Lecture PowerPoint to accompany Foundations in Microbiology Seventh Edition Talaro Chapter 14 To run the animations you must be in Slideshow View. Use the buttons on the animation to play, pause, and turn audio/text on or off. Please Note: Once you have used any of the animation functions (such as Play or Pause), you must first click in the white background before you can advance to the next slide. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 14.1 Defense Mechanisms of the Host • Host Defenses – Innate, natural defenses: present at birth, provide nonspecific resistance to infection – Adaptive immunities: specific, must be acquired 2 3 14.1 Defense Mechanisms of the Host • To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals – First line of defense – any barrier that blocks invasion at the portal of entry – nonspecific – Second line of defense – protective cells and fluids; inflammation and phagocytosis – nonspecific – Third line of defense – acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific 4 5 Figure 14.1 6 Physical or Anatomical Barriers: First Line of Defense Skin and mucous membranes of respiratory, urogenital, eyes, and digestive tracts – Outermost layer of skin is composed of epithelial cells compacted, cemented together, and impregnated with keratin; few pathogens can penetrate if intact – Flushing effect of sweat glands – Damaged cells are rapidly replaced – Mucous coat impedes attachment and entry of bacteria – Blinking and tear production – Stomach acid – Nasal hair traps larger particles 7 Figure 14.2 8 Nonspecific Chemical Defenses • Sebaceous secretions • Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears • High lactic acid and electrolyte concentration in sweat • Skin’s acidic pH • Hydrochloric acid in stomach • Digestive juices and bile of intestines • Semen contains an antimicrobial chemical • Vagina has acidic pH 9 Genetic Defenses • Some hosts are genetically immune to the diseases of other hosts • Some pathogens have great specificity • Some genetic differences exist in susceptibility 10 14.2 Structure and Function of the Organs of Defense and Immunity • • The study of the body’s second and third lines of defense is called immunology Functions of a healthy functioning immune system: 1. Surveillance of the body 2. Recognition of foreign material 3. Destruction of entities deemed to be foreign 11 Figure 14.3 12 Immune System • • Large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue Four major subdivisions of immune system are: 1. 2. 3. 4. Reticuloendothelial system (RES) Extracellular fluid (ECF) Bloodstream Lymphatic system 13 Immune System Definitions • White blood cells (leukocytes) – innate capacity to recognize and differentiate any foreign material • Nonself – foreign material • Self – normal cells of the body • Pathogen-associated patterns (PAMPs) – molecules shared by microorganisms • Pathogen recognition receptors (PRRs) – receptors on WBCs for PAMPs 14 Body Compartments that Participate in the Immune System • The reticuloendothelial system • The spaces surrounding tissue cells that contain extracellular fluid • The bloodstream • The lymphatic system 15 Figure 14.4 16 Reticuloendothelial System (RES) • Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs • Inhabited by phagocytic cells – mononuclear phagocyte system – macrophages ready to attack and ingest microbes that passed the first line of defense 17 Figure 14.5 18 Origin, Composition, and Functions of the Blood • Whole blood consists of plasma and formed elements (blood cells) – Serum is the liquid portion of the blood after a clot has formed – minus clotting factors • Plasma – 92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functions 19 Figure 14.6 20 A Survey of Blood Cells • Hemopoiesis – production of blood cells • Stem cells – undifferentiated cells, precursor of new blood cells • Leukocytes – White blood cells – Granulocytes: lobed nucleus – Agranulocytes: unlobed, rounded nucleus 21 Figure 14.7 22 Granulocytes • Neutrophils – 55-90% - lobed nuclei with lavender granules; phagocytes • Eosinophils – 1-3% - orange granules and bilobed nucleus; destroy eukaryotic pathogens • Basophils – 0.5% - constricted nuclei, dark blue granules; release potent chemical mediators – Mast cells: nonmotile elements bound to connective tissue 23 Agranulocytes • Lymphocytes – 20-35%, specific immune response – B (humoral immunity) • Activated B cells produce antibodies – T cells (cell-mediated immunity) • Activated T cells modulate immune functions and kill foreign cells • Monocytes, macrophages – 3-7% - largest of WBCs, kidney-shaped nucleus; phagocytic – Macrophages: final differentiation of monocytes – Dendritic cells: trap pathogens and participate in immune reactions 24 Erythrocytes and Platelet Lines • Erythrocytes: develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin • Platelets: formed elements in circulating blood that are not whole cells 25 26 Lymphatic System 1. Provides an auxiliary route for return of extracellular fluid to the circulatory system 2. Acts as a drain-off system for the inflammatory response 3. Renders surveillance, recognition, and