Chapter 15 Revised


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Chapter 15 Revised

  1. 1. 15 Innate Immunity
  2. 2. Innate Resistance <ul><li>Innate (Immunity) Resistance – that which present at birth; before contact with microbes or their products </li></ul><ul><li>Nonspecific – not directed against a particular agent, but against anything foreign (not part of the body) </li></ul><ul><li>Resistance to most plant and animal Pathogens </li></ul><ul><li>Resistance due to physiological processes of humans that are incompatible with those of the Pathogen </li></ul><ul><ul><li>Correct chemical receptors not present on human cells. </li></ul></ul><ul><ul><li>Temperature and pH may be incompatible with those necessary for the Pathogens survival. </li></ul></ul><ul><li>Pathogens for which humans don’t have Innate Resistance to can cause disease. </li></ul>
  3. 3. First Line of Defense <ul><li>Structures, chemicals, processes that work to prevent pathogens entering the body </li></ul><ul><li>Nonspecific Defenses </li></ul><ul><li>Includes the Skin and Mucous Membranes of the Respiratory, Digestive, Urinary, and Reproductive Systems </li></ul>PLAY Animation: Host Defenses
  4. 4. Skin – Physical Components of Defense <ul><li>Two major layers </li></ul><ul><ul><li>Epidermis </li></ul></ul><ul><ul><ul><li>Outer layer composed of multiple layers of tightly packed cells </li></ul></ul></ul><ul><ul><ul><ul><li>Few Pathogens can penetrate these layers </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Shedding of dead skin cells removes attached microorganisms </li></ul></ul></ul></ul><ul><ul><ul><li>Epidermal Dendritic Cells </li></ul></ul></ul><ul><ul><ul><ul><li>Also termed Langerhans Cells </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Phagocytize Pathogens, and important in Adaptive (Specific) Immunity </li></ul></ul></ul></ul>
  5. 5. Skin – Physical Components of Defense <ul><ul><li>Dermis </li></ul></ul><ul><ul><ul><li>Contains protein fibers of Collagen </li></ul></ul></ul><ul><ul><ul><ul><li>Give skin strength and pliability to resist abrasions that could introduce microorganisms </li></ul></ul></ul></ul>
  6. 6. Skin – Chemical Components of Defense <ul><li>Perspiration secreted by Sweat Glands </li></ul><ul><ul><li>Salt – inhibits growth of Pathogens by drawing water from their cells </li></ul></ul><ul><ul><li>Antimicrobial Peptides – Sweat Glands secret Dermicidins </li></ul></ul><ul><ul><li>Lysozyme – destroys cell wall of many bacteria </li></ul></ul><ul><li>Sebum secreted by Sebaceous (Oil) Glands </li></ul><ul><ul><li>Helps keep skin pliable and less likely to break or tear </li></ul></ul><ul><ul><li>Lowers the pH of the skin to a level inhibitory to many bacteria </li></ul></ul>
  7. 7. Mucous Membranes <ul><li>Line all body cavities open to the outside environment </li></ul><ul><li>Two distinct layers </li></ul><ul><ul><li>Epithelium </li></ul></ul><ul><ul><li>Deeper Connective Tissue layer that supports the Epithelium </li></ul></ul>
  8. 8. Epithelium <ul><li>Thin, outer covering of the Mucous Membranes </li></ul><ul><li>Unlike surface Epidermal Cells of Skin, Epithelial cells of Mucous Membranes are living. </li></ul><ul><li>Tightly packed to prevent entry of Pathogens </li></ul><ul><li>Continual shedding of cells carries attached microorganisms away. </li></ul>
  9. 9. Respiratory System Figure 15.2
