Sunday, July 16, 2006

The Immune System

The Immune system in short: Except for the nervous system, the immune system is the most complex biological system we have. It consists of master glands, principally the thymus; various sites that harbor immune cells; and different classes of "soldier" cells, which carry out specialized functions--including cells that prompt, cells that alert, cells that facilitate, cells that activate, cells that surround, cells that kill, even cells that clean up. Many immune cells also synthesize and secrete special molecules that act as messengers, regulators, or helpers in the process of defending against invaders.

Antigens: The Signalers. Antigens are the fingerprints of immunity. They are identifying molecules that reside on the surface of cells and, like fingerprints, are unique to the cells that bear them. All of our body cells have antigens that signal "self-self-self"-- a message that they are part of us and therefore not to be attacked. Microorganisms, viruses, or any agent that invades our bodies also have identifying antigens on their surfaces, which signal "foreign-foreign-foreign" to the immune system, readying it for immediate attack.

That's why organ transplants are difficult; the antigens on newly-introduced cells sound the "foreign" alarm. To prevent the rejection of transplanted tissues, a patient is given drugs that suppress the immune system. If the immune system overreacts to an outside antigen, the result is an allergy. Hayfever, for example, is a hyperresponse to grass, pollen, or ragweed antigens. When our immune system reacts inappropriately to the antigens on our own cells, the result is an autoimmune disorder. Lupus erythematosus and rheumatoid arthritis are examples of autoimmune diseases, in which our own tissues are attacked from within by our immune defenses.

If our immune systems fail to react properly to an outside agent--say a virus or bacterium--the result is a serious infection. Finally, if our immune systems fail to identify and destroy our own cells after they become abnormal, the result is cancer-cell development and, possibly, the growth of tumors. How can the immune system react to our own cancer cells if the antigens on our cells are supposed to signal "self" to ward off attack?

The answer reveals the special mechanism by which our bodies prevent cancer. Once a cell turns malignant, certain antigens on its surface also change. These altered molecules--known as "cancer-specific" antigens--signal "foreign" to the immune system. Cancer antigens are the giveaway--the slight change in fingerprints that can enable our defenses to detect a dangerous "inside job." Fortunately, our immune cells are not only guards, policemen, and soldiers; they're detectives as well. They have to be, because the outlaw cancer cell often cloaks its identity as a traitor to the community of cells. (These antigens have been found in some cancer types but not all.

The search continues, because cancer-specific antigens can be used in vaccines or other immunological approaches to preventing and treting cancer.)

Certain B-cells also remember their encounters with foreign agents. As a result, antibodies are produced swiftly when the same invader attacks again. Immunologic memory is the basis for vaccines, which introduce small amounts of antigen to prime our bodies for subsequent attacks. T-Cells: The Prime Players: T-cells are the stars of cell-mediated immunity, the branch consisting of subgroups of interacting cells. T-cells are so named because they "grow up" in the thymus, the walnut-sized gland located under the breastbone.

Although all immune cells are "born" in the bone marrow, different types follow different developmental pathways. T-cells migrate to the thymus. There, with the aid of various thymic hormones, immature T-cells grow, learn to recognize and attack antigens, and develop a range of specialized activities. The thymus is the master gland of cell-mediated immunity, a veritable training school for different classes of T-cells. Mature T-cells are harbored in the spleen and lymph nodes, waiting there for the sound of an alarm signaling an intruder. As with B-cells, the T-cell line also generates memory cells that prime the bdoy for repeat attacks by a familiar invader.

The main subcategories of T-cells include:
T-helper cells orchestrate the actions of other immune cells. They are essential to the performance of their fellow B-cells of the humoral branch; certain antibody reactions depend on help from the helper T's. T-helpers, which are also referred to as CD4 cells (so named for one of their cell-surface receptors), are the primary targets of HIV, the virus that causes AIDS. HIV's destruction of T-helpers, which are crucial conductors of immunity, is the reason why people with AIDS eventually lose their capacity to fight off infections and cancer cells.

