Innate Immunity

Describe the factors involved in the process of inflammation and the immune response, including innate and acquired immunity

The innate immune system consists of protective mechanisms which are present life-long, and typically forms the first line of defence against pathogens.

Key features of innate immunity include:

• Immediacy
• Non-specific response
• Not modified by repeat exposures

The innate immune system consists of three components:

• Physicochemical barriers
• Humoral mechanisms
• Cellular Mechanisms

Physicochemical Barriers

These include:

• Skin
• Mucous membranes
  • Mucous
  • Mucociliary elevator
• Gastric acid
• Urination
  Optimised by high flow rates and low residual bladder volumes.

Innate Humoral Mechanisms

Humoral mechanisms describes the role of inflammatory proteins in innate immunity:

• Complement
  The complement system is a complex group of about 25 plasma proteins important in both innate and adaptive immunity.
  • The complement system is activated by:
    • Antigen-antibody complexes
      The 'classical pathway.'
    • Substances in the bacteria cell wall
      The 'alternative pathway.'
  • Complement has a number of inflammatory functions:
    • Destruction of bacteria
      Several complement proteins come together to form a membrane attack complex, which creates large pores in cell membranes, causing water to diffuse in and bacteria to burst.
    • Opsonisation of bacteria
      Bound complement acts as a binding site for phagocytes.
    • Activation of monocytes and phagocytes
    • Chemotaxis
      Attracts leucocytes.
    • Mast cell degranulation
      Augments inflammation.

• Acute-Phase Proteins
  Inflammatory proteins with a number of effects:
  • Opsonisation
  • Inflammatory mediators
    Increase blood flow and delivery of inflammatory cells via three mechanisms:
    • Dilatation and increased capillary permeability
    • Endothelial activation increasing leukocyte adhesion
    • Attraction of neutrophils and monocytes

• Proteolytic enzymes
  Bactericidal enzymes located in saliva, tears, respiratory mucous, and neutrophils.

Innate Cellular Mechanisms

Cellular components of the innate immune system include:

• Mast cells
  Exist in loose connective tissue and mucosa, and contain many intracellular granules of heparin and histamine.

• Leukocytes
  • Neutrophils (60% of all leukocytes)
    Phagocytose bacteria and fungi (15-20 per neutrophil). This process consists of a number of steps:
    • Exit circulation by marginating along capillary border when activated
    • Migrate via chemotaxis towards the tissue insult
    • Phagocytose opsonised bacteria and fungi
    • Kill organisms with a respiratory burst:
      A granule containing hydrogen peroxide, hydroxyl and oxygen radicals fuses with the target cell membrane, destroying both the target and the neutrophil.
  • Monocytes
    Become macrophages when they leave circulation and enter tissue. Macrophages have a lifespan of 2-4 months, and can phagocytose up to 100 bacteria before it dies. Functions include:
    • Phagocytosis and destruction of pathogen
      Especially intracellular pathogens (listeria, mycobacteria), parasites, and fungi.
    • Breakdown of damaged body cells
    • Present antigen to T-helper cells
    • Secretion of inflammatory mediators
  • Eosinophils
    Kill multicellular parasites.
  • Basophils
    Contain heparin and histamine.
  • Lymphocyte
    Subtype of leukocyte important in adaptive immunity. Include:
    • Natural Killer cells
      Active against viral and tumour cells.
    • B cells
    • T cells

References

1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.