HOST DEFENSES –

INNATE/NON-SPECIFIC/GENERAL RESISTANCEGOAL IS TO LIMIT/ELIMINATE ANY INFECTION

A. PHYSICAL BARRIERSB. CHEMICAL BARRIERSC. PHAGOCYTOSIS

1. BLOOD COMPONENTS AND CIRCULATION

2. BLOOD CELLS AND HEMATOPOEISISBLOOD CELL

FORMATION/DEVELOPMENT3. PHAGOCYTOSIS MECHANISM

D. INFLAMMATIONE. COMPLEMENT SYSTEMF. OPSONIZATIONG. CYTOKINES

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MAMMALIAN IMMUNE SYSTEM

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INNATE RESISTANCE – BORN WITH IT – GENERAL RESISTANCE

A. PHYSICAL (ANATOMICAL) BARRIERS

1. SKIN a. EPIDERMIS – OUTER LAYER

KERATIN – INSOLUBLE PROTEINS –NAILS, HAIR,EPIDEMIS

b. DERMIS – INNER LAYER – BOUND TO MUSCLE BYCONNECTIVE TISSUE

2. BLADDER - FLUSHING

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3. MUCOUS MEMBRANES – LINE RESPIRATORY, DIGESTIVE, UROGENITAL TRACTS; RESIST PENETRATION

MUCUS – SECRETION – TRAPS MICROORGANISMS

- CONTAINS LYSOZYME – HYDROLYZES PEPTIDOGLYCAN

PATHOGENS WHICH COLONIZE MUCOUS MEMBRANES:NEISSERIA GONORRHOEAEMYCOBACTERIUM TUBERCULOSISSTRETOCOCCUS PYOGENESTREPONEMA PALLIDUM

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B. CHEMICAL BARRIERS

1. TEARS, SWEAT - LYSOZYME, FLUSHING2. SALIVA - DIGESTIVE

ENZYMES

3. INTERFERONS – ANTIVIRAL PROTEINS; CYTOKINES;

INTER-CELLULAR SIGNALLING PROTEINS

PRODUCED BY VIRUS-INFECTED CELLS BUT ACT ON UN-INFECTED CELLS TO LIMIT

VIRUS PRODUCTION;

HYDROLYSIS OF VIRAL RNA;

INHIBIT VIRUS PROTEIN SYNTHESIS;

HOST SPECIFC; NOT VIRUS SPECIFC

4. CATIONIC PEPTIDES – ALTER BACTERIAL CYTOPLASMIC

MEMBRANE PERMEABILITY; 12-24

AMINO ACIDS/CHAIN

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C. PHAGOCYTOSIS1. BLOOD COMPONENTS & CIRCULATION

BLOOD - FLUID PLUS CELLS; PLASMA - FLUID WITHOUT CELLS;SERUM - FLUID REMAINING

AFTER CLOT FORMS TRAPPING CELLS (IN THE CLOT)

HEART > LUNGS – ACQUIRES O2 > HEARTHEART > ARTERIES > ARTERIAL

CAPILLARIES(GIVES UP 02) > VENOUS

CAPILLARIES >VEINS >HEART

ARTERIAL CAPILLARIES; FLUID & WBC LEAVE, ENTER TISSUES (INTERSTITIAL FLUID) > CAPILLARIES OF LYMPH SYSTEM;

FLUID NOW CALLED LYMPH > LYMPH VESSELS, NODES > VEINS (MIXES WITH RBC; NOW CALLED BLOOD)

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BLOOD & LYMPH CIRCULATION

ARTERIES• PLASMA• RBC• WBC

VEINS• PLASMA• RBC• WBC

ARTERIALCAPILLARIES

VENOUSCAPILLARIES

LYMPHCAPILLARIES

LYMPHVESSELS• LYMPH• WBC

LYMPH NODES

TISSUE SPACESINTERSTITAL

FLUIDAND WBC

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2. BLOOD CELLS - RBC – CARRY OXYGENWBC – LEUCOCYTES

WBC7000/MICROLITER

GRANULOCYTES

NEUTROPHILS – PHAGOCYTOSIS 4000 60%

STAIN AT NEUTRAL pHBASOPHILS VASOACTIVE

70 1MEDIATORS;ALLERGIES

STAIN WITH BASIC DYEEOSINOPHILS PHAGOCYTOSIS

200 3STAIN WITH ACIDIC DYE

AGRANULOCYTES

LYMPHOCYTES - IMMUNITY2000 30

MONOCYTES - BECOME 400 6

MACROPHAGES

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2. CONTINUED - HEMATOPOIESIS

