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.
Monoclonal Antibodies
Through a technique known as hybridoma technolgoy, scientists are now able to obtain, in quantity, substances secreted by cells of the immune system -- both antibodies and lymphokines. The ready supply of these materials has not only revolutionized immunology but has also created a resounding impact throughout medicine and industry.
A hybridoma is created by fusing two cells, a secreting cell from the immune system and a long-lived cancerous immune cell, within a single membrane. The resulting hybrid cell can be cloned thus producing many identical offspring. Each of these daughter clones will secrete, over a long period of time, the immune cell product. A B-cell hybridoma secretes a single specific antibody.
Such monoclonal antibodies, as they are known, have opened remarkable new approaches to preventing, diagnosing, and treating disease. Monoclonal antibodies are used, for instance, to distinguish subsets of B cells and T cells. This knowledge is helpful not only for basic research but also for identifying different types of leukemias and lymphomas and allowing physicians to tailor treatment accordingly. Quantitating the numbers of B cells and helper T cells is all-important in immune disorders such as AIDS. Monoclonal antibodies are being used to track cancer antigens, and alone or linked to anti-cancer agents, to attack cancer metastases.
Monoclonal antibodies are essential to the manufacture of genetically engineered proteins. They single out the desired protein so it can be separated from the jumble of molecules surrounding it. Monoclonal antibodies are also the key to developing new types of vaccines.
With growing experience, scientists have devised several sophisticated variants on the monoclonal antibody. For example, they have created some monoclonal antibodies of human rather than mouse origin. Human monoclonal antibodies can be used for therapy without risking an immune reaction to mouse proteins. They have also succeeded in "humanizing" mouse antibodies by splicing the mouse genes for the highly specific antigen-recognizing portion of the antibody into the human genes that encode the rest of the antibody molecule.
Other monoclonal antibodies have been designed to behave like enzymes. These so-called catalytic antibodies or ABZYMES speed up, or catalyze, selected chemical reactions by binding to a chemical reactant and holding it in a highly unstable "transition state." By cutting the proteins they bind to, such antibodies may be useful for such things as dissolving blood clots or destroying tumor cells. Other researchers, by fusing two hybridoma cells that produce two different antibodies, have created hybrid hybridomas that secrete artificial antibodies made up of two non-identical halves. While one arm of the bispecific anti-body binds to one antigen, the second arm binds to another. One may bind a marker molecule and the second to a target cell, creating an entirely new way to stain cells. Or, one arm of a chimeric antibody may bind to a killer cell while the other locks to a tumor cell, creating a lethal bridge between the two.
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