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Lec.8 Medical Physiology Z.H.Al-Zubaydi IMMUNITY Body Defenses Our bodies normally are exposed to bacteria, viruses, fungi, and parasites, which occur especially in the skin, the mouth, the respiratory passageways, the intestinal tract, the lining membranes of the eyes, and even the urinary tract. Many of these agents are capable of causing serious disease if they invade the deeper tissues. In addition, we are exposed intermittently to other highly infectious bacteria and viruses besides those that are normally present in our bodies, and these cause lethal diseases such as pneumonia, streptococcal infection, and typhoid fever. The body's defenders against these tiny organisms are two systems: I. Non Specific defense system responds immediately to protect the body from all foreign substances. II. Specific defense system [ Immune System; a functional system rather than an organ system] mount the attack against particular foreign substances. The resulting highly specific resistance to diseases is called immunity. Nonspecific Body Defenses [In native Immunity] the term nonspecific body defense refers to the mechanical barriers that cover body surfaces and to cells and chemicals that act on the initial protection of the body from invading pathogens (harmful or disease-causing microorganisms). Surface Membrane Barriers The body's first line of defense against the invasion of disease-causing microorganisms is the skin and mucous membranes. As long as the skin is unbroken, its keratinized epidermis is a strong physical barrier to most microorganisms that swarm on the skin. Intact mucous membranes provide similar mechanical barriers within the body, these membranes produce a variety of protective chemicals: 1. The acid pH of skin secretions inhibits bacterial growth, and sebum contains chemicals that are toxic to bacteria. Vaginal secretions of adult females are also very acidic. 2. The stomach mucosa secretes hydrochloric acid and proteindigesting enzymes. Both kill pathogens. 3. Saliva and lacrimal fluid contain lysozyme, an enzyme that destroys bacteria. 4. Sticky mucus traps many microorganisms that enter digestive and respiratory passageways. Some mucosae also have structural modifications that fend off potential invaders [Mucus-coated hairs inside the nasal cavity trap inhaled particles, and the ciliated mucosa of respiratory tract sweep dust]. Although the surface barriers are very effective, they are broken from time to time by small nicks and cuts resulting [ex.; brushing teeth or shaving]. When this happens and microorganisms do invade deeper tissues, other nonspecific mechanisms come into play to defend the body. Cells and Chemicals For its second line of defense, the body uses an enormous number of cells and chemicals to protect itself including: 1- Phagocytes A phagocyte such as a macrophage or neutrophil, engulfs a foreign particle much the way an amoeba ingests a food particle. Flowing cytoplasmic extensions bind to the particle and then pull it inside, enclosing it in a vacuole. The vacuole then fused with the enzymatic contents of a lysosome. and its contents are broken down or digested. 2- Natural Killer Cells Natural killer (NK) cells, which are a unique group lymphocytes that can lyse and kill cancer cells and virus-infected body cells well before immune system is enlisted in the fight. Unlike lymphocytes of the immune system, which recognize and react only against specific virus infected or tumor cells, natural killer cells are less picky. They attack the target cell's membrane release a lytic chemical called perforins. 3- Inflammatory Response The inflammatory response is a nonspecific response that is triggered whenever body tissues are injured (in response to physical trauma, intense heat, and irritating chemicals, as well as to infection by viruses and bacteria). The four signs and major symptoms of an acute inflammation are redness, heat, swelling, and pain. The inflammatory process begins with a chemical "alarm." When cells are injured, they release inflammatory chemicals, including histamine and kinins, that (1) cause blood vessels in the involved area to dilate and capillaries to become leaky, (2) activate pain receptors, and (3) attract phagocytes and white blood cells to the area. (This latter phenomenon is called chemotaxis because the cells are following a chemical gradient.) 4- Antimicrobial chemicals The body's most important antimicrobial chemicals are: I. Complement proteins include 20 plasma proteins that circulate in the blood in an inactivate state. When complement becomes attached or fixed to foreign cells and form complement fixation it is activated. One of this fixation results is the formation of membrane attack complex (MAC) that produce lesion and holes in the foreign cell's surface. These allow water to rush into the cell causing it to brust. II. Interferon when viruses damage the body by entering tissue cells to regenerate their ATP or to make proteins. The virus infected cells secret small proteins called interferon that diffuse to nearby cells and bind to their membrane receptors, this binding hinders the ability of viruses to multiply within these cells. 