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Non Specific Host Defenses Innate Immunity Host Defenses • Nonspecific (innate) or specific • Specific (adaptive immune system) Innate & Adaptive • Part of same immune system • Innate evolved first • Both depend upon activities of WBCs & proteins in plasma Nonspecific Defenses • Those that protect against any kind of pathogen – Receptors on macrophages – Induces ctokines First Line of Defense • Physical (structural) barriers • Chemical barriers • Normal flora Second Line of Defense • • • • • Cellular defenses Inflammation Fever Molecular defenses Physical & chemical barriers prevent entry of microbe • Other defenses destroy microbe or inactivate toxic products Physical Barriers • Skin- epidermis outer layer – Langerhans cells participate in immunity – Skin cells die and shed with bacteria and viruses – Microbes do grow in moist areas of skin Mucous Membranes • Cover tissues & organs exposed to exterior – Thin and less protective than skin • Cilia- on mucus membranes, propel items in mucus upward • Epiglottis- covers larynx when swallowing • Vaginal secretions and flow of urine Chemical Factors • Sebum- oily substance produced by sebaceous glands • pH of skin is low Chemical Factors • Perspiration-flushes bacteria • Gastric juice • Helicobacter pylori neutralizes acids Normal Flora • Change pH, competition for nutrients & receptors • Stimulate immune system Second Line of Defense • Phagocytosis –. • Phagocytes are forms of WBCs (leukocytes) • Leukocytes usually increase during infections • Viruses & some bacteria decrease WBC Leukocytes • Differential WBC count • Plasma-fluid contains formed elements & proteins Types of Leukocytes • Based on appearance under microscope • Granulocytes-presence of large granules in cytoplasm • Three kinds based on how granules stain Neutrophils • Phagocytic and motile, active in initial stages of infection • Contain oxidative chemicals • Emigration-squeezing between cells Basophils (0.5-1%) • Not thought to be phagocytic • Release histamine & other chemicals • Important in inflammation and allergic reactions • Mast cells prevalent in connective tissue and along blood vessels Eosinophils (2-4%) • Phagocytic and can leave blood • Produce toxic proteins against certain parasites -helminths • Attach to parasite’s surface • Discharge peroxide ions to destroy parasites Dendritic Cells • • • • Arise from monocytes Motile, branched phagocytes act as scouts Antigen presenting cells ---lymph nodes Connection to adaptive immune system Agranulocytes • Monocytes & lymphocytes • Have granules but not visible under scope after staining • Monocytes(3-8%) -not active phagocytes until leave blood Macrophages • Fixed macrophages – neutrophils • Longer to reach site, larger in #s Activated Macrophages • Activated by certain T lymphocytes • During chronic infections (TB) Lymphocytes (20-25%) • Not phagocytes, in lymphoid tissue-tonsils, lymph nodes, thymus etc. • Specific immunity-antibodies (B cells) and T cells • Natural killer cells are nonspecific Process of Phagocytosis • Chemotaxis • Escape from phagocytes Adherence & Ingestion • Bind microbe to plasma membrane of phagocyte • Escape mechanisms Digestion • Lysosomes in phagocyte fuse with phagosome • Elimination via exocytosis Escape Digestion • Staph- leukocidins which destroy phagosome • Pathogens secrete membrane attack complexes-holes in membranes Prevention of Fusion • Ability to survive or escape from phagosome • Live in macrophage and grow • Some do not avoid phagocytes Extracellular Killing • Viruses and worms • Eosinophils excrete toxic enzymes Natural Killer Cells • Recognize glycoproteins • Secrete cytotoxic proteins that trigger death of cell • Virus causes cell to stop making certain surface proteins: markers for self • NK kills host cells without markers • Recognize and kill tumor cells Inflammation • • • • Acute -local response & resolves Chronic- long lasting response Response to damage to body tissue: cytokines Redness, pain, heat and swelling-sometimes loss of function • Functions of inflammation – Inflammation • Prostaglandins • Clotting factors go to injury site – Change in Capillaries • Vasodilation and increase permeability of blood vessels • Caused by release of chemicals by damaged tissue, phagocytes, complement • Kinins- present in plasma become activated Inflammation • Vasodilation • Increased permeability – edema • Pain Phagocytosis • Migration of phagocytes -chemotaxis • Margination • Emigration Phagocytosis • • • • Neutrophils arrive first, then monocytes Monocytes maturate into macrophages Clean up site and die Last stage • Host wins Chronic Inflammation • Neither host nor bug wins • Formation of granulomatous tissuegranulomas • Pocket of tissue that surrounds and walls off inflammatory agent Fever • Result of infection from bacteria and virusessystemic response-> 100.5 • Caused by pyrogens-toxins (lipid A) and cytokines • Gram negative bacteria phagocytized and degraded in vacuoles To Adjust to Higher Setting • Respond with blood vessel constriction • Increase rate of metabolism • Skin remains cool while shivering causing chills • Chills indicate body temperature is rising To Return to Lower Setting • Sweating, vasodilation, skin becomes warm – this is crisis • Body temp decreases • Fever is a defense mechanism unless too high Defense Mechanism • • • • IL-1 increases T lymphocytes High temp intensifies effect of interferons Patient feels ill and rests Aspirin and acetaminophen reduce fever Complement • Serum proteins >30 that help to lyse foreign cells, cause inflammation and phagocytosis • Activation of complement • C proteins act in a cascade • Activation of protein C3 triggers a sequence of events- nonspecific Activation of C3 • Splits into C3a & C3b • C3b enhances phagocytosis • C3b causes cytolysis Cytolysis • • • • C3b splits C5 C5b binds to C6 & C8 Attach to microbe C8 and C9 attach and form membrane attack complex • Cell lyses dt holes in membrane Inflammation • C3a & C5a bind to mast cells (basophils) • C5a is a chemotactic agent Interferons • Anti viral proteins released by host cells • Interfere with viral multiplication • Host cell specific but not virus specific – • Different types of cells in animals produce different interferons Human Interferon • 3 types – alpha interferon – beta interferon – gamma interferon • Alpha & beta usually produced early in viral infections • Gamma appears later Interferon • Presence of ds RNA indicates cell is infected • Viral infected cells release alpha and beta interferons – Diffuse to neighboring cells – Virus can’t replicate Antiviral Treatment • Interferon therapy – Limited dt short lasting effect – Recombinant interferon • Pure and fast – Hep C-PEG interferon