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Transcript
Lymphatic and Immune Systems (Chapter 21) Lecture # 8: The Immune System Objectives 1- Identify the body’s three lines against pathogens. 2- Contrast nonspecific resistance with immunity. 3- Define specific immunity. 4- Contrast cellular and humoral immunity. 5- Describe the chemical properties of antigens. 6- Describe and contrast the development and functions of T and B lymphocytes. Defenses Against Pathogens Pathogens: They are environmental agents capable of producing disease (infectious organisms, toxic chemicals, and radiation). The human body has three lines of defenses against pathogens. They may be nonspecific or specific. a) First line 1- Nonspecific of defense Resistance 2- Specific Resistance External barriers: Skin and mucous membranes. b) Second line of defense Leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever. c) Third line of defense It is the Immune System, which not only defeats a pathogen but leaves the body with a “memory” of it, so it can defeat it faster in the future. Nonspecific Resistance 1- Nonspecific Resistance It guards equally against a broad range of pathogens. Their effectiveness does not depend on prior exposure. a) First Line of Defense 1- Skin It makes it mechanically difficult for microorganisms to enter the body because of the toughness of keratin. The skin is too dry and nutrient-poor to support microbial growth. The skin is coated with defensins, peptides that kill microbes by creating holes in their membranes; and acid mantle, thin film of lactic acid from sweat which inhibits bacterial growth. 2- Mucous membranes The digestive, respiratory, urinary, and reproductive tracts are open to the exterior and protected by mucous membranes. Mucus physically traps microbes. Mucus, tears, and saliva contains lysozyme, an enzyme that destroys bacterial cell walls. b) Second Line of Defense It consists of several nonspecific defense mechanisms: Leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever. 1-Leukocytes and Macrophages 2- Antimicrobial proteins 3- Immune surveillance 4- Fever 5- Inflammation A) Interferon b) Complement System 1-Leukocytes and Macrophages Neutrophils They spend most of their life wandering in the connective tissue killing bacteria by phagocytosis and digestion. When a neutrophil detects bacteria in the immediate area, the lysosomes migrate to the cell surface and degranulate and discharge into tissue fluid. Here the enzymes produce a respiratory burst. Respiratory Burst: The neutrophils rapidly absorb oxygen and produce toxic chemicals: superoxide anion (O2 ) , hydrogen peroxide (H2O2), and hypochlorite (HClO). These toxic chemicals form a chemical killing zone around the neutrophil that destroy more bacteria than the neutrophil can destroy by phagocytosis. The neutrophil also is killed by these chemicals. Eosinophils They are found especially in the mucous membranes standing guard against parasites, allergens (allergy causing agents), and other pathogens. They kill tapeworms and roundworms by producing superoxide, hydrogen peroxide, and toxic proteins. Basophils Basophils and mast cells (a type of connective tissue cell), secrete chemicals that aid mobility and action of other leukocytes: Leukotrienes that activate and attract neutrophils and eosinophils. Histamine that is a vasodilator which increases blood flow speeds delivery of leukocytes to the area. Heparin, which inhibits the formation of clots that would impede leukocyte mobility. Lymphocytes All lymphocytes look more or less alike in blood films, but there are three basic categories. The circulating blood contains: 80% T cells, 15% B cells, and 5% NK cells They have many diverse functions as cells of the Immune System. Monocytes Monocytes are leukocytes that emigrate from the blood into the connective tissue and transform into macrophages. The macrophage system are all the body’s avidly phagocytic cells, except leukocytes. Cells of the macrophage system have different specialized forms in different specific localities: Histiocytes in loose connective tissue, Microglia in central nervous system, Alveolar macrophages in lungs, Hepatic macrophages in liver. 2- Antimicrobial proteins a) Interferon b) Complement system a) Interferons They are proteins secreted by certain cells infected by viruses. They are of no benefit to the cell that secretes them, but alert neighboring cells and protect them from becoming infected. b) Complement system It is a group of 30 or more globular proteins that make powerful contributions to both nonspecific resistance and specific immunity. The proteins circulate in the blood in inactive form and are activated by presence of the pathogen. The activation of complement brings about four methods of pathogen destruction: The complement system may be activated in three ways: 1- Classical pathway 2- Alternative pathway 3- Lectin pathway 3- Immune surveillance Natural killer (NK) cells (NK lymphocytes) They are large lymphocytes that attack and destroy bacteria, transplanted tissue, and host cells infected with viruses or that have turned cancerous. They are responsible for immune surveillance. 