Primary Immunodeficiency (PI) : Immune Defenses, Genes, Symptoms

by National Institute of Health

(Page 2 of 13)

The Immune Defenses

The immune defense system is a body-wide network of organs, tissues, cells, and protein substances that work together to defend the body against attacks by "foreign" invaders. Those invaders are primarily germs - tiny, infection-causing organisms such as bacteria and viruses, parasites and fungi.

The immune system is amazingly complex. It can recognize millions of different enemies, and it can enlist specialized cells and secretions to seek out and destroy each of them. (Substances recognized as foreign that provoke an immune response are called antigens.)

The organs of the immune system are known as lymphoid organs because they are home to lymphocytes, small white blood cells that are key components of the immune defenses. Bone marrow is soft tissue in the hollow center of bones, and it is the original source of all blood cells. The thymus is an organ that lies behind the breastbone; that is where some lymphocytes mature. The spleen, located in the upper left of the abdomen, serves as headquarters for many immune system activities.

Lymphocytes can travel throughout the body, using the blood vessels or a system of lymphatic vessels. The lymphatic vessels carry a clear fluid known as lymph. Scattered along the lymphatic vessels are small, bean-shaped lymph nodes, where immune cells gather and interact.

Clumps of lymphoid tissue are found in many parts of the body, especially in the linings of the digestive tract and the airways and lungs - areas that protect gateways into the body. These tissues include the tonsils, adenoids, and appendix.

The immune system makes use of many types of white blood cells. These include two main kinds of lymphocytes, T lymphocytes (T cells) and B lymphocytes (B cells); and a class of cytotoxic lymphocytes called natural killer (NK) cells. Additionally, there are large white blood cells known as phagocytes (neutrophil and monocyte).

Genes and PI

In the past few years, scientists have succeeded in identifying the genes that are responsible for many PI diseases. These include X-Linked Agammaglobulinemia, X-linked Hyper-IgM Syndrome, Wiskott-Aldrich Syndrome, Ataxia Telangiectasia, four forms of Chronic Granulomatous Disease, and several forms of SCID. The search for other genes that cause PI is under way and more are being discovered.

Sometimes the same, or nearly the same, symptoms can be the product of different defective genes on different chromosomes. For example, SCID can be caused by mutations in different genes. One genetic defect blocks activation of B cells and T cells. Another genetic defect prevents immune cells from getting rid of toxic chemicals. In every case, however, the end result is the same: major immune defenses are non-functional.

Once researchers have identified the defective gene, they try to find out what it normally does, what protein it makes, and how that protein contributes to the immune response. Some proteins, for example, relay signals that tell immune cells to multiply and mature. Other proteins help the immune system to eliminate excess or unwanted cells.

The next step is to ascertain what happens when the protein is missing or distorted and how the faulty protein causes disease.

Learning about a disease-causing gene and its protein product raises the exciting prospect of finding a cure for the disease. One possibility might be to replace a mutated gene through gene therapy. Another way might be to supply the missing protein as a medicine.

Signs and Symptoms

The most common problem in PI disease is an increased susceptibility to infection. For people with PI, infections may be common, severe, lasting, or hard to cure.

Even healthy youngsters may get frequent colds, coughs, and earaches. For example, many infants and young children with normal immunity have one to three ear infections per year. Children with PI, however, can get one infection after another. Or they get two or three infections at a time. Weakened by infection, the child may fail to gain weight or fall behind in growth and development.

Despite the usual antibiotics, the infections of PI often drag on and on, or they keep coming back - that is, they become chronic. One common problem is chronic sinusitis (infection and inflammation of the sinuses, air passages in bones of the cheeks, forehead, and jaw). Another common problem is chronic bronchitis (infection and inflammation of the airways leading to the lungs).

Serious infections, especially bacterial infections, may cause a youngster to be hospitalized repeatedly. Pneumonia is an infection of the smallest airways and airsacs in the lungs, which prevents oxygen from reaching the blood and makes breathing hard. Meningitis, an infection of the membranes that surround the brain and spinal cord, causes fever and severe headache, and can lead to seizures, coma, and even death. Osteomyelitis is an infection that invades and destroys bones. Cellulitis is a serious infection of connective tissues just beneath the skin.

Some people with PI develop blood poisoning, an infection that flourishes in the bloodstream and spreads rapidly through the body. Some people may develop deep abscesses, pockets of pus that form around infections in the skin or in body organs.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.