Immunodeficiency Health Article

Definition

Immunodeficiency disorders are characterized by an immune system that is lacking, impaired, or defective. As a result, patients with immunodeficiency disorders have increased susceptibility to infection and neoplasia (cancer development). They have more frequent infections that are generally more severe and last longer than those experienced by persons with healthy, functioning immune systems. Patients with immunodeficiency disorders also are susceptible to infection with organisms that do not normally infect healthy people.

Description

The immune system is the body's primary defense against infections. Any defect in the immune system decreases the body's ability to combat infections. Patients with immunodeficiency disorders may suffer more frequent infections, heal more slowly, and have a higher incidence of some cancers.

The normal immune system involves a complex interaction of cells and molecules that can recognize and attack invaders such as bacteria, viruses, and fungi. It also plays a role in fighting cancer. The immune system has both innate and adaptive components. Innate immunity is the immune protection present at birth. Adaptive immunity develops throughout life and has two components, humoral immunity and cellular immunity.

The innate immune system consists of the skin (which serves as a barrier to prevent organisms from entering the body), white blood cells called phagocytes, a system of proteins called the complement system, and chemicals called interferon. When phagocytes encounter an invading organism, they surround and engulf it to destroy it. The complement system attacks bacteria. The elements of the complement system create a hole in the outer layer of the target cell, which leads to the death of the cell.

The adaptive component of the immune system is extremely complex and is still not entirely understood. Basically, it has the ability to recognize a foreign organism, tumor cell, or foreign chemical as an invader, and to develop a response to attempt to eliminate it.

The humoral response of adaptive immunity involves a type of cell called B lymphocytes that manufacture proteins called antibodies (also called immunoglobulins). Antibodies attach themselves to the foreign substance allowing phagocytes to begin engulfing and destroying the invading organism. The action of antibodies also activates the complement system. The humoral response is particularly useful for attacking bacteria.

The cellular response of adaptive immunity is useful for attacking viruses, some parasites, and possibly cancer cells. The main type of cell in the cellular response is the T lymphocyte. There are helper T lymphocytes and killer T lymphocytes. Helper T lymphocytes play a role in recognizing invading organisms and help killer T lymphocytes

to multiply. As the name suggests, killer T lymphocytes destroy the target cell or organism.

Defects can occur in any component of the immune system. They can also occur in several components simultaneously, and are then referred to as combined immunodeficiency. Defects can be congenital or acquired.

Congenital immunodeficiency disorders

Congenital immunodeficiency is present at the time of birth and is the result of genetic defects. Though more than 70 different types of congenital immunodeficiency disorders have been identified, they are rare. They may be caused by defects in either B lymphocytes or T lymphocytes, or both, and can also occur in the innate immune system.

B LYMPHOCYTE DEFICIENCY. If there is an abnormality in either the development or function of B lymphocytes, then the ability to make antibodies is impaired. Impaired antibody production results in increased susceptibility to recurrent infections. Bruton's agammaglobulinemia, also known as X-linked agammaglobulinemia, is one of the most common congenital immunodeficiency disorders. The defect results in a decrease or absence of B lymphocytes and therefore a decreased ability to produce antibodies. Patients with this disorder are particularly susceptible to infections of the throat, skin, middle ear, and lungs. It is seen only in males because it is caused by a genetic defect on the X chromosome. Since males have only one X chromosome, they always have the disorder if the defectiveâgene is present. Females may have the defective gene; however, since they have two X chromosomes, only one will have the defective gene and the other will have a normal gene to counter the defective gene. Women may pass the defective gene to their male offspring.

Another type of B lymphocyte deficiency involves a group of disorders called selective immunoglobulin deficiency syndromes. There are five different types of immunoglobulins—IgA, IgG, IgM, IgD, and IgE. The most common type of immunoglobulin deficiency is selective IgA deficiency. Some patients with selective IgA deficiency experience no symptoms while others have occasional lung infections and diarrhea. In another immunoglobulin disorder, IgG and IgA antibodies are deficient and there is increased IgM. Patients with this disorder tend to develop severe bacterial infections.

Common variable immunodeficiency is another type of B lymphocyte deficiency. In this disorder production of one or more of the immunoglobulin types is decreased and the antibody response to infections is impaired. This disorder generally develops between the ages of 10 and 20 years. Symptoms vary among affected patients, however, most suffer frequent infections and some also experience anemia and rheumatoid arthritis. Many patients with common variable immunodeficiency develop cancer.

T LYMPHOCYTE DEFICIENCIES. Severe defects in the ability of T lymphocytes to mature results in impaired immune responses to infection with viruses, fungi, and certain types of bacteria. These infections are often severe and can be fatal. DiGeorge syndrome is a T lymphocyte deficiency that begins during fetal development, although it is not inherited. Children with DiGeorge syndrome either have no thymus or have an underdeveloped thymus. Since the thymus directs the production of T lymphocytes, people with this immunodeficiency have very low numbers of T lymphocytes. They are susceptible to recurrent infections and usually have physical abnormalities as well, which may include lowset ears, a small receding jawbone, and widely spaced eyes. In some cases no treatment is required for DiGeorge syndrome because T lymphocyte production spontaneously improves. Either an underdeveloped thymus begins to produce more T lymphocytes or organ sites other than the thymus compensate by producing more T lymphocytes.

COMBINED IMMUNODEFICIENCIES. Some types of immunodeficiency disorders affect both B lymphocytes and T lymphocytes. For example, severe combined immunodeficiency disease (SCID) is caused by defective development or function of both of these types of lymphocytes. It results in impaired humoral and cellular immune responses. SCID is usually recognized during the first year of life. It tends to cause thrush (a fungal infection of the mouth), diarrhea, failure to thrive, and other serious infections. Treatment requires bone marrow transplant and, if left untreated, children with SCID generally die from infections before the age of two years.

DISORDERS OF INNATE IMMUNITY. Disorders of innate immunity affect phagocytes or the complement system. These disorders also result in recurrent infections.