2 Physical barriers http://www.ucihs.uci.edu/derm/images/skin.gif Skin: Layered tissue, puncture resistant. High in keratin, water repellant. Secretions maintain low pH. Outer layers slough off, reducing microbial load. Self-repairing.
3 Mucous membranes Tissues lining openings to the outside: Mouth, genito-urinary tract, etc (anything pink). Easier for microbes to invade, but coated with mucus which traps microbes; this combined with some type of movement removes microbes from area: Flushing action: tears, urine, saliva, other secretions. Action of cilia: propel mucus & microbes toward GI tract. http://www.ich.ucl.ac.uk/factsheets/test_procedure_operations/tonsils_adenoids_remove d/mouth.gif
4 Cellular defenses- Blood 60% Plasma Water and salts (electrolytes) Proteins: albumin, immunoglobulins, fibrinogen, complement, etc. 40% Formed Elements (cells mostly) RBCs (erythrocytes, red cells) carry oxygen WBCs (leukocytes, white cells) fight infection Platelets involved in clotting, release prostaglandins. http://dragondebris.com/burning_man_2000/bigs/blood.jpg
5 White blood cells http://www.clinical-blood-testing.com/images/white%20blood%20cells.jpg Lymphocytes: 20-50% of total, T and B cells, deal with specific immunity Monocytes: 2-8% of total, grow up to become macrophages, big eaters Granulocytes Neutrophils: 50-70%, numerous short-lived phagocytes Eosinophils: 1-5%, stain red, attack parasites Basophils: 0.1%, stain blue, release histamine Granulocytes named according to microscopic appearance, presence of granules, type of stain, etc.
6 Blood clotting Complicated pathway featuring inactive proteins becoming activated. Prothrombin to thrombin; Fibrinogen to fibrin Platelets respond to physical roughness, release factors that lead to clotting. Response to endotoxin results in blood clotting within the vessels: intravascular coagulation. Definition: Serum is plasma without the clotting factors. Allow blood to clot, result is serum. Clotting factors are used up, gone.
7 More about Macrophages Large and mean, clean up debris as well as microbes. Important link between non-specific immunity and specific immunity Wandering vs. fixed macrophages Wandering macrophages patrol bloodstream, stepping into tissues when called Fixed reside in specific organs, get fancy names like Kupffer cells, histiocytes, depending on home.
8 Phagocytosis-1 What and who Cell-eating, a process by which cells engulf and destroy microbial invaders, debris, foreign material. Neutrophils (PMNs) and macrophages are the major phagocytic cells in the body. Steps in the Process Chemotaxis: phagocytes respond to (move toward) various chemicals (cytokines) released by host cells and by microbes. Attachment: cell binds to material/microbe.
9 Phagocytosis-2 Process continued Engulfment: target brought into cell by endocytosis. Now in cytoplasm in a vesicle. Digestion: vesicle (phagosome) containing microbe fuses with lysosome. Microbe is subjected to: Hydrolytic enzymes, hydrogen peroxide, bleach, superoxide Residual, undigested material is tossed out. For every step in the process, some microbe has found a way to interfere and save itself!!
10 Protection from phagocytosis Anti-phagocytic coatings Capsules, M-protein; arent grabbed and engulfed Prevent phagosome-lysosome fusion Prevention of destruction in phago-lysosome Hide from phagocytes by entering non- professional phagocytes. Kill phagocytic cells leukocidins medlib.med.utah.edu/.../ AIDS/AIDS030.html
11 Extracellular killing Eosinophils Attach to parasites (protozoa, worms) larger than they are, release enzymes that attack pest. Natural killer cells Non-specific lymphocytes (different from T and B cells) which attack virus-infected cells and kill them. Death of virus-infected host cells is a major way of fighting a viral infection; T cells do the same.
12 The Lymph system Parallel circulatory system Series of vessels and nodes Drains off excess body fluids from tissues, returns fluids to cardiovascular system Lymph nodes filter out microbes Nodes filled with macrophages and lymphocytes Fluid flows thru slowly, maximizes contact Other lymphoid tissue Spleen, thymus, MALT/GALT, tonsils http://www.acm.uiuc.edu/sigbio/project/updated-lymphatic/lymph_node.gif
13 Inflammation Rubor, calor, tumor, dolor: redness, local heat, swelling, and pain. (and loss of function). Largely all explained by increased blood flow and vessel permeability in area of injury. Inflammation is a host response to tissue injury! Injury doesnt have to be accompanied by microbes, but often is in real life. Process limits spread of microbes, brings anti- microbial factors to the area.
14 Inflammation-2 Tissue damage activates mast cells Mast cells release histamine, a substance that Contracts smooth muscle Dilates capillaries and venules Fluid leaks into tissue, WBC line up and pass through vessel was into tissue (diapedesis) WBCs = neutrophils THEN macrophages, move into area, carry out phagocytosis Fibrinogen activates to fibrin, produces inflammatory barrier. Walls off microbes.
15 Inflammation-3 Pus: accumulation of fluid, live and dead cells. A pyogen promotes pus formation Usually, pus released to outside or absorbed. Repair: fibroblast multiply to create a patch With minor damage, normal cells repair wound. Too much damage, fibroblasts and fibers make up granulation tissue, leave scar. A granuloma is a pocket of scar tissue Chronic inflammation Normal tissue gradually replaced by non-functional scar tissue; can eventually lead to organ failure.
16 Inflammation-4 The signs and symptoms of inflammation are mostly explained by the vasodilation and increased permeability of blood vessels Increased redness: more blood in area. Edema: leakage and accumulation of fluid. Increased heat: more blood flow from warm interior. Pain: pressure from swelling, also chemical mediators of pain like prostaglandins, bradykinin Inflammation is separate from Fever
17 Fever Pyrogen: a substance that causes fever Exogenous pyrogen: external substance that activates the bodys temperature setting systems LPS Endogenous pyrogen: Interleukin-1, substance produced by macrophages Il-1 travels to hypothalamus, changes body thermostat Chills result from bodys attempt to warm itself to reach the new correct temperature.
18 Fever-2 Fever is good for you Raises temperature above whats optimal for pathogen, allows host defense more time. May inactivate toxins or enzymes. Speeds up host metabolic rate, faster response. Makes patient feel ill so youll stay home and rest! Leukocyte-endogenous mediator (LEM) Causes fever and hides iron. Battle over Fe; hemolysins and siderophores vs. transferrin and LEM; you hide it, germs try to find it. Too high a fever is dangerous, though.
19 Chemical defenses Secretions: Fatty acids in sebum on skin, low pH and are toxic Lysozyme in tears, saliva, other fluids Blood and fluid proteins Complement: collection of >20 blood proteins that work in cascade fashion. Stimulate inflammation, act as opsonins, lyse cells; work together with antibodies. Interferon: several types, warn neighboring cells of local viral infection, induce anti-viral state. Function also as interleukins
20 Microbial Antagonism Normal Microbiota aids host defenses by Competing w/ pathogens for nutrients Occupying host surfaces Killing invaders with bacteriocins Changing conditions, e.g. pH Stimulating host defenses Leaking into body, keeping defenses on alert Producing vitamins benefiting overall host health