  10. 10. Microbial Antagonism <ul><li>Normal Microbiota help protect the body by competing with potential Pathogens. </li></ul><ul><li>Various activities of the Normal Microbiota make it hard for Pathogens to compete. </li></ul><ul><ul><li>Consumption of nutrients makes them unavailable to Pathogens </li></ul></ul><ul><ul><li>Create an environment unfavorable to other microorganisms by changing pH </li></ul></ul>
  11. 11. Microbial Antagonism <ul><ul><li>Helps stimulate the body’s Second Line of Defense </li></ul></ul><ul><ul><li>Promote overall health by providing vitamins to host </li></ul></ul>
  12. 12. Other First-Line Defenses <ul><li>Many body organs secrete chemicals with antimicrobial properties </li></ul><ul><li>Lacrimal (Tear) Glands that bathe the eye </li></ul>
  13. 13. Lacrimal Apparatus Figure 15.3
  14. 14. Second Line of Defense <ul><li>Operates when pathogens succeed in penetrating the Skin or Mucous Membranes </li></ul><ul><li>Nonspecific Defense </li></ul><ul><li>Composed of cells, antimicrobial chemicals, and processes, but no physical barriers </li></ul><ul><ul><li>Many of these components are contained or originate in the Blood. </li></ul></ul>
  15. 15. Blood <ul><li>Composed of cells and portions of cells within a fluid called Plasma </li></ul><ul><ul><li>Plasma mostly water containing Electrolytes, dissolved gases, nutrients, and proteins </li></ul></ul><ul><ul><ul><li>Serum – Plasma from which the Clotting Factors, a group of Plasma Proteins, have been removed </li></ul></ul></ul><ul><ul><ul><li>Include Iron-binding compounds </li></ul></ul></ul><ul><ul><ul><li>Other Plasma Proteins include Complement Proteins and Antibodies </li></ul></ul></ul><ul><ul><li>Formed Elements -- the cells and cell fragments in the Plasma </li></ul></ul>
  16. 16. Formed Elements <ul><li>Three types of Formed Elements </li></ul><ul><ul><li>Erythrocytes (Red Blood Cells) – carry oxygen and carbon dioxide in the blood </li></ul></ul><ul><ul><li>Platelets (Thrombocytes) – cell fragments involved in Blood Clotting </li></ul></ul><ul><ul><li>Leukocytes (White Blood Cells) – involved in defending the body against invaders </li></ul></ul><ul><ul><ul><li>Two groups </li></ul></ul></ul><ul><ul><ul><ul><li>Granulocytes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Agranulocytes </li></ul></ul></ul></ul>
  17. 17. Granulocytes <ul><li>Their cytoplasm contains visible granules that stain different colors based on the dye used </li></ul><ul><li>Three types </li></ul><ul><ul><li>Basophils – stain dark blue or purple with the Basic Dye Methylene Blue </li></ul></ul><ul><ul><li>Eosinophils – stain red/orange with the Acidic Dye Eosin </li></ul></ul><ul><ul><li>Neutrophils – stain pink with a mixture of Acidic and Basic Dyes </li></ul></ul><ul><li>Neutrophils and Eosinophils can phagocytize Pathogens </li></ul><ul><li>Neutrophils and Eosinophils are capable of Diapedesis – changing shape to squeeze through blood vessel walls </li></ul>
  18. 18. Diapedesis Figure 15.6
  19. 19. Agranulocytes <ul><li>Cytoplasm appears uniform under a Light Microscope; lack visible cytoplasmic granules </li></ul><ul><li>Two types </li></ul><ul><ul><li>Lymphocytes – most involved in Adaptive Immunity </li></ul></ul><ul><ul><li>Monocytes – leave the blood and mature into Macrophages which phagocytic and involved in Adaptive (Specific) Immunity </li></ul></ul>
  20. 20. Macrophages <ul><li>Phagocytic cells of the Second Line of Defense </li></ul><ul><li>Wandering Macrophages leave the blood via Diapedesis and phagocytize throughout the body. </li></ul><ul><li>Fixed Macrophages do not move throughout the body, and often phagocytize within a specific organ. </li></ul><ul><ul><li>Include Alveolar Macrophages (in lungs), Microglia (in Central Nervous System), Küpffer Cells (in liver) </li></ul></ul><ul><li>All Macrophages, plus Monocytes attached to Endothelial Cells; constitute the Mononuclear Phagocytic System </li></ul>
