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IMMUNE SYSTEM Introduction: All living tissues are subject to the constant threat of invasion by disease producing organisms (pathogens) such as: viruses, bacteria, fungi, protozoan, parasitic warms and other agents. IMMUNITY: The defense of the body against the invasion of many pathogens. The vertebrate following have the following lines of defense against pathogens: 1. Physical and chemical barriers at body surfaces (nonspecific targets) 2. nonspecific immune response ( nonspecific targets) 3. specific immune response (specific targets). Barriers at body's surfaces: 1. Intact skin; mucous membrane that line body's surfaces are physical barrier to infections. 2. Infection-fighting chemicals (e.g. lysozomes in tears & saliva) & gastric fluid in the stomach are chemical barriers 3. Normally harmless bacterial inhabitants of skin, vagina & gut. 4. Flushing effect of tears, urination & diarrhea. Complement system: 1. When certain microbes (e.g. bacteria, parasitic protistans &enveloped viruses) invade a tissue, a set of twenty plasma proteins (enzymes) interact as a system called complement system. 2. They are produced mostly in liver cells by monocytes & macrophages. 3. The complement system takes part in both nonspecific & specific defense. 4. complement proteins circulates in inactive form. If even a few molecules of one kind are activated, they trigger cascading reactions that activate many molecules of another complement protein until huge numbers are mobilized and result in: a. some inserted into plasma membrane (protein) of the pathogens forming pores that lead to lysis that result in cell death. b. Some create chemical concentration gradients that attract phagocyte to an irritated or damaged tissue. Also encourage phagocytes to dine. (to function) c. Other proteins form a phagocyte-attracting coat on the surface of the invading cells. d. Some repair tissue damage-clotting mechanism. 1 Non specific immune: When tissue becomes damaged, they take a part in non- specific response. Non-specific response reacts in tissue damage in general, not one pathogen or another. Recognition of self from non-self e.g. reaction to toxins, transplant, results in phagocytosis and may be followed by inflammation. Both phagocytosis and inflammation try to destroy invaders & establish homestasis in damaged tissue. Phagocytosis: A form of defense against bacteria and external agents. The most important kind of defense are the white blood cells. They arise from stem in the bone marrow. Many circulate in blood & lymph and take up stations in lymph nodes as well as spleen, liver, kidneys & brain. Kinds of white blood cells involve in nonspecific response are: צּNeutrophils: fast acting phagocytes, take port in inflammation, phagocytize bacteria, they ingest, kill & digest bacterial cells to simple particles. צּEsinophils: secrete enzymes that make holes in parasitic worms. צּBasophils: secrete histamine & other substances that may help keep inflammation going after it starts. צּMacrophages (big eaters). They engulf and digest foreign agents they also help clean up damaged tissues. צּImmature macrophages circulating in blood are celled monocytes. צּPhagocytes should be able to recognize their invaders. צּAll cells including bacteria have markers that are recognize the person's antibodies called MHC proteins (Major Histo Compatibility complex proteins). צּThese markers are on the surface of the body's own cells allow lymphocytes to distinguish self (body's own cells) from non-self (foreign agents). צּIt enables your antibodies to recognize your body cell and not attack them. צּPathogens have antigens (non-self marker). צּIt recognized as an invader, your antibodies attached to invader receptors sites, this activate complement proteins which coat antigen and makes it attractive for phagocytosis by phagocytic cells. 2 Inflammation: A series of events that destroy invaders & repair the tissue ( a complex response to local tissue damaged). Inflammatory response develops in a local tissue when cells are damaged or killed, as by infection. In proceeds during both nonspecific & defenses of tissues. Symptoms of inflammation: 1. Most cells reside in connective tissues & function like basophiles, take part in inflammatory response. They senthesize & release histamine & other substances into interstial fluid. Their secretions trigger vasodilation of arterioles that snake through the damaged tissue. When the arterioles become engorged with blood, the effected tissue reddens & become warmer owing to bloodborne metabolic heat. 2. released histamine also increases the permeability of capillaries in the tissue. Thus the capillaries become leaky plasma proteins that normally do not leave the blood. When some protein leak out, osmotic pressure increases in the surrounding interstitial fluid. In combination with the higher blood pressure brought about by the increased blood flow to the tissue, ultra filtration increases & reabsorption decreases across the capillary wall. Edema results from the fluid imbalance across the capillary wall. The tissue swells with fluid. 