1. WHY DO WE HAVE AN IMMUNE SYSTEM?

2. Non specific immunity Inflammatory Response Non-specific Cellular response Physical & chemical barriers Specific immunity Immunological surveillance Clonal Selection theory T cells B cells Infectious Disease Transmission Epidemiology Vaccination Public Health Immune system diseases Disease survival mechanisms BIG PICTURE NK cells phagocytes

3. Cells of the Immune System – many cells we will look specifically at these ….. Bone graft Multipotential stem cell Hematopoietic stem cell Platelets Macrophage Erythrocytes Eosinophil Neutrophil Megakaryocyte Mast cell Basophil T lymphocyte Natural killer cell Dendritic cell B lymphocyte Lymphoid progenitor cell Myeloid progenitor cell Monocyte Marrow Bone

4. THE HUMAN BODY HAS THE CAPACITY TO PROTECT ITSELF AGAINST PATHOGENS, SOME TOXINS AND CANCER CELLS THROUGH THE IMMUNE SYSTEM GLOSSARY TERMS; PATHOGEN – DISEASE CAUSING ORGANISMS TOXINS – POISONS PRODUCED BY ORGANISMS IMMUNITY – BODY’S ABILITY TO RESIST INFECTION BY A PATHOGEN OR DESTROY THE ORGANISM IF IT SUCCEEDS

5. LEARNING OUTCOMES DISTINGUISH BETWEEN THE NON-SPECIFIC AND SPECIFIC IMMUNE SYSTEM IDENTIFY THE THREE LINES OF DEFENCE EXPLAIN THE NON-SPECIFIC DEFENCES

6. IMMUNE SYSTEM ORGANISATION SPLIT INTO 2 AREAS – NON SPECIFIC AND SPECIFIC 1.NON-SPECIFIC IMMUNITY WORKS AGAINST ANY TYPE OF DISEASE-CAUSING AGENT 2.SPECIFIC IMMUNITY WORKS AGAINST A PARTICULAR PATHOGEN

7. NON-SPECIFIC PHYSICAL BARRIERS EPITHIAL CELLS THE FIRST LINE OF DEFENCE AGAINST INFECTION. LINE THE SURFACES AND CAVITIES OF THE ENTIRE BODY. FORM SHEETS/ LAYERS OF CLOSELY PACKED CELLS. SECRETIONS SOME EPITHELIAL CELLS PRODUCE SECRETIONS SUCH AS ENZYMES, HORMONES AND LUBRICATING FLUIDS THAT CAN DEFEND AGAINST INFECTION. MUCUS TRAPS DIRT AND GERMS, PREVENTING THEM FROM ENTERING THE BLOOD. VARIOUS GLANDS PRODUCE ANTIMICROBIAL SECRETIONS THAT HELP KILL MICROBES.

8. OTHER PHYSICAL DEFENCES TINY HAIRS AT THE ENTRANCE TO THE NOSE. COUGH AND SNEEZE REFLEXES. ‘FRIENDLY’ BACTERIA.

9. NON-SPECIFIC IMMUNITY FIRST LINE OF DEFENCE ARE PHYSICAL AND CHEMICAL BARRIERS Line of defence Specific (s) or non-specific (ns) Mechanism employedFunction 1stNSSkin barrierEpithelial cells intact 1stNSMucus Cilia Traps microbes in respiratory and gastrointestinal tract Remove microbe by sweeping 1stNSAcidContains hydrochloric acid at pH 1.5 - 2.5 which has a disinfecting action on the stomach wall and contents. 1stNSSweat and sebaceousLow pH inhibits microbial growth 1stNSSaliva and tearsEnzymes lysozyme digests bacterial walls so it destroys them Remember lysozyme - ZZZZZ for sleep in your eye!

