2023 HUB105 Lec 12 Innate (PDF)

Lecture 12 Innate (nonspecific) Immunity BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape  Roles of the lymphatic system in body defenses LS responsible for defending the body. The body’s ability to resist infection and disease through...

Lecture 12 Innate (nonspecific) Immunity BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape  Roles of the lymphatic system in body defenses LS responsible for defending the body. The body’s ability to resist infection and disease through activation of specific defence mechanisms is known as Immunity. Body defenses provide resistance to fight infection, illness, and disease Two mechanisms of defense 1. Innate/ Nonspecific defense immunity 2. Adaptive/ Specific defense immunity Complementary defense mechanisms, that when functioning correctly provide adequate resistance to infection and disease. Roles of the lymphatic system in body defenses body defenses provide resistance to fight infection, illness, and disease two categories of defenses: 1. Nonspecific defenses - don’t distinguish one threat from another; is present at birth - incl. physical barriers, phagocytic cells, immunological surveillance, interferons, inflammation and fever - provide nonspecific resistance 2. Specific defenses (Immunity) - protect against particular threats; develop after birth after exposure to environmental hazards or infections, and forms 3rd line of defense - dependent on lymphocyte activity - provide specific resistance nonspecific and specific defenses operate together to provide resistance to infection and disease  Innate immunity Seven major categories of nonspecific defenses Physical barriers (1st line of defense) Phagocytes Immunological surveillance Interferons 2nd line of defense Complement Inflammatory response Fever Nonspecific Defenses Surface(physical) barriers Provide effective protection from microbes to underlying tissues through specialized accessory structures, secrection or multiple layers. Outer layer of skin: shedding of epidermal cells removes microbes Hair: act as filters eg nose Epithelial layers of internal passageways secrete mucous and have cilia that trap and move foreign materials to the exterior. Digestive, respiratory, reproductive and urinary tract Secretions that flush away materials and that kill or inhibit microorganisms Tear, sweat glands, urine, stomach acid; also contain lysozymes (destructive enzymes that contain microbe-killing chemicals) and antibodies. Nonspecific Defenses Phagocytes Forms 1st line of cellular defense, phagocytes are cells that ingest and destroy microbes, cell debris and other foreign material thru a process called Phagocytosis, this occurs b4 lymphocytes detects its presence. Phagocytosis: the phagocyte projects pseudopodia (projections of plasma membrane and cytoplasm) and surrounds solid particles/microbe forming a phagocytic vesicle (phagosome) that it engulfs and its contents digested by lysosomal enzymes Two classes of phagocytic cells: - microphages leave the bloodstream and enter peripheral tissues that are injured or infected o Eg. neutrophils and eosinophils - macrophages (fixed or free) are actively phagocytic cells derived from circulating monocytes - mobile macrophages and microphages can move through capillary wall by a process called diapedesis and may also be attracted/repelled by chemicals in surrounding fluids through chemotaxis Phagocytosis  Nonspecific Defenses Interferons (IFN) Are small proteins (eg cytokines) released by activated lymphocytes, macrophages or virally infected cells. In the presence of virus, IFN triggers the production of antiviral proteins from uninfected/normal cells – Antiviral proteins then interfere with or inhibit viral replication, which helps slow down the spread of infections. – Do not kill viruses IFN also stimulate the activities of macrophages and NK cells (natural killer.) http://www.tutorvista.com/content/biology/bi ology-iv/immune-system/immunity.php Nonspecific Defenses Immunological surveillance Natural killer (NK) cells constantly monitor of normal tissues, type of lymphocyte Make up 5–10% of circulating lymphocytes NK cells recognize abnormal cells by detecting the presence of antigens not found on the membranes of normal cells eg transplanted cells, virus-infected cells and cancer cells NK cells are less selective and adhere to targets, secrete proteins perforin, via exocytosis, which create large pores in the target cell membrane which eventually lyse (disintegration of the cell by rupturing of the cell membrane) and kill the bacterium, cancer cell or virus- infected cell NK cells respond quicker to a wide variety pathogens and attack any cell with foreign antigens to help slow down the spread of infection. Nonspecific Defenses Complement system 11 C proteins found within the blood plasma and cell membranes form the Complement (C) proteins that complement the action of the antibodies. Interact with one another in chain reactions: a particular C protein binds to either an antibody attached to the bacterial wall or directly to the bacterium and then interacts with a series of other C proteins Two pathways activate the complement system 1. Classical pathway 2. Alternative pathway In both pathways it ends with the conversion of inactive complement protein C3 to active form C3b Nonspecific Defenses Complement system Classical pathway: Rapid activation, as C1 binds to an antibody already attached to a specific antigen (toxin/foreign particle) this catalyses a series of reactions that activates other C proteins, ending with the active form of C3b. Alternative pathway: Slower activation as antibodies not present , pathway activated when interactions occur betwn C proteins, Factor B,D and properdin, triggered by exposure to bacteria, some parasites and virus infected cells, ending with the activation of C3 to C3b. Nonspecific Defenses Complement system Nonspecific Defenses Complement system Nonspecific Defenses Complement system Complement activation results in: 1.Increases local inflammation and blood flow to area 2.Promotes chemotaxis to attract phagocytes 3.Stimulates phagocytosis, as C proteins bind to antibodies (opsonins) that attach to pathogens are easily engulfed, this effect is known as opsonization. 