germ. The immune system can continue producing new antibodies whenever the body is attacked again by the same organism or resistance can be bolstered by booster shots of the vaccine.

For research purposes there were repeated efforts to obtain a laboratory specimen of one single antibody in sufficient quantities to further study the mechanisms and applications of antibody production. Success came in 1975 when two British biologists, César Milstein (1927– ) and Georges Kohler (1946– ) were able to clone immunoglobulin (Ig) cells of a particular type that came from multiple myeloma cells. Multiple myeloma is a rare form of cancer in which white blood cells keep turning out a specific type of Ig antibody at the expense of others, thus making the individual more susceptible to outside infection. By combining the myeloma cell with any selected antibody-producing cell, large numbers of specific monoclonal antibodies can be produced. Researchers have used other animals, such as mice, to produce hybrid antibodies which increase the range of known antibodies.

Monoclonal antibodies are used as drug delivery vehicles in the treatment of specific diseases, and they also act as catalytic agents for protein reactions in various sites of the body. They are also used for diagnosis of different types of diseases and for complex analysis of a wide range of biological substances. There is hope that monoclonal antibodies will be as effective as enzymes in chemical and technological processes, and that they currently play a significant role in genetic engineering research.