HOST DEFENSES – INNATE/NON-SPECIFIC/GENERAL RESISTANCE GOAL IS TO LIMIT/ELIMINATE ANY INFECTION

1. HOST DEFENSES – INNATE/NON-SPECIFIC/GENERAL RESISTANCE GOAL IS TO LIMIT/ELIMINATE ANY INFECTION A. PHYSICAL BARRIERS B. CHEMICAL BARRIERS C. PHAGOCYTOSIS 1. BLOOD COMPONENTS AND CIRCULATION 2. BLOOD CELLS AND HEMATOPOEISIS BLOOD CELL FORMATION/DEVELOPMENT 3. PHAGOCYTOSIS MECHANISM D. INFLAMMATION E. COMPLEMENT SYSTEM F. OPSONIZATION G. CYTOKINES 1

2. 2 MAMMALIAN IMMUNE SYSTEM

3. 3 INNATE RESISTANCE – BORN WITH IT – GENERAL RESISTANCE PHYSICAL (ANATOMICAL) BARRIERS 1. SKIN a. EPIDERMIS – OUTER LAYER KERATIN – INSOLUBLE PROTEINS –NAILS, HAIR, EPIDEMIS b. DERMIS – INNER LAYER – BOUND TO MUSCLE BY CONNECTIVE TISSUE 2. BLADDER - FLUSHING

4. 4 3. MUCOUS MEMBRANES – LINE RESPIRATORY, DIGESTIVE, UROGENITAL TRACTS; RESIST PENETRATION MUCUS – SECRETION – TRAPS MICROORGANISMS - CONTAINS LYSOZYME – HYDROLYZES PEPTIDOGLYCAN PATHOGENS WHICH COLONIZE MUCOUS MEMBRANES: NEISSERIA GONORRHOEAE MYCOBACTERIUM TUBERCULOSIS STRETOCOCCUS PYOGENES TREPONEMA PALLIDUM

5. B. CHEMICAL BARRIERS 1.TEARS, SWEAT - LYSOZYME, FLUSHING 2.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 5

6. C. PHAGOCYTOSIS 1. 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 > HEART HEART > 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) 6

7. BLOOD & LYMPH CIRCULATION 7 • VEINS • PLASMA • RBC • WBC • ARTERIES • PLASMA • RBC • WBC • LYMPH • VESSELS • LYMPH • WBC VENOUS CAPILLARIES ARTERIAL CAPILLARIES LYMPH CAPILLARIES TISSUE SPACES INTERSTITAL FLUID AND WBC LYMPH NODES

8. 8 2. BLOOD CELLS - RBC – CARRY OXYGEN WBC – LEUCOCYTES WBC 7000/MICROLITER GRANULOCYTES NEUTROPHILS – PHAGOCYTOSIS 4000 60% STAIN AT NEUTRAL pH BASOPHILS VASOACTIVE 70 1 MEDIATORS; ALLERGIES STAIN WITH BASIC DYE EOSINOPHILS PHAGOCYTOSIS 200 3 STAIN WITH ACIDIC DYE AGRANULOCYTES LYMPHOCYTES - IMMUNITY 2000 30 MONOCYTES - BECOME 400 6 MACROPHAGES

9. 9

10. 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 10

11. 11 HUMAN BLOOD CELLS

12. 2. CONT’DMYELOID STEM CELLS FORM: GRANULOCYTES –NEUTROPHILS – PHAGOCYTOSIS EOSINOPHILS – PHAGOCYTOSIS BASOPHILS – ALLERGIES MEGAKARYOCYTES – FRAGMENT INTO THROMBOCYTES = PLATELETS (CLOTTING) AGRANULOCYTES – MONOCYTES – DIFFERENTIATE INTO MACROPHAGES AND DENDRITIC CELLS INGEST AND PROCESS FOREIGN INVADERS FOR ANTIGEN PRESENTATION RETICULOCYTES (IMMATURE RBC) > RBC 13

13. 2. CONT’DLYMPHOID 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 14

14. 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 PATHOGENS PHAGOCYTIZE 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

15. 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 15

16. 16

17. 3. CONT’D PHAGOCYTOSIS BY A WBC A. CHEMOTAXIS (NOT SHOWN) B. ADHERENCE C. INGESTION D. DIGESTION 17 B. NEISSERIA GONORRHOAE WBC CYTOPLASMIC MEMBRANE C. LYSOSOME WITH DIGESTIVE ENZYMES PHAGOSOME D. PHAGOLYSOSOME BACTERIAL FRAGMENTS SPIT OUT

18. 18

19. 19 • 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

20. 20 LYMPHOCYTE MIGRATING THROUGH WALL OF CAPILLARY

21. 21

22. 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 INFLAMMATION OPSONIZATION OF PATHOGENS: OPSONIZATION = ENHANCED PHAGOCYTOSIS BY NEUTROPHILS ACTIVATION OF MEMBRANE ATTACK COMPLEXES WHICH LYSE EUKARYOTIC CELLS/ENHANCE SUSCEPTIBILITY OF PROKARYOTES TO LYSOZYME 22

23. 23 MEMBRANE ATTACK COMPLEX

24. 24 MEMBRANE ATTACK COMPLEX

25. F. OPSONIZATION PHAGOCYTOSIS ENHANCEMENT BY COATING OF INVADERS (FOREIGN OBJECTS) BY ANTIBODIES, COMPLEMENT OR BOTH PHAGOCYTIC CELLS BIND BACTERIAL CELLS BOUND BY ANTIBODIES BOUND BY COMPLEMENT BEST WHEN BOUND BY ANTIBODIES AND COMPLEMENT 25

26. OPSONIZATION 26

27. 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 PRODUCTION INTERFERONS – LIMIT VIRAL INFECTION 27

28. 28 CYTOKINE ACTIVITIES PROGRAMMED CELL DEATH