Transcript NonSpecific Defense Mechanisms

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
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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
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• 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
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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
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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
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Inflammation
• Prostaglandins
• Clotting factors go to injury site
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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
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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
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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
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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
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• 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