FORMATION OF BLOOD CELLULAR COMPONENTS

HEMATOPOIETIC STEM CELLS – MULTIPOTENT -

DEVELOP INTO ALL DIFFERENT BLOOD CELLS

FORM IN BONE MARROW

DIFFERENTIATE INTO

MYELOID STEM CELLS – MYELOID = PROGRAMED TO DEVELOP IN BONE MARROW, SPINAL CORD

LYMPHOID STEM CELLS – LYMPHOID = PROGRAMED TO DEVELOP IN LYMPH TISSUE = THYMUS,

SPLEEN, LYMPH NODES, BONE MARROW

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HUMANBLOOD CELLS

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2. CONT’D MYELOID STEM CELLS FORM:

GRANULOCYTES – NEUTROPHILS – PHAGOCYTOSISEOSINOPHILS –

PHAGOCYTOSISBASOPHILS –

ALLERGIES

MEGAKARYOCYTES – FRAGMENT INTO THROMBOCYTES = PLATELETS

(CLOTTING)

AGRANULOCYTES – MONOCYTES – DIFFERENTIATE INTOMACROPHAGES

AND DENDRITIC CELLSINGEST AND

PROCESS FOREIGN INVADERS FOR ANTIGEN PRESENTATION

RETICULOCYTES (IMMATURE RBC) > RBC

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2. CONT’D LYMPHOID STEM CELLS FORM:

AGRANULOCYTES

LYMPHOCYTES

T CELLS – HELP B CELLS IN HUMORAL IMMUNITY

& FUNCTION IN CELL-MEDIATED

IMMUNITY

B CELLS - HUMORAL IMMUNITY – DIFFERENTIATE

INTO PLASMA CELLS AND SECRETE ANTIBODIES

NATURAL KILLER CELLS

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2. CONT’D MONOCYTES AND THEIR DESTINY

CIRCULATE ~ 8 HRS, MIGRATE INTO TISSUES 14

MATURE INTO MACROPHAGES/DENDRITIC CELLS WHICH

HAVE RECEPTORS FOR COMMON COMPONENTS OF

PATHOGENSPHAGOCYTIZE INVADERS – CONTRIBUTE TO

INNATE RESISTANCE

DIGEST INVADERS AND DISPLAY FRAGMENTS ON THEIR

SURFACES AS PART OF STIMULATING IMMUNITY –

CONTRIBUTE TO ACQUIRED

IMMUNITY

MACROPHAGES - ALL TISSUES, ESPECIALLY LYMPH NODES, LYMPH VESSELS

DENDRITIC CELLS – LOCALIZE IN MUCOUS MEMBRANES

3. PHAGOCYTOSIS EVENTS (MECHANISM)

NEUTROPHILS, MACROPHAGES, DENDRITIC CELLS

INNATE RESISTANCE & ACQUIRED IMMUNITY

a. PATHOGEN RECOGNITION: PHAGOCYTE RECEPTORS BIND PATTERNS COMMON ON

INVADERS -- E.G., LIPOPOLYSACCHARIDES ON

GRAM NEGATIVES

b. INTRACELLULAR DIGESTION - PHAGOSOME, LYSOSOME, PHAGOLYSOSOME

DIGESTIVE ENZYMES (HYDROLYSIS)

REACTIVE OXYGEN INTERMEDIATES

c. EXOCYTOSIS – PHAGOLYSOSOME FUSES WITH MEMBRANE, RELEASE COMPONENTS.

