Chapter 14 Nonspecific Host Defenses

Defense Mechanisms of the Host  The survival of the host depends upon an elaborate network of defenses that keeps harmful microbes and other foreign materials from penetrating the body  Should they penetrate, additional host defenses are summoned to prevent them from becoming established in tissues  To protect the body against pathogens, the immune system relies on an overlapping network of physical barriers, immunologically active cells, and a variety of chemicals that allow the components of the immune system to coordinate their responses 2

Defense Mechanisms of the Host  The host defenses are a multilevel network of innate, nonspecific protections and specific immunities sometimes known as the first, second, and third lines of defense  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  The interaction and cooperation of these three levels of defense normally provide complete protection against infection 3

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Barriers at the Portal of Entry: A First Line of Defense  A number of defenses are a normal part of the body’s anatomy and physiology  These innate nonspecific defenses can be divided into physical, chemical, and genetic barriers that impede the entry of microbes and foreign agents 5

Physical or Anatomical Barriers at the Body’s Surface  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  vomiting and defecation  nasal hair traps larger particles 6

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 antimicrobial chemical  Vagina has acidic pH 7

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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

Structure and Function of the Organs of Defense and Immunity  The study of all features of the body’s second and third lines of defense is called immunology  Functions of a healthy functioning immune system:  constant surveillance of the body  recognition of foreign material - pathogens  attack and destruction of entities deemed to be foreign 11

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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:  reticuloendothelial system (RES)  extracellular fluid (ECF)  bloodstream  lymphatic system 13

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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 15

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Origin, Composition, and Functions of the Blood  Whole blood consists of plasma and blood cells – red blood cells and white 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 17

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White Blood Cells  Neutrophils % - lobed nuclei with lavender granules; phagocytes  Eosinophils – 1-3% - orange granules and bilobed nucleus; destroy eucaryotic pathogens  Basophils, mast cells – 0.5% - constricted nuclei, dark blue granules; release potent chemical mediators  Lymphocytes – 20-35% - large nucleus B (humoral immunity) and T cells (cell-mediated immunity) involved in the specific immune response  Monocytes, macrophages – 3-7%- large nucleus; phagocytic 20

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Lymphatic System  Provides an auxiliary route for return of extracellular fluid to the circulatory system  Acts as a drain-off system for the inflammatory response  Renders surveillance, recognition, and protection against foreign material 22

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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 24

Lymphatic Vessels  Lymphatic capillaries permeate all parts of the body except the CNS  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 25

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 (Peyer’s patches), MALT (tonsils) 26

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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 28

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Actions of the Second Line of Defense  Recognition  Inflammation  Phagocytosis  Interferon  Complement 30

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) 31

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Inflammatory Response  Classic signs and symptoms characterized by:  Redness – increased circulation and vasodilation in injured tissue 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 34

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36 Insert figure Events in inflammation

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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 38

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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 phagcytosis; 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 40

Phagocytes and Phagocytosis  3 main types of phagocytes:  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  macrophages – derived from monocytes; scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes 41

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Phagocytosis  General activities of phagocytes:  To survey tissue compartments and discover microbes, particulate matter and dead or injured cells  To ingest and eliminate these materials  To extract immunogenic information from foreign matter 44

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Interferon  Small protein produced by certain white blood cells and tissue cells  alpha interferon- lymphocytes and macrophages  beta interferon – fibroblasts and epithelial cells  gamma interferon – 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 46

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Complement  Consists of 26 blood proteins that work in concert to destroy bacteria and viruses  Complement proteins are activated by cleavage  Classical pathway – activated by the presence of antibody bound to microorganism  Alternative pathway – begins when complement proteins bind to normal cell wall and surface components of microorganisms 48

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