Nonspecific Defenses

Nonspecific defenses include physical and chemical barriers, the inflammatory response, and interferons. Physical barriers include the intact skin and mucous membranes. These barriers are aided by various antimicrobial chemicals in tissue and fluids. An example of such a substance is lysozyme, an enzyme present in tears that destroys the cell membranes of certain bacteria.

Inflammatory Response
Another line of defense is the inflammatory response, in which white blood cells called monocytes and granulocytes (e.g., basophils and neutrophils) reach an injured area. Basophils release histamine, which results in increased local blood flow and increased permeability of the capillaries and allows phagocytizing cells, such as neutrophils and monocytes (macrophages), into the area. The same response sometimes results in fever. Leakage of the clotting protein fibrinogen and other substances into the injured area results in blockage of tissue by clots, which wall off the injured area to retard the spread of bacteria or their toxins.

Interferons
Interferons are proteins released by a virus-invaded cell that prompt surrounding cells to produce enzymes that interfere with viral replication. They are the reason that, in most instances, infection with one virus precludes infection by a second virus.

Nonsusceptibility
Nonsusceptibility is the inability of certain disease-carrying organisms to grow in a particular host species. Nonsusceptibility may be caused by such conditions as lack of availability of particular growth substances needed by the infecting microorganism or body temperature unsuitable for the invading microorganism. For example, chickens are nonsusceptible to anthrax because the bacteria cannot grow at the body temperature normal for that animal. Read more: immunity: Nonspecific Defenses Infoplease.com http://www.infoplease.com/ce6/sci/A0858763.html#ixzz26Gy1Ziw3

The Immune Response

The principal parts of the immune system are the bone marrow, thymus, lymphatic system, tonsils, and spleen. The lymph nodes, tonsils, and spleen act to trap and destroy antigens from the lymph, air, and blood, respectively. Antigens are molecules that the body reacts to by producing antibodies, highly specific proteins also known as immunoglobulins. Antigens include bacteria and their toxins, viruses, malignant cells, foreign tissues, and the like. Their destruction is accomplished by white blood cells (lymphocytes and the granulocytes and monocytes mentioned above), which are produced and constantly replenished by the stem cells of the bone marrow. The two types of lymphocytes are called B lymphocytes (B cells) and T lymphocytes (T

cells). B cells are responsible for production of antibodies in what is called humoral immunity after the ancient medical concept of the body humors.

B Lymphocytes
The presence of antigens in contact with receptor sites on the surface of a B lymphocyte stimulates the lymphocyte to divide and become a clone (a line of descendant cells), with each cell of the clone specific for the same antigen. Some cells of the clone, called plasma cells, secrete large quantities of antibody; others, called memory cells, enter a resting state, remaining prepared to respond to any later invasions by the same antigen. Antibody secretion by lymphocytes can be stimulated or suppressed by such variables as the concentration of antigens, the way the antigen fits the lymphocyte's receptor regions, the age of the lymphocyte, and the effect of other lymphocytes. According to the modified clonal selection theory originally postulated by the Australian immunologist Sir Macfarlane Burnet (for which he was awarded the 1960 Nobel Prize for Physiology or Medicine), a lymphocyte is potentially able to secrete one particular, specific humoral, or free-circulating, antibody molecule. It is believed that early in life lymphocytes are formed to recognize thousands of different antigens, including a group of autoimmune lymphocytes, i.e., cells recognizing antigens of the organism's own body. The immune system is self-tolerant; i.e., it does not normally attack molecules and cells of the organism's own body, because those lymphocytes that are autoimmune are inactivated or destroyed early in life, and the cells that remain, the majority, recognize only foreign antigens. Burnet's theory was confirmed with the development of monoclonal antibodies.

Antibodies
The antibodies produced by B cells are a type of globulin protein called immunoglobulins. There are five classes of immunoglobulins designated IgA, IgD, IgE, IgG, and IgM; gamma globulin (IgG) predominates. Antibody molecules are able to chemically recognize surface portions, or epitopes, of large molecules that act as antigens, such as nucleic acids, proteins, and polysaccharides. About 10 amino acid subunits of a protein may compose a single epitope recognizable to a specific antibody. The fit of an epitope to a specific antibody is analogous to the way a key fits a specific lock. The amino acid sequence and configuration of an antibody were determined in the 1960s by the biochemists Gerald Edelman, an American, and R. R. Porter, an Englishman; for this achievement they shared the 1972 Nobel Prize for Physiology or Medicine. The antibody molecule consists of four polypeptide chains, two identical heavy (i.e., long) chains and two identical light (i.e., short) chains. All antibody molecules are alike except for certain small segments that, varying in amino acid sequence, account for the specificity of the molecules for particular antigens. In order to recognize and neutralize a specific antigen, the body produces millions of antibodies, each differing slightly in the amino acid sequence of the variable regions; some of these molecules will chemically fit the invading antigen.