5- Fever although high fevers are dangerous because excess heat scrambles enzymes and other body proteins, mild to moderate fever seems to be benefit to the body. Bacteria require large amounts of iron and zinc to multiply, but during a fever the liver and spleen gather up these nutrients. Also fever increase the metabolic rate of tissue cells in general, speeding up repair process Specific Body Defenses [Acquired Immunity] Sometimes referred to as the body's third line of defense, the immune system is a functional system that recognizes foreign molecules (antigens) and acts to inactivate or destroy them. Normally it protects us from a wide variety of pathogens, as well as from abnormal body cells. There are three important aspects of the immune response: 1. It is antigen specific—It recognizes and acts against particular pathogens or foreign substances. 2. It is systemic—Immunity is not restricted to the initial infection site. 3. It has "memory"—It recognizes and mounts even stronger attacks on previously encountered pathogens. Antigens An antigen (Ag) is any substance capable of exciting our immune system and provoking an immune response. Most antigens are large, complex molecules that are not normally present in our bodies or nonself. It is also important to remember that our own cells are richly studded with a variety of protein molecules (self-antigens).which they are strongly antigenic to other people. This helps explain why our bodies reject cells of transplanted organs or foreign grafts unless special measures (drugs and others) are taken to cripple or stifle the immune response. Cells of the Immune System The cells of the immune system are lymphocytes and macrophages. Lymphocytes exist in two major types. The B lymphocytes, or B cells, produce antibodies and oversee humoral immunity, whereas the T lymphocytes, or T cells, are non-antibody producing lymphocytes that constitute the cell-mediated arm of immunity. Unlike the two types of lymphocytes, macrophages do not respond to specific antigens but instead play an essential role in helping the lymphocytes. Lymphocytes Like all blood cells, lymphocytes originate from hemocytoblasts in red bone marrow. The immature lymphocytes released from the marrow are essentially identical. Whether a given lymphocyte matures into a B cell or a T. T cells arise from lymphocytes that migrate to the thymus, where they undergo a maturation process of 2 to 3 days, directed by thymic hormones (thymosin and others). Within the thymus, the immature lymphocytes divide rapidly and their numbers increase enormously, but only those maturing T cells have the ability to identify foreign antigens. B cells develop immunocompetence in bone marrow, but little is known about the factors that regulate B cell maturation. After becoming immunocompetent, both T cells and B cells migrate to the lymph nodes and spleen. Macrophages Macrophages, which also become widely distributed throughout the lymphoid organs and connective tissues, arise from monocytes formed in the bone marrow. They act as antigen presenters in the specific defense system. Macrophages also secrete cytokine proteins, called monokines, that are important in the immune. Humoral Immunity [Antibody-Mediated Response] Immature B lymphocytes is stimulated to its development into a fully mature B cells when an antigen binds to its surface receptors. This binding event sensitizes, or activates, the lymphocyte to undergo clonal selection. The lymphocyte begins to grow and then multiplies rapidly to form cells all exactly like itself and bearing the same antigen-specific receptors. The resulting is identical cells descended from the same ancestor cell is called a clone, and clone formation is the primary humoral response to that antigen. Most of the B cell clone members, or descendants, become plasma cells. After an initial lag period, these antibody-producing "factories" act in producing the same highly specific antibodies at a rate of about 2000 antibody molecules per second. (The B cells themselves produce only very small amounts of antibodies.) However, this flurry of activity lasts only 4 or 5 days; then the plasma cells begin to die. Antibody levels in the blood during this primary response peak in about 10 days and then slowly decline. B cell clone members that do not become plasma cells become long-lived memory cells capable of responding to the same antigen at later meetings with it. Memory cells are responsible for the immunological "memory" mentioned earlier. These later immune responses, called secondary humoral responses, are much faster, more prolonged, and more effective because all the preparations for this attack have already been made (fig.13). Within hours after recognition of the old antigen, a new army of plasma cells is being generated, and antibodies begin to flood into the bloodstream. Within 2 to 3 days, blood antibody levels peak (at much higher levels than seen in the primary response), and their levels remain high for weeks to months. Figure (13):Primary and secondary responses