1Non-specific Host Defenses

• Physical barriers

• Cellular defense

• Processes:– Phagocytosis– Inflammation

• Chemical defenses

2Physical barriers

http://www.ucihs.uci.edu/derm/images/skin.gif

Skin:

Layered tissue, puncture resistant.

High in keratin, water repellant.

Secretions maintain low pH.

Outer layers slough off, reducing microbial load.

Self-repairing.

3Mucous 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.

http://www.ich.ucl.ac.uk/factsheets/test_procedure_operations/tonsils_adenoids_removed/mouth.gif

4Cellular 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

5White blood cells

http://www.clinical-blood-testing.com/images/white%20blood%20cells.jpg

Lymphocytes: 20-50% of total,T and B cells, deal with specific immunityMonocytes: 2-8% of total,“grow up” to become macrophages, “big eaters”

GranulocytesNeutrophils: 50-70%, numerous short-lived phagocytesEosinophils: 1-5%, stain red, attack parasitesBasophils: 0.1%, stain blue, release histamineGranulocytes named according to microscopic appearance, presence of granules, type of stain, etc.

6Blood 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.

7More 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.

8Phagocytosis-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.

9Phagocytosis-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.

• For every step in the process, some microbe has found a way to interfere and save itself!!

10Protection 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 “non-professional” phagocytes.

• Kill phagocytic cells– leukocidins

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

11Extracellular 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.

12The 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-lymphatic/lymph_node.gif

13Inflammation

• 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 anti-

microbial factors to the area.

14Inflammation-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.

15Inflammation-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.

16Inflammation-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

17Fever

• 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”.

18Fever-2

• 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.

19Chemical 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 >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

20Microbial 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