The Immune System / What is The Immune System?

submitted by Dr. Gary Farr Last Updated June, 20, 2002

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Immune complexes are clusters of interlocking antigens and antibodies. Under normal conditions immune complexes are rapidly removed from the bloodstream by macrophages in the spleen and Kupffer cells in the liver. In some circumstances, however, immune complexes continue to circulate. Eventually they become trapped in the tissues of the kidneys, lung, skin, joints, or blood vessels. Just where they end up probably depends on the nature of the antigen, the class of antibody-IgG, for instance, instead of IgM-and the size of the complex. There they set off reactions that lead to inflammation and tissue damage.

Immune complexes work their damage in many diseases. Sometimes, as is the case with malaria and viral hepatitis, they reflect persistent low-grade infections. Sometimes they arise in response to environmental antigens such as the moldy hay that causes the disease known as farmer's lung. Frequently, immune complexes develop in autoimmune disease, where the continuous production of autoantibodies overloads the immune complex removal system.
 

Lack of one or more components of the immune system results in immunodeficiency disorders. These can be inherited, acquired through infection or other illness, or produced as an inadvertent side effect of certain drug treatments.

People with advanced cancer may experience immune deficiencies as a result of the disease process or from extensive anticancer therapy. Transient immune deficiencies can develop in the wake of common viral infections, including influenza, infectious mononucleosis, and measles. Immune responsiveness can also be depressed by blood transfusions, surgery malnutrition, and stress.

Some children are born with defects in their immune systems. Those with flaws in the B cell components are unable to produce antibodies (immunoglobulins). These conditions, known as agammaglobulinemias or hypogammaglobulinemias, leave the children vulnerable to infectious organisms; such disorders can be combated with injections of immunoglobulins.

Other children, whose thymus is either missing or small and abnormal, lack T cells. The resultant disorders have been treated with thymic transplants.

Very rarely, infants are born lacking all the major immune defenses; this is known as severe combined immunodeficiency disease (SCID). Some children with SCID have lived for years in germ-free rooms and "bubbles." A few SCID patients have been successfully treated with transplants of bone marrow (Bone Marrow Transplants).

The devastating immunodeficiency disorder known as the acquired immunodeficiency syndrome (AIDS) was first recognized in 1981. Caused by a virus (the human immunodeficiency virus, or HIV) that destroys T4 cells and that is harbored in macrophages as well as T4 cells, AIDS is characterized by a variety of unusual infections and otherwise rare cancers. The AIDS virus also damages tissue of the brain and spinal cord, producing progressive dementia.

 

AIDS infections are known as "opportunistic" because they are produced by commonplace organisms that do not trouble people whose immune systems are healthy, but which take advantage of the "opportunity" provided by an immune defense in disarray. The most common infection is an unusual and life-threatening form of pneumonia caused by a one-celled organism (a Protozoa) called Pneumocystis carinii. AIDS patients are also susceptible to unusual lymphomas and Kaposi's sarcoma, a rare cancer that results from the abnormal proliferation of endothelial cells in the blood vessels.

Some persons infected with the AIDS virus develop a condition known as AIDS-related complex, or ARC, characterized by fatigue, fever, weight loss, diarrhea, and swollen lymph glands. Yet other persons who are infected with the AIDS virus apparently remain well; however, even though they develop no symptoms, they can transmit the virus to others.

AIDS is a contagious disease, spread by intimate sexual contact, by direct inoculation of the virus into the bloodstream, or from mother to child during pregnancy. Most of the AIDS cases in the United States have been found among homosexual and bisexual men with multiple sex partners, and among intravenous drug abusers. Others have involved men who received untreated blood products for hemophilia; persons who received transfusions of inadvertently contaminated blood-primarily before the AIDS virus was discovered and virtually eliminated from the nation's blood supply with a screening test; the heterosexual partners of persons with AIDS; and children born to infected mothers.