  21. 21. Lab Analysis of Leukocytes <ul><li>Differential White Blood Cell Count test can signal signs of disease. </li></ul><ul><ul><li>Increased Eosinophils can indicate allergies or parasitic worm infection. </li></ul></ul><ul><ul><li>Bacterial diseases often show increase in leukocytes and in Neutrophils </li></ul></ul><ul><ul><li>Viral infections show increase in Lymphocytes </li></ul></ul>
  22. 22. Components of the Second Line of Defense <ul><li>Phagocytosis </li></ul><ul><li>Extracellular killing by Leukocytes </li></ul><ul><li>Nonspecific Chemical Defenses </li></ul><ul><li>Inflammation </li></ul><ul><li>Fever </li></ul>
  23. 23. Phagocytosis <ul><li>Phagocytes – cells capable of phagocytosis </li></ul><ul><li>Phagocytosis is not completely understood </li></ul><ul><li>Can be divided into five stages </li></ul><ul><ul><li>Chemotaxis </li></ul></ul><ul><ul><li>Adherence </li></ul></ul><ul><ul><li>Ingestion </li></ul></ul><ul><ul><li>Killing </li></ul></ul><ul><ul><li>Elimination </li></ul></ul>PLAY Animation: Phagocytosis
  24. 24. Phagocytosis (continued) <ul><li>Chemotaxis – movement in response to a chemical stimulus </li></ul><ul><ul><li>Phagocytes move toward chemical stimulus (Positive Chemotaxis) via Pseudopodia </li></ul></ul><ul><ul><li>Phagocytes attracted to chemicals released by microbes, damaged host cells, activated Leukocytes, and components of Complement </li></ul></ul><ul><li>Adherence –binding of Phagocyte to microbe by attaching to complementary molecules on its surface (such as Glycoproteins) </li></ul><ul><ul><li>Bacterial Capsule or M Protein (in Streptococcus pyogenes ) may interfere with Adherence. </li></ul></ul><ul><ul><li>Opsonins (Antibodies or Complement Proteins) that coat microbe facilitate it; thus enhance Phagocytosis </li></ul></ul>
  25. 25. Phagocytosis (continued) <ul><li>Ingestion – envelopment of microbe by Phagocyte via its Pseudopodia, and taking it in by Endocytosis </li></ul><ul><ul><li>Microbe contained within Phagosome (membrane of which was originally part of Phagocyte’s Cytoplasmic Membrane) </li></ul></ul><ul><li>Killing – enzymatic destruction of microbe within Phagocyte’s Lysosomes which fuse with Phagosome forming Phagolysosome </li></ul><ul><ul><li>Digestive Enzymes from Lysosomes usually kill and break down microbial cell. </li></ul></ul><ul><ul><li>M Protein (in S. pyogenes ) and waxy cell walls (in Mycobacterium tuberculosis ) may prevent Lysosome activity. </li></ul></ul>
  26. 26. Phagocytosis (continued) <ul><li>Elimination – excretion of microbial cell remnants from Phagocyte by Exocytosis </li></ul><ul><ul><li>In some Phagocytes (Dendritic Cells and Macrophages) microbial cell surface markers may remain attached to phagocytic cell’s Cytoplasmic Membrane to help activate Lymphocytes. </li></ul></ul>
  27. 27. Phagocytosis Figure 15.8
  28. 28. Host Cell Protection <ul><li>The host’s cells are protected from destruction by the Phagocytes. </li></ul><ul><ul><li>Some Phagocytes have receptors for bacterial surface components, such as flagellar proteins or cell wall components, that are lacking on the body’s cells. </li></ul></ul><ul><ul><li>Opsonins such as Complement and Antibody attached to microbial cell provide a signal to the Phagocyte. </li></ul></ul>
