Immunoglobulins and immunoglobu-lin deficiency syndromes

Immunoglobulins are proteins that are also called antibodies. The five different classes of immunoglobulins are formed in response to the presence of antigens. The specificity of an immunoglobulin for a particular antibody is exquisitely precise

The five classes of immunoglobulins are designated IgA, IgD, IgG, IgE, and IgM. These share a common structure. Two so-called heavy chains form a letter "Y" shape, with two light chains linked to each of the upper arms of the Y. The heavy chains are also known as alpha, delta, gamma, epsilon, or mu. The light chains are termed lambda or kappa.

The IgG class of immunoglobulin is the most common. IgG antibody is routinely produced in response to bacterial and viral infections and to the presence of toxins. IgG is found in many tissues and in the plasma that circulates throughout the body. IgM is the first antibody that is produced in an immune response. IgA is also produced early in a body's immune response, and is commonly found in saliva, tears, and other such secretions. The activity of IgD is still not clear. Finally, the IgE immunoglobulin is found in respiratory secretions.

The different classes of immunoglobulins additionally display differences in the sequence of amino acids comprising certain regions within the immunoglobulin molecule. For example, differences in the antigen-binding region, the variable region, accounts for the different antigen binding specificities of the various immunoglobulins. Differences in their structure outside of the antigen binding region, in an area known as the constant region, accounts for differences in the immunoglobulin in other functions. These other functions are termed effector functions, and include features such as the recognition and binding to regions on other cells, and the stimulation of activity of an immune molecule known as complement .

The vast diversity of immunoglobulin specificity is due to the tremendous number of variations that are possible in the variable region of an immunoglobulin. A certain immune cell known as a B cell produces each particular immunoglobulin. Thus, at any particular moment in time, there are a myriad of B cells actively producing a myriad of different immunoglobulins, in response to antigenic exposure.

Immunoglobulins can exist in two forms. They can be fixed to the surface of the B cells that have produced them. Or they can float freely in body fluids, essentially patrolling until a recognizable antigen is encountered. The protection of the body from invading antigens depends on the production of immunoglobulins of the required type and in sufficient quantity.

Conditions where an individual has a reduced number of immunoglobulins or none at all of a certain type is known as an immunoglobulin deficiency syndrome. Such syndromes are typically the result of damage to B cells.

People with immunoglobulin deficiencies are prone to more frequent illness than those people whose immune systems are fully functional. Often the illnesses are caused by bacteria , in particular bacteria that are able to form a capsule surrounding them. A capsule is not easily recognized by even an optimally performing immune system . As well, immunoglobulin deficiency can render a person more susceptible to some viral infections, in particular those caused by echovirus, enterovirus, and hepatitis B.

Immunoglobulin deficiencies can take the form of a primary disorder or a secondary disorder. A secondary deficiency results from some other ongoing malady or treatment. For example, chemotherapy for a cancerous illness can compromise the immune system, leading to an immunodeficiency . Once the treatment is stopped the immunodeficiency can be reversed. A primary immunodeficiency is not the result of an illness or medical treatment. Rather, it is the direct result of a genetic disorder or a defect to B cells or other immune cells.

X-linked agammaglobulinemia results in an inability of B cells to mature. This results in the production of fewer B cells and in a lack of "memory" of an infection. Normally, the immune system is able to rapidly respond to antigen that has been encountered before, because of the "memory" of the B cells. Without this ability, repeated infections caused by the same agent can result.

Another genetically based immunoglobulin deficiency is known as selective IgA deficiency. Here, B cells fail to switch from producing IgM to produce IgA. The limited amount of IgA makes someone more prone to infections of mucosal cells. Examples of such infections include those in the nose, throat, lungs, and intestine.

Genetic abnormalities cause several other immunodeficiency syndromes. A missing stretch of information in the gene that codes for the heavy chain of IgG results in the production of an IgG that is structurally incomplete. The result is a loss of function of the IgG class of antibodies, as well as the IgA and IgE classes. On a subtler level, another genetic malfunction affects the four subclasses of antibodies within the IgG class. The function of some of the subclasses are affected more so than other subclasses. Finally, another genetic mutation destroys the ability of B cells to switch from making IgM to manufacture IgG. The lack of flexibility in the antibody capability of the immune system adversely affects the ability of the body to successfully fight infections.

Transient hypogammaglobulinemia is an immunodeficiency syndrome that is not based on a genetic aberration. Rather, the syndrome occurs in infants and is of short-term in duration. The T cells of the immune system do not function properly. Fewer than normal antibodies are produced, and those that are made are poor in their recognition of the antigenic target. However, as the immune system matures with age the proper function of the T cells is established. The cause of the hypogammaglobulinemia is not known.

Immunoglobulin deficiency syndromes are curable only by a bone marrow transplant, an option exercised in life-threatening situations. Normally, treatment rather than cure is the option. Prevention of infection, through the regular use of antimicrobial drugs and scrupulous oral health are important to maintain health in individuals with immunoglobulin deficiency syndromes.

See also Immunochemistry; Immunodeficiency disease syndromes; Immunodeficiency diseases; Immunodeficiency; Immunogenetics; Immunologic therapies; Immunological analysis techniques; Immunology; Immunosuppressant drugs