4- Fever It is an abnormally elevation of body temperature (over 37.0 0C or 98.6 0F). It results from trauma, infections, drug reactions, brain tumors, and other causes. Fever is produced by: Exogenous pyrogens (surface glycolipids of bacteria and viruses). Endogenous pyrogens (polypeptides produced by macrophages and neutrophils). Fever is an adaptive defense mechanism, in moderation, does more good than harm because: -Promotes interferon activity. -Elevates metabolic rate and accelerates tissue repair. -Inhibits reproduction of bacteria and viruses. 5- Inflammation Inflammation is a local defensive response to tissue injury of any kind, including trauma and infection. The general purposes of inflammation are: 1- To limit spread of pathogens, then destroy them. 2- To remove debris from damaged tissue. 3- To initiate tissue repair. Four Cardinal Signs of Inflammation: 1- redness 2- swelling 3- heat 4- pain Inflammation and Immunity are regulated by many chemicals called cytokines. (Table 21.1) Cytokines They are small proteins that serve as a chemical communication network among immune cells. Three major processes of inflammation: 1- Mobilization of Defenses 2- Containment and Destruction of Pathogens 3- Tissue Clean up and Repair 1- Mobilization of Defenses Splinter Mast cells, endothelial cells and damaged cells release inflammatory chemicals. From damaged tissue Basophils and Mast cells They trigger inflammation by releasing histamine and leukotrienes (vasodilators), and heparin (anticoagulant). Inflammatory chemicals Bacteria Increase blood flow beyond normal (hyperemia) From mast cells 4 Phagocytosis From blood Neutrophils 3 1- Margination: The ability to adhere to the wall of blood vessels. Chemotaxis Increased permeability Mast cells 2- Diapedesis: The ability to crawl thorough the gaps between the endothelial cells. 3- Chemotaxis: The ability to move toward inflammatory chemicals. 4- Phagocytosis: The ability to engulf solid particles. 2 Diapedesis 1 Neutrophils Margination Blood capillary or venule Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2- Tissue Cleanup Monocytes: They are the primary agents of tissue cleanup and repair. ◦ arrive in 8 to 12 hours and become macrophages. ◦ engulf and destroy bacteria, damaged host cells, and dead and dying neutrophils. Edema It contributes to tissue cleanup. swelling compresses veins and reduces venous drainage forces open valves of lymphatic capillaries promoting lymphatic drainage. lymphatics collect and remove bacteria, dead cells, proteins, and tissue debris better than blood capillaries. Pus It consists of the accumulation of dead neutrophils, bacteria, other cellular debris, and tissue fluid form a pool of yellowish fluid. Abscess It is the accumulation of pus in a tissue cavity. 3- Tissue Repair Platelet-derived growth factor secreted by blood platelets and endothelial cells in injured area: stimulates fibroblasts to multiply. synthesize collagen. Hyperemia delivers oxygen, amino acids, and other necessities for protein synthesis. Increased heat increases metabolic rate, speeds mitosis, and tissue repair. Fibrin clot forms a scaffold for tissue reconstruction. Pain makes us limit the use of a body part so it has a chance to rest and heal. Specific Resistance Specific Resistance: It results from prior exposure to a pathogen and usually provides future protection only against that particular one. Third line of defense. It is the immune system, which not only defeats a pathogen but leaves the body with a “memory” of it, so it can defeat it faster in the future. Specific Immunity Two characteristics distinguish immunity from nonspecific resistance: 1-Specificity Immunity is directed against a particular pathogen. Immunity to one pathogen does not protect against others. 2-Memory When re-exposed to the same pathogen, the body reacts so quickly that there is no noticeable illness. Two Types of Immunity 1- Cellular (cell-mediated) immunity It employs lymphocytes directly attack and destroy foreign cells or diseased host cells. It is a means of ridding the body of pathogens that reside inside human cells, where they are inaccessible to antibodies . Cellular immunity kills the cells that harbor the pathogens. T lymphocytes or T cells are responsible for cellular immunity. 