Why do we have an immune system?

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

National Cancer Institute Understanding Cancer and Related Topics Understanding the Immune System Cells of the Immune System – many cells we will look specifically at these ….. Bone graft Macrophage Mast cell Eosinophil Erythrocytes Marrow Basophil Monocyte Megakaryocyte Bone Hematopoietic stem cell Multipotential stem cell Myeloid progenitor cell Neutrophil Platelets Cells destined to become immune cells, like all blood cells, arise in your body’s bone marrow from stem cells. Some develop into myeloid progenitor cells while others become lymphoid progenitor cells. The myeloid progenitors develop into the cells that respond early and nonspecifically to infection. Neutrophils engulf bacteria upon contact and send out warning signals. Monocytes turn into macrophages in body tissues and gobble up foreign invaders. Granule-containing cells such as eosinophils attack parasites, while basophils release granules containing histamine and other allergy-related molecules. Lymphoid precursors develop into the small white blood cells called lymphocytes. Lymphocytes respond later in infection. They mount a more specifically tailored attack after antigen-presenting cells such as dendritic cells (or macrophages) display their catch in the form of antigen fragments. The B cell turns into a plasma cell that produces and releases into the bloodstream thousands of specific antibodies. The T cells coordinate the entire immune response and eliminate the viruses hiding in infected cells. Lymphoid progenitor cell Dendritic cell T lymphocyte B lymphocyte Natural killer cell NCI Web site: http://cancer.gov/cancertopics/understandingcancer

feedback Different type of homework – interspersed extended responses with exam style questions and finally revision tools More understanding and Less copying of slides only those with or the summary slides only

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 non-specific 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 Non-specific immunity works against any type of disease-causing agent 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. Use jelly cubes (from an ice-cube tray) as model body cells and glitter (or similar) as bacteria/viruses/fungi. When the glitter is sprinkled on the cells it sticks and begins to penetrate the cell. Repeat the experiment and this time coating the model cells with clingfilm (to represent epithelial cells – physical barrier). The glitter cannot reach the body cells. Repeat the experiment for a third time and this time coat the clingfilm with a layer of petroleum jelly (to represent secretions). Again the glitter cannot reach the body cells – instead they become trapped by the epithelial cell secretions.

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 1st NS Skin barrier Epithelial cells intact Mucus Cilia Traps microbes in respiratory and gastrointestinal tract Remove microbe by sweeping Acid Contains hydrochloric acid at pH 1.5 - 2.5 which has a disinfecting action on the stomach wall and contents. Sweat and sebaceous Low pH inhibits microbial growth 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 and allows tissue repair to start

Mast cells histamine vasodilation and increased capillary permeability  secrete cytokines  phagocytosis  complement / antimicrobial proteins  clotting and tissue repair

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

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 Granzyme Apoptosis 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

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

WANTED! $10,000 REWARD Phagocytes and natural killer cells For indiscriminate killing of pathogens Phagocytes and natural killer cells Members of the notorious white blood cell gang $10,000 REWARD

Make a comic strip for each cell – nk cell and phagocyte Key words to include ... Apoptosis Exocytosis Pore Lysosome

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-specific defence but also specific defence system by triggering lymphocytes (next lesson)

Clotting system The final stage of inflammation is tissue repair. What do you remember from unit 2? What molecules involved? What is prothrombin / fibrinogen?

Clotting system Platelets form a plug to seal off the site of injury and clotting elements trigger the coagulation cascade, which strengthens the platelet plug. remodelling takes place as the healing process winds down. The final repair may be imperfect – this results in a scar.

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 2nd NS Inflammatory response Inflammatory response initiated by histamine and serotonin release from basophils/mast cells attracts phagocytes to infected region. Reduces spread of infection throughout organism. Cellular response of phagocytes (phagocytosis) Ingestion and digestion of foreign particles/microbes by neutrophils, eosinophils, monocytes and macrophages. 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.