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 tissue- granulomas Pocket of tissue that surrounds and walls off inflammatory agent

Fever Result of infection from bacteria and viruses- systemic response-> 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