Immunodeficiency Health Article

Definition

Immunodeficiency disorders are a group of disorders in which part of the immune system is missing or defective. The body's ability to fight infections is, therefore, impaired. As a result, a child with an immunodeficiency disorder has frequent infections that are generally more severe and last longer than in a healthy child.

Description

The immune system is the body's main defense against infections. Any defect in the immune system decreases a person's ability to fight infections. A person with an immunodeficiency disorder may get more frequent infections, heal more slowly, and have a higher incidence of some cancers.

The normal immune system involves a complex interaction of certain types of cells that can recognize and attack foreign 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 made up of immune protections people are born with. Adaptive immunity develops throughout life. It adapts to fight off specific invading organisms. Adaptive immunity is divided into two components: humoral immunity and cellular immunity.

The innate immune system is made up of the skin (which acts 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 interferons. When phagocytes encounter an invading organism, they surround and engulf it in order to destroy it. The complement system also attacks bacteria. The elements in 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 as of the early 2000s still not entirely understood. Basically, it has the ability to recognize an organism or tumor cell as not being a normal part of the body and to develop a response to attempt to eliminate it.

The humoral response of adaptive immunity involves a type of cell called B lymphocytes. B lymphocytes manufacture proteins called antibodies (which are sometimes also called immunoglobulins). The terms antibody and immunoglobulin are often used interchangeably, although immunoglobulin refers to the larger classification system for antibodies. There are five types or classes of immunoglobulin that antibodies fit into, and each has a slightly different role in response against bacteria and viruses. Antibodies attach themselves to the invading foreign substance. This allows the phagocytes to begin engulfing and destroying the 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. The helper T lymphocytes play a role in recognizing invading organisms, and they also help killer T lymphocytes to multiply. As the name suggests, killer T lymphocytes act to destroy the target organism.

Defects can occur in any component of the immune system or in more than one component (combined immunodeficiency). Different immunodeficiency diseases involve different components of the immune system. The defects can be inherited (congenital) or acquired.

Congenital immunodeficiency disorders

Congenital immunodeficiency is present at the time of birth and is the result of genetic defects. These immunodeficiency disorders are also called primary immunodeficiencies. Even though more than 70 different types of congenital immunodeficiency disorders have been identified, they rarely occur. Congenital immunodeficiencies may occur as a result of defects in B lymphocytes, T lymphocytes, or both. They also can occur in the innate immune system.

HUMORAL IMMUNITY DISORDERS The congenital immunodeficiency disorder, Bruton's agammaglobulinemia, also known as X-linked agammaglobulinemia, results in a decrease or absence of B lymphocytes and, therefore, a decreased ability to make antibodies. People 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 defect if the gene is present. Females can have the defective gene, but since they have two X chromosomes, there will be a normal gene on the other X chromosome to counter it. Women may pass the defective gene on to their sons.

B LYMPHOCYTE DEFICIENCIES If there is an abnormality in either the development or function of B lymphocytes, the ability to make antibodies will be impaired. This deficit makes the body susceptible to recurrent infections.

A type of B lymphocyte deficiency involves a group of disorders called selective immunoglobulin deficiency syndromes. The five different types of immunoglobulins are called IgA, IgG, IgM, IgD, and IgE. The most common type of immunoglobulin deficiency is selective IgA deficiency, occurring in about one in every 500 white persons. The amounts of the other antibody types are normal. 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. People with this disorder tend to get severe bacterial infections.

Common variable immunodeficiency (CVID) is another type of B lymphocyte deficiency. In this disorder, the production of one or more of the immunoglobulin types is decreased, and the antibody response to infections is impaired. It generally develops in people between the ages of ten and 20. The symptoms vary among affected people. Most people with this disorder have frequent infections, and some also experience auto-immune phenomena, such as autoimmune hemolytic anemia or rheumatoid arthritis. Persons with CVID develop cancer at a higher rate than the general population, particularly lymphomas.

T LYMPHOCYTE DEFICIENCIES Severe defects in the ability of T lymphocytes to mature result in impaired immune responses to infections with viruses, fungi, and certain types of bacteria. These infections are usually severe and can be fatal.

DiGeorge syndrome is a genetic syndrome most frequently associated with a chromosomal deletion (22q11.2). This syndrome is often associated with T lymphocyte deficiencies. Children with DiGeorge syndrome either do not have a thymus or have an underdeveloped thymus. Since the thymus is a major organ that directs the production of T lymphocytes, these patients have low numbers of T lymphocytes. If the T cell count is very low the patients are susceptible to recurrent infections. The syndrome can be associated with other physical abnormalities. For example, these individuals may have distinctive facial features such as thin upper lip and flattened nasal bridge, and they may have low calcium from hypoparathyroidism or cardiac defects. If the entire syndrome is not present (as is the usual case), the syndrome is called incomplete DiGeorge, and if all elements are present and the thymus is absent, the syndrome is called complete. Children with complete DiGeorge are particularly susceptible to viral and fungal infections.

In some cases, no treatment is required for DiGeorge syndrome because T lymphocyte production 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 the defective development or function of these two types of lymphocytes. It results in impaired humoral and cellular immune responses. SCID usually is recognized during the first year of life. It tends to cause fungal infections, including severe thrush that does not respond to usual treatment; severe diarrhea; and serious bacterial infections. If the deficiency is not treated (usually by bone marrow transplant), a person with SCID usually dies from infection before the age of two years. The most common form of SCID is X-linked, i.e. the defect is on the X chromosome and, therefore, occurs only in boys. In the early 2000s new genetic defects leading to SCID are being identified each year.

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