4.1.4 Non-specific Immune Responses

• Vertebrate animals have developed complex mechanisms to defend themselves against the invasion of pathogens
• The different methods of defence can be divided into four categories:
  • Physical: body tissues act as barriers, preventing the entry of pathogens
    • E.g. skin, mucous membrane of the alimentary canal

  • Cellular: cells detect and signal the presence of pathogens. Protective substances are secreted and the pathogens are ingested and digested
  • Chemical: secreted substances generate an inhospitable environment for the growth of pathogens. These substances can trap pathogens, cause them to burst, or prevent them from entering cells and reproducing
  • Commensal organisms: the harmless bacteria and fungi present on and in the body compete with pathogens for nutrients

First line of defence

• A human has three lines of defence
• The first line of defence prevents the entry of pathogens and is comprised of the following:
  • Skin
  • Mucous membranes
  • Expulsive reflexes
  • Chemical secretions

Skin

• Skin posses an outer layer of dry, dead, hardened cells filled with keratin
  • Keratin is a tough fibrous protein

• This layer of cells acts as a physical barrier to pathogens
• There are secretions of sebum that contain fatty acids which have antimicrobial properties
• Evaporation of sweat from the skin leaves behind a salt residue
• The lack of moisture, low pH and high salinity creates an inhospitable environment for the growth of microorganisms

Mucous membranes

• Mucous membranes line the gut, airways and reproductive system
• The mucous membrane consists of epithelial cells and mucus-secreting cells like goblet cells
• Mucus contains lots of glycoproteins with long carbohydrate chains. These chains are what make mucus sticky
• Viruses, bacteria, pollen and dust float about in the air that we breathe in
• Mucus in the airways (trachea, bronchi and bronchioles) can trap these particles
• The particles are then moved towards the back of the throat by cilia
  • Cilia are small hair-like structures on the surface of cells. Some ciliated epithelial cells have motile cilia that beat and move in a wave-like manner to move mucus along the airway

Expulsive reflexes

• When a pathogen irritates the lining of an airway it can trigger an expulsive reflex; a cough or sneeze
• Both a cough and sneeze result in a sudden expulsion of air. This expelled air contains secretions from the respiratory tract along with the foreign particles that have entered

Chemical secretions

• Lysozymes are antimicrobial enzymes that breakdown the cell wall of bacteria
  • These special enzymes are found in body fluids such as blood, tears, sweat, and breast milk

• Hydrochloric acid is produced by the cells that line the stomach
  • The acid creates a low pH inside the stomach which helps to kill any bacteria that has been ingested alongside food
  • The cells of the gut secrete mucus to prevent being damaged by hydrochloric acid

Commensal microorganisms

• On average roughly 1kg of a human's weight is made up of the bacteria on or inside their body
• Candida albicans and E. coli are examples of bacteria commonly found on and in humans
• These microorganisms grow on the skin, in the mouth and intestines however they do not cause disease
  • Their growth is limited by the defence mechanisms

• Hosting these microorganisms can have a major benefit for humans
• They compete with pathogenic microorganisms and prevent them from invading host tissue
• Antibiotics often kill friendly gut bacteria which can allow for opportunistic pathogens to grow

Second line of defence

• When a pathogen manages to evade the first line of defence then the second line of defence will respond
  • The second line of defence involves phagocytic cells and antimicrobial proteins responding to the invading pathogens

• Second-line responses include:
  • Blood clotting
  • Inflammation
  • Wound repair
  • Phagocytosis

Blood clotting

• When the body is wounded it responds rapidly
• A break in the mucous membranes or skin membranes causes the release of molecules that trigger a chemical cascade which results in blood clotting
• Blood clotting prevents excess blood loss, the entry of pathogens and provides a barrier (scab) for wound healing to occur
• The chemical cascade involves a large number of steps and several plasma proteins
  • A small initial stimulus is amplified to produce a large amount of fibrin so that the wound is quickly sealed

The blood clotting cascade

Inflammation

• The surrounding area of a wound can sometimes become swollen, warm and painful to touch; this is described as inflammation
• Inflammation is a local response to infection and tissue damage. It occurs via chemical signalling molecules which cause the migration of phagocytes into the tissue and increased blood flow
• Body cells called mast cells respond to tissue damage by secreting the cell signalling molecule, histamine
• Histamine stimulates the following responses:
  • Vasodilation increases blood flow through capillaries
  • "Leaky" capillaries allow fluid to enter the tissues and creating swelling
  • A portion of the plasma proteins leave the blood
  • Phagocytes leave the blood and enter the tissue to engulf foreign particles
  • Cells release cytokines that trigger an immune response in the infected area

• Cytokines are cell-signalling compounds that stimulate inflammation and an immune response
  • They are small proteins molecules
  • Interleukins are a group of cytokines
  • Interleukin 1 (IL-1) and interleukin 6 (IL-6) promote inflammation
  • IL-1 targets the brain, causing drowsiness and fever

Wound repair

• A scab is formed as a result of blood clotting
• Underneath this scab, there are stem cells that divide by mitosis to heal the wound
• Wound healing occurs in a number of overlapping stages:
  • New blood vessels form
  • Collagen is produced
  • Granulation tissue forms to fill the wound
  • Stem cells move over the new tissue and divide to produce epithelial cells
  • Contractile cells cause wound contraction
  • Unwanted cells die

The process of wound repair involving the formation of granulation tissue

• All of the above are examples of non-specific immune responses
  • Non-specific defences are present in humans from birth. The rapid response is the same for every pathogen; they do not distinguish between pathogens
  • They are not always effective