NonSpecific Host Defenses

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Chapter 16

• Non-Specific Host Defenses

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• Immunity 2 intrinsic defense systems that act
  both independently and cooperatively
• Functional system rather than an organ system
• Innate or nonspecific system
• Always prepared Responds quickly to all foreign
  substances
• Provides two barricades
• 1st line of defense physical and chemical
  barriers
• 2nd line of defense cellular and molecular
  defenses, fever, and inflammation
• 2. Adaptive or specific system
• 3rd line of defense cell and humeral immunity
• Takes longer attacks specific pathogens

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Innate (nonspecific) Defenses

• Physical barriers
• Chemical barriers
• Cellular defenses
• Inflammation
• Fever
• Molecular defenses

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• Physical and chemical barriers
• 1st line of defense skin and mucosa and their
  secretions
• Unbroken skin is almost an impermeable physical
  barrier
• Skin is heavily keratinized keratin is
  resistant to weak acids, bases and toxins
• Mucosa covers tissues exposed to exterior
• Hairs and mucus serve as mechanical barriers
• Skin and mucosa also secrete a variety of
  protective chemicals
• Acidity of skin and vaginal secretions inhibit
  bacteria growth
• Sebum contains chemicals toxic to bacteria
• Stomach mucosa secretes concentrated Hydrochloric
  Acid and protein digesting enzymes
• Salvia and lacrimal fluid contain the enzyme
  lysozyme
• Sticky mucus traps many microbes

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• Internal Defenses
• 2nd line of defense Cellular defenses,
  inflammation, fever and molecular defenses
• Cellular Defenses
• Phagocytes neutrophils, eosinophils, basophils,
  mast cells and macrophages derived from monocytes
  
• Free macrophages wander in search of debris and
  pathogens
• Fixed macrophages permanent residents of organs
• Kupffer cells in the liver
• Neutrophils become phagocytes when they encounter
  infectious material in tissues
• Eosinophils are weak phagocytes, but are
  important in defense against parasitic worm
  infection
• Mast cells are important in allergic responses
  but also bind to and ingest bacteria
• Basophils release histamines to initiate
  inflammation

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Mechanism of Phagocytosis

• Phagocyte must find pathogen
• Pathogens and damaged tissues release chemicals
• Phagocytes follow the chemical signal
  (chemotaxis)
• Microbe adheres to phagocyte
• Phagocyte ingests pathogen
• Phagocyte forms pseudopod that engulfs microbe
• Phagocytic vesicle forms around microbe
• Phagocyte digests pathogen
• Vesicle fuses with lysosome forming phagolysosome
• Microbe is killed and digested by lysosomal
  enzymes leaving a residual body
• Indigestible materials are removed from cell by
  exocytosis

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• Phagocyte must be able to recognize microbes
  carbohydrate signature
• bacterial capsule prevent recognition and
  adherence
• Adherence is more probable and efficient when
  complement proteins and antibodies coat microbes
• opsonization provide handles to adhere to
• Some pathogens are resistant to lysosomal enzymes
  
• Mycobacteria
• Some pathogens produce toxins
• Destroy phagocytes
• Neutrophils produce antibiotic-like chemicals
  called defensins and an oxidizing chemical like
  bleach
• may destroy themselves releasing it

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• Natural Killer Cells (NK) large granular
  lymphocytes
• Unique type of defensive cells that can lyse and
  kill cancer cells and virus infected cells
• nonspecific eliminate a variety of cells
• Not phagocytic attack microbes membrane by
  releasing cytolytic perforins
• Also release powerful chemicals that enhance
  inflammation

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The Lymphatic System

• 3 major functions
• Collects excess fluid from spaces between body
  cells
• Transports digested fats to the cardiovascular
  system
• Provides many non-specific and specific defense
  mechanisms against disease

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• The lymphatic system consists of two
  semi-independent parts
• Network of lymphatic vessels
• Collect excess interstitial fluid and return it
  to blood stream
• Fluid is picked up by lymphatic capillaries,
  flows into successively larger collecting
  vessels, then through trunks into ducts
• Once fluid enters lymphatic vessels it is called
  lymph
• Various lymphoid tissues and organs
• Lymphocytes, lymph nodes, spleen, thymus,
  tonsils, appendix and peyers patches

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Summary of Lymphatic Functions

• Lymphatic vessels
• Help maintain blood volume
• Lymphatic organs and tissues
• Contain macrophages that remove and destroy
  foreign matter from lymph and blood
• Provide sites from which the immune system can be
  mobilized

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Other Lymphoid Organs
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• Inflammation tissue response to injury
• Prevents spread of infection
• Disposes of debris and pathogens
• Sets the stage for repair
• 4 cardinal signs
• Redness
• Swelling
• Heat
• Pain

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• Inflammation begins with a chemical alarm
• flood of inflammatory chemicals
• Injured tissues, phagocytes, lymphocytes, mast
  cells and blood cells release them
• Histamine, kinins, prostaglandins, complement and
  cytokines
• Induce vasodilatation increases blood flow to
  area resulting in hyperemia swelling with blood
• Responsible for redness and heat
• Exudate (protein rich fluid) seeps out into
  tissues causing edema and presses on local nerve
  endings
• Responsible for swelling and pain

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• Edema is not harmful it is beneficial
• Helps dilute harmful substances
• Brings in large quantities of oxygen and
  nutrients needed for repair
• Allows entry of clotting proteins which form a
  gel like fibrin mesh that isolates injured area
  and prevents spread of bacteria and other harmful
  substances
• Soon after inflammation the damaged area is
  invaded by phagocytes
• Following chemical signals

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Method of Phagocyte Mobilization

• Leukocytosis
• Leukocytosis-inducing factors are released by
  injured cells to promote an increase in the
  number of leukocytes in the blood
• Margination
• Damaged tissue cells form cell adhesion molecules
  (CAMs) called selectins to provide attachment
  site for CAMs on neutrophils (integrins)
• Diapedesis (emigration)
• Neurtophils leave capillaries and enter tissues
• Chemotaxis
• Inflammatory chemicals act as homing devices to
  attract neutrophils to damaged tissues
• May get pus formation
• mixture of dead tissue cells, dead or dying
  neutrophils and both living and dead pathogens

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• Fever
• abnormally high body temperature
• Systemic response to invading pathogens
• Hypothalamus is bodys thermostat
• Usually set at about 360C (980F)
• Pyrogens secreted by leukocytes and macrophages
  signal temp to be reset higher
• High fevers are dangerous due to protein damage
• Mild or moderate is a benefit to body
• Causes spleen to sequester materials necessary
  for bacterial growth, like iron and zinc
• Increased temp speeds up metabolism speeds up
  tissue repair
• May exceed bacterial temperature range for growth
• Some bacterial toxins may be inactivated
• Lets you know you are ill

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• Molecular Defenses
• Interferons (IFNs)
• Secreted by virus infected cells to warn near by
  cells
• Stimulates them to secrete viral blocking
  proteins
• Not virus specific protects against a variety
  of viruses
• Complement group of 20 plasma proteins (C1
  C9)
• When activated, releases chemicals that enhance
  almost all aspects of inflammation
• Also kills microbes through cell lysis
• Our own body cells have an proteins that
  inactivate complement
• Complement can be activated by 2 pathways
• Classical pathway
• Alternative pathway
• Each pathway involves a cascade activating
  complement proteins converging at C3 cutting it
  into
• Initiates cell lysis, promotes phagocytosis and
  inflammation

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