Immune System

The immune system is made up of more than 100 million immune cells comprising a complex array of organs, cells and molecules. Its mission is to keep infectious microorganisms out of your body or destroy any that get in.

For every virus or bacterium, there is an immune cell designed to hunt it down and destroy it. Using research on such cells and advanced technologies, scientists are developing drugs and techniques that can modify the immune response and help defend against diseases such as cancer and AIDS.

But bacteria and viruses are cunning adversaries — constantly devising new ways to breach immune defenses. Sometimes, after a new drug is developed, it is discovered that the microorganism assumed a dangerous new disguise.

Here's a look inside the immune system, including its remarkably intricate defense mechanisms, vulnerabilities and future capabilities to fend off today's invincible enemies.

Aligned for battle

Each part of the immune system contributes to the growth, development or activation of sophisticated white blood cells (lymphocytes) that play a major role in immune response.

White blood cells originate in bone marrow. Some migrate to your thymus gland (under the breastbone) where they develop into specialized types of immune cells. From bone marrow and the thymus, some white blood cells gather in lymph nodes and organs, including the spleen, tonsils, adenoids, appendix and small intestine.

Other white blood cells circulate in the blood and in lymphatic vessels (which transport a colorless fluid called lymph). Lymph also carries microorganisms and dead cells from infections into lymph nodes where they are eliminated. The blood and lymphatic vessels also transport white blood cells to sites of infection.

Soldier cells

The body's remarkable arsenal of white blood cells is the key to an immune response. The main defenders include:

B cells and T cells — These are special types of white blood cells known as lymphocytes. They recognize and coordinate an attack against specific microorganisms.

B cells chiefly work by producing antibodies. Each B cell is designed to make a specific antibody, which battles a specific microorganism. B cells also can develop into plasma cells that secrete thousands of identical antibodies.

T cells coordinate immune defenses and kill organisms on contact within the cells. They also work by secreting potent chemicals called lymphokines, which orchestrate the immune response. Lymphokines are particularly effective in the defense against cancerous cells or cells infected by viruses.

Phagocytes — The name for these white blood cells originates from the Greek word meaning "eaters." They gobble up everything unwanted, from a speck of dust or grain of pollen to a virus.

A macrophage is a versatile type of phagocyte. As scavengers, macrophages rid the body of worn-out cells and other debris. They also play a vital role in initiating the immune response.

Chemical killers — Other white blood cells — neutrophils, eosinophils and basophils — are "cell eaters." In addition, they release powerful chemicals that destroy microorganisms.

Scouting the enemy

The marvel of the immune system is its ability to distinguish between what's "you" from what's "new."

As immune cells wait for an enemy to appear, they constantly bump against millions of substances in your blood — red blood cells, other white blood cells, proteins and hormones.

Any "new" substance that triggers an immune response is called an antigen. As immune cells learn to recognize and ignore your body's own cells, they learn to recognize and destroy antigens.

Cell recognition works by use of a "chemical ID card," that every substance carries — from a dust mite to the flu virus to one of your own cells. It is marked by a unique molecular pattern on its surface. All cells in your body have the same molecular pattern.

White blood cells learn to recognize and ignore cells identified by your body's own pattern. During the learning process, many immune cells react against your body's own cells and become inactivated.

Front-line defenses

The immune system is equipped with elaborate defenses. As antigens attempt to invade your body, they meet with increasingly sophisticated layers of protective defenses. Your first lines of protection include:

Physical barriers — Skin is an effective shield from invaders, harmful or not. The respiratory system also provides a barrier by trapping irritants in nasal hairs and mucus, carrying mucus upward and outward on cilia (tiny hairlike projections lining your respiratory tract), coughing and sneezing.

Skin and the mucous membranes lining the respiratory and digestive tracts also contain macrophages and antibodies. Fluids such as saliva, sweat and tears contain destructive enzymes. Stomach acid kills most microorganisms ingested in food or water.

General defenses — Antigens that slip through physical barriers are met by scavenger cells circulating through blood and lymphatic vessels. These cells attack antigens in a general way, without using specific mechanisms against particular antigens.

