Antibody and antigen

IgG

Resources

The antibody and antigen reaction is an important protective mechanism against invading foreign substances. The antibody and antigen reaction, together with phagocytosis, constitute the immune response (humoral immune response). Invading foreign substances are antigens, while the antibodies, or immunoglobulins, are

specific proteins generated (or previously present in blood, lymph, or mucosal secretions) to react with a specific antigen.

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.

Once the immune system has created an antibody for an antigen, it retains the capability of being able to produce the specific antibodies for subsequent exposure to that antigen. This long-term memory of the immune system provides the basis for the practice of vaccination against disease. The immune system is capable of producing countless structurally different antibodies, each of which is unique to the particular antigen that is recognized as foreign by the immune system.

There are three 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 (Ig).

Antibodies have a Y-shape. The branches are variable in their composition, while the stalk portion is common to most antibodies. 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, one 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, which 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

IgG is the most common type of antibody. It is the most common 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. 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 ruminant animals, such as horses, pigs, cows, and sheep. They pass their antibodies to their offspring only through their milk.

IgA is found in body fluids such as tears, saliva, mucosa, 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.

IgM is the largest of the antibodies. It is effective against larger microorganisms. Because of its large size (it combines 5 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. As a typical infection progresses, many B cells shift from IgM production to production of IgG 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.

IgD acts in conjunction with B cells and T cells to help them in location of antigens. Research continues on establishing more precise functions of this antibody.

IgE is the antibody that is responsible for allergic reactions; it attaches 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 other foreign materials such as 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.

The process of protection against future exposure to an antibody by the deliberate introduction of an antigenic molecule is called vaccination. 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 an immunity to it. Rejected in England by most doctors who thought the practice was barbarous, smallpox vaccination was adopted by a few English

KEY TERMS

B cell— Immune system white blood cell that produces antibodies.

Booster— A dose of antigen given after an initial immunization to provide stronger immunity.

Complement system— A series of 20 proteins that “complement” the immune system; complement proteins destroy virus-infected cells and enhance the phagocytic activity of macrophages.

HLA (human leukocyte antigen)— The genetic markers showing tissue compatibility.

Immunoglobulin— The protein molecule that serves as the primary building block of antibodies.

Rh incompatibility disease— A lethal blood disease of the fetus or newborn infant caused by transmission of maternal antibodies across the placenta to the fetus. It is due to Rh factor incompatibility between the mother and the fetus.

T cells— Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.

Universal donor/recipient— Blood type O is the universal donor; blood type AB is the universal recipient.

physicians of the period; they demonstrated an almost 100% 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.

Because of our knowledge of the role played by antibodies and antigens within the immune system, there is now greater understanding of the principles of vaccines and the immunizations they bring. 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 (1927-2002) and Georges Kohler (1946-1995) were able to clone Ig-producing 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 they will be as effective as enzymes in chemical and technological processes and that they will play a role in genetic engineering research.

See also Anaphylaxis; Transplant, surgical.

Resources

BOOKS

Golldsby, Richard A., Thomas J. Kindt, Janis Kuby, and Barbara A. Osborne. Immunology. 5th ed. New York: W.H. Freeman & Co., 2003.

Janeway, C. Immunobiology. New York: Garland Science, 2004.

Strauss, Hans J., Yutaka Kawakami, and Giorgio Parmiani. Tumor Antigens Recognized by T Cells and Antibodies. Boca Raton: CRC, 2003.

Jordan P. Richman

Antibody and antigen

The antibody and antigen reaction is an important protective mechanism against invading foreign substances. The antibody and antigen reaction, together with phagocytosis, constitute the immune response (humoral immune response). Invading foreign substances are antigens while the antibodies, or immunoglobulins, are specific proteins generated (or previously and present in blood , lymph or mucosal secretions) to react with a specific antigen.

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.

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 which 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.

Functions of antibody types

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

IgG is the most common type of antibody. It is the most common 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 ruminant animals, such as horses , pigs , cows, and sheep . They pass their antibodies to their offspring only through their milk.

IgA

This antibody is found in body fluids such as tears, saliva, mucosa, 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.

IgM

Since this is the largest of the antibodies, it is effective against larger microorganisms. Because of its large size (it combines 5 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. As an typical infection progresses, many B cells shift from the IgM production to production of IgG 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.

IgD

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.

IgE

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.

Types of antigens

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.

