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The body defenses 66 The body's defenses Nonspecific mechanisms provide general barriers to infection: The microbe must penetrate an external barrier formed by the skin and mucous membrane, which cover the surface and line the openings of an animal's body. If it succeeds, the pathogen encounters the second line of nonspecific defense: Nonspecific defense mechanisms Specific mechanisms (Immune system) First line of defense -Skin Second line of defense Third line of defense -Phagocytic white blood -Lymphocytes cells -Mucous membranes -Antimicrobial proteins -Antibodies and their secretions -The inflammatory response -The skin and mucous membranes: The intact skin is a barrier that can't normally penetrated by bacteria or viruses. The mucous membranes that lining the digestive, respiratory, genitourinary tracts bar the entry of potentially harmful microbes.Skin and mucous membranes also constitutes a chemical barriers by secreting. Example: Secretions from oil and sweat glands give the skin a pH ranging from 3-5, which is acidic enough to discourage many microorganisms from colonizing there. Saliva, tears, and mucous secretions contain antimicrobial protective protein called lysozyme. an enzyme that digests the cell walls of many bacteria and destroys many microbes entering the upper respiratory system and the openings around the eyes. The body defenses 67 Mucous: The viscous fluid secreted by cells of the mucous membranes, also traps particles that contact it. Microbes entering the upper respiratory system are often caught in the mucus and are then swallowed or expelled. Lining the trachea are specialized epithelial cells equipped with cilia that sweep out microbes and other particles trapped by the mucus, preventing them from entering the lungs. Microbes present in food passes through the highly acidic gastric juice inside the stomach which destroys most microbes before passing to the intestinal tract. Phagocytic white cells and natural killer cells: The body's internal mechanisms of nonspecific defense depend mainly on phagocytosis, the ingestion of invading particles by certain types of white blood cells. The phagocytic cells called neutrophils comprise about 60% to 70% of all WBCs. Attracted by chemical signals, neutrophils can leave the blood and enter infected tissue by amoeboid movement, destroying microbes there. The migration toward the source of a chemical attractant is called chemotaxis. Also, neutrophils tend to self-destruct and their average life is only a few days. Monocytes, performs 5% of WBCs, provide an even more effective phagocytic defense. After maturation, monocytes circulate in blood for hours, then migrate into tissues, enlarging and developing into macrophages (big eaters). Macrophages, the largest phagocytic cells, are especially effective, long-living phagocytes. These amoeboid cells extend pseudopodia that pull in microbes. (Fig. 39.3)P854.and destroys it by digestive enzymes and reactive forms of oxygen within the macrophages. The body defenses 68 Mechanisms for evading phagocytosis: 1. Certain bacteria, have special capsules to which the macrophage can't attach. 2. Others have developed a resistance to the lytic enzymes of the phagocyte and can even reproduce within macrophages. Some macrophages reside permanently in organs and connective tissues. In the lungs, for example, they are alveolar macrophages; in the liver, they are called Kupffer's cells. Fixed macrophages are especially numerous in the lymph nodes and spleen, key organs of the lymphatic system (Fig. 39.4) mnp855. Eosinophils, about 1.54% of WBCs which have only limited phagocytic activity but contain destructive enzymes within cytoplasmic granules. It function against larger parasitic invaders, such as worms. Eosinjophils position themselves against the external wall of a worm and discharge the destructive enzymes from their granules. Natural killer cells: They do not attack microorganisms directly, but rather destroy the body's own infected cells, especially cells harboring viruses, which can reproduce only within host cells. The natural killers also assault aberrant cells that could form tumors, by attacking the membrane of the target cell, which causes that cell to lyse (break open). Antimicrobial proteins A variety of proteins function in nonspecific defense either by attacking microorganisms directly or by impeding their reproduction. The complement system: is a group of at least 20 proteins, named for its cooperation with (complementation) other defense mechanisms. The complement proteins act together in a cascade of activation steps that culminates with lysis of invading microbes. Some components of the complement system also function in chemotaxis as attractants for the recruitment of phagocytes to sites of infection. The body defenses (Fig. 39.3 P854)and (fig. 39.4 p855) 69 The body defenses 70 Interferons: First identified in 1957, where it is substances that virus-infected cells produce, helping other cells interfere with, or resist infection by, the virus. Types of interferon (alpha, beta, and gamma). Interferons are secreted by an infected cell as an early, nonspecific defense before specific antibodies appear. Interferons are most effective in controlling short-term infections, such as cold and influenza. In addition to its role as an antiviral agent, interferon-gamma activates phagocytes, enhancing their ability to ingest and kill microorganisms. The inflammatory response Damage to tissue by a physical injury, such as a cut, or by the entry of microorganisms, triggers an inflammatory response (Fig. 39.5) P 856 Vasodilation occurs, then blood supply increase to the infected area (redness and heat). Blood vessles becomes more permeable and edema occurs. There are chemical signals where histamine secreted by basophils and mast cells. Histamine triggers local vasodilation. Also WBCs release prostaglandin. Blood clotting is another sign of repair process. Phagocyte migration from blood to the infected area is an important factor in immune response. Neutrophils reach first then monocytes which change to macrophages. The pus that often accumulates at the site of an infection consists of mostly of dead cells and the fluid that leaked from the capillaries during the inflammatory response. Another