One general defense mechanism is the inflammatory response. It halts disease-causing microorganisms early in an invasion and confines them to a localized area.

When you're injured, bacteria multiplies at the site. Immune cells cause small blood vessels near the injury to widen (dilate). Increased blood flow leads to redness and warmth. Swelling occurs when immune cells cause blood vessels to leak fluid into surrounding tissues.

Nearby lymph nodes then trap microorganisms and trigger production of more immune cells that kill bacteria and help contain the infection. Macrophages clean up dead bacteria and damaged tissue.

Complement — This complex series of circulating proteins "complements" the work of antibodies. When complement contacts an invading organism, each component of the complement system is activated in turn (complement cascade). The result is a protein complex that attaches to the organism's surface and destroys it by puncturing its cell membrane.

Stronger defenses

Antigens that pass through the front lines of defense confront two layers of more sophisticated defenses. These defenses rely mainly on B cells and T cells to recognize a specific antigen and tailor an attack.

Antibody-antigen defense — Each antibody made by a B cell fits a particular antigen. Antibodies can ambush bacteria but can't penetrate cells where viruses may hide.

Because immune cells never know which potential disease-causing antigen they'll encounter next, they must always be prepared. This discovery earned researchers the 1987 Nobel Prize in medicine.

The scientists found antibodies are capable of mixing and matching DNA in "mini-gene" segments, similar to building with different-colored snap-and-lock blocks. The mini-genes combine and recombine into the optimum pattern to make antibodies that fit any particular antigen.

Cellular defenses — T cells concentrate on trickier assignments, such as finding viruses that hide inside cells. For help in finding the foe, macrophages act as "undercover agents," moving among cells to help identify antigens. Macrophages engulf the antigen, break it down and display fragments of antigen as markers on their surfaces. Once a virus is identified, some T cells release proteins that bind to the infected cells and direct the attack.

Future immunity

At birth, the immune system is relatively weak. Through infancy and childhood, natural immunity matures. Time also strengthens immunity by offering the kind of protection acquired by having an infection or being vaccinated against it.

Each exposure to an antigen forms T and B "memory" cells. After recovery from chickenpox, for example, the immune system stores a few B and T memory cells for chickenpox. The next time the virus is contacted, memory cells multiply and stop the infection from spreading.

Vaccines work similarly. When vaccinated, killed or weakened live forms of an infectious organism stimulate an immune response without causing the accompanying illness. Memory cells provide immunity for years or even a lifetime.

Immune response

The strength of immune response depends on the specific antigen, your health, age and genetic makeup. If the immune system is healthy, it can make enough immune cells to destroy most infections. Yet even a normal immune system faces obstacles that can weaken its response:

Age — In general, immune defenses are preserved and sometimes enhanced with age. For example, you acquire immunity to more diseases, such as viral illnesses, as you grow older.

However, some immune responses are more susceptible to age-related decline. With age, the number of immune cells doesn't necessarily decrease, but they may respond less quickly and effectively to invading organisms.

Heredity — Genes determine the molecular ID pattern that properly marks body cells as your own. Genes also shape the makeup of antibodies and other immune cells. Genetic differences may help explain why you can resist an infection while your spouse can't, or why allergies run in families.

Immune system failure

Not only can the immune system weaken, it can also be overwhelmed. These conditions can occur when an immune system simply doesn't work as it should:

Allergy — This is an overreaction by your immune system to an otherwise harmless substance, such as pollen or pet dander.

Contact with an allergy-causing substance triggers production of a specific kind of antibody (immunoglobulin E or IgE). IgE binds to the surface of special histamine-containing cells called mast cells. If another molecule of the allergen (e.g., dog dander ) comes in contact with the IgE-primed cell, histamine and other powerful inflammatory chemicals are released. This leads to the familiar symptoms of allergy and asthma — redness and swelling of your eyes, sneezing, difficult breathing and hives.

Autoimmune diseases — In these conditions, your body makes antibodies and T cells directed against your own cells.