MACROPHAGES & DENDRITIC CELLS DISPLAY COMPONENTS AS ANTIGENS (ON SURFACE) -

SPECIFIC IMMUNITY

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3. CONT’D PHAGOCYTOSIS BY A WBCA. CHEMOTAXIS (NOT SHOWN)B. ADHERENCEC. INGESTIOND. DIGESTION WBC CYTOPLASMIC

MEMBRANEB. NEISSERIAGONORRHOAE

C.

D. PHAGOLYSOSOME

PHAGOSOME

LYSOSOMEWITH

DIGESTIVEENZYMES

BACTERIAL FRAGMENTSSPIT OUT

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D. INFLAMMATION – GENERAL RESPONSE TO TISSUE INJURY –

REDNESS, WARMTH, PAIN, SWELLING, ALTERED FUNCTION

INJURY - SIGNALS RELEASED AND ACTIVATE ENDOTHELIUM(INNER LINING) OF NEARBY CAPILLARIES

SELECTINS – DISPLAYED ON ENDOTHELIUM, ATTRACT NEUTROPHILS

MARGINATION – NEUTROPHIL INTEGRINS SYNTHESIZED;DISPLAYED ON SURFACE; BIND SELECTINS; LOCALIZE NEUTROPHILS TO CAPILLARY WALLS

DIAPEDESIS – NEUTROPHILS SQUEEZE THRU CAPILLARY WALLS

INTO INTERSTITIAL FLUID

EXTRAVASION – CHEMOTAXIS TO INJURY/INVADING MICRO-ORGANISMS; ATTACK!

INFLAMMATORY MEDIATORS – INCREASED BLOOD FLOW; INCREASED CAPILLARY PERMEABILITY

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LYMPHOCYTE MIGRATING THROUGH WALL OF CAPILLARY

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E. COMPLEMENT SYSTEM~30 SERUM PROTEINS, DEFEND AGAINST MICROBES,

ENHANCE PHAGOCYTOSIS, BRIDGE INNATE AND ACQUIRED IMMUNITY

ACTIVATED BY INVASION: MACROPHAGE DESTRUCTION OF INVADERS RESULTS IN DEGRADATION PRODUCTS WHICH ACTIVATE COMPLEMENT

ACTIVATED COMPLEMENT CAUSES:RELEASE OF PEPTIDE MEDIATORS OF

INFLAMMATIONOPSONIZATION OF PATHOGENS: OPSONIZATION =

ENHANCED PHAGOCYTOSIS BY NEUTROPHILS

ACTIVATION OF MEMBRANE ATTACK COMPLEXES WHICH

LYSE EUKARYOTIC CELLS/ENHANCE

SUSCEPTIBILITY OF PROKARYOTES TO LYSOZYME

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MEMBRANEATTACK

COMPLEX

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MEMBRANE ATTACK COMPLEX

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F.OPSONIZATION

PHAGOCYTOSIS ENHANCEMENT BY COATING OF INVADERS (FOREIGN OBJECTS) BY ANTIBODIES, COMPLEMENT OR BOTH

PHAGOCYTIC CELLS BIND BACTERIAL CELLSBOUND BY ANTIBODIESBOUND BY COMPLEMENTBEST WHEN BOUND BY ANTIBODIES AND

COMPLEMENT

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OPSONIZATION

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G. CYTOKINES

PROTEINS PRODUCED AND RELEASED BY ONE CELL TYPE TO COMMUNICATE WITH AND REGULATE THE ACTIVITY OF

ANOTHER CELL TYPE

REGULATORS OF INNATE RESISTANCE AND SPECIFIC IMMUNE RESPONSE

INTERLEUKINS –PRODUCED BY ONE LEUKOCYTE TYPE, ACT ON ANOTHER TYPE

OF LEUKOCYTE

LYMPHOKINES - PRODUCED BY ONE TYPE OF

LYMPHOCYTES; ACT ON ANOTHER LYMPHOCYTE

POPULATION

CHEMOKINES - REGULATE INFLAMMATION – ERYTHROPOEITIN – STIMULATE RBC PRODUCTIONINTERFERONS – LIMIT VIRAL INFECTION

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CYTOKINEACTIVITIES

PROGRAMMED CELL DEATH

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