The Anatomy of the Immune System

The organs of the immune system are stationed throughout the body. They are generally referred to as lymphoid organs because they are concerned with the growth, development, and deployment of lymphocytes, the white cells that are the key operatives of the immune system. Lymphoid organs include the bone marrow and the thymus, as well as lymph nodes, spleen, tonsils and adenoids, the appendix, and clumps of lymphoid tissue in the small intestine known as Peyer's patches. The blood and lymphatic vessels that carry lymphocytes to and from the other structures can also be considered lymphoid organs.

Cells destined to become immune cells, like all other blood cells, are produced in the bone marrow, the soft tissue in the hollow shafts of long bones. The descendants of some so-called stem cells become lymphocytes, while others develop into a second major group of immune cells typified by the large, cell-and particle-devouring white cells known as phagocytes.

The two major classes of lymphocytes are B cells and T cells. B cells complete their maturation in the bone marrow. T cells, on the other hand, migrate to the thymus, a multilobed organ that lies high behind the breastbone. There they multiply and mature into cells capable of producing immune response-that is, they become immunocompetent. In a process referred to as T cell "education," T cells in the thymus learn to distinguish self cells from nonself cells; T cells that would react against self antigens are eliminated.



Upon exiting the bone marrow and thymus, some lymphocytes congregate in immune organs or lymph nodes. Others-both B and T cells-travel widely and continuously throughout the body. They use the blood circulation as well as a bodywide network of lymphatic vessels similar to blood vessels.

Laced along the lymphatic routes-with clusters in the neck, armpits, abdomen, and groin-are small, bean-shaped lymph nodes. Each lymph node contains specialized compartments that house platoons of B lymphocytes, T lymphocytes, and other cells capable of enmeshing antigen and presenting it to T cells. Thus, the lymph node brings together the several components needed to spark an immune response.

The spleen, too, provides a meeting ground for immune defenses. A fist-sized organ at the upper left of the abdomen, the spleen contains two main types of tissue: the red pulp that disposes of worn-out blood cells and the white pulp that contains lymphoid tissue. Like the lymph nodes, the spleen's lymphoid tissue is subdivided into compartments that specialize in different kinds of immune cells. Microorganisms carried by the blood into the red pulp become trapped by the immune cells known as macrophages. (Although people can live without a spleen, persons whose spleens have been damaged by trauma or by disease such as sickle cell anemia, are highly susceptible to infection; surgical removal of the spleen is especially dangerous for young children and the immunosuppressed.)

Non encapsulated clusters of lymphoid tissue are found in many parts of the body. They are common around the mucous membranes lining the respiratory and digestive tracts-areas that serve as gateways to the body. They include the tonsils and adenoids, the appendix, and Peyer's patches.

The lymphatic vessels carry lymph, a clear fluid that bathes the body's tissues. Lymph, along with the many cells and particles it carries-notably lymphocytes, macrophages, and foreign antigens, drains out of tissues and seeps across the thin walls of tiny lymphatic vessels. The vessels transport the mix to lymph nodes, where antigens can be filtered out and presented to immune cells.

Additional lymphocytes reach the lymph nodes (and other immune tissues) through the bloodstream. Each node is supplied by an artery and a vein; lymphocytes enter the node by traversing the walls of the very small specialized veins.



All lymphocytes exit lymph nodes in lymph via outgoing lymphatic vessels. Much as small creeks and streams empty into larger rivers, the lymphatics feed into larger and larger channels. At the base of the neck, large lymphatic vessels merge into the thoracic duct, which empties its contents into the bloodstream.

Once in the bloodstream, the lymphocytes and other assorted immune cells are transported to tissues throughout the body. They patrol everywhere for foreign antigens, then gradually drift back into the lymphatic vessels, to begin the cycle all over again.

The immune system stockpiles a tremendous arsenal of cells. Some staff the general defenses, while others are trained on highly specific targets. To work effectively, however, most immune cells require the active cooperation of their fellows. Sometimes they communicate through direct physical contact, sometimes by releasing versatile chemical messengers.