3. Then tissue nociceptors give rise to sensation of pain. 4. Complement protein initiate blood dotting & it also stimulates the mast cells. Among the plasma protein that leak into tissue are complement proteins & clotting factors.. 5. Macrophages secrete interleukin 1, it is chemical which: act on the temperature center of brain & the temperature increases killing some pathogens. The increase in temperature known as fever. It induces drowsiness, which reduces the body's demand for energy, so more energy can be diverted to the tasks of defense &tissue repair. If stimulates formation of both B & and T cells. 3 Specific immune response. If the nonspecific responses fail to check invaders, then the body starts specific immune response. Specific response is directed against only one kind of pathogens. Immune responses are carried out by interaction among macrophages & viruses lymphocytes (helper T-cells, killer T-cells, suppressor T-cells, B-cells & memory cells). Cells of immune system communicates with one another by cell- to – cell contact & by chemical sensation, which stimulate raped growth and divisions of: B-cells, helper T-cells, & killer T-cells into large armies against particular invaders. MHC markers on the surface of body's own cells allow lymphocytes to distinguish self from non-self. Lymphocytes are able to recognize a particular antigen. Any molecule configuration that triggers formation of lymphocytes armies & is their target is an antigens. Lymphocytes are central to the body's third line of defense (immune system). Immune system consist of : lymphatic organs, tissue and cells as well as products of these cells including antibodies ®ulatory agents. the defense includes: leucocytes lymphocytes cell secretions antibodies plasma proteins complement system characteristics of immune system: 1. Immunological specificity: where lymphocytes directed against specific antigen . 2. Immunological memory: A subsequent encounter with the same antigen triggers a more rapid, secondary response, of greater magnitude ( some lymphocytes that form during a first time is set for a future battle with the same pathogen) . nb Recognition of self and non-self cells (an immune response normally is not made against the body's own self marker protein). 3. 4 Immunological specificity & memory involve the following events: Recognition of antigen Repeated cell division, which gives huge number of lymphocyte. Differentiation into subpopulations of effectors and memory cells with receptors those are specific for one kind of antigen. Effectors helper Tcells, cytotoxic T-cells, effector B-cells and antibodies act as once. Memory cells: A portion of B-cells & T- cells populations produced during a first encounter with a specific invader but not used in bottle; they circulate through the body and respond rapidly to any subsequent attacks y the same type of invaders. B&T cells: B-cells: Originate & maturates in bone marrow. Reside in spleen & lymph nodes, circulate in blood and lymph. Directly recognize antigen & then undergo clonal secretion. On activation by ant5igen they mature & differentiate into : a. Effector cells ( plasma cells ) , which produce & secret antibodies (provide antibody- mediated immunity against bacteria) b. Memory cells, which remember particular antyigen for future attack for secondary immune response. Antibodies: 1. are protein molecules. 2. often Y-shaped, each with binding sites to specific antigen (antigen binding receptor) 3. when it binds to antigen: toxins are neutralized, pathogens are tagged for destruction by phagocytes or the complement system & attachment of pathogens to body cells is prevented. 