Nonspecific/Innate 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.
• In the third line of defense, special proteins called antibodies are produced in response to foreign substances called antigens.
• Nonspecific host defense mechanisms are general and serve to protect the body against many harmful substances.
• Examples of First Line of Defense:

  1. Skin
  2. Mucous membrane
  3. Secretion of skin and mucous membrane
• In addition to the skin as a physical barrier, there are other factors (e.g., pH and temperature of skin, perspiration, cilia, and various enzymes in secretions such as lysozyme) that are components of the first line of defense.
• Microbial antagonism – when indigenous microbiota prevent colonization of “new arrivals” as a result of competition for sites and nutrients and production of lethal substances.
• The nose has internal hairs, which act as a physical barrier to infection. Cells in the nose produce mucus . This traps pathogens before they can enter the lungs. When the nose is blown, mucus is removed and any pathogens are trapped within it.
• Human sweat is capable of warding off more than potential friends and lovers. Researchers at Eberhard-Karls University in Tübingen, Germany, have isolated a new antibiotic, dubbed dermcidin, which is secreted in sweat and may serve as a first line of defence against microbial pathogens.
• Examples of second line of defense:

  1. Transferrin
  2. Fever
  3. Interferons
  4. The complement system
  5. Acute-phase proteins
  6. Cytokines
  7. Inflammation
  8. Phagocytosis
• Transferrin – levels of this glycoprotein increase in response to systemic bacterial infections; it binds to iron depriving pathogens of this vital nutrient.
• Fever is stimulated by pyrogenic substances.
• Interferons - these are small antiviral proteins produced by virus-infected cells; they prevent viruses from multiplying.
• Three types of interferons:

  1. alpha
  2. beta
  3. gamma
• The three types of interferons are induced by different stimuli such as viruses, tumors, bacteria, and foreign cells.
• Interferons are not virus-specific, but they are species-specific.
• The complement system is a group of about 30 different proteins found in normal blood plasma — “complementary” to the immune system
• Complement components interact with each other in a stepwise manner known as the complement cascade.
• Opsonization is a process by which phagocytosis is facilitated by the deposition of opsonins (e.g., antibodies or certain complement fragments) onto objects (e.g., pathogens).
• Acute-phase proteins – plasma proteins that increase rapidly in response to infection, inflammation, or tissue injury; (e.g., is C-reactive protein).
• Cytokines - are chemical mediators released from many different types of cells in the body; they enable cells to communicate with each other—within the immune system and between the immune system and other systems of the body.
• Some cytokines (called chemokines) are chemoattractants; they recruit phagocytes to sites where they are needed.
• The term "cytokine" is derived from a combination of two Greek words - "cyto" meaning cell and "kinos" meaning movement. Cytokines are cell signalling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma.
• The three major events in acute inflammation are:

  1. An increase in the diameter of capillaries, (vasodilation) which increases blood flow to the site
  2. ncreased permeability of the capillaries, allowing the escape of plasma and plasma proteins
  3. Exit of leukocytes from the capillaries and their accumulation at the site of injury
• The body responds to any local injury, irritation, microbial invasion, or bacterial toxin by a complex series of events referred to as inflammation.
• The primary purposes of the inflammatory response are to:

  – Localize an infection

  – Prevent the spread of microbial invaders

  – Neutralize any toxins being produced at the site

  – Aid in the repair of damaged tissue
• The four major signs and symptoms of inflammation are redness, heat, swelling (edema), and pain.
• Sequence of Events in Inflammation:

  1. Tissue injury
  2. Vasodilation
  3. Increased permeability
  4. Emigration of leukocytes
  5. Chemotaxis
  6. Phagocytosis
• The accumulation of fluid, cells, and cellular debris at the inflammation site is known as an inflammatory exudate.
• In many inflammatory responses (e.g., arthritis or pancreatitis), there is no exudate and no invading microbes.
• Pyogenic microbes (pus-producing microbes) such as staphylococci and streptococci result in additional pus formation.
• If the exudate is thick and greenish-yellow, containing many live and dead leukocytes, it is known as a purulent exudate or pus.
• Phagocytic white blood cells are called phagocytes, and the process by which they surround and engulf (ingest) foreign material is called phagocytosis.
• The three major categories of leukocytes (white cells) found in blood are:

  1. monocytes
  2. lymphocytes
  3. granulocytes
• The three types of granulocytes are:

  1. eosinophils
  2. basophils
  3. neutrophils
• The most important groups of phagocytes in the human body are macrophages and neutrophils.
• Four Steps in Phagocytosis:

  1. Chemotaxis
  2. Attachment
  3. Ingestion
  4. Digestion
• Capsules initially serve to protect the organism from phagocytosis.
• Some bacteria produce an exoenzyme called leukocidin, which kills phagocytes.