WHY DO WE HAVE AN IMMUNE SYSTEM Immune

Immune system diseases Non specific immunity Disease survival mechanisms Physical & chemical barriers Infectious

Cells of the Immune System – many cells we will look specifically at these

THE HUMAN BODY HAS THE CAPACITY TO PROTECT ITSELF AGAINST PATHOGENS, SOME TOXINS AND

LEARNING OUTCOMES • DISTINGUISH BETWEEN THE NONSPECIFIC AND SPECIFIC IMMUNE SYSTEM • IDENTIFY THE

IMMUNE SYSTEM ORGANISATION SPLIT INTO 2 AREAS – NON SPECIFIC AND SPECIFIC 1. NON-SPECIFIC

NON-SPECIFIC PHYSICAL BARRIERS EPITHIAL CELLS • THE FIRST LINE OF DEFENCE AGAINST INFECTION. •

OTHER PHYSICAL DEFENCES • TINY HAIRS AT THE ENTRANCE TO THE NOSE. • COUGH

NON-SPECIFIC IMMUNITY • FIRST LINE OF DEFENCE ARE PHYSICAL AND CHEMICAL BARRIERS Line of

IMMUNE SYSTEM ORGANISATION • SECOND LINE OF DEFENCE IS THE INFLAMMATORY RESPONSE • THIS

• Cytokines (cell signalling molecules – many types like TNF, IL 1 -10

MAST CELLS HISTAMINE VASODILATION AND INCREASED CAPILLARY PERMEABILITY SECRETE CYTOKINES PHAGOCYTOSIS COMPLEMENT / ANTIMICROBIAL

PHAGOCYTOSIS A phagocyte is motile (moves towards pathogen when chemicals detected or antigens). It

NATURAL KILLER CELLS ll 2 1 rane on et targ ce mb e m

NATURAL KILLER (NK) CELLS FINAL NON-SPECIFIC DEFENCE • FOR VIRUS AND TUMOUR CELLS PREDOMINANTLY

NK CELLS Perforin Granzym e Apoptosi s • Perforin released forming a pore into

COMPLEMENT SYSTEM • THE PRESENCE OF BACTERIA AT THE SITE OF INFECTION STIMULATES ANTIMICROBIAL

CYTOKINES. . • MADE BY DAMAGED TISSUE / WHITE BLOOD CELLS • ENHANCE MIGRATION

CLOTTING SYSTEM • THE FINAL STAGE OF INFLAMMATION IS TISSUE REPAIR. • WHAT DO

NON-SPECIFIC IMMUNITY • SECOND LINE OF DEFENCE ARE INFLAMMATION CASCADE AND CELLULAR RESPONSES Line

SUMMARY SLIDE NON-SPECIFIC DEFENCES PHYSICAL DEFENCES • EPITHELIAL CELLS ON THE BODY SURFACE AND

SUMMARY SLIDE NON-SPECIFIC DEFENCES INFLAMMATORY RESPONSE • RELEASE OF HISTAMINE BY MAST CELLS CAUSES

SUMMARY SLIDE NON-SPECIFIC DEFENCES CELLULAR MECHANISMS • A VARIETY OF SPECIALISED WHITE BLOOD CELLS

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WHY DO WE HAVE AN IMMUNE SYSTEM?

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

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

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

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

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

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.

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

NON-SPECIFIC IMMUNITY • FIRST LINE OF DEFENCE ARE PHYSICAL AND CHEMICAL BARRIERS Line of defence Specific (s) or non-specific (ns) Mechanism employed Function 1 st NS Skin barrier Epithelial cells intact 1 st NS Mucus Traps microbes in respiratory and gastrointestinal tract Remove microbe by sweeping Cilia 1 st NS Acid Contains hydrochloric acid at p. H 1. 5 - 2. 5 which has a disinfecting action on the stomach wall and contents. 1 st NS Sweat and sebaceous Low p. H inhibits microbial growth 1 st NS Saliva and tears Enzymes lysozyme digests bacterial walls so it destroys them Remember lysozyme - ZZZZZ for sleep in your eye!

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

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

• 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 allows tissue repair to start

MAST CELLS HISTAMINE VASODILATION AND INCREASED CAPILLARY PERMEABILITY SECRETE CYTOKINES PHAGOCYTOSIS COMPLEMENT / ANTIMICROBIAL PROTEINS

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

NATURAL KILLER CELLS ll 2 1 rane on et targ ce mb e m r Oute 1. Protein from NK cell inserts a pore into the target cell membrane 3 3 en dg n a d aye al rel 2. Signal molecule from NK enters cell ed itch es sw n 3. Sig n o 4. “suicide” proteins made 4 protease vital cell protein 5. “suicide” protein function to make degradative enzymes (protease / DNAase). Destroying vital proteins/DNA 4 Useless fragments of DNA 5 DNAase DNA 5 Useless fragments of protein

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

NK CELLS Perforin Granzym e Apoptosi s • Perforin released forming a pore into target cell membrane • Granzymes enter the cell, switch on genes • 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

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.

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-

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

NON-SPECIFIC IMMUNITY • SECOND LINE OF DEFENCE ARE INFLAMMATION CASCADE AND CELLULAR RESPONSES Line of defence Specific (s) or non-specific (ns) Mechanism employed Function 2 nd NS Inflammatory response initiated by histamine and serotonin release from basophils/mast cells attracts phagocytes to infected region. Reduces spread of infection throughout organism. 2 nd NS Cellular response of phagocytes (phagocytosis) Ingestion and digestion of foreign particles/microbes by neutrophils, eosinophils, monocytes and macrophages. 2 nd NS Cellular 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

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

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.

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.