2- Humoral (antibody-mediated) immunity It is mediated by antibodies that do not directly destroy a pathogen, but tag them for destruction by other mechanisms. It can only work against the extracellular stage of infectious micro-organisms. B lymphocytes or B cells are responsible for humoral immunity T lymphocytes or T cells are responsible for cellular immunity. B lymphocytes or B cells are responsible for humoral immunity. Some B lymphocytes differentiates into plasma cells, which are the cells responsible for antibody production. Cellular Immunity Cellular (cell-mediated) immunity is a form of specific defense in which the T lymphocytes directly attack and destroy diseased or foreign cells, and the immune system remembers the antigens and prevents them from causing disease in the future. Cellular immunity involves four classes of T cells: 1- Cytotoxic T cells or killer T cells They are the “effectors” of cellular immunity that carry out attack on enemy cells. They are called killer T cells, but are not the same as natural killer cells. 2- Helper T cells They promote cytotoxic T cell and B cell action and nonspecific resistance. They are destroy by HIV, which affects the central coordinating agent of nonspecific defense, humoral immunity, and cellular immunity. 3- Regulatory T cells They inhibit multiplication and cytokine secretion by other T cells and thus limit immune response. 4- Memory T cells They descend from the cytotoxic T cells and are responsible for memory in cellular immunity. Cytotoxic T cells deliver a lethal hit of toxic chemicals: 1-Perforin and granzymes that kill cells in the same manner as NK cells. 2- Interferons that inhibit viral replication and recruit and activate macrophages. 3- Tumor necrosis factor (TNF) that aids in macrophage activation and kills cancer cells. Humoral Immunity Humoral immunity is a more indirect method of defense than cellular immunity B lymphocytes of humoral immunity produce antibodies that bind to antigens and tag them for destruction by other means. An antibody is a defensive gamma globulin found in the blood plasma, tissue fluids, body secretions, and some leukocyte membranes. Some B lymphocytes differentiates into plasma cells, which are the cells responsible for antibody production. Once released by plasma cells, antibodies use four mechanisms to render antigens harmless: 1-Neutralization Antibodies mask pathogenic region of antigen. 2-Complement fixation When antigen binds the antibody changes its shape and initiates complement binding, which leads to inflammation, phagocytosis, immune clearance, or cytolysis. 3-Agglutination Antibody has 2-10 binding sites; binds to multiple enemy cells immobilizing them from spreading. 4-Precipitation Antibody binds antigen molecules (not cells); creates antigen-antibody complex that precipitates Antigen: It is any molecule that triggers an immune response Primary response The primary immune response is the immune reaction brought about by the first exposure to an antigen. The primary response leaves one with an immune memory of the antigen. Secondary response The secondary or anamnestic response is produced by the reexposition to the same antigen. It is a greater response in a much sorter time. Forms of Immunity 1- Active Immunity a) Natural Active Immunity It is the production of one’s own antibodies or specific T cells as a result of infection or natural exposure to antigen. b) Artificial Active Immunity It is the production of one’s own antibodies or specific T cells as a result of vaccination against disease. Vaccine It consists of the administration of dead or attenuated (weakened) pathogens that stimulate the immune response without causing the disease. Booster shots They are the periodic immunizations to stimulate immune memory to maintain a high level of protection. Forms of Immunity 2- Passive Immunity a) Natural Passive Immunity It is the temporary immunity that results from antibodies produced by another person. Ex: The fetus acquires antibodies from mother through placenta and milk. b) Artificial Passive Immunity It is the temporary immunity that results from the injection of immune serum (antibodies) from another person or animal. Ex: Treatment for snakebite, botulism, rabies, tetanus, and other diseases. Forms of Immunity 1- Active Immunity 2- Passive Immunity The body makes its own antibodies The body acquires the antibodies from another person or animal a) Natural Active Immunity b) Artificial Active Immunity c) Natural Passive Immunity d) Artificial Passive Immunity It is the production of one’s own antibodies or T cells as a result of infection or natural exposure to antigen. It is the production of one’s own antibodies or T cells as a result of vaccination against disease. It is the temporary immunity that results from antibodies produced by another person in a natural way. It is the temporary immunity that results from the injection of antibodies from another person or animal.