In order to have room for enough cells to match millions of possible foreign invaders, the immune system stores just a few of each specificity. When an antigen appears, those few specifically matched cells are stimulated to multiply into a full-scale army. Later, to prevent this army from overexpanding wildly, like a cancer, powerful suppressor mechanisms come into play.





Lymphocytes are small white blood cells that bear the major responsibility for carrying out the activities of the immune system; they number about one trillion. The two major classes of lymphocytes are: B cells, which grow to maturity independent of the thymus, and T cells, which are processed in the thymus. Both B cells and T cells recognize specific antigen targets.
B cells work chiefly by secreting soluble substances called antibodies into the body's fluids, or humors. (This is known as humoral immunity.) Antibodies typically interact with circulating antigens such as bacteria and toxic molecules, but are unable to penetrate living cells. T cells, in contrast, interact directly with their targets, attacking body cells that have been commandeered by viruses or warped malignancy. (This is cellular immunity.)

Although small lymphocytes look identical, even under the microscope, they can be told apart by means of distinctive molecules they carry on their cell surface. Not only do such markers distinguish between B cells and T cells, they distinguish among various subsets of cells that behave differently. Every mature T cell, for instance, carries a marker known as T3 (or CD3); in addition, most helper T cells carry a T4 (CD4) marker, a molecule that recognizes class II MHC antigens. A molecule known as T8 (CD8), which recognizes class I MHC antigens, is found on many suppressor/cytotoxic T cells. In addition, different T cells have different kinds of antigen receptors-either alpha/beta or gamma/delta.

Mounting a Response

Infections remain the most common cause of human disease. Produced by bacteria, viruses, parasites and fungi, infections may range from relatively mild respiratory illnesses such as the common cold, to debilitating conditions like chronic hepatitis, to life-threatening diseases such as AIDS and meningitis.



To fend off the threatening horde, the body as devised astonishingly intricate defenses. Microbes attempting to enter the body must first find a chink in the body's external protection. The skin and the mucous membranes that line the body's portals not only pose a physical barrier, they are also rich in scavenger cells and IgA antibodies.

Next, invaders must elude a series of nonspecific defenses-those cells and substances equipped to tackle infectious agents without regard for their antigenic peculiarities. Many potential infections are cut short when microbes are intercepted by patrolling scavenger cells or disabled by complement or other enzymes or chemicals. Virus-infected cells, for instance, secrete interferon, a chemical that rouses natural killer cells.

Disorders of the Immune System

Allergies

The most common types of allergic reactions-hay fever, some kinds of asthma, and hives-are produced when the immune system response to a false alarm. In a susceptible person, a normally harmless substance-grass pollen or house dust, for example-is perceived as a threat and is attacked.
Such allergic reactions are related to the antibody known as immunoglobulin E. Like other antibodies, each IgE antibody is specific; one reacts against oak pollen, another against ragweed. The role of IgE in the natural order is not known, although some scientists suspect that it developed as a defense against infection by parasitic worms.

The first time an allergy-prone person is exposed to an allergen, he or she makes large amounts of the corresponding IgE antibody. These IgE molecules attach to the surfaces of mast cells (in tissue) or basophils (in the circulation). Mast cells are plentiful in the lungs, skin, tongue, and linings of the nose and intestinal tract.

When an IgE antibody siting on a mast cell or basophil encounters its specific allergen, the IgE antibody signals the mast cell or basophil to release the powerful chemicals stored within its granules. These chemicals include histamine, heparin, and substances that activate blood platelets and attract secondary cells such as eosinophils and neutrophils. The activated mast cell or basophil also synthesizes new mediators, including prostaglandins and leukotrienes, on the spot.

It is such chemical mediators that cause the symptoms of allergy, including wheezing, sneezing, runny eyes and itching. They can also produce anaphylactic shock, a life-threatening allergic reaction characterized by swelling of body tissues, including the throat, and a sudden fall in blood pressure.

Cancers

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.

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