10. IMMUNE SYSTEM ORGANISATION SECOND LINE OF DEFENCE IS THE INFLAMMATORY RESPONSE THIS OCCURS IF THE FIRST LINE ARE BREACHED, BY A CUT/ PIERCING OR AN INVASION OF AN INFECTIOUS ORGANISMS

11. IMMUNE SYSTEM ORGANISATION SECOND LINE OF DEFENCE IS THE INFLAMMATORY RESPONSE THIS OCCURS IF THE FIRST LINE ARE BREACHED, BY A CUT/ PIERCING OR AN INVASION OF AN INFECTIOUS ORGANISMS First line are breached, by a cut/piercing or an invasion of an infectious organisms, bacteria, trauma, toxins, heat or any other cause Mast cells (type of white blood cell) in the connective tissue, releases histamine Histamine causes blood vessels to become more permeable Vasodilation of blood vessels by injured site; causing swelling due to stretchy capillary wall

12. Cytokines (cell signalling molecules – many types like TNF, IL 1-10 etc.) also released by damaged cells / tissues Enhanced migration of phagocytes to the damaged tissue by cytokines (phagocytes move to site) – next slide Cytokines also attract antimicrobial proteins to the infected site which amplify immune response Cytokines attract blood clotting chemicals (complement) to injury site thus preventing any blood loss / infection to the wound and allows tissue repair to start

13. MAST CELLS  HISTAMINE  VASODILATION AND INCREASED CAPILLARY PERMEABILITY  SECRETE CYTOKINES  PHAGOCYTOSIS  COMPLEMENT / ANTIMICROBIAL PROTEINS  CLOTTING AND TISSUE REPAIR

15. PHAGOCYTOSIS A phagocyte is motile (moves towards pathogen when chemicals detected or antigens). It then engulfs pathogen (endocytosis) – forming a phagocytic vesicle (vacuole) which merges with a lysosome. Lysosomes contain digestive enzymes, which disposes of the pathogen and released by exocytosis. The phagocyte releases more cytokines – positive feedback

16. NATURAL KILLER CELLS 1. Protein from NK cell inserts a pore into the target cell membrane 2. Signal molecule from NK enters cell 3. Signal relayed and genes switched on 5. “suicide” protein function to make degradative enzymes (protease / DNAase). Destroying vital proteins/DNA 4. “suicide” proteins made Outer membrane on target cell 1 2 3 3 4 4 5 5 DNAase protease DNA Useless fragments of DNA vital cell protein Useless fragments of protein

17. NATURAL KILLER (NK) CELLS FINAL NON-SPECIFIC DEFENCE FOR VIRUS AND TUMOUR CELLS PREDOMINANTLY DISTINCT CLASS OF LYMPHOCYTES WHICH CAN WORK WITH ANTIBODY-DEPENDENT CELLULAR CYTOTOXITY HOWEVER THEY ARE NOT SPECIFIC – WILL ATTACK CELLS (DECIDE SELF/FOREIGN BY LACK OF SELF ANTIGEN (MHC). A PORE RELEASED FROM NATURAL KILLER (NK) CELL NK CELL THEN RELEASES SIGNALLING MOLECULES THIS SIGNALS GENETIC CONTROL OF BOTH SELF DESTRUCTIVE ENZYMES BEING RELEASED AND DNA / VITAL PROTEIN BREAKDOWN PROCESS OF “CELL SUICIDE”, PROGRAMMED CELL DEATH IS CALLED APOPTOSIS

18. NK CELLS Perforin Perforin released forming a pore into target cell membrane Granzyme Granzymes enter the cell, switch on genes Apoptosis Stimulating the cell to produce enzymes that degrade DNA – inducing apoptosis SECONDARY AFFECT WHICH LINKS TO THE SPECIFIC IMMUNE SYSTEM IS BOTH NK CELLS AND PHAGOCYTES SECRETE CYTOKINES (INTERLEUKINS ) THAT SERVE TO STIMULATE THE SPECIFIC IMMUNE RESPONSE THROUGH THE ACTIVATION OF T CELLS

19. NATURAL KILLER CELLS 1. Protein from NK cell inserts a pore into the target cell membrane 2. Signal molecule from NK enters cell 3. Signal relayed and genes switched on 5. “suicide” protein function to make degradative enzymes (protease / DNAase). Destroying vital proteins/DNA 4. “suicide” proteins made Outer membrane on target cell 1 2 3 3 4 4 5 5 DNAase protease DNA Useless fragments of DNA vital cell protein Useless fragments of protein

20. COMPLEMENT SYSTEM THE PRESENCE OF BACTERIA AT THE SITE OF INFECTION STIMULATES ANTIMICROBIAL PROTEINS KNOWN AS ‘COMPLEMENT’ TO ARRIVE AT THE SITE OF INFECTION. THE COMPLEMENT SYSTEM HELPS THE BODY TO RID ITSELF OF INFECTION BY AMPLIFYING THE IMMUNE RESPONSE.

