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Transcript
Maintain fluid balance Protect body from infection and disease 21-1 Immunity Lipid absorption fluids from all capillary beds are filtered immune cells stand ready to respond to foreign cells or chemicals encountered Lacteals in small intestine absorb dietary lipids Fluid recovery absorbs plasma proteins and fluid (2 to 4 L/day) from tissues and returns it to the bloodstream interference with lymphatic drainage leads to severe edema 21-2 Lymph is a clear, colorless fluid, similar to plasma but much less protein Lymphatic capillaries are closed at one end and much ‘leakier’ than blood capillaries 21-3 Larger lymphatics have 3 layers tunica interna: endothelium and valves tunica media: elastic fibers, smooth muscle tunica externa: thin outer layer 21-4 Lymphatic capillaries Collecting vessels: course through many many lymph lymph nodes nodes Lymphatic trunks: drain major portions of body Collecting ducts : right lymphatic duct – receives lymph from R arm, R side of head and thorax; empties into R subclavian vein thoracic duct - larger and longer, begins as a prominent sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, L arm, L side of head, neck and thorax; empties into L subclavian vein 21-5 21-6 21-7 Lymph flows at low pressure and speed Moved along by rhythmic contractions of lymphatic vessels Flow aided by skeletal muscle pump (like veins) Thoracic pump aids flow from abdominal to thoracic cavity (also like veins) Valves prevent backward flow The rapidly flowing blood in subclavian veins draws lymph into the vascular system Exercise significantly increases lymphatic return 21-8 Natural killer (NK) cells can find and destroy tumor cells T lymphocytes (mature in thymus) B lymphocytes (mature in bone marrow) activation makes cells that produce antibodies Antigen Presenting Cells - APCs macrophages (from monocytes) dendritic cells (in epidermis, mucous membranes and lymphatic organs) 21-9 Diffuse lymphatic tissue lymphocytes in mucous membranes and connective tissues of many organs Mucosa-Associated Lymphatic Tissue (MALT): prevalent in passages open to exterior Lymphatic nodules dense oval masses of lymphocytes, congregate in response to pathogens Peyer patches: more permanent congregation, clusters found at junction of small to large intestine 21-10 At well defined sites; have connective tissue capsules Primary lymphatic organs site where T and B cells become immunocompetent red bone marrow and thymus Secondary lymphatic organs immunocompetent cells populate these tissues lymph nodes, tonsils, and spleen 21-11 Lymph nodes – are the only organs that filter lymph Fewer efferent vessels, slows flow through node Lymph nodes are divided into compartments containing stroma (reticular CT) and parenchyma (lymphocytes and APCs) Lymph nodes are subdivided into cortex and medulla reticular cells, macrophages phagocytize foreign matter lymphocytes respond to antigens lymphatic nodules-germinal centers for B cell activation 21-12 Fig. 21.12 a and b 21-13 Collective term for all lymph node diseases Lymphadenitis swollen, painful node responding to foreign antigen Lymph nodes are common sites for metastatic cancer swollen, firm and usually painless 21-14 Palatine tonsils Lingual tonsils pair at posterior margin of oral cavity most often infected pair at root of tongue Pharyngeal tonsil (adenoid) single tonsil on wall of pharynx 21-15 Very large in babies. Begins to involute at about 14 years T lymphocytes mature here. Secretes thymopoietin, thymulin and thymosins. 21-16 Parenchyma appears in fresh specimens as red pulp: sinuses filled with erythrocytes white pulp: lymphocytes, macrophages 21-17 Why is the ‘white pulp’ blue? Functions blood reservoir RBC disposal immune reactions: filters blood, quick to detect antigens 21-18 Your immune system’s structure and function is much like that of an earth army fighting alien invaders. It is there in times of peace and in times of war. To distinguish ‘self’ from ‘non-self’ to destroy ‘non-self’ The fortifications The human body’s first line of defense is a set of physical barriers and chemical agents that prevent foreign invaders from getting inside. An outer layer of intact skin Hair in the nostrils Mucous membranes Cilia Tears Sweat Mucous Oils Acid in stomach Urine The soldiers and their weapons