Non Specific Host Defenses - Innate Immunity

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Non Specific Host Defenses - Innate Immunity Powered By Docstoc
					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

• 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

• 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

• Monocytes & lymphocytes • Have granules but not visible under scope after staining • Monocytes(3-8%) -not active phagocytes until leave blood

• 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

• 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

• • • • 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

• 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

• Vasodilation

• Increased permeability – edema

• Pain

• Migration of phagocytes -chemotaxis

• Margination • Emigration

• • • • 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

• 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

• 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

• • • • 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

• C3a & C5a bind to mast cells (basophils)

• C5a is a chemotactic agent

• 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

• 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

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