  29. 29. Extracellular Killing by Leukocytes <ul><li>Three Cell types that kill extracellularly </li></ul><ul><ul><li>Eosinophils </li></ul></ul><ul><ul><ul><li>Mainly attack parasitic Helminths (worms) by attaching to their surface, or to Antibodies attached to worm’s surface </li></ul></ul></ul><ul><ul><ul><li>Secrete toxins that weaken or kill the Helminth </li></ul></ul></ul><ul><ul><ul><li>Eosinophilia -- elevated Eosinophil levels; often indicative of a Helminth infestation </li></ul></ul></ul>
  30. 30. Extracellular Killing by Leukocytes (cont.) <ul><ul><li>Natural Killer Lymphocytes (NK Cells) – large Lymphocytes that attack foreign (those that are not part of body) and abnormal body cells, but do not target specific microbes, as do other Lymphocytes </li></ul></ul><ul><ul><ul><li>Secrete toxins onto the surface of virus-infected cells and tumors </li></ul></ul></ul><ul><ul><ul><li>Differentiate normal body cells because they have membrane proteins similar to the NK Cells </li></ul></ul></ul>
  31. 31. Extracellular Killing by Leukocytes (cont.) <ul><ul><li>Neutrophils </li></ul></ul><ul><ul><ul><li>Produce chemicals that kill nearby invaders </li></ul></ul></ul><ul><ul><ul><ul><li>Enzymes that form Superoxide Radicals and Hydrogen Peroxide (Oxidants) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>An Enzyme that converts these Oxidants into Hypochlorite (active ingredient in bleach) </li></ul></ul></ul></ul><ul><ul><ul><li>Generate Extracellular Fibers that bind to and kill bacteria </li></ul></ul></ul><ul><ul><ul><li>Extracellular Fibers composed of DNA and Histones, and formed into NETs (Neutrophil Extracellular Traps) to bind microbes and expose them to high concentrations of antimicrobial chemicals </li></ul></ul></ul>
  32. 32. Nonspecific Chemical Defenses <ul><li>Augment Phagocytosis </li></ul><ul><ul><li>Some attack Pathogens directly </li></ul></ul><ul><ul><li>Some enhance other features of Innate Immunity </li></ul></ul><ul><li>Includes various chemicals </li></ul><ul><ul><li>Lysozyme </li></ul></ul><ul><ul><li>Complement </li></ul></ul><ul><ul><li>Interferon </li></ul></ul><ul><ul><li>Defensins </li></ul></ul>
  33. 33. Complement System (Complement) <ul><li>Set of Serum Proteins designated numerically according to the order of their discovery </li></ul><ul><li>Complement activation results in Lysis of the foreign cells </li></ul><ul><li>Complement can be activated in several ways </li></ul><ul><ul><li>Classical Pathway </li></ul></ul><ul><ul><li>Alternate Pathway </li></ul></ul>
  34. 34. The Classical Pathway <ul><li>Complement named for the events of this originally discovered pathway </li></ul><ul><li>Various complement proteins act nonspecifically to “complement” the action of Antibodies </li></ul><ul><li>In this Pathway: binding of Antibodies to Antigen activates Complement </li></ul><ul><li>Complement Enzymes split Complement Molecules into Fragments which 1) combine to form new enzymes, or 2) dilate blood vessels and increase their permeability, enhancing Diapedesis, or 3) increase Inflammation, or 4) attract Phagocytes by Chemotaxis, or 5) are Opsonins </li></ul>
  35. 35. The Classical Pathway (continued) <ul><li>This Pathway followed by the Complement Cascade – sequence of reactions involving Complement Proteins in which product of one reaction is the enzyme that catalyzes the next reaction </li></ul><ul><li>Membrane Attack Complexes (MACs) – end products of Complement Cascade which punch holes in foreign cells’ cytoplasmic membrane, allowing water to flow into cells and lyse them </li></ul><ul><li>Gram (-) Bacteria more sensitive to MACs than Gram (+) due to their exposed Outer Membrane </li></ul>