Non-specific (innate) Neutrophils Make antibodies Macrophages Natural Killer Cells Specific (adaptive) Lymphocytes B cells make antibodies T cells help them If something gets past the external barriers, the second line of defense are ‘innate’ immune defenses, primarily white blood cells. Page 530 Nonspecific defenses - broadly effective, no prior exposure first line of defense external barriers second line of defense – innate immune system phagocytic cells, antimicrobial proteins, inflammation and fever Specific defense - results from prior exposure, protects against only a particular pathogen third line of defense – adaptive immune system 21-27 Phagocytize bacteria These are most likely to dramatically increase in numbers during bacterial infection Create a killing zone degranulation antimicrobial proteins are discharged into tissue fluid respiratory burst toxic chemicals are created (O2.-, H2O2) 21-28 Phagocytize antigen-antibody complexes Antiparasitic effects Promote action of basophils, mast cells Enzymes block excess inflammation, limit action of histamine 21-29 Aid mobility and action of WBC’s by release of histamine (vasodilator) blood flow to infected tissue heparin (anticoagulant) prevents immobilization of phagocytes 21-30 Circulating precursors to macrophages Specialized macrophage-like cells are found in specific localities Dendritic cells epidermis, oral mucosa, esophagus, vagina, and lymphatic organs Microglia (CNS) Alveolar macrophages (lungs) Kupffer cells (liver) 21-31 There are 3 types but they look identical under a microscope! Act to destroy cancer cells Kill virus-infected cells Make antibodies The lymphocytes circulating in human blood are 80% T cells 15% B cells 5% NK cells These are the cells that confer immunity through a vaccination! 21-32 Interferons Made by cells when they are invaded by a virus Induce neighbor cells to activate anti-viral defenses Can stimulate destruction of some cancer cells Complement system More than 20 different proteins Are activated by the presence of pathogens (like a booby trap) 21-34 Mechanisms of action enhanced inflammation phagocytosis promoted by opsonization cytolysis membrane attack complex forms on target cell immune clearance RBCs carry Ag-Ab complexes to macrophages in liver and spleen 21-35 NK cells (Natural Killer Cells) destroy bacteria, cells infected by viruses, and cancer cells also destroy transplanted cells 21-36 Swelling Pain Redness & heat Purulence hyperemia Page 531 Three major processes mobilization of body defenses 2. containment and destruction of pathogens 3. tissue clean-up and repair 1. 21-38 Kinins, histamine, and leukotrienes are secreted by damaged cells stimulates vasodilation that leads to hyperemia causes redness and heat local metabolic rate, promotes cell multiplication and healing dilutes toxins, provides O2, nutrients, waste removal stimulates permeability of blood capillaries allows blood cells, plasma proteins (antibodies, complement proteins, fibrinogen) into tissue 21-39 Leukocyte Deployment margination selectins cause leukocytes to adhere to blood vessel walls diapedesis (emigration) leukocytes squeeze between endothelial cells into tissue space 21-40 Chemotaxis leukocytes are attracted to chemotactic chemicals Neutrophils are quickest to respond phagocytosis respiratory burst secrete cytokines for recruitment of macrophages and neutrophils macrophages and T cells secrete colony-stimulating factor to stimulate leukopoiesis 21-41 Total WBC: 4,500 - 10,000 Bands or stabs: 3 - 5 % Granulocytes Neutrophils (or segs): 50 - 70% relative value (2500-7000 absolute value) Eosinophils: 1 - 3% relative value (100-300 absolute value) Basophils: 0.4% - 1% relative value (40-100 absolute value) Agranulocytes (or mononuclears) Lymphocytes: 25 - 35% relative value (1700-3500 absolute value) Moncytes: 4 - 6% relative value (200-600 absolute value) Defense mechanism: does more good than harm promotes interferon activity accelerating metabolic rate and tissue repair inhibiting pathogen reproduction A cytokine named interleukin 1 called a pyrogen secreted by macrophages stimulates anterior hypothalamus to secrete PGE2 Prosatglandin E2 resets the body’s thermostat higher > 105F may cause delirium, 111F- 115F, coma-death Stages of fever onset (spiking a fever) stadium defervescence (breaking a fever) What if your patient is shivering with a normal or very slightly raised temp? 21-44 Depends on lymphocytes Specificity and memory Cellular immunity: cell-mediated (T cells) Humoral immunity: antibody mediated (B cells) This is the half of the immune system that confers immunity through a vaccination! 