2002.05
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How the immune system works

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The immune system is a bodywide network of cells and organs that has evolved to defend the body against attacks by "foreign" invaders.

The proper targets of the immune defenses are infectious organisms-bacteria such as these streptococci; Fungi (this one happens to be the mold from which penicillin is made); Parasites, including these worm-like microbes that cause schistosomiasis; and Viruses such as this herpes virus.

Markers of Self
At the heart of the immune response is the ability to distinguish between self and nonself. Every body cell carries distinctive molecules that distinguish it as "self." Normally the body's defenses do not attack tissues that carry a self marker; rather, immune cells coexist peaceably with other body cells in a state known as self-tolerance.

Markers of Non-Self
Foreign molecules, too, carry distinctive markers, characteristic shapes called epitopes that protrude from their surfaces. One of the remarkable things about the immune system is its ability to recognize many millions of distinctive non-self molecules, and to respond by producing molecules such as these antibodies-and also cells-that can match and counteract each one of the non-self molecules.

Any substance capable of triggering an immune response is known as an antigen. An antigen can be a bacterium or a virus, or even a portion or product of one of these organisms. Tissues or cells from another individual also act as antigens; that's why transplanted tissues are rejected as foreign.

Organs of the Immune System
The organs of the immune system are stationed throughout the body. They are known as lymphoid organs because they are concerned with the growth, development, and deployment of lymphocytes-white blood cells that are key operatives of the immune system.

Lymphatic System
The organs of the immune system are connected with one another and with other organs of the body by a network of lymphatic vessels similar to blood vessels. Immune cells and foreign particles are conveyed through the lymphatics in lymph, a clear fluid that bathes the body's tissues.

Lymph Node
Lymph nodes are small, bean-shaped structures that are laced throughout the body along the lymphatic routes. Lymph nodes contain specialized compartments where immune cells congregate, and where they can encounter antigens.

Cells of the Immune System
Cells destined to become immune cells, like all blood cells, arise in the bone marrow from so-called stem cells. Some develop into myeloid cells, a group typified by the large, cell- and particle- devouring white blood cells known as phagocytes; phagocytes include monocytes, macrophages, and neutrophils.

Other myeloid descendants become granule-containing inflammatory cells such as eosinophils and basophils. Lymphoid precursors develop into the small white blood cells called lymphocytes. The two major classes of lymphocytes are B cells and T cells.

B Cells
B cells work chiefly by secreting soluble substances known as antibodies. Each B cell is programmed to make one specific antibody. When a B cell encounters its triggering antigen (along with various accessory cells), it gives rise to many large plasma cells. Each plasma cell is essentially a factory for producing that one specific antibody.

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Antibody
Each antibody is made up of two identical heavy chains and two identical light chains, shaped to form a Y. The sections that make up the tips of the Y's arms vary greatly from one antibody to another; this is called the variable region.

It is these unique contours in the antigen-binding site that allow the antibody to recognize a matching antigen, much as a lock matches a key. The stem of the Y links the antibody to other participants in the immune defenses. This area is identical in all antibodies of the same class-for instance, all IgEs-and it's called the constant region.

IgG, IgD, and IgE
Antibodies belong to a family of large protein molecules known as immunoglobulins. Scientists have identified nine chemically distinct classes of human immunoglobulins, four kinds of IgG and two kinds of IgA, plus IgM, IgE, and IgD. Immunoglobulins G, D, and E are similar in appearance.

IgG, the major immunoglobulin in the blood, is also able to enter tissue spaces; it works efficiently to coat microorganisms, speeding their uptake by other cells in the immune system. IgD is almost exclusively found inserted into the membrane of B cells, where it somehow regulates the cell's activation. IgE is normally present in only trace amounts, but it is responsible for the symptoms of allergy.

IgA and IgM
IgA-a doublet-concentrates in body fluids such as tears, saliva, and the secretions of the respiratory and gastrointestinal tracts. It is, thus, in a position to guard the entrances to the body.

IgM usually combines in star-shaped clusters. It tends to remain in the bloodstream, where it is very effective in killing bacteria.

Antibody Genes
Scientists long wondered how all the genetic information needed to make millions of different antibodies could fit in a limited number of genes. The answer is that antibody genes are pieced together from widely scattered bits of DNA, and the possible combinations are nearly endless.

As this gene forms, it assembles segments that will determine the variable-V, diversity-D, joining-J, and constant-C segments of this antibody molecule, a typical IgM heavy chain.

T Cells
T cells contribute to the immune defenses in two major ways. Some help regulate the complex workings of the immune system, while others are cytotoxic and directly contact infected cells and destroy them. Chief among the regulatory T cells are "helper/inducer" T cells.

They are needed to activate many immune cells, including B cells and other T cells. Another subset of regulatory T cells acts to turn off or suppress immune cells. Cytotoxic T cells help rid the body of cells that have been infected by viruses as well as cells that have been transformed by cancer. They are also responsible for the rejection of tissue and organ grafts.

Cytokines
Cytokines are diverse and potent chemical messengers secreted by the cells of the immune system-and the chief tool of T cells.

Lymphocytes, including both T cells and B cells, secrete lymphokines, while monocytes and macrophages secrete monokines.

Binding to specific receptors on target cells, cytokines recruit many other cells and substances to the field of action. Cytokines encourage cell growth, promote cell activation, direct cellular traffic, and destroy target cells-including cancer cells.

Because they serve as a messenger between white cells, or leukocytes, many cytokines are also known as interleukins.

Natural Killer Cells
At least two types of lymphocytes are killer cells-cytotoxic T cells and natural killer cells. To attack, cytotoxic T cells need to recognize a specific antigen, whereas natural killer or NK cells do not.

Both types contain granules filled with potent chemicals, and both types kill on contact. The killer binds to its target, aims its weapons, and delivers a burst of lethal chemicals.

Phagocytes and Granulocytes
Phagocytes are large white cells that can engulf and digest foreign invaders. They include monocytes, which circulate in the blood, and macrophages, which are found in tissues throughout the body, as well as neutrophils, cells that circulate in the blood but move into tissues where they are needed.

Macrophages are versatile cells; they act as scavengers, they secrete a wide variety of powerful chemicals, and they play an essential role in activating T cells. Neutrophils are not only phagocytes but also granulocytes: they contain granules filled with potent chemicals.

These chemicals, in addition to destroying microorganisms, play a key role in acute inflammatory reactions. Other types of granulocytes are eosinophils and basophils. Mast cells are granule-containing cells in tissue.

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