Allergy and Autoimmune Disorders

The immune system is a complex network of organs, tissues, cells, and proteins that fights off invaders. The immune system must strike a balance between a strong enough response to prevent infection and cancer and a response too strong which will damage cells and tissues. Allergy and autoimmune disorders result when the immune system overreacts or reacts inappropriately. Examples include hay fever, systemic lupus erythematosus, and rheumatoid arthritis.

Allergies
The most common types of allergic diseases occur when the immune system responds to a false alarm. In an allergic person, a normally harmless material such as grass pollen, food particles, mold, or house dust mites is mistaken for a threat and attacked.

Allergies such as pollen allergy are related to the antibody known as IgE. Like other antibodies, each IgE antibody is specific. For example, one acts against oak pollen and another against ragweed. Some common allergies are:
 * Animal material (fur, pet dander)
 * Dust mite feces (especially as a factor in asthma
 * Drugs
 * Venom and insect stings
 * Mold
 * Latex
 * Plant pollens (hay fever)
 * Plant secretions (poison oak, ivy, sumac)

Autoimmune diseases
Sometimes the immune system’s recognition apparatus breaks down, and the body begins to manufacture T cells and antibodies directed against self antigens in its own cells and tissues. As a result, healthy cells and tissues end up being attacked by the immune system.

An allergic reaction occurs after plasma cells produce IgE antibody against a specific antigen, and mast cells become activated.

Misguided T cells and autoantibodies, as they are known, contribute to many autoimmune diseases. Misguided T cells can attack insulin-producing cells of the pancreas, contributing to an autoimmune form of diabetes. In addition, an antibody known as rheumatoid factor is common in people with rheumatoid arthritis. People with systemic lupus erythematosus (SLE) have antibodies to many types of their own cells and cell components. SLE patients can develop a severe rash, serious kidney inflammation, and disorders of other important tissues and organs.

No one knows exactly what causes an autoimmune disease, but multiple factors are likely to be involved. These include elements in the environment, such as viruses, certain drugs, and sunlight, all of which may damage or alter normal body cells. Hormones are suspected of playing a role because most autoimmune diseases are far more common in women than in men. Heredity, too, seems to be important. Many people with autoimmune diseases have characteristic types of self-marker molecules.

Immune Complex Diseases
Immune complexes are clusters of interlocking antigens and antibodies. Normally, immune complexes are rapidly removed from the bloodstream. Sometimes, however, they continue to circulate and eventually become trapped in the tissues of the kidneys, lungs, skin, joints, or blood vessels. There, they set off reactions with complement that lead to antigen-antibody complexes. Antigen-antibody complexes can become trapped in and damage the kidneys and other organs.

Immune complexes work their mischief in many diseases. These include malaria, scarlet fever, and viral hepatitis, as well as many autoimmune diseases.

Immune System and Cancer
When normal cells turn into cancer cells, some of the antigens on their surface change. These cells, like many body cells, constantly shed bits of protein from their surface into the circulatory system. Often, tumor antigens are among the shed proteins.

These shed antigens prompt action from immune defenders, including cytotoxic T cells, natural killer cells, and macrophages. According to one theory, patrolling cells of the immune system provide continuous body-wide surveillance, catching and eliminating cells that undergo malignant transformation. Tumors develop when this immune surveillance breaks down or is overwhelmed.

Research
Scientists are now able to mass-produce immune cell secretions, both antibodies and lymphokines, as well as specialized immune cells. The ready supply of these materials not only has revolutionized the study of the immune system itself but also has had an enormous impact on medicine, agriculture, and industry.

Monoclonal antibodies are identical antibodies made by the many clones of a single B cell. Monoclonal antibody technology makes it possible to mass produce specific antibodies to order. Because of their unique specificity for different antigens, monoclonal antibodies are promising treatments for a range of diseases. Researchers make monoclonal antibodies by injecting a mouse with a target antigen and then fusing B cells from the mouse with other long-lived cells. The resulting hybrid cell becomes a type of antibody factory, turning out identical copies of antibody molecules specific for the target antigen.

Mouse antibodies are “foreign” to people, however, and might trigger an immune response when injected into a human. Therefore, researchers have developed “humanized” monoclonal antibodies. To construct these molecules, scientists take the antigen-binding portion of a mouse antibody and attach it to a human antibody scaffolding, greatly reducing the foreign portion of the molecule.

Because they recognize very specific molecules, monoclonal antibodies are used in diagnostic tests to identify invading pathogens or changes in the body’s proteins. In medicine, monoclonal antibodies can attach to cancer cells, blocking the chemical growth signals that cause the cells to divide out of control. In other cases, monoclonal antibodies can carry potent toxins into certain cells, killing the dangerous cells while leaving their neighbors untouched.

Gene Therapy
Genetic engineering also holds promise for gene therapy, replacing altered or missing genes or adding helpful genes. One disease in which gene therapy has been successful is SCID, or severe combined immune deficiency disease.

SCID is a rare genetic disease that disables a person’s immune system and leaves the person unable to fight off infections. It is caused by mutations in one of several genes that code for important components of the immune system. Until recently, the most effective treatment for SCID was transplantation of blood-forming stem cells from the bone marrow of a healthy person who is closely related to the patient. However, doctors have also been able to treat SCID by giving the patient a genetically engineered version of the missing gene.

Using gene therapy to treat SCID is generally accomplished by taking blood-forming cells from a person’s own bone marrow, introducing into the cells a genetically changed virus that carries the corrective gene, and growing the modified cells outside the person’s body. After the genetically changed bone marrow cells begin to produce the enzyme or other protein that was missing, the modified blood-forming marrow cells can be injected back into the person. Once back inside the body, the genetically modified cells can produce the missing immune system component and begin to restore the person’s ability to fight off infections.

Cancer is another target for gene therapy. In pioneering experiments, scientists are removing cancer-fighting lymphocytes from the cancer patient’s tumor, inserting a gene that boosts the lymphocytes’ ability to make quantities of a natural anticancer product, then growing the restructured cells in quantity in the laboratory. These cells are injected back into the person, where they can seek out the tumor and deliver large doses of the anticancer chemical.

Although scientists have learned much about the immune system, they continue to study how the body launches attacks that destroy invading microbes, infected cells, and tumors while ignoring healthy tissues. New technologies for identifying individual immune cells are now allowing scientists to determine quickly which targets are triggering an immune response. Improvements in microscopy are permitting the first-ever observations of living B cells, T cells, and other cells as they interact within lymph nodes and other body tissues.

In addition, scientists are rapidly unraveling the genetic blueprints that direct the human immune response, as well as those that dictate the biology of bacteria, viruses, and parasites. The combination of new technology and expanded genetic information will no doubt reveal even more about how the body protects itself from disease.