Unit 5. Section 3.final.Sversion (1).pptx

Unit 5 Section 3: Innate Non-specific Host Defenses ( chapter 17) Overview of Immunity Immunity • Immunity- The body’s ability to resist infectious disease through innate and acquired mechanisms • Immune system- collection of cells, tissues and molecules that protect the body from numerous patho...

Unit 5 Section 3: Innate Non-specific Host Defenses ( chapter 17) Overview of Immunity Immunity • Immunity- The body’s ability to resist infectious disease through innate and acquired mechanisms • Immune system- collection of cells, tissues and molecules that protect the body from numerous pathogenic microbes and toxins in our environment • Immunology-the scientific study of how the immune system functions in the body to prevent or destroy foreign material, including pathogens The Relationship Between Host Resistance and Disease. Innate and acquired immunity: overview • Innate • 1st line of defense • Physical barriers: intact skin, mucous membranes, and their secretions • 2nd line of defense • Phagocytic white blood cells • Inflammation/fever • Antimicrobial substances • Acquired • 3rd line of defense • Specialized lymphocytes: B and T cells • Antibodies Innate and acquired immunity: Overview Innate immunity• Nonspecific resistance • an inborn set of preexisting defenses against infectious agents • includes the skin, mucous membranes, and secretions • Responds within minutes or a few hours after infection • Holds off pathogens while acquired response is mounted Innate and acquired immunity: Overview • Acquired immunity• specific resistance • A response to a specific immune stimulus that involves immune defensive cells and frequently leads to the establishment of host immunity Involves production of lymphocytes and antigens specific to the pathogen causing infection. Innate response • Physical, chemical, and microbiological barriers limit entry of pathogens. 17.1 Physical Defenses Innate response • Physical defenses: physical barriers• skin ( constantly sloughs off, keratin) • Microbes may enter if skin is compromised: burn, puncture wound, bite Figure 17.3 Innate response • Physical defenses: physical barriers• Mucosa- most epithelial lining of digestive, urogenital and respiratory tracts Figure 17.5 Innate response • Physical defenses: mechanical defenses • Sweeping action of mucus • Flushing action of tears and urine Figure 17.7 Innate response • Physical defenses: microbiome • Microbiota- population of microorganisms residing in the body without causing disease – Outcompete pathogens for nutrients and attachment sites on the skin and mucosa – Indigenous-permanent transienttemporary A Sampling of the Indigenous Microbiota of the Human Body. 17.2 Chemical Defenses Innate response •Chemical defenses: Chemical and Enzymatic Mediators Found in Body Fluids •Sebum and oleic acid •Lysozyme • found in human tears, mucus, and saliva •weakens peptidoglycan( attacks NAG-NAM) in Gram positive cells •Low pH •acid in vaginal tract, urinary tract, GI tract •However, hepatitis A, polio, Helicobacter survive pH Innate response • Chemical defenses: Chemical and Enzymatic Mediators Found in Body Fluids • Digestive enzymes and bile • Amylase, lipase, bile, etc. • Lactoferrin • Sequesters iron • Surfactant in lungs Innate response • • • • • Chemical defenses: Antimicrobial peptides Defensins Family of antimicrobial peptides found in various secretions throughout the body Target cell membranes Innate response • Chemical defenses: Plasma Protein Mediators • primarily produced in the liver and secreted into the blood in response to inflammatory molecules from the immune system Innate response • Chemical defenses: Plasma Protein Mediators: acute-phase proteins Innate response • • • Chemical defenses: Plasma Protein Mediators: The Complement system Group of 30 inactive blood proteins circulating in bloodstream that function in a series of reactions that assist in inflammatory response and phagocytosis by marking pathogens for destruction . Opsonins attach to microbes to increase the ability of phagocytes to attach (opsonization). The formation of a membrane attack complex (MAC) • The membrane attack complex causes cell lysis. • Only attacks Gram negative cells Innate response • • • Chemical defenses: Cytokines are soluble proteins that act as communication signals between cells. In a nonspecific innate immune response, various cytokines may be released to stimulate production of chemical mediators or other cell functions, such as cell proliferation, cell differentiation, inhibition of cell division, apoptosis, and chemotaxis. Figure 17.10 • Autocrine, paracrine, and endocrine actions describe which cells are targeted by cytokines and how far the cytokines must travel to bind to their