Innate Immunity Cellular Responses

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

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 - 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

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

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

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