Antibodies act in several ways. For example, they combine with some antigens, such as bacterial toxins, and neutralize their effect; they remove other substances from circulation in body fluids; and they bind certain bacteria or foreign cells together, a process known as agglutination. Antibodies attached to antigens on the surfaces of invading cells activate a group of at least 11 blood serum proteins called complement, which cause the breakdown of the invading cells in a complex series of enzymatic reactions. Complement proteins are believed to cause swelling and eventual rupture of cells by making holes in the lipid portion of the cell's membrane.

T Lymphocytes
After their production in the bone marrow, some lymphocytes (called T lymphocytes or T cells) travel to the thymus, where they differentiate and mature. The T cells interact with the body's own cells, regulating the immune response and acting against foreign cells that are not susceptible to antibodies in what is termed cell-mediated immunity. Three classes of T lymphocytes have been identified: helper T cells, suppressor T cells, and cytotoxic T cells. Each T cell has certain membrane glycoproteins on its surface that determine the cell's function and its specificity for antigens. One type of function-determining membrane glycoprotein exists in two forms called T4 or T8 (CD4 or CD8 in another system of nomenclature); T4 molecules are on helper T cells, T8 molecules are on suppressor and cytotoxic T cells. Another type of membrane glycoprotein is the receptor that helps the T cell recognize the body's own cells and any foreign antigens on those cells. These receptors are associated with another group of proteins, T3 (CD3), whose function is not clearly understood. T cells distinguish self from nonself with the help of antigens naturally occurring on the surface of the body's cells. These antigens are, in part, coded by a group of genes called the major histocompatibility complex (MCH). Each person's MCH is as individual as a fingerprint. When a cytotoxic T lymphocyte recognizes foreign antigens on the surface of a cell, it again differentiates, this time into active cells that attack the infected cells directly or into memory cells that continue to circulate. The active cytotoxic T cells can also release chemicals called lymphokines that draw macrophages. Some (the killer T cells) release cell-killing toxins of their own; some release interferon. Helper T cells bind to active macrophages and B lymphocytes and produce proteins called interleukins, which stimulate production of B cells and cytotoxic T cells. Although poorly understood, suppressor T cells appear to help dampen the activity of the immune system when an infection has been controlled. Read more: immunity: The Immune Response Infoplease.com http://www.infoplease.com/ce6/sci/A0858764.html#ixzz26GycUX8J

Active and Passive Immunity

Naturally acquired active immunity occurs when the person is exposed to a live pathogen, develops the disease, and becomes immune as a result of the primary immune response. Artificially acquired active immunity can be induced by a vaccine, a substance that contains the

antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease (see vaccination). Artificially acquired passive immunity is a short-term immunization by the injection of antibodies, such as gamma globulin, that are not produced by the recipient's cells. Naturally acquired passive immunity occurs during pregnancy, in which certain antibodies are passed from the maternal into the fetal bloodstream. Immunologic tolerance for foreign antigens can be induced experimentally by creating conditions of high-zone tolerance, i.e., by injecting large amounts of a foreign antigen into the host organism, or low-zone tolerance, i.e., injecting small amounts of foreign antigen over long periods of time. Read more: immunity: Active and Passive Immunity Infoplease.com http://www.infoplease.com/ce6/sci/A0858765.html#ixzz26GzbJZrz

cell'-mediated immu'nity

Pronunciation: (sel'm"d-"tid), [key] Immunol. immunity independent of antibody but dependent on the recognition of antigen by T cells and their subsequent destruction of cells bearing the antigen or on the secretion by T cells of lymphokines that enhance the ability of phagocytes to eliminate the antigen. Also called cellular immunity. Cf. antibodymediated immunity.

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an'tibody-me'diated immu'nity

Pronunciation: (an'ti-bod" m'd-"tid, an't-), [key] Immunol. immunity conferred to an individual through the activity of B cells and their progeny, which produce circulating antibodies in response to the presence of a foreign substance and recognize the substance upon renewed exposure. Also called humoral immunity. Cf. cell-mediated immunity.

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