Immunodeficiency is a condition in which the body's immune system is not able to fight off infections or tumors as well as a normal immune system would. As a result, the person tends to get sick frequently, with unusually severe and repeated infections and sometimes cancers or other chronic (long-lasting) diseases.
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The immune system, which protects the body from disease, works through a complicated web of cells and chemicals. It has many intertwined parts. A defect in any one of these parts can damage the body's ability to fight off disease. Such a defect is called an immunodeficiency disease.
Immunodeficiency diseases fall into two broad categories: primary and secondary. Most cases of primary immunodeficiency occur in infants or children as a result of genetic abnormalities. Because many have a sex-linked * genetic cause, most affected newborns are male. Secondary immunodeficiency is far more common because many different medical conditions can cause it.
What Are Primary Immunodeficiency Diseases?
Many immunodeficiency diseases already are present when a person is born, although sometimes they show up later. The reason for the problem may not be known, but often the cause is a defect in one of the genes * . Depending on which gene is affected, specific chemicals or cells in the immune system may be missing, may be in short supply, or may not work properly. From birth onward, a person with an immunodeficiency is likely to get frequent infections. Skin, bone, and nerve problems sometimes occur as well, and the person later may develop autoimmune diseases * , such as rheumatoid arthritis, or cancers of the immune system, such as lymphoma (lim-FO-ma) or leukemia (loo-KEY-mee-a).
The disorder can range from mild to so severe that the person dies of an infection in childhood. Whether mild or severe, this kind of illness is called a primary immunodeficiency disease, meaning that it is not caused by another condition.
* sex-linked genetic traits involve the chromosomes that determine whether a person is male or female. They usually affect boys, who have only one X chromosome.
* genes are chemicals in the body that help determine a person's characteristics, such as hair or eye color. They are inherited from a person's parents and are contained in the chromosomes found in the cells of the body.
* autoimmune disease is a disease where the immune system attacks and destroys normal cells in the body.
Severe combined immunodeficiency disease (SCID)
The most complete form of this condition is a rare illness called severe combined immunodeficiency disease, or SCID. A person who has SCID is born with an immune system that does not work at all. The most famous case was that of a Texas boy named David, who lived in a germ-free plastic bubble to protect him from infection. Known as "the bubble boy," David died in 1985 at age 12.
At the opposite end of the continuum is a condition like IgA deficiency, which is the absence of just one protein, called an immunoglobulin. This condition is common, occurring in as many as 1 out of every 400 Americans. Although people with IgA deficiency tend to have allergies and to get colds or bronchitis, many have no symptoms at all.
What Are Secondary Immunodeficiency Diseases?
Sometimes people are born with healthy immune systems that later become damaged. The damage may be the result of malnutrition, burns, excessive exposure to x-rays, or certain immune-suppressing medications such as corticosteroids (cor-ti-ko-STER-oids).
Some diseases can cause immune system damage. These include diabetes, kidney failure, sickle-cell anemia, leukemia, lymphoma, and cirrhosis * of the liver. Many people with diabetes, for instance, get infections of the skin and urinary tract.
This kind of immune system disorder is called secondary immuno-deficiency because it is secondary to (caused by) other medical problems. If the underlying problem is treated, often the immune system will recover partially or completely.
How Is AIDS Different?
The most common and best known immunodeficiency disease is AIDS (acquired immunodeficiency syndrome). Untreated, AIDS can affect the immune system as severely as SCID. AIDS is a secondary immuno-deficiency disease, because most people who get AIDS were born with normal immune systems that later were damaged.
AIDS is said to be "acquired," or contracted, rather than genetic or inborn. With AIDS, the cause of the damage to the immune system is a virus called HIV (the human immunodeficiency virus). Unlike the causes of other immunodeficiency diseases, the virus can spread from person to person through contact with blood or through sexual activity. As a result, AIDS has quickly become common around the world, killing millions of people since the disease was first reported in 1981.
How Does the Immune System Work?
To understand immunodeficiency diseases, it helps to know a little about how the immune system works.
* cirrhosis (si-RO-sis) of the liver is scarring often caused by alcoholism or chronic active hepatitis (a long-lasting liver infection).
Elements of the immune system circulate through the body via the lymphatic system. In this system, a clear fluid called lymph helps carry white blood cells, especially lymphocytes (LIMF-o-sites) around the body. The word "lymph" comes from a Greek word meaning a clear stream. The organs and tissues of the lymphatic system include the thymus (a gland in the chest), the spleen (an organ in the abdomen), the tonsils (tissue in the throat), and bone marrow (tissue inside the bones).
Humoral immunity and B cell lymphocytes
B cell lymphocytes are white blood cells named for bone marrow, because that is where they grow to maturity. B cells produce antibodies, proteins that circulate in the lymph system and bloodstream. The antibodies attach to antigens, distinctive proteins on germs or other foreign * cells. The antibodies mark the germs or foreign cells so that other immune system cells can destroy them. The B cells produce antibodies to a germ only after they have learned to recognize the germ, in other words, after a person has been infected at least once with the germ. The immune response that involves B cells and antibodies is called humoral (HEW-moral) immunity. It is the reason that healthy people get measles only once. After that, they are immune to the disease.
