Innate Immunity Cellular Responses

Introduction

Macrophage

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  • If pathogens breach the barriers formed by the skin and mucus membranes, they must be detected and destroyed by cellular and humoral means
  • The cells involved with innate protection are:
    • Blood granulocytes, or Polymorphonuclear Cells
      • Notable for their multi-lobed nuclei
      • Neutrophils: phagocytose bacteria
      • Eosinophils: kill parasites by the release of granules
      • Basophils/ mast cells: kill parasites by the release of granules
    • Blood monocytes: phagocytose bacteria
    • Tissue mast cells and macrophages: phagocytose bacteria
  • Effectively, innate cellular response seeks to hold off the infection until the adaptive response can back it up with a more specific attack

Macrophages

Monocytes - J. Bredl, RVC 2008
  • The role of macrophages in Innate Immunity is to act as primary phagocytes
  • Macrophages are present within tissues and take the form of distinct, tissue-specific populations:
    • Alveolar macrophages
    • Tissue histiocytes
    • Glomerular macrophages
    • Hepatic Küpffer cells
    • CNS microglia
    • Sinus-lining macrophages of the lymph nodes and spleen
  • Monocytes (immature macrophages) are circulating phagocytes
    • Circulate for 6-8 hours
    • Can function as phagocytes within the blood and as newly migrated cells in tissues
    • Chiefly function to replace the various tissue macrophage populations

Neutrophils

Neutrophils - J. Bredl, RVC 2008
  • Neutrophils are the principal, highly active phagocytes in the blood
    • Comprise 30-70% of white blood cells depending on species
    • Kill and digest microbes in a similar way as macrophages
  • Neutrophils can also cause extracellular bacterial killing by disrupting bacterial membranes
    • Secrete small antibacterial peptides
      • E.g. defensins and bactenecins
  • Neutrophils produce vasoactive peptides
    • E.g. histamine and bradykinin
    • Cause a great increase in extravasation of blood granulocytes and monocytes and plasma proteins at the site of infection
  • Neutrophils are the archetypal cell associated with acute inflammation
    • Are attracted to sites of inflammation by:
      • Complement activation
      • Cytokine production
      • Changes to vascular endothelium
    • Neutrophil activation in an inflammatory lesion results in the release of prostaglandins
      • Responsible for vasoactive changes and for pain
  • The accumulation of dead and dying neutrophils at the site of infection is called pus
    • Their removal from the site after the removal of infection is an important step in the resolution of the lesion

Eosinophils

Eosinophil - J. Bredl, RVC 2008
  • Eosinophils are less common than neutrophils, and they are not phagocytic
    • Make up <5% of the leukocytes in normal blood
  • Eosinophil numbers are increased:
    • Slightly during the resolution phase of inflammation
    • Many-fold in parasite-infected animals
      • The presence of a large proportion of eosinophils in a blood smear is highly indicative of parasitaemia
  • Mainly function by targeting the surface of parasites by means of specific antibody or complement
    • Release a large range of toxic molecules that break down the parasite integument
  • Prominent in allergic (anaphylactic) reactions

Basophils / Mast Cells

Basophil - J. Bredl, RVC 2008
  • Basophils/mast cells are principally localised at epithelial surfaces
    • Very small numbers are present in blood
      • Less than 0.5% circulating leukocytes
  • They have two principal functions:
    1. Induction of acute inflammation
      • Trauma and/ or bacterial infection causes the production of cytokines by the mast cells that induce a classical acute inflammatory response
    2. Response to parasite infection
      • Specific IgE binds cells
      • Subsequent contact with antigen causes the mast cells to degranulate
      • Release enzymes and vasoactive substances that can result in a high level of mucus secretion and smooth muscle contraction
  • Also produce factors that influence local host cell physiology
    • Various mediators increase the ratio of phagocyte to microbe