Non-specific Host Defenses

1
Non-specific Host Defenses

• Physical barriers
• Cellular defense
• Processes
• Phagocytosis
• Inflammation
• Chemical defenses

2
Physical barriers
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
3
Mucous membranes
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 or to where they can be
coughed out.
http//www.ich.ucl.ac.uk/factsheets/test_procedure
_operations/tonsils_adenoids_removed/mouth.gif
4
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/bloo
d.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
20blood20cells.jpg
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Blood clotting

• 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.

7
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, osteoclasts,
  neuroglia, depending on home.

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Phagocytosis-1

• 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.

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Visual of phagocytosis
A macrophage of a mouse stretching its arms to
engulf two particles, possibly pathogens
http//en.wikipedia.org/wiki/Macrophage
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Phagocytosis-2

• 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.

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Cartoon of phagocytosis
Exocytosis
Phagosome-lysosome fusion
lysosomes
phagosome
endocytosis
http//content.answers.com/main/content/wp/en/thum
b/b/bc/400px-Phagocytosis.png
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For every step in the process, some microbe has
found a way to interfere and save itself!!

• Anti-phagocytic coatings
• Capsules, M-protein arent grabbed and engulfed
• Prevent phagosome-lysosome fusion
• Prevention of destruction in phago-lysosome
• Hide from phagocytes by entering
  non-professional phagocytes.
• Kill phagocytic cells
• leukocidins

medlib.med.utah.edu/.../ AIDS/AIDS030.html
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Extracellular killing

• 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.
• Also attack tumor cells

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The Lymph system

• 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-lym
phatic/lymph_node.gif
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Tonsil
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Inflammation

• 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 doesnt have to be accompanied by
  microbes, but often is in real life.
• Process limits spread of microbes, brings
  anti-microbial factors to the area.

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Inflammation-2

• 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.
• Coagulase increases streptokinase breaks down

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Inflammation-3

• 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.

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Inflammation-4

• 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

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Fever

• Pyrogen a substance that causes fever
• Exogenous pyrogen external substance that
  activates the bodys temperature setting systems
• LPS
• Endogenous pyrogen Interleukin-1, substance
  produced by macrophages
• Il-1 travels to hypothalamus, changes body
  thermostat
• Chills result from bodys attempt to warm itself
  to reach the new correct temperature.

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Fever-2

• Fever is good for you
• Raises temperature above whats 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 youll 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.

22
Chemical defenses

• 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 gt20 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

23
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