21-45 Active immunity produces memory cells Natural – you catch the measles Artificial – you’re vaccinated for the measles Passive immunity is not long lasting Natural - fetus acquires antibodies from mother Natural – nursing child gets antibodies from colostrum Artificial - treatment for snakebite or tetanus 21-46 Trigger an immune response Complex molecules > 10,000 amu, unique structures proteins, polysaccharides, glycoproteins, glycolipids 21-47 Stem cells in red bone marrow Mature in thymus 21-48 Immature T cells must be able to recognize signals from other parts of the immune system If they don’t – they are destroyed Immature T cells must not recognize proteins on your tissue cells as ‘foreign’ Only 2% of If they do – they are destroyed immature T cells survive these steps that are called ‘selection’ Stem cells in red bone marrow Mature in thymus Circulate through blood and lymph Naïve T cells colonize lymph nodes, Peyer’s patches, tonsils, spleen 21-50 Sites of development bone marrow B cells also undergo selection (just not in the thymus) Self-tolerant B cells form B cell clones each cell in a clone has the same antigen receptors 21-51 DCs and macrophages (some B cells) display antigens to T cells T cells attack foreign cells and diseased host cells; memory of Ag Three classes of T cells: 1. Cytotoxic T cells (Tc cells) carry out attack 2. Helper T cells: help promote Tc cell and B cell action 3. Memory T cells: provide immunity from future exposure to antigen 21-53 T Cells must be activated by APCs before they go to work. Cytotoxic T cells directly attack enemy cells Lethal hit mechanism 1. 2. 3. docks on cell with antigen-MHC-I protein complex releases perforin, granzymes - kills target cell interferons - decrease viral replication and activates macrophages tumor necrosis factor: kills cancer cells 21-55 Cytotoxic T cell binding to cancer cell 21-56 Memory T cells following clonal selection some T cells become memory cells long-lived; in higher numbers than naïve cells T cell recall response upon reexposure to same pathogen, memory cells launch a quick attack 21-57 Helper T cells (TH cells) have been informed of the invader by APCs Helper T cells (TH cells) stimulate the B cells that have the right ‘weapon’ for this disease The B cells turn into Plasma cells Plasma cells make antibodies that circulate in the blood and can incapacitate the pathogen Memory some B cells differentiate into memory cells 21-58 21-59 ALL antibodies are proteins! Antibodies are IgG is Y-shaped. the most important 80% of your component of circulating humoral antibody is IgG. immunity! There are other classes of Ig Antibody and immunoglobulin are synonyms Immune system capable of as many as 1 trillion different antibodies Somatic recombination DNA segments shuffled and form new combinations of base sequences to produce antibody genes Somatic hypermutation B cells in lymph nodules rapidly mutate creating new sequences 21-61 Neutralization Complement fixation antigen binds to IgM or IgG, antibody changes shape, initiates complement binding; primary defense against foreign cells, bacteria Agglutination antibodies mask pathogenic region of antigen antibody has 2-10 binding sites; binds to multiple enemy cells immobilizing them Precipitation antibody binds antigen molecules (not cells); creates antigenantibody complex that precipitates, phagocytized by eosinophil 21-62 21-63 21-64 Excessive immune reaction against antigens that most people tolerate - allergens Type I Antibody mediated (IgE), acute reaction Type II Antibody mediated (IgG, IgM), subacute Type III Antibody mediated (IgG, IgM), subacute Asthma, Hay fever, Anaphylaxis glomerulonephritis, systemic lupus Type IV Cell mediated, delayed (12 to 72 hrs) TB test Poison ivy 21-65 Failure of self tolerance cross-reactivity abnormal exposure of self-antigens changes in structure of self-antigens Production of autoantibodies 21-66 Severe Combined Immunodeficiency Disease (SCID) hereditary lack of T and B cells vulnerability to opportunistic infection currently treatable with gene therapy 21-67