There is presently no cure for AIDS, although the antiviral agent zidovuzine (AZT) appears to hold the virus in check, at least for a time. Many other antiretroviral drugs are being tested, as are agents to bolster the immune system and agents to prevent or treat opportunistic infections. Research on vaccines to prevent the spread of AIDS is also under way.

Cells of the immune system, like those of other body systems, can proliferate uncontrollably; the result is cancer. Leukemias are caused by the proliferation of white blood cells, or leukocytes. The uncontrolled growth of antibody-producing (plasma) cells can lead to multiple myeloma. Cancers of the lymphoid organs, known as lymphomas, include Hodgkin's disease. These disorders can be treated-some of them very successfully-by drugs and/or irradiation.

When the immune response is severely depressed-as the result of inherited defects, cancer therapy, or AIDS-one possible remedy is a transfer of healthy bone marrow. Bone marrow transplants are also used to treat patients with cancers of the blood, the blood-forming organs, and the lymphoid system-the leukemias and lymphomas.

Once in the circulation, transplanted bone marrow cells travel to the bones where the immature cells grow into functioning B and T cells. Like other transplanted tissue, however, bone marrow from a donor must carry self markers that closely match those of the person intended to receive it. This match is essential not only to prevent the transplant from being rejected, but also to fend off a life-threatening situation known as graft-versus-host disease. In graft-versus-host disease, mature T cells from the donor attack and destroy the tissues of the recipient.

To prevent graft-versus-host disease, scientists have developed techniques to "cleanse" the donor marrow of potentially dangerous mature cells. These include chemicals and, more recently, a monoclonal antibody (OKT3) that specifically recognizes and eliminates mature T cells.

For cancer patients who face immunosuppressive therapy but who have no readily matched donor, doctors have used "autologous" transplants: the person's bone marrow is removed, frozen, and stored until therapy is complete; then the cells are thawed and reinfused.

Since organ transplantation was introduced over a quarter of a century ago, it has become a widespread remedy for life-threatening disease. Several thousand kidney transplants are performed each year in the United States alone. In addition, physicians have succeeded in transplanting the heart, lungs, liver and pancreas.

The success of a transplant-whether it is accepted or rejected-depends on the stubbornness of the immune system. For a transplant to "take," the body of the recipient must be made to suppress its natural tendency to get rid of foreign tissue.

Scientists have tackled this problem in two ways. The first is to make sure that the tissue of the donor and the recipient are as similar as possible. Tissue typing, or histocompatibility testing, involves matching the markers of self on body tissues; because the typing is usually done on white blood cells, or leukocytes, the markers are referred to as human leukocyte antigens (HLA). Each cell has a double set of six major antigens, designated HLA-A, B, C, and three types of HLA-D-DR, DP, and DQ. (HLA-A, B, and C are the same as the class I antigens encoded by the genes of the major histocompatibility complex; HLA-D region molecules are the class II MHC antigens.)

Each of the HLA antigens exist-in different individuals-in as many as 20 varieties, so that the number of possible HLA types reaches about 10,000. Histocompatibility testing relies on antibodies to determine if a potential organ donor and recipient share two or more HLA antigens, and thus are likely to make a good "match." The best matches are identical twins; next best are close relatives, especially brothers and sisters.

The second approach to taming rejection is to lull the recipient's immune system. This can be achieved through a variety of powerful immunosuppressive drugs. Steroids suppress lymphocyte function; the drug cyclosporine holds down the production of the lymphokine interleukin-2, which is necessary for T cell growth. When such measures fail, the graft may yet be saved with a new treatment: OKT3 is a monoclonal antibody that seeks out the T3 marker carried on all mature T cells. By either destroying T cells or incapacitating them, OKT3 can bring an acute rejection crisis to a halt.

Not surprisingly, any such all-out assault on the immune system leaves a transplant recipient susceptible to both opportunistic infections and lymphomas. Although such patients need careful medical followup, many of them are able to lead active and essentially normal lives.

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