  36. 36. The Alternate (Properdin) Pathway <ul><li>Activation occurs independent of Antibodies; instead occurs when Complement Proteins (B, D, and Properdin) bind to Endotoxins or Glycoproteins in Cell of Bacteria or Fungi </li></ul><ul><li>Useful in early stages of infection before Antibodies have formed </li></ul><ul><li>Complement Cascade also follows this Pathway, resulting in formation of MACs and Cell Lysis </li></ul>
  37. 37. Complement – Two Pathways Figure 15.10
  38. 38. Classical Complement Cascade Figure 15.11
  39. 39. Inactivation of Complement <ul><li>Complement System nonspecific and MACs can form on most cells’ exposed cell membrane </li></ul><ul><li>Body’s own cells can withstand Complement Cascade </li></ul><ul><ul><li>Membrane-bound Proteins on normal body cells bind to and break down activated Complement Proteins </li></ul></ul><ul><ul><li>This stops Complement Cascade before cell damage occurs </li></ul></ul>PLAY Animation: The Complement System
  40. 40. Interferons (IFNs) <ul><li>Protein molecules secreted by virus-infected host cells to nonspecifically inhibit the spread of viral infections </li></ul><ul><li>Cause many symptoms typically associated with viral infections (malaise, headache, muscle aches, chills, and fever) </li></ul><ul><li>Three Classes produced by different cell types </li></ul><ul><ul><li>Alpha Interferon from Monocytes, Macrophages, and some Lymphocytes </li></ul></ul><ul><ul><li>Beta Interferon from Fibroblasts </li></ul></ul><ul><ul><li>Gamma Interferon from activated T Lymphoytes and NK Lymphocytes (NK Cells) </li></ul></ul>
  41. 41. Interferons (continued) <ul><li>Interferons do not protect virus-infected cells that secrete them, but neighboring cells by interfering with viral replication in them, and by activating NK Lymphocytes </li></ul><ul><li>Not specific; Interferon secretion stimulated by one type of virus can help protect against other viruses </li></ul><ul><li>Alpha and Beta Interferons have same action </li></ul><ul><ul><li>They bind to receptors on other cells’ cytoplasmic membrane stimulating them to produce Antiviral Proteins (AVPs) which activated when they bind to viral nucleic acids </li></ul></ul><ul><ul><li>Some AVPs breakdown cells’ mRNA; others block protein synthesis at ribosomes – both preventing viral replication in cell </li></ul></ul>
  42. 42. Interferons (continued) <ul><li>AVPs stop all protein synthesis in cell (for both virus and host cell) for 3-4 days. </li></ul><ul><li>This often enables cell to rid itself of virus, and yet survive brief period without protein synthesis. </li></ul><ul><li>Gamma Interferon (Macrophage Activating Factor) stimulates activity of Phagocytes – both Macrophages and Neutrophils </li></ul>
  43. 43. Interferons (continued) <ul><li>Alpha and Beta Interferons are present early in the infection. </li></ul><ul><li>Interferon Gamma appears later in the course of infection, since T Lymphocyte activation is part of the Specific Immune Response which occurs after the Nonspecific Response </li></ul>
  44. 44. The Characteristics of Human Interferons Table 15.3
  45. 45. Interferon Therapy <ul><li>It was thought that this might be a good antiviral treatment. </li></ul><ul><li>Recombinant DNA Technology used to produce various Interferons </li></ul><ul><ul><li>Synthetic Genes for Human Interferons inserted into genomes of Escherichia coli and Saccharomyces cerevisiae </li></ul></ul><ul><ul><li>Interferons produced in this way are pure and can be made in large quantities. </li></ul></ul>