4. only B-cells produce them as follows: Bone marrow stem cells B-cells which mature in bone marrow & on entering lymph nodes these get stimulated by antigens present to become plasma cells, which secrete antibodies immunoglobulins, there are five classes : IgM. IgG, IgA, IgD&IgE. 5 T- cells: arise in bone marrow, & mature in thymus gland. Provide cell-mediated immunity against viruses & cancer cells. T-cells receptors recognize & bind antigen-MHC complexes on antigenpresenting cells (any cell displaying antigen-MHC complex at its surfaces). Types of T-cells: T-killer/ cells (cytotoxic cells) : destroy body cells already infected by bacteria, fungi, viruses, they may also destroy cancer. T-helper cells: master switch of the immune response they stimulate the rapid division of B-cells (help in function) & killer T-cells (wich amont counter attack). T-memory cells: for future attack. T-suppresser cells: the controller cells, they slow down or prevent immune responses. Stimulus of antigen to tissue: If primary contact occurs: Nonspecific immune response is triggered, it target any thing detected as foreign and results in phagocytosis and inflammation. Non specific response may be followed by specific immune response. In specific response: The macrophages offer information about invaders to specific lymphocytes. If the lymphocytes programmed to react that invader it becomes: Natural killer cells (NK). Synsitized B-cells (memory cells & plasma cells that secrete antibodies): which target extra-cellular invaders e.g. bacteria. This results it that the antibodies binds to antigen& prepares invader to lysed by complement proteins or phagocytozed by macrophages. Synsitized T-cells : a) T- suppressor cells: prevent harmful uncontrolled spiraling of immune response. b) T-killer cells: they rapidly clone to form an army & target intra cellular invaders, viruses, fungi, parasites, cancer cells and grafts. This result in direct attack of infection, mutant or foreign cells. Macro phages are recruited, phagocytosis and inflammation are triggered. c) T- helper cells: they secrete interleukin & help in B-cells division & function, they activate; stimulate rapid division of killer T-cells 6 d) T-memory cells: for future attack. If secondary contact occurs: B-memory cells come into action more antibodies are secreted. T-killer cells function. The second attack is more long and rapid than the first one because everything will happen as in the first, but this time the memory cells will come into action. When memory cells encounter the same type of pathogen, it divides at once into a large clone of active B-cells & T-cells. Type of immune system: Specific immune response may be: 1) Cellular- mediated immune response: ♫ It is considered cellular immunity. ♫ Against the pathogens that already penetrated host cells, where they remain hidden from antibodies (response of T-cells to antigen). ♫ Macrophages become activated T-killer cells are sensitized & attack antigen. ♫ Memory cells are produced, it is considered long lasting immunity. 2) Antibody-mediated immune response: ♫ It is considered humeral immunity. ♫ Take place outside the cells (blood and lymph) ♫ It is derived from B-cells plasma cells antibodies (response of B-cells to antigen). ♫ Memory cells are not produced, there fore immunity is short lived. Immunization (vaccination): ♫ Refers to a variety of processes which promote increased immunity against specific disease. ♫ Introducing of the antigen into body provokes the immune response & produces memory cells for future attack. Vaccine: ♫ an antigen containing preparation, swallowed or injected, designed to increase immunity to certain diseases by inducing formation of armies of effector & memory B&T cells. ♫ It may: i. Killed or weakened pathogen. ii. Inactivated by products of dangerous pathogens. Immunity: It is the resistance of the body toward a pathogenic microbe & its toxin. Types: natural & acquired immunity. 7 Natural immunity: It is hereditary & passed from one generation to the next one. 1. natural active immunity. It is cellular-cell mediated. Produced when an individual is exposed to infection and overcomes it by the primary immune response. T&B memory cells produce long-lasting immunity 2. natural passive immunity: it is humeral-mediated. Produced when antibodies of the mother pass through the placenta to the fetus or new born throw the mother's milk It's short-lasting immunity. Acquired immunity: It acquired to body through life time. Artificially produced by vaccination (immunization). 1. acquired active immunity: cellular-cell mediated. Produced when killed or weakened antigesns are introduced into the body by vaccination. This promote primary immune response. On the vaccinated individual, then memory cells will produced long-lasting immunity. 2. acquired passive immunity: it is humeral mediated. Produced when prepared antibodies are given to patient through immunization. It is short lived immunity. Abnormal deficient immune responses: Allergy: Body makes secondary immune response to harmless substanmce (allergens) e.g. dust, pollen, perfume, some foods. Maybe heredity causes histamine secretion. Auto immune response: An attacks by lymphocytes in the body's own cells. e.g. thyrotoxicosis. Immune deficiency is a weakened or non-existent capacity to amount an immune response. Aids (acquired immune deficiency syndrome): virus called HIV (human Immune Deficiency Virus). 8 (figure 40-9). (40-10) 9