Transcript Non-specific Host Defenses

Non-specific Host Defenses
• Physical barriers
• Cellular defense
• Processes:
– Phagocytosis
– Inflammation
• Chemical defenses
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Physical barriers
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Skin:
Layered tissue, puncture
resistant.
High in keratin, water repellant.
Secretions maintain low pH.
Outer layers slough off,
reducing microbial load.
Self-repairing.
http://www.ucihs.uci.edu/derm/images/skin.gif
Mucous membranes
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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
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
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White blood cells
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.
http://www.clinical-blood-testing.com/images/white%20blood%20cells.jpg
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Blood clotting
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• 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.
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.
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Phagocytosis-1
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• 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.
Phagocytosis-2
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• 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!!
Protection from phagocytosis
• Anti-phagocytic coatings
– Capsules, M-protein; aren’t grabbed and engulfed
• Prevent phagosome-lysosome fusion
• Prevention of destruction in phago-lysosome
• Hide from phagocytes by entering “nonprofessional” phagocytes.
• Kill phagocytic cells
– leukocidins
medlib.med.utah.edu/.../ AIDS/AIDS030.html
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Extracellular killing
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• 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.
The Lymph system
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• 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
Inflammation
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• 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 doesn’t have to be accompanied by
microbes, but often is in real life.
– Process limits spread of microbes, brings antimicrobial factors to the area.
Inflammation-2
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• 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.
Inflammation-3
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• 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.
Inflammation-4
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• 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
Fever
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• Pyrogen: a substance that causes fever
– Exogenous pyrogen: external substance that
activates the body’s temperature setting systems
• LPS
– Endogenous pyrogen: Interleukin-1, substance
produced by macrophages
– Il-1 travels to hypothalamus, changes body
thermostat
• Chills result from body’s attempt to warm itself to
reach the new “correct temperature”.
Fever-2
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• Fever is good for you
– Raises temperature above what’s 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 you’ll 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.
Chemical defenses
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• 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
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
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