Privileged Immunity

A child developing in the womb carries foreign antigens from its father as well as immunologically compatible self antigens from its mother, and might be expected to trigger a graft rejection. But the uterus is an "immunologically privileged" site where immune responses are subdued. One source of protection appears to be a substance produced by the child, perhaps in response to antibodies from the mother. The substance promotes the development of special white blood cells in the uterus, and these cells release a factor that blocks the actions of IL-2. Another substance, produced by the uterus, helps disguise antigens on the fetal surface of the placenta, shielding them from the mother's immune defenses.

Immunity & Cancer

The immune system provides one of the body's main defenses against cancer. When normal cells turn into cancer cells, some of the antigens on their surface change. These new or altered antigens flag immune defenders, including cytotoxic T cells, natural killer cells, and macrophages.

According to one theory, patrolling cells of the immune system provide continuing bodywide surveillance, spying out and eliminating cells that undergo malignant transformation. Tumors develop when the surveillance system breaks down or is overwhelmed. Some tumors may elude the immune defenses by hiding or disguising their tumor antigens. Alternatively, tumors may survive by encouraging the production of suppressor T cells; these T cells act as the tumor's allies, blocking cytotoxic T cells that would normally attack it.

Blood tests show that people can develop antibodies to many types of tumor antigens (although the antibodies may not actually be effective in fighting the tumor). Skin testing (similar to skin testing for tuberculosis) has demonstrated that tumors provoke cellular immunity as well. Furthermore, studies indicated that cancer patients have a better prognosis when their tumors are infiltrated with many immune cells. Immune responses may underlie the spontaneous disappearance of some cancers.

Tests using antibodies derived from batches of human serum can detect various tumor-associated antigens-including carcinoembryonic antigen (CEA) and alphafetoprotein (AFP)-in blood samples. Because such antigens develop not only in cancer but in other diseases as well, the antibody tests are not useful for cancer screening in the general population. They are however, valuable in monitoring the course of disease and the effectiveness of treatment in patients known to have cancer.

Scientists have developed monoclonal antibodies (Hybridoma Technology) that are targeted specifically at tumor antigens. Linked to radioactive substances, these antibodies can be used to track down and reveal hidden cancer metastases within the body. Monoclonal antitumor antibodies are also being used experimentally to treat cancer-either in their native form or as immunotoxins, linked to natural toxins, anticancer drugs, or radioactive substances.

Other efforts to attack cancer through the immune system center on stimulating or replenishing the patient's immune responses with substances known as biological response modifiers. Among these are interferons (now obtained through genetic engineering) and interleukins. In some cases biological response modifiers are injected directly into the patient; in other cases they are used in the laboratory to transform some of the patient's own lymphocytes into tumor-hungry cells known as lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TILS), which are then injected back into the patient. Researchers are even using structures from the tumor cells themselves to construct custom-made anticancer "vaccines."

The Immune System and the Nervous System

A new field of research, known as psychoneuroimmunology, is exploring how the immune system and the brain may interact to influence health. For years stress has been suspected of increasing susceptibility to various infectious diseases or cancer. Now evidence is mounting that the immune system and the nervous system may be inextricably interconnected.

Research has shown that a wide range of stresses, from losing a spouse to facing a tough examination, can deplete immune resources, causing levels of B and T cells to drop, natural killer cells to become less responsive, and fewer IgA antibodies to be secreted in the saliva.

Biological links between the immune system and the central nervous system exist at several levels. One well-known pathway involves the adrenal glands, which, in response to stress messages from the brain, release corticosteroid hormones into the blood. In addition to helping a person respond to emergencies by mobilizing the body's energy reserves, these "stress hormones" decrease antibodies and reduce lymphocytes in both number and strength.

More recently, it has become apparent that hormones and neuropeptides (hormone-like chemicals released by nerve cells), which convey messages to other cells of the nervous system and organs throughout the body, also "speak" to cells of the immune system. Macrophages and T cells carry receptors for certain neuropeptides; natural killer cells, too, respond to them. Even more surprising, some macrophages and activated lymphocytes actually manufacture typical neuropeptides. At the same time, some lymphokines, secreted by activated lymphocytes such as interferon and the interleukins, can transmit information to the nervous system. Hormones produced by the thymus, too, act on cells in the brain.

In addition, the brain may directly influence the immune system by sending messages down nerve cells. Networks of nerve fibers have been found that connect to the thymus gland, spleen, lymph nodes, and bone marrow. Moreover, experiments show that immune function can be altered by actions that destroy specific brain areas.

The image that is emerging is of closely interlocked systems facilitating a two-way flow of information, primarily through the language of hormones. Immune cells, it has been suggested, may function in a sensory capacity, detecting the arrival of foreign invaders and relaying chemical signals to alert the brain. The brain, for its part, may send signals that guide the traffic of cells through the lymphoid organs.

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