Cell-mediated immunity and T cell lymphocytes
T cell lym-phocytes grow to maturity in the thymus gland. They have several different roles. Helper T cells (also called CD4 cells) signal B cells to start making antibodies. They also can activate macrophages. Macro-phages are immune system cells that engulf foreign cells and process them so they can be destroyed by other cells, such as killer T cells and natural killer cells (other kinds of immune system cells). The immune response that involves T cells is called cell-mediated immunity. Many other kinds of cells and internal chemicals are involved in this branch of the immune system.
How Serious Are Immunodeficiency Diseases?
Primary immunodeficiency diseases are grouped according to which part of the immune system is defective. B cell, or antibody, deficiencies are the most common, and include IgA deficiency, mentioned earlier. These tend to be the mildest and most treatable diseases, with people living normal life spans in many cases.
With T cell deficiencies, disease severity and chance of survival vary widely. One of the better known disorders in this group is DiGeorge syndrome, in which infants are born without a thymus, and with facial and heart abnormalities.
Disorders that affect both B and T cells are particularly dangerous. These include SCID, mentioned earlier, and Wiskott-Aldrich syndrome, a sex-linked genetic defect seen in boys.
* foreign means coming from outside a person's body.
People with primary and secondary immun-odeficiency tend to have frequent infections, particularly infections caused by organisms that seldom cause illness in healthy people. Such infections are called opportunistic infections, because they take advantage of a person's weakened immune system. Opportunistic infections include thrush (an infection of the mouth with Candida albicans, often seen in children) and viral infections, such as cytomegalovirus, herpes simplex, and Epstein-Barr virus.
How Is Immunodeficiency Diagnosed and Treated?
In addition to having opportunistic infections, people with immunodeficiency often seem unhealthy, with general weakness. They may be malnourished, and they may have skin rashes, hair loss, persistent diarrhea, or coughing.
Doctors may be able to diagnose immunodeficiency from symptoms and a medical history, but usually laboratory tests are needed to confirm the diagnosis. Pinpointing the nature of the deficiency can require sophisticated tests that only a few advanced laboratories can perform.
a Gene Therapy Pioneer
On September 14, 1990, a four-year-old girl from Ohio sat playing quietly in her hospital bed while a solution containing white blood cells equipped with new genes dripped slowly through a needle into her vein. The girl, Ashanthi DeSilva, had been born with a serious immunodeficiency disease known as adenosine deaminase deficiency (or ADA deficiency). Because of a defective gene, she lacked an enzyme her immune system needed to work. Her treatment at the U.S. National Institutes of Health marked the first authorized test of gene therapy on a person in the United States.
In the nine years that followed, some 3,000 people received experimental gene therapy for various diseases, including several more children with ADA deficiency. As a result of this therapy, Ashanthi, who also received an enzyme treatment called PEG-ADA, was able to go to school like other children instead of staying isolated from others to prevent infection. She was reported to have grown into a thriving preteen.
Doctors credited both the gene therapy and the enzyme treatment with having helped her, but they said neither could be considered a cure. Her father said the enzyme treatment, which started first, saved her life, but the gene therapy "gave her life," meaning she had the vigor to enjoy living like any other child her age.
Antibody deficiency can be treated with monthly doses of the immunoglobulins (immune system proteins) that are lacking. Severe combined immunodeficiency disease often can be treated by giving the person a transplant of healthy bone marrow, which then can grow and help produce healthy immune system cells. Such transplants, however, can be risky. For T cell deficiencies like DiGeorge syndrome, transplants of thymus tissue sometimes work. For AIDS, combinations of drugs are given to fight the underlying virus.
In general, people with immunodeficiency need to be protected from infection. Antibiotics sometimes are given continuously to prevent bacterial infection. If infection does occur, it needs to be treated promptly, with medication, if possible. For many viral infections, however, no treatment currently exists.
AIDS and HIV
Cirrhosis of the Liver
Inflammatory Bowel Disease
U.S. National Institute of Allergy and Infectious Diseases (NIAID),
Office of Communications, Building 31, Room 7A50, 31 Center Drive, MSC
2520, Bethesda, MD 20892-2520. NIAID publishes brochures and posts fact
sheets at its website, including
Understanding the Immune System, Understanding Autoimmune Diseases,
Primary Immunodeficiency Disease.
American Autoimmune Related Diseases Association, 15475 Gratiot Avenue,
Detroit, MI 48205.
The Immune Deficiency Foundation, 25 West Chesapeake Avenue, Townson, MD
21204. This organization provides information about primary immune
The National Jewish Center for Immunology and Respiratory Medicine, 1400
Jackson Street, Denver, CO 80206. This organization provides information
on immune system diseases and research.