Killer T-cells, also known as cytotoxic T-cells, are able to liquidate invading microbes, viruses, or cancer cells. Once alerted by other immune cells, and activated by messenger molecules, the killer T's go into action. They have nimble receptors on their surface that reconfigure their structure to fit snugly into their adversaries' antigens. Once attached, the T-cell injects a load of toxic chemicals into the invader, puncturing its surface membrane and causing its insides to gush out into the fluid environment.

Suppressor T-cells are vital to maintaining properly balanced immune responses. Sometimes called CD8 cells, they are able to suppress or dampen the actions of other immune cells. Without the activity of suppressor Ts, immunity could easily get out of hand, resulting in allergic or autoimmune reactions. But CD8 cells are multi- faceted--they can also destroy virus-infected cells. That's why their strength and numbers are considered crucial to individuals infected by HIV.

Macrophages, which begin their cellular lives as monocytes, are the garbagemen of the immune system. They clean up waste products in the aftermath of an immune cell attack. But macrophages are also critically involved in the earliest phases of our immune responses. They kick off the immunologic cascade by processing and presenting antigens to lymphocytes, which then initiate full-fledged cellular and humoral reactions. Macrophages also release messenger molecules, such as interleukin- 1, that stimulate and inform lymphocytes while the immune attack ensues. Another product of macrophages, tumor necrosis factor (TNF), is like the body's own chemotherapy--it has the noteworthy ability to liquidate cancer cells. Immune responses require breathtakingly complex interactions throughout the entire immune network.

T-helper cells need antigens presented to them by macrophages, and they depend on numerous signals from other cells and messenger molecules. B-cells depend on T-helpers to do their job, so both branches--cell-mediated and humoral--ultimately depend on macrophages. Unlike T- and B-cells, macrophages are "non-specific": they don't latch onto invaders in a perfectly targetted "lock-and-key" fashion. But they do swallow up and present invaders to specific T-cells, and clean up the messy aftermath. Another group of non-specific immune cells, from neither B- or T-cell lineages, are the natural killer cells, or "NK cells."

NK cells have the capacity to recognize viruses and cancer cells without having encountered them before, without having antigens served up to them by other cells, and without a specific lock-in-key receptor. Through mechanisms not fully understood, NK cells execute "quick strikes" against virus-infected and cancer cells, killing them with stunning efficiency. In animal studies, NK cells have been shown responsible for stopping the spread of cancer cells throughout the body. Immunologists suspect that NKs serve the same life-saving function in humans, as well. A vital mind-body connection has been uncovered with NK cells.

A multitude of methdologically sound studies have demonstrated relationships between how we cope with stress and the vitality of our NK cells. These cells represent a bridge between psychological factors and our resistance to viral and malignant diseases. Cell Products and Messenger Molecules: Our immune cells manufacture a vast number of biological products. These are molecules whose functions vary as widely as the scientific names given them: "biological response modifiers," "cytokines," "cell products," "growth factors,""messenger molecules," and just plain "biologicals."

Regardless of their titles, these substances carry information and instructions from one group of immune cells to another, changing behavior and coordinating immune responses. These molecules are couriers, communicators, helpers, growth inducers, and suppressors. Among the most well-known immune-cell products are the interferons, which have antiviral and anticancer properties, and the interleukins, many of which fight cancer, as well. There are many sub-types of interferon and interleukin, each of which perform distinct functions--but all are critical links in the immunologic chain reaction.

Scores of other products, each with its own name and properties, regulate the activities of our immune cells. As mentioned, one of PNI's most surprising discoveries is that brain chemicals- -the neuropeptides and neurotransmitters--also carry messages to immune cells. (Receptors for these brain chemicals have been found on lymphocytes, macrophages, and natural killer cells.) Moreover, recent research has shown that the immune system itself produces neuropeptide-like molecules, and brain cells appear to make immune chemicals, such as interleukin-1. We are just beginning to understand the true reciprocity of the brain-immune dialogue. Brain and body make and receive the same kinds of chemicals in order to communicate effectively. They "speak" the same language--the language of messenger molecules.

Copyright @ Henry Dreher, 1995.

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