Vaccination

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 an 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 an almost 100% 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.

Monoclonal antibodies

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 they will be as effective as enzymes in chemical and technological processes and that they will play a role in genetic engineering research.

See also Anaphylaxis; Transplant, surgical.

Resources

books

Roitt, Ivan M., Peter J. Delves Roitt's Essential Immunology. 10th. ed. Oxford: Blackwell Scientific Publications, 2001.

Sompayrac, Lauren M. How the Immune System Works. Oxford: Blackwell Scientific Publications, 1999.

Jordan P. Richman

KEY TERMS

B cell

—Immune system white blood cell that produces antibodies.

Booster

—A dose of antigen given after an initial immunization to provide stronger immunity.

Complement system

—A series of 20 proteins that "complement" the immune system; complement proteins destroy virus-infected cells and enhance the phagocytic activity of macrophages.

HLA (human leukocyte antigen)

—The genetic markers showing tissue compatibility.

Immunoglobulin

—The protein molecule that serves as the primary building block of antibodies.

Rh incompatibility disease

—A lethal blood disease of the fetus or newborn infant caused by transmission of maternal antibodies across the placenta to the fetus. It is due to Rh factor incompatibility between the mother and the fetus.

T cells

—Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.

Universal donor/recipient

—Blood type O is the universal donor; blood type AB is the universal recipient.

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.

See also Antibody-antigen, biochemical and molecular reactions; Antibody formation and kinetics; Antibody, monoclonal; Antigenic mimicry; Immune stimulation, as a vaccine; Immunologic therapies; Infection and resistance; Infection control; Major histocompatibility complex (MHC)

Antibody and antigen

Antibodies, also called immunoglobulins, are proteins manufactured by the body that help fight against foreign substances called antigens. When an antigen enters the body, it stimulates the immune system to produce antibodies. (The immune system is the body's natural defense system.) The antibodies attach, or bind, themselves to the antigen and inactivate it.

Every healthy adult's body has small amounts of thousands of different antibodies. Each one is highly specialized to recognize just one kind of foreign substance. Antibody molecules are typically Y-shaped, with a binding site on each arm of the Y. The binding sites of each antibody, in turn, have a specific shape. Only antigens that match this shape will fit into them. The role of antibodies is to bind with antigens and inactivate them so that other bodily processes can take over, destroy, and remove the foreign substances from the body.

Antigens are any substance that stimulates the immune system to produce antibodies. Antigens can be bacteria, viruses, or fungi that cause infection and disease. They can also be substances, called allergens, that bring on an allergic reaction. Common allergens include dust, pollen, animal dander, bee stings, or certain foods. Blood transfusions containing antigens incompatible with those in the body's own blood will stimulate the production of antibodies, which can cause serious, potentially life-threatening reactions.

Classes of antibodies and their functions

There are five classes of antibodies, each having a different function. They are IgG, IgA, IgM, IgD, and IgE. Ig is the abbreviation for immunoglobulin, or antibody.

IgG antibodies are the most common and the most important. They circulate in the blood and other body fluids, defending against invading bacteria and viruses. The binding of IgG antibodies with bacterial or viral antigens activates other immune cells that engulf and destroy the antigens. The smallest of the antibodies, IgG moves easily across cell membranes. In humans, this mobility allows the IgG in a pregnant woman to pass through the placenta to her fetus, providing a temporary defense to her unborn child.

IgA antibodies are present in tears, saliva, and mucus, as well as in secretions of the respiratory, reproductive, digestive, and urinary tracts. IgA functions to neutralize bacteria and viruses and prevent them from entering the body or reaching the internal organs.

IgM is present in the blood and is the largest of the antibodies, combining five Y-shaped units. It functions similarly to IgG in defending against antigens but cannot cross membranes because of its size. IgM is the main antibody produced in an initial attack by a specific bacterial or viral antigen, while IgG is usually produced in later infections caused by the same agent.

Words to Know

Allergen: A foreign substance that causes an allergic reaction in the body.

B cells: Cells produced in bone marrow that secrete antibodies.

Immune response: The production of antibodies in response to foreign substances in the body.

Immunity: The condition of being able to resist the effects of a particular disease.

Immunization: The process of making a person able to resist the effects of specific foreign antigens.

Inoculate: To introduce a foreign antigen into the body in order to stimulate the production of antibodies against it.

Monoclonal antibodies: Identical antibodies produced by cells cloned from a single cell.