systemic response to infection is fever. Some WBCs has the ability to secrete a molecules called pyrogens which can set body thermostat at high temperature. A very high fever is dangerous but moderate temperature may share in defense. Where it inhibit the growth of some microorganisms by decreasing the amount of iron available. The body defenses Fig. 39.5 p856 71 The body defenses 72 The immune system defends the body against specific invaders: an overview First line of defense Second line of defense Third line of defense Microorganisms The immune system develops a specific response against each type of foreign microbe, toxin, or transplanted tissue. Key features for the immune system 1. Specificty: The immune system has the ability to recognize and eliminate particular microorganism and foreign molecules, a certain strain of flu virus, for example. A foreign substance that elicits this immune response is called an antigen. The immune system respond to an antigen by activating specific proteins called antibodies. Antigens that rigger an immune response includes molecules belonging to viruses, bacteria, fungi, protozoa, and parasitic worms. Antigenic molecules also mark the surfaces of such foreign materials as pollen, insect venom, and transplanted tissue, such as skin or organs. 2. Diversity: The immune response has the ability to respond to millions of kinds of invaders, each recognized by its antigenic markers. This diversity of response is possible because there variety of lymphocytes populations, each population bearing receptors for a particular antigen. 3. Memory: The immune system has the ability to "remember" antigens it has encountered and to react to them more promptly and effectively on subsequent exposures. The body defenses 73 This is called acquired immunity. Example: If we had chickenpox as a child, we are unlikely to get it again. 4. Self/Nonself recognition: The immune system distinguishes the body's own molecules from foreign molecules (antigens).Failure of self/nonself recognition can lead to autoimmune disorders, in which the immune system destroys the body's own tissues. Active versus passive acquired immunity: Immunity donated by recovering from an infectious disease such as chickenpox is called active immunity because it depends on the response of person's own immune system. Active immunity Naturally acquired Response of person's own immune system example: chickenpox Artificially acquired Response of person's own immune system example: vaccination (vaccine is may be inactivated bacterial toxins, killed microorganisms, or living but weakened microorganisms. The body defenses 74 Antibodies can also be transferred from one individual to another, providing passive immunity. (passive immunity persists for only few weeks or months). This occurs naturally when preganant women's body passes some of her antibodies across the placenta to the fetus. Certain antibodies are also passed from the mother to her nursing infant in breast milk (colostrum). Humoral immunity and cell-mediated immunity: The immune system can actually mount two different types of responses to antigens: Humoral response Results in the production of antibodies, which are secreted by certain lymphocytes. Then circulates in blood as soluble proteins in blood plasma and lymph. The circulating antibodies of the humoral branch defend mainly against toxins, free bacteria, and viruses present in body fluids. Cell-mediated response Depends on the direct action of cells (certain types of lymphocytes, which are active against fungi, protozoa, and worms. The body defenses 75 Cells of the immune system: The vertebrate body is populated by two main classes of lymphocytes: B-cells (B lymphocytes): which carry out the humoral immune response T-cells (T lymphocytes), which function mainly in the cell-mediated immune response. Lymphocytes originate from pluripotent stem cells in bone marrow, or in the fetus, mainly in liver. Lymphocytes are alike; they differentiate into T cells or B cells, depending on where they continue their maturation (Fig. 39.6) p858 Lymphocytes that migrate from the bone marrow to the thymus, a gland in the upper region of the chest, develop into T cells (T for thymus). Lymphocytes that remain in the bone marrow and continue their maturation there become B cells. Mature B cells and T cells are most concentrated in lymph nodes, the spleen. Both B cells and T cells are equipped with specific antigen receptors on their plasma membranes. T cells receptors recognize antigens as specifically as antibodies. When antigens bind to specific receptors on the surface of a lymphocyte, the lymphocyte is activated to divide and differentiate, giving rise to a population of effector cells, the cells that actually defend the body in an immune response. In the case of humoral response, B cells activated by antigen binding give rise to effector cells called plasma cells, which secrete antibodies that help eliminate that particular antigen. Cytotoxic T cells (Tc) kill infected cells and cancer cells. Helper T cells (TH) secrete protein factors called cytokines, which regulate both B cells and T cells so it play an important role in humoral and cell-mediate responses. The body defenses 76 The body defenses 77 Clonal selection of lymphocytes is the cellular basis for ummunological specificity and diversity: How immune system response to millions of potential antigens? Fig. 39.7. The body defenses 78 The molecular basis of antigen-antibody specificity: Most antigens are proteins or large polysaccharides. The molecules are often outer components of the cell walls of bacteria, capsules, coats of viruses. Transplanted organs, blood cells from individuals and species incite an immune response. The surfaces of foreign substances such as pollen also include antigens. Antibodies do not generally recognize the antigen as a whole molecule, but it recognized a specific site on the antigen surface called antigenic determinant or epitope. Fig. 39.10 p 862 The body defenses Antibodies constitute a class of proteins called immunoglobulins (Igs). Every antibody molecule has at least two identical sites that bind to the epitope that provoked its production. Five types of Ig are known: IgG, IgM, IgA, IgD, and IgE. Fig. 39.11 P 863 79 The body defenses How antibodies work: Fig. 39.12 P865 80