Innate Immune System

The innate immune system provides a local and generalised response to infection with a pathogen, and has mechanisms for recognising and destroying pathogens that do not require recognition of specific antigens (unlikely the specific immune system).

 

Definitions

Cytokines are proteins that act like local hormones – send signals and stimulate a response.

Pathogen-Associated Molecular Patterns (PAMPs) are various substances that are unique to pathogens, such as double stranded RNA, unmethylated DNA (from bacteria), mannose-containing carbohydrates (from bacteria) and lipopolysaccharide (from bacteria cell walls).

Toll Like Receptors (TLRs) are the receptors on cells of the innate immune system (most notably macrophages) that allow them to recognise PAMPs.

Opsonins are any molecule that binds to a pathogen or pathogenic material and signals to phagocytes to destroy that pathogen by phagocytosis. I think of them as act like forks, spearing the pathogen on the forked end and attaching to the phagocyte on the handle end, thereby helping the phagocyte to eat the pathogen.

 

Components of the Innate Immune System

  • Macrophages (from Monocytes)
  • Neutrophils
  • Interferons
  • Natural Killer Cells

 

Recognition

Macrophages have Toll-Like Receptors (TLRs) that allow them to recognise features that are generic to pathogens, called pathogen-associated molecular patterns (PAMPs). These molecules are not present on human cells, and therefore the innate immune system recognises that there is a foreign invader into the body and the immune system needs to kick into action.

Macrophages respond to recognising a pathogen by:

  • Phagocytosis
  • Releasing cytokines that cause inflammation
  • Releasing interferons that prevent viral entry and replication in cells

 

Phagocytosis

One key function of the innate immune system is phagocytosis. Phago– means eating and –cytosis relates to cells. Phagocytosis is the process of recognising pathogens or abnormal or infected cells, ingesting them and killing them.

Macrophages, neutrophils and so a lesser extent eosinophils are responsible for phagocytosis. Macrophages are the first line of defence as they are always present in tissues, however once a pathogen invades a tissues and the inflammatory response is started, neutrophils that are circulating in the blood are recruited into the tissue to help with the phagocytic process.

Phagocytosis involves four stages:

  1. Attachment
  2. Ingestion
  3. Killing
  4. Degradation

 

Inflammation

Macrophages respond when they recognise pathogens by releasing various cytokines:

  • Interleukins
  • Colony-stimulating factor
  • Tumour necrosis factor
  • Growth factor
  • Chemokine

These cytokines lead to inflammation, activating various components of the immune system (see next page). Inflammation helps the innate immune system by:

  • Actives more macrophages
  • Recruiting monocytes that differentiate into macrophages when they enter the tissue
  • Recruits and activates neutrophils
  • Recruits and activates natural killer cells
  • Brings opsonins that help macrophages and neutrophils recognise and phagocytose pathogens

 

Interferons

Interferons are cytokines that are produced by macrophages, lymphocytes (particularly natural killer cells), endothelial and epithelial cells. They act by:

  • Blocking viral entry into cells
  • Block viral replication inside cells
  • Activate macrophages and natural killer cells

 

Natural Killer Cells

  • Types of lymphocytes that are not specific to one antigen (unlike T and B cells). They are part of the innate immune system.
  • They can recognise infected or abnormal (tumour / cancerous) cells without requiring MHC or specific antigen receptors.
  • They are also stimulated by interleukin-2 and -12 (a cytokine from activated macrophages)
  • They have two functions:
    • They spray their target with cytokines that either stimulates apoptosis (cell death) in the cell (killing the virus inside) or creates a hole in the cell membrane causing cell lysis (like punching a hole in an inflatable swimming pool).
    • Secretes interferon-gamma (IFN-γ), a cytokine that further activates macrophages.
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