protection against foreign material 27 Figure 14.8 28 Lymphatic Fluid • Lymph is a plasma-like liquid carried by lymphatic circulation • Formed when blood components move out of blood vessels into extracellular spaces • Made up of water, dissolved salts, 2-5% proteins • Transports white blood cells, fats, cellular debris, and infectious agents 29 Lymphatic Vessels • Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus • Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles • Functions to return lymph to circulation; flow is one-direction – toward the heart – eventually returning to blood stream 30 Figure 14.9 31 Lymphoid Organs and Tissues • Classified as primary and secondary • Primary lymphoid organs – sites of lymphocytic origin and maturation – thymus and bone marrow • Secondary lymphoid organs and tissues – circulatory-based locations such as spleen and lymph nodes; collections of cells distributed throughout body tissues – skin and mucous membranes – SALT, GALT, MALT 32 Lymphoid Organs • Thymus – high rate of growth and activity until puberty, then begins to shrink; site of T-cell maturation • Lymph nodes – small, encapsulated, bean-shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities • Spleen – structurally similar to lymph node; filters circulating blood to remove worn out RBCs and pathogens • Miscellaneous – GALT, Peyer’s patch 33 34 14.3 Actions of the Second Line of Defense • • • • • Recognition Inflammation Phagocytosis Interferon Complement 35 Recognition • Protein receptors within cell membrane of macrophages, called Toll-like receptors • Detect foreign molecules and signal the macrophage to produce chemicals which: – Stimulate an inflammatory response (nonspecific) – Promote the activity of B and T cells (specific) 36 Figure 14.11 37 Inflammatory Response Classic signs and symptoms characterized by: • Redness – increased circulation and vasodilation in injured tissues in response to chemical mediators and cytokines • Warmth – heat given off by the increased blood flow • Swelling – increased fluid escaping into the tissue as blood vessels dilate – edema; WBC’s, microbes, debris, and fluid collect to form pus; helping prevent spread of infection • Pain – stimulation of nerve endings • Possible loss of function 38 Figure 14.12 39 Figure 14.13 Insert figure 14.13 Events in inflammation 40 Figure 14.14 41 Unique Characteristics of Leukocytes • Diapedesis – migration of cells out of blood vessels into the tissues • Chemotaxis – migration in response to specific chemicals at the site of injury or infection 42 Figure 14.15 Diapedesis and chemotaxis of leukocytes 43 Fever • Initiated by circulating pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction – Exogenous pyrogens – products of infectious agents – Endogenous pyrogens – liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF) • Benefits of fever: – Inhibits multiplication of temperature-sensitive microorganisms – Impedes nutrition of bacteria by reducing the available iron – Increases metabolism and stimulates immune reactions and protective physiological processes 44 Phagocytosis General activities of phagocytes: 1. To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells 2. To ingest and eliminate these materials 3. To extract immunogenic information from foreign matter 45 46 Phagocytes and Phagocytosis Main types of phagocytes: 1. Neutrophils – general-purpose; react early to bacteria and other foreign materials, and to damaged tissue – Eosinophils – attracted to sites of parasitic infections and antigen-antibody reactions 2. Macrophages – derived from monocytes; scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes 47 Figure 14.16 Developmental stages of monocytes 48 Figure 14.17 Site-specific macrophages 49 Mechanisms of Phagocytic Recognition, Engulfment, and Killing • Chemotaxis and ingestion: phagocytes migrate and recognize PAMPs – Phagosome • Phagolysosome: lysosome fused with phagosome (death ~30 minutes) • Destruction and elimination – Oxygen-dependent system (respiratory burst) – Liberation of lactic acid, lysozyme, and nitric oxide 50 Figure 14.18 51 Interferon • Small protein produced by certain white blood cells and tissue cells – Interferon alpha – lymphocytes and macrophages – Interferon beta – fibroblasts and epithelial cells – Interferon gamma – T cells • Produced in response to viruses, RNA, immune products, and various antigens • Bind to cell surfaces and induce expression of antiviral proteins • Inhibit expression of cancer genes 52 Figure 14.19 53 54 Complement • Consists of 26 blood proteins that work in concert to destroy bacteria and viruses • Complement proteins are activated by cleavage (cascade reaction) • Pathways – Classical – activated by the presence of antibody bound to microorganism – Lectin pathway – nonspecific reaction of a host serum protein that binds mannan – Alternative – begins when complement proteins bind to normal cell wall and surface components of microorganisms 55 Stages in the Complement Cascade • • • • Initiation Amplification and cascade Polymerization Membrane attack 56 57 Figure 14.20(a) 58 Figure 14.20(b, c, d) 59 Figure 14.21 60