intended target cells’ receptors. Innate response • • Chemical defenses: Cytokines Chemokines, interleukins, and interferons • Chemokines are cytokines that stimulate migration of neutrophils and macrophages to infected tissues. • Interleukins stimulate and modulate most functions of the immune system Innate response • Chemical defenses: Cytokines • Chemokines, interleukins, and interferons • Interferons (IFNs) are protein cytokines that trigger: – macrophage activation. – production of substances to interfere with RNA viral reproduction. • Production is triggered when a virion releases its genome into the cell • IFN- alpha and beta bind to receptors and adjacent cells, turning on production of antiviral proteins within that cell • These inhibit translation and degrade mRNA of both the virus and host Figure 17.11 • Interferons are cytokines released by a cell infected with a virus. Interferon-α and interferon-β signal uninfected neighboring cells to inhibit mRNA synthesis, destroy RNA, and reduce protein synthesis (top arrow). Interferon-α and interferon-β also promote apoptosis in cells infected with the virus (middle arrow). Interferon-γ alerts neighboring immune cells to an attack (bottom arrow). Although interferons do not cure the cell releasing them or other infected cells, which will soon die, their release may prevent additional cells from becoming infected, thus stemming the infection. Innate Immunity • Chemical defenses: Inflammation eliciting mediators • • • • • • Histamine-proinflammatory molecule released by basophils and mast cells in response to stimulation by other cytokines and chemical mediators Leukotrines- lipid-based chemical mediators produced by leukocytes and other tissue cells; promote inflammation and allergic responses Prostaglandins- , chemical mediators that promote the inflammatory effects of kinins and histamines. Prostaglandins can also help to set the body temperature higher, leading to fever, which promotes the activities of white blood cells and slightly inhibits the growth of pathogenic microbes Bradykinin- activated form of a proinflammatory molecule induced in the presence of invader microbes; opens gaps between cells in blood vessels, allowing fluid and cells to leak into surrounding tissues EDEMA : the process of leaking fluid that comes out from a broken blood vessel of the cell 17.3 Cellular defenses Innate response • Cellular barriers • Monocytes, macrophages, neutrophils • Carry out phagocytosis and trigger inflammatory response Blood • Consists of fluid, clotting agents, and formed elements • Serum- fluid portion of blood – aqueous solution of minerals, salts, proteins, and other organic substances – When clotting agents, such as fibrinogen and prothrombin are present, the fluid is referred to as plasma. Blood: formed elements • Blood platelets • are small, disk-shaped cells that originate in the bone marrow. • erythrocytes (red blood cells) • leukocytes (white blood cells) Figure 17.12: Hematopoiesis • All the formed elements of the blood arise by differentiation of hematopoietic stem cells in the bone marrow. Elements of Blood: leukocytes • Leukocytes- Any of a number of types of white blood cells • No pigment in cytoplasm • Appear gray when unstained • Produced in bone marrow • About 4,000 to 12,000 per microliter of blood • There are 6 types of white blood cells Major Leukocytes of the Human Immune System Granulocytes: Neutrophils, eosinophils, and basophils • Concentrated in the skin, lungs, and GI tract • Contain cytoplasmic granules • Phagocytic against microbes during initial phase of infection Neutrophils • • • • • Multilobed cell nucleus Stain pale lylac with acidic and basic dye Referred to as “polymorphonuclear(PMN)” cells Function as phagocytes Short life span Neutrophils • Neutrophils are usually first cell type arriving, but macrophages kill majority of pathogens • Some neutrophils may transform into extracellular fibers: NETS- Neutrophil Extracellular Traps • Plasma membrane of dying neutrophil ruptures, DNA and antimicrobial proteins mix , forming fibers where invading pathogens can get caught and killed by antimicrobials Formation of NETs Adapted from Lee, Warren, L. and Grinstein, S., Science 303 (2004): 1477-1478. Eosinophils • Named so because show red or pink cytoplasmic granules upon addition of acidic eosin dye • Contain cytotoxic proteins in the granules that defend against multicellular parasites such as helminths • Involved in development of allergies and asthma Basophils and mast cells • Named so because cytoplasmic granules stain blue-purple upon addition basic dye methylene blue. • Produce histamine, important in inflammation/allergic responses Agranulocytes: monocyte, macrophage, and lymphocyte • Lack visible granules Monocyte • Single, bean shaped cell nucleus • 2-week lifespan • Not actively phagocytic until leave circulating blood, enter tissues, where they mature into • macrophages- several months – Phagocytic ,and more effective than neutrophils – Concentrated in spleen, lymph nodes, and thymus Lymphocyte • Single, large nucleus • Not phagocytic • Migrate from bone marrow to the lymph nodes after maturation • B and T lymphocytes- key role in acquired immunity NK cells • Natural killer cells are a type of mononuclear lymphocytes, defective cells that attack and destroy cancer cells and infected cells without the involvement of the immune system. • Formed in bone marrow and migrate to tonsils, lymph nodes, and spleen, where they await activation. • On stimulation, they secrete several cytokines, triggering acquired immune responses by macrophages and other immune cells. • While those events develop, they move into the blood and lymph where they act as potent nonspecific killers of tumor cells and virus-infected cells. NK cells • NK cells attack “nonself” cells by releasing cytotoxic mediators like perforins (drill holes) and granzymes ( induce apoptosis) • They do not attack if Natural Killer (NK) Cell Recognition. target Adapted from Delves and I.M. Roitt, N Engl J Med. 343 (2000): 37-49. contains Figure 17.17 • Natural killer cell with perforin-containing granules. (credit: modification of work by Rolstad B) Dendritic cells • In skin and in tissues where pathogens can enter • Crucial to innate immunity and activation of acquired immunity. Innate Immunity Defense Barriers to Pathogens. 17.4 Pathogen Recognition and Phagocytes Pathogen recognition Pathogen associated molecular patterns (PAMPS) • Pathogen-Associated Molecular Patterns (PAMPS) are small molecular sequences that are recognized by macrophages, and dendritic cells to trigger the innate immune response • Include sequences in LPS, peptidoglycan, flagellin, lipopeptides • Recognized by Pattern Recognition Receptors (PRRs) on the plasma membrane of macrophages, dendritic cells. Figure 17.20 • Phagocytic cells contain pattern recognition receptors (PRRs) capable of recognizing various pathogen-associated molecular patterns (PAMPs). These PRRs can be found on the plasma membrane or in internal phagosomes. When a PRR recognizes a PAMP, it sends a signal to the nucleus that activates genes involved in phagocytosis, cellular proliferation, production and secretion of antiviral interferons and proinflammatory cytokines, and enhanced intracellular killing. Pathogen degradation: phagocytosis Phagocytosis • Phagocytosis is a nonspecific defense mechanism to clear microbes from infected tissues • is the capturing and digesting of foreign particles, including pathogens, by phagocytes • Occurs at the site of infection and lymphoid tissue • Release cytokines to trigger inflammatory response • Chemokines are cytokines that stimulate migration of neutrophils and macrophages to infected tissues. – Opsonins attach to microbes to increase the ability of phagocytes to attach (opsonization). Phagocytosis • Steps • Begins with attachment of microbe to cell surface of phagocyte via filopodia • formation phagosome and fusion with lysosomes phagolysosomes • Enzymes and other products kill and digest the pathogen • Elimination of bacterial debris during egestion The Mechanism of Phagocytosis. False-color transmission electron micrograph of lysosomes (yellow) in a macrophage © Dr. Gopal Murti/Photo Researchers, Inc. 17.5 Inflammation and fever Inflammation • Nonspecific local defensive response by body to injury/trauma • Characterized by redness, pain, heat, swelling, and sometimes loss of function • Develops after mechanical injuries, such as injury or blow to skin or from exposure to a chemical agent, or infection by pathogen • Process in place to limit spread of infection • Must be short lived Inflammation • Steps • Macrophages initiate phagocytosis and secrete several cytokines triggering vasodilation(local dilation of capillary walls) • This allows the flow of plasma into the injured tissue and fluid accumulation(edema) at site of injection • Chemokines attract additional phagocytes toward the infected tissue. • Eventually, formation of fibrin clot occurs, which prevents the spread of pathogens to the blood. The Process of Inflammation. Fever • Abnormally high body temperature that remains elevated above the normal 37C. • Moderate fever benefits host defenses. • Supports immune response by – inhibiting rapid growth of microorganisms – encouraging rapid tissue repair. – heightening phagocytosis. – Pyrogens- are cytokines produced by: – some leukocytes and viruses – fragments from pathogens. • They affect the hypothalamus, causing elevated body temperature. Fever © Blend Images/Jupiterimages