Nonspecific Host Defense Mechanisms

• Host defense mechanisms


  Ways in which the body protects itself from pathogens—referred to as three lines of defense

  
• The first two lines of defense are nonspecific
• The third line of defense, the immune response, is very specific

  
• Antibodies


  Special proteins produced in response to foreign substances called antigens
• Lines of Defense


  1. First line

  2. Second line

  3. Third line
• Categories of Host Defense Mechanisms

  • Nonspecific
  • Specific

  
• Nonspecific host defense mechanisms


  • General and serve to protect the body against many harmful substances
  • Example: innate or inborn resistance

  
• Exact factors that produce innate resistance are not well understood
• Other nonspecific host defense mechanisms

  • Mechanical and physical barriers to invasion
  • Chemical factors
  • Microbial antagonism
  • Fever
  • Inflammatory response
  • Phagocytic white blood cells

  
• First Line of Defense

  • Skin and mucous membranes as physical barriers
  • Cellular and chemical factors (e.g., pH, temperature, perspiration, cilia, enzymes)
  • Microbial antagonism (indigenous microbiota preventing colonization of "new arrivals")
• Second Line of Defense

  • Transferrin (binds to iron depriving pathogens)
  • Fever (stimulated by pyrogenic substances, augments host's defenses)
  • Interferons (small antiviral proteins produced by virus-infected cells)
  • Complement system (group of proteins that interact in a stepwise manner to assist in pathogen destruction)
  • Acute-phase proteins (plasma proteins that increase rapidly in response to infection, inflammation, or tissue injury)
  • Cytokines (chemical mediators that enable cells to communicate)

  
• Inflammation


  1. Increase in capillary diameter (vasodilation)

  2. Increased capillary permeability (allowing escape of plasma and proteins)

  3. Exit of leukocytes from capillaries and accumulation at site of injury
• Purposes of Inflammation


  • Localize an infection
  • Prevent spread of microbial invaders
  • Neutralize any toxins
  • Aid in repair of damaged tissue
• Sequence of Events in Inflammation

  1. Tissue injury

  2. Vasodilation

  3. Increased permeability

  4. Emigration of leukocytes

  5. Chemotaxis

  6. Phagocytosis
• Inflammatory exudate


  Accumulation of fluid, cells, and cellular debris at the inflammation site
• Purulent exudate or pus


  Thick, greenish-yellow exudate containing many live and dead leukocytes
• Pyogenic microbes (pus-producing microbes) such as staphylococci and streptococci result in additional pus formation
• Phagocytosis


  The process by which phagocytic white blood cells (phagocytes) surround and engulf (ingest) foreign material
• Categories of leukocytes (white cells)

  • Monocytes
  • Lymphocytes
  • Granulocytes (eosinophils, basophils, neutrophils)
• Opsonization


  A process by which phagocytosis is facilitated by the deposition of opsonins (e.g., antibodies or certain complement fragments) onto objects (e.g., pathogens)
• Four steps in Phagocytosis

  1. Chemotaxis

  2. Attachment

  3. Ingestion

  4. Digestion
• Capsules initially serve to protect pathogens from phagocytosis (antiphagocytic function)
• Some bacteria produce an exoenzyme called leukocidin, which kills phagocytes
• Some bacteria (e.g., Mycobacterium tuberculosis) are not destroyed within the phagolysosome
• The mechanism by which each pathogen evades digestion by lysosomal enzymes differs from pathogen to pathogen, and is not yet fully understood
• Disorders and conditions that adversely affect phagocytic and inflammatory processes

  • Leukopenia (abnormally low number of circulating leukocytes)
  • Disorders and conditions affecting leukocyte motility and chemotaxis
  • Disorders and conditions affecting intracellular killing by phagocytes (e.g., chronic granulomatous disease, CGD)
• Additional factors that can impair host defense mechanisms

  • Nutritional status
  • Increased iron levels
  • Stress
  • Cancer and cancer chemotherapy
  • Various genetic defects
  • Age
  • AIDS
  • Drugs (e.g., steroids)