For example, some types of insulin-dependent diabetes may partly be caused by an attack on the pancreas from a person's own antibodies. Self-destructive antibodies are also associated with chronic muscle weakness (myasthenia gravis) and rheumatoid arthritis.

What causes the breakdown of the immune system's recognition is undetermined. Scientists believe multiple factors — heredity, viruses, certain drugs or even sunlight — may play a role.

Immune-deficiency diseases — These conditions occur when one or more parts of the immune system are deficient or missing. The defects can be inherited or acquired from a viral infection such as AIDS. Toxic effects of radiation or some drugs also can cause them.

Cancers of the immune system — When immune cells reproduce uncontrollably, the result is a cancer of the immune system such as leukemia, multiple myeloma or lymphoma.

Promising treatments

The strategies underlying most new treatments are similar: Capitalize on the immune system's ability to fight disease by enhancing its response. Or, in the case of an autoimmune disease, by suppressing the immune response to stop progression of disease. These strategies are developing hand-in-hand with advances in biotechnology, such as recombinant DNA technology.

Recombinant DNA technology is a process of mass-producing a specific protein to treat a disease. This technology has led to more than 20 new treatments, drugs and vaccines plus several hundred in various stages of investigation.

DNA technology has helped doctors develop a cancer treatment that stimulates the immune system using synthetic versions of the proteins released by T cells (interferons). It has also enabled scientists to create growth factors that cause bone marrow to produce more blood cells. Doctors can use synthetic growth factors to regenerate blood cells after a bone-marrow transplant and in treatment for AIDS.

Advances in biotechnology and research are also driving developments in these areas:

Rheumatoid arthritis — A protein called tumor necrosis factor (TNF) may be an important cause of inflammation that can lead to joint damage. Using recombinant DNA technology, scientists developed an antibody (Etanercept) that inactivates the inflammatory protein. People given large doses of the antibody experienced significant improvements.

Organ transplantation — Thousands of Americans are alive because of transplanted tissue and organs including bone marrow, kidney, heart, lung, liver, pancreas and small bowel. But a transplanted organ provokes a furious immune response, which treats the transplanted tissue as foreign. Researchers are working to develop immunosuppresive drugs and other techniques that dampen this side of your immune response, but still allow your body to defend against infection.

Cancer — Because cancer develops within your own cells, it's not easily recognized by the immune system. Once cancer is established, it may block some defense mechanisms that normally attacks cancer. The resulting immunosuppression is a focus of research, such as the development of cancer vaccines that trigger a strong immune response early enough to prevent cancer cells from establishing.

Intensive work to find an AIDS vaccine is helping the development of vaccines against certain types of leukemia and lymphoma, caused by a similar type of virus. But doctors predict cancer vaccines ultimately will be used in combination with traditional treatments to kill the few cancer cells remaining after surgery, chemotherapy or radiation therapy.

Other new treatments for cancer use recombinant DNA technology to increase the numbers of immune cells. In one treatment, doctors remove lymphokines and activated T cells from a person, cause multiplication in the laboratory, and then reintroduce them into the person.

Another experimental treatment uses a type of lymphokine called interleukin 2 to enhance immune response. After laboratory preparation, interleukin 2 is injected into a person with cancer. It causes remission by stimulating production of immune cells. However, the treatment has troublesome side effects such as fever, chills, low blood pressure and joint pain.

Researchers also are using B cells to make large numbers of identical antibodies (monoclonal antibodies) designed to attack a specific cancer. When combined with drugs, toxins or radioactive materials, monoclonal antibodies also can carry chemicals to destroy specific cancer cells.

Current understanding of the immune system reveals just a small piece of an intricate puzzle. Yet doctors are using what they know in a wide range of investigational treatments. At Mayo Clinic and other centers, researchers are using gene therapy to boost immune response in people with colon cancer. Investigators inject a gene into tumor cells that causes the cells to display a stronger "foreign" ID marker. The hope is that this use of gene therapy will enable the immune system to recognize and destroy tumor cells more easily.

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