Type IV Hypersensitivity

Type IV Hypersensitivity

Sensitisation phase: Type VI hypersensitivity-Brian Catchpole RVC 2008

Type VI hypersensitivity-Brian Catchpole RVC 2008

Cell mediated hypersensitivity:

Exposure to antigen causes CD4+ T helper cells to be activated leading to colonal expansion (takes 1-2 weeks). On subsiquent exposure with the same antigen sensitised CD4+ T helper cells secrete cytokines which attract and activate macrophages. The macrophages have an increased ability to phagocytose pathogens, which is very important for the clearance of intracellular pathogens. However if antigen persists, the lytic products of the macrophages can damage healthy tissues.

Involves TH-1 releasing cytokines which activate macrophages and other T cells.

• CD4+ T cell mediated:
  • Abnormal activation of macrophages in healthy tissues.
  • Macrophage production of inflammatory mediators and MMP enzymes cause tissue damage.

• CD8+ T cell mediated:
  • Cytotoxic T lymphocytes (CTLs) kill healthy cells mistakenly thinking they are infected by a virus.

3 types:

Contact

• Involves simple chemicals (antigens) which bind to skin proteins:
  • Nickle
  • Rubber
  • Poison ivy

Distinguishing contact from immediate hypersensitivity

	Atopic dermatitis	Contact dermatitis
Pathogenesis	Type I	Type II
Time	20 mins	24-48 hours
Distribution	face, nose, eyes, feet, perineum	hairless regions
Antigens	foods, pollens, fleas, inhaled allergens	chemicals, dyes
Diagnosis	"prick" test	patch test for delayed hypersensitivity
Pathology	mast cells, eosinophils	mononuclear cells

Granulomatous

• Intense activation of T cells, cytokine release and macrophage activation cause necrosis of surrounding tissue, granuloma formation leading to destruction of host tissue.
• Composed of epithelial cell, giant cells and macrophages in response to infection, for example:
  • Mycobacterium tubercle
  • Schistosome eggs
• Granulomas can obstruct normal organ function:
  • Lungs: fills up with cells leading to impaired function
  • Brain/liver: very severe

Tuberculin test

• Injection of intradermal antigen into the skin.
• A skin reaction (infiltration of lymphocytes and monocytes) peaking at 48-72 hours indicates prior exposure to the antigen or ongoing infection.
• It is used for TB testing cattle; the antigen is purified protein derivative-PPD from Mycobacterium tuberculosis.
• Presently in the UK the animal is culled if it has a positive skin reaction.