4.Pores (holes) form in target cell membranes, as C proteins (C5-C9) bind and form a unit called the membrane attack complex (MAC), which creates http://www.tutorvista.com/content/biology/ pores/channels in the membrane which biology-iv/immune-system/immunity.php destroys the target cell. Nonspecific Defenses Inflammation Can be produced by any stimulus that kills cells or damages loose connective tissue A localized condition in which part of the body becomes reddened, swollen, hot, and painful, to any injury or infection. Restore homeostasis, inflammation helps by disposing of foreign material at site of injury, prevents spread and helps repair tissue damaged. Inflammatory response (defensive response) is characterised by 4 symptoms: – Swelling (tumor), Redness (rubor), Heat (calor), Pain (dolor) mast cells, which release histamine and heparin, play a pivotal role Response is initiated by these chemical mediators that produce vasodilation, chemotactic attraction, increased vascular permeability. Inflammation and the Steps in Tissue Repair Nonspecific Defenses Inflammation Inflammatory response: o Injury to tissue causes the release of chemical mediators at the site such as histamine and heprin (mast cells and macrophages), interferons, complement and prostaglandins and leukotrienes. o These substances contribute to vasodilation, the increase of the diameter of blood vessels allowing more blood to flow to the area. o Also increases permeability to the area allowing additional proteins, clotting factors, complement and phagocytes to pass out of the blood vessels to help remove damaged cells, dead pathogens, prevents the spread of pathogens (interferons) and help repair the tissue. o Along with these responses the chemical mediators also act as chemotactic factors and attract phagocytes to the site via chemotaxis. o Inflammation can be localized or systemic. Nonspecific Defenses Inflammation Local inflammation: the inflammatory response is confined to a specific area of the body, with characteristic symptoms of redness, heat, swelling and pain. Systemic inflammation: Is an inflammatory response that occurs in many parts of the body and has additional symptoms such as increase phagocytosis, production of fever promoting chemicals (inc. body temp inhibits microbe growth) and increases fluid permeability from blood vessels to the tissue. Systemic inflammation if severe can cause shock and death due to decrease of blood volume. Nonspecific Defenses Fever the maintenance of a body temperature higher than 37.2°C circulating proteins called pyrogens re-set the “thermostat” in the part of the hypothalamus that contains nuclei regulating body temperature pathogens, bacterial toxins, and antigen-antibody complexes may act as pyrogens or stimulate the release of pyrogens from macrophages within limits, a high body temperature may be beneficial: o increases body metabolism o accelerates defenses o inhibits some viruses and bacteria  Figure (Part 1 of 2) Nonspecific Defenses Physical barriers Duct of eccrine Prevent approach of and Hair Secretions sweat gland deny access to pathogens Eg. Skin, mucous, hair, Epithelium Secretions have lysozymes (destructive enzyme) (sweat and sebaceous glands ) Phagocytes (1st line cellular defense) Remove debris and Pathogens Eg microphages and Macrophages Fixed Diapedesis movement and macrophage Neutrophil Free Eosinophil Attracted/repelled via Chemotaxis macrophage Monocyte Immunological surveillance Lysed Destruction of abnormal abnormal cells, by protein perforin cell that create large pore in cell memb. Natural Eg NK cells. killer cellSecrete Perforins (large pores in CM) Interferons Coordinate the Interferons released by defenses against viral activated lymphocytes, infections; slow the spread of disease. macrophages, or (production of antiviral proteins that virus-infected cells block viral replication in cells)  Figure (Part 2 of 2) Nonspecific Defenses Complement system Attacks and breaks down the cell walls; attracts phagocytes; stimulates inflammation. Lysed Eg. 11 different Complement proteins pathogen (proteins interact in a chain reaction to destroy bacteria.) Complement proteins Inflammatory response 1. Blood flow increased is a localized, tissue-level 2. Phagocytes activated response that tends to limit the spread of an 3. Capillary permeability increased injury or infection, has multiple effects when 4. Complement activated mast cells release histamine 5. Clotting reaction walls off region and heprin. 6. Regional temperature increased Signs : swelling, redness, heat, pain. 7. Adaptive defenses activated Mast cell Fever is an elevation of body Body temperature rises above 37.2ºC in temperature this accelerates response to pyrogens (a protein that resets the body temp. areas in tissue metabolism , the activity of defenses, inhibits pathogens Revision Questions: 1. Define the following: immunity, innate immunity, adaptive immunity, phagocytosis, inflammation, chemotaxis, chemotaxis factor. 2. Explain the function of the physical barriers and describe its defense methods. 3. Name 2 categories of phagocytic cells and give an example of each. 4. Explain why phagocytic cells move towards infected tissue. 5. Briefly describe how NK cells attack microbes. 6. Explain the importance of the complement mechanism in innate defenses. 7. Name and describe the 2 complement pathways. 8. Several defense mechanisms stimulated with the activation of complement, explain this process. 9. Explain the inflammatory response. 10. Name 2 types of inflammatory responses and explain their function.