Proteins: Large molecules that are essential to the structure and functioning of all living cells.

Vaccine: Preparation of a live weakened or killed microorganism of a particular disease administered to stimulate antibody production.

IgD is present in small amounts in the blood. This class of antibodies is found mostly on the surface of B cells—cells that produce and release antibodies. IgD assists B cells in recognizing specific antigens.

IgE antibodies are present in tiny amounts in serum (the watery part of body fluids) and are responsible for allergic reactions. IgE can bind to the surface of certain cells called mast cells, which contain strong chemicals, including histamine. (Histamines are substances released during an allergic reaction. They cause capillaries to dilate, muscles to contract, and gastric juices to be secreted.) When an allergen such as pollen binds with its specific IgE antibody, it stimulates the release of histamine from the mast cell. The irritating histamine causes the symptoms of an allergic reaction, such as runny nose, sneezing, and swollen tissues.

Tests that detect the presence of specific antibodies in the blood can be used to diagnose certain diseases. Antibodies are present whenever antigens provoke an immune reaction in the test serum.

The immune response

When a foreign substance enters the body for the first time, symptoms of disease may appear while the immune system is making antibodies to fight it. Subsequent attacks by the same antigen stimulate the immune memory to immediately produce large amounts of the antibody originally created. Because of this rapid response, there may be no symptoms of disease, and a person may not even be aware of exposure to the antigen. They have developed an immunity to it. This explains how people usually avoid getting certain diseases—such as chicken pox—more than once.

Immunization

Immunization is the process of making a person immune to a disease by inoculating them against it. Inoculation is the introduction of an antigen into the body—usually through an injection—to stimulate the production of antibodies.

The medical practice of immunization began at the end of the eighteenth century, when English physician Edward Jenner (1749–1823) successfully used extracts of body fluid from a dairymaid (a woman employed in a dairy) infected with cowpox (a mild disease) to inoculate a young boy against smallpox, a then-common and often fatal viral disease. Jenner called his method "vaccination," using the Latin words vacca, meaning "cow," and vaccinia, meaning "cowpox." Because the two diseases are caused by similar viruses that have the same antigens, antibodies that work against cowpox will also fight smallpox.

In 1885, a rabies vaccine developed by French scientist Louis Pasteur (1822–1895) from the spinal fluid of infected rabbits proved to be successful. Since that time, vaccines have been developed for many diseases, including diphtheria, polio, pertussis (whooping cough), measles, mumps, rubella (German measles), hepatitis, and influenza. Vaccines are made from either weakened live or killed microorganisms. When introduced into the body, they stimulate the production of antibodies, providing active immunity against bacterial and viral diseases.

Monoclonal antibodies

Monoclonal (mono means "one") antibodies are identical antibodies produced by clones (exact copies) of a single cell. The cell from which the clones are made is created by combining a B cell containing a specific antibody with a myeloma (a form of cancer) cell. The resulting hybrid produces the specific antibody of the parent B cell and divides indefinitely like the parent cancer cell. Clones of the hybrid cell produce virtually unlimited amounts of one type, or monoclonal, antibodies. Monoclonal antibodies are used in many medical diagnostic tests, such as pregnancy tests, and in the treatment of cancer and other diseases.

Autoimmune Disease

Autoimmune diseases occur when the body's immune system loses the ability to recognize the difference between self and nonself. This results in the body producing antibodies, called autoantibodies, against its own tissues. Normally, antibodies are only produced against microorganisms that invade the body. The inability to make a distinction between self and nonself may lead to the destruction of body tissue and result in a number of chronic, debilitating diseases.

The cause of autoimmune reactions is not known. It is thought that infection by viruses and bacteria may trigger an autoimmune response. In addition, exposure to certain chemicals and ultraviolet light may alter proteins in the skin; the body may then become sensitive to these proteins and produce autoantibodies against them. Certain individuals seem to be genetically predisposed to have autoimmune responses. Some diseases that are associated with autoimmune responses are rheumatoid arthritis, lupus erythematosus, and pernicious anemia.

[See also Allergy; Blood; Immune system; Rh factor; Transplant, surgical; Vaccine ]

Antibody

In 1890 scientists transferred blood from animals with diphtheria to animals never exposed to the disease. The second group of animals became resistant (or immune) to diphtheria. Over the next decade, investigators such as Emil von Behring, Shibasabura Kitasato, Karl Landsteiner, and Paul Ehrlich studied this phenomenon and discovered that this transfer of immunity occurred because of proteins called antibodies. This type of immunity was called humoral immunity. The word "humoral" refers to body fluids, and antibodies are found in the liquid part of the blood. Antibodies are an extremely important part of the body's defense against infection.