  46. 46. Inflammation <ul><li>Nonspecific Localized Response to tissue damage resulting from various causes – chemicals, heat, UV, trauma, and Pathogens </li></ul><ul><li>Characterized by Redness, Heat, Swelling, and Pain; sometimes also loss of function </li></ul><ul><li>Two types </li></ul><ul><ul><li>Acute Inflammation </li></ul></ul><ul><ul><li>Chronic Inflammation </li></ul></ul>PLAY Animation: Inflammation
  47. 47. Acute vs. Chronic Inflammation <ul><li>Acute Inflammation </li></ul><ul><ul><li>Develops quickly and is short lived </li></ul></ul><ul><ul><li>Is usually beneficial, since results in elimination of what caused it </li></ul></ul><ul><ul><li>Important in the Second Line of Defense; it involves </li></ul></ul><ul><ul><ul><li>Dilation and Increased Permeability of the Blood Vessels (due to release of Inflammatory Chemicals by Macrophages, Basophils, Mast Cells, Platelets, and damaged cells)) </li></ul></ul></ul><ul><ul><ul><li>Migration of Phagocytes [involves Chemotaxis, Margination (sticking to blood walls), and Diapedesis (squeezing between cells in blood vessel wall)] </li></ul></ul></ul><ul><ul><ul><li>Tissue Repair (by Stem Cells or Fibroblasts) </li></ul></ul></ul><ul><ul><li>Chronic Inflammation </li></ul></ul><ul><ul><ul><li>Develops slowly and lasts a long time </li></ul></ul></ul><ul><ul><ul><li>Can cause damage to tissues, resulting in disease </li></ul></ul></ul>
  48. 48. Inflammatory Chemicals (Mediators) <ul><li>Vasodilators: Histamine, Serotonin, Prostaglandins, Bradykinin </li></ul><ul><li>Increase Capillary Permeability: Prostaglandins and Leukotrienes </li></ul><ul><li>Chemotactic Factors: Collagen, Fibrin, Mast Cell secretions, Bacterial Peptides </li></ul>
  49. 49. Events in Inflammation Figure 15.17.1
  50. 50. Events in Inflammation Figure 15.17.2
  51. 51. Chemical Mediators of Inflammation Table 15.4
  52. 52. Fever <ul><li>A body core temperature over 37  C </li></ul><ul><li>Results when chemicals called Pyrogens trigger the Hypothalamus to increase the body’s core temperature </li></ul><ul><li>Various types of Pyrogens stimulate production of Interleukin 1 (IL-1). These include: </li></ul><ul><ul><li>Bacterial Toxins </li></ul></ul><ul><ul><li>Cytoplasmic contents of bacteria released by Lysis </li></ul></ul><ul><ul><li>Antibody-Antigen Complexes </li></ul></ul>
  53. 53. Fever Production <ul><li>IL-1 production causes the Hypothalamus to secrete Prostaglandin which resets Hypothalamic “Thermostat”. </li></ul><ul><li>Communication with brain initiates temperature ↑ by 1) Muscle Contractions, 2) Increased Metabolic Activity, and 3) Constriction of Blood Vessels (reduce heat loss). </li></ul><ul><li>Chills associated with Fever are due to the reduced blood flow of constricted vessels – signal Fever onset. </li></ul><ul><li>↓ in IL-1 production results in the body’s temperature returning to normal by 1) Sweating, 2) Vasodilation, and 3) ↓ in Metabolic Rate </li></ul><ul><li>Aspirin & Acetaminophen ↓ Fever by blocking Prostaglandin Synthesis. </li></ul>
  54. 54. Benefits of Fever <ul><li>Enhances the effects of Interferons </li></ul><ul><li>Inhibits growth of some microorganisms (when above their Optimum Temperature range) </li></ul><ul><li>May enhance the performance of 1) Phagocytes, and 2) Cells of Specific Immunity </li></ul><ul><li>May also accelerate the process of Tissue Repair </li></ul><ul><li>Adverse Effects of Fever: 1) Denature Proteins 2) Inhibit Nerve Impulses </li></ul>
  55. 55. A Summary of Some Nonspecific Components of the First and Second Lines of Defense Table 15.5