21. CYTOKINES.... MADE BY DAMAGED TISSUE / WHITE BLOOD CELLS ENHANCE MIGRATION OF PHAGOCYTES (CHEMOTAXINS - CHEMOATTRACTANTS) WHICH ENGULF/DIGEST PATHOGEN AND RELEASE MORE CYTOKINES DELIVER ANTIMICROBIAL PROTEINS FASTER WHICH AMPLIFIES IMMUNE RESPONSE DELIVER BLOOD CLOTTING CHEMICALS (COMPLEMENT) WHICH SEALS THE WOUND AND HELPS TISSUE REPAIR HAVE A DUAL PURPOSE; NOT ONLY IN THE NON-SPECIFIC DEFENCE BUT ALSO SPECIFIC DEFENCE SYSTEM BY TRIGGERING LYMPHOCYTES (NEXT LESSON)

22. CLOTTING SYSTEM THE FINAL STAGE OF INFLAMMATION IS TISSUE REPAIR. WHAT DO YOU REMEMBER FROM UNIT 2? WHAT MOLECULES INVOLVED? WHAT IS PROTHROMBIN / FIBRINOGEN?

23. NON-SPECIFIC IMMUNITY SECOND LINE OF DEFENCE ARE INFLAMMATION CASCADE AND CELLULAR RESPONSES Line of defence Specific (s) or non- specific (ns) Mechanism employedFunction 2ndNSInflammatory responseInflammatory response initiated by histamine and serotonin release from basophils/mast cells attracts phagocytes to infected region. Reduces spread of infection throughout organism. 2ndNSCellular response of phagocytes (phagocytosis) Ingestion and digestion of foreign particles/microbes by neutrophils, eosinophils, monocytes and macrophages. 2ndNSCellular response of natural killer cells (NK cells) Attack virus and cancer cells by releasing molecule which forms a pore in target cells membrane which signals apoptosis by self destroying enzymes

24. SUMMARY SLIDE NON-SPECIFIC DEFENCES PHYSICAL DEFENCES EPITHELIAL CELLS ON THE BODY SURFACE AND CAVITY LININGS FORM A PHYSICAL BARRIER (SKIN/TRACHEA/OESOPHAGUS ETC.) CHEMICAL DEFENCES MUCUS MEMBRANES SECRETE STICKY MUCUS TRAPPING MICROORGANISMS ACID FROM EPITHELIAL CELLS IN STOMACH DESTROY INGESTED MICROORGANISMS SKIN SEBACEOUS/SWEAT GLANDS PRODUCE LOW PH SECRETIONS THAT ARE TOO LOW FOR MOST MICROBES TO SURVIVE

25. SUMMARY SLIDE NON-SPECIFIC DEFENCES INFLAMMATORY RESPONSE RELEASE OF HISTAMINE BY MAST CELLS CAUSES VASODILATION AND INCREASED CAPILLARY PERMEABILITY. THE INCREASED BLOOD FLOW AND THE SECRETION OF CYTOKINES RESULTS IN THE ACCUMULATION OF PHAGOCYTES AND THE DELIVERY OF ANTIMICROBIAL PROTEINS AND CLOTTING ELEMENTS TO THE SITE OF INFECTION.

26. SUMMARY SLIDE NON-SPECIFIC DEFENCES CELLULAR MECHANISMS A VARIETY OF SPECIALISED WHITE BLOOD CELLS PROVIDE PROTECTION AGAINST PATHOGENS. PHAGOCYTES RECOGNISE SURFACE ANTIGEN MOLECULES ON PATHOGENS AND DESTROY THEM BY PHAGOCYTOSIS. NATURAL KILLER (NK) CELLS INDUCE THE PATHOGEN TO PRODUCE SELF DESTRUCTIVE ENZYMES IN APOPTOSIS. BOTH PHAGOCYTES AND NK CELLS RELEASE CYTOKINES WHICH STIMULATE THE SPECIFIC IMMUNE RESPONSE. COMPLEMENT SYSTEM AMPLIFIES THIS IMMUNE RESPONSE.