Antibodies are also called gamma globulins and immunoglobulins (abbreviated "Ig"). Vertebrate animals make antibodies, but invertebrate animals do not. They are made by white blood cells called B lymphocytes (or B cells). Antibodies are capable of attaching to foreign invaders, targeting them for destruction. They can do this because of their structure.

Structure

Antibodies are Y-shaped molecules. At the end of each arm of the Y is a pocket called an antigen binding site. An antigen is a piece of a foreign invader that starts an immune response. An antigen fits inside the antigen binding site of an antibody because the structures match, like a key in a lock. Each antibody has antigen binding sites different from other antibodies. Consequently, each antibody recognizes a different piece of a foreign invader. This explains how the immune system specifically identifies a wide variety of foreign invaders.

Each antibody is composed of four chains of amino acids . There are two light chains and two heavy chains. The arms of the antibody contain both light and heavy chains. They are called the variable regions because this is where antigen binding sites are located. The genes that determine the variable region's structure undergo a series of rearrangements as a B cellmatures. Millions of possible antibodies can be produced by this rearrangement. However, once the genes are rearranged, the B cell is committed to making only one type of antibody.

The base of the Y contains only heavy chains and is called the constant region. The constant region determines the antibody's class. Mammals make five main classes of antibodies. Each class works differently to protect the body from disease.

Classes of Antibodies

IgM and IgD are two classes of antibodies. They are found on the surface of mature B cells. If a B cell encounters an invader with antigens that match its antibodies (like a key in a lock), the antigen is brought inside and then displayed on the surface, akin to waiving the enemy's captured flag. This alerts other immune cells that it is ready to be activated. If the B cell gets the appropriate signals from T cells , it becomes activated, dividing rapidly and secreting antibodies into the surrounding fluid. B cells that release antibodies are also called plasma cells. The first class of antibodies secreted by B cells is IgM. Like all antibodies, IgM travels through the body's fluids, binding to antigens to eliminate the invader. IgM antibodies are often found in groups of five, forming a structure called a pentamer.

The B cell may then switch the class of antibodies it is secreting to more effectively remove the invader. It will most likely start producing the IgG class of antibodies. Unlike other antibodies, IgG can be transferred across the placenta from mother to fetus.

B cells may also produce IgA antibodies. Because IgA is found in secretions such as milk, tears, saliva, sweat, and mucus, it represents an important first line of defense against invaders trying to enter the body. IgA antibodies are often found in groups of two, forming a structure called a dimer.

Finally, B cells may produce IgE antibodies. IgE provides protection against parasitic infections. IgE binds to white blood cells called mast cells and basophils. When an antigen is encountered, IgE signals these cells to release chemicals that cause inflammation. This process is responsible for the symptoms of many allergies.

The binding of antibodies to antigens protects the body in several ways. The invader may simply be neutralized, unable to infect healthy cells. Secondly, large numbers of antibodies can bind large numbers of antigens, forming an immune complex. Immune complexes are large and precipitate out of solution, increasing the chance that white blood cells called phagocytes will destroy them. In fact, any antigen with an attached antibody is likely to be phagocytosed. This is because phagocytes can bind to antibodies, allowing phagocytes to more easily recognize the antigen. Finally, blood proteins called complement can destroy the membranes of foreign cells. Complement proteins do this more easily when antibodies are attached to the target. Phagocytosis and complement proteins are both examples of nonspecific immunity.

As the research since the late 1800s has shown, interactions between specific antibodies and nonspecific defenses give the immune system a powerful tool to eliminate invaders.

see also Autoimmune Disease; Immune Response; Nonspecific Defense; T Cell

John M. Ripper

Bibliography

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Friedlander, Mark P., Jr., and Terry M. Phillips. The Immune System: Your Body's Disease-Fighting Army. Minneapolis, MN: Lerner Publications Company, 1998.

National Institutes of Health. Understanding the Immune System. Washington, DC: National Institutes of Health, 1993.

Nossel, Gustav J. "Life, Death, and the Immune System." Scientific American 269, no. 3 (1993): 53–62.

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