Autoimmune Diseases and Allergies

• Autoimmune disease is caused by an immune response targeted at “self” molecules known as a failure of self-tolerance. It is caused by the activation of autoreactive T and B cells as regulatory T cells fail to balance themselves.
• Self tolerance is a failure to respond to self-antigens.
• Immune mediated disease is increasingly common. There is a huge spectrum of disease as lymphocytes respond to a variety of self antigens. Dogs are the most common next to horses and cats. It is not commonly observed in production animals.
• Allergic disease is a hypersensitivity to environmental antigens causing an excessive immune response. It is often mediated by IgE and most involve Type I and Type IV hypersensitivity reaction. There is often an impairment of the T-Reg function.
• Within hypersensitivity reactions, animal must be sensitised, and subsequent exposure leads to hypersensitivity reaction. Responses can be appropriate to eliminate pathogens but are often considered inappropriate if it is excessive.
• Hypersensitivity has four classes:

  • Type I - Immediate
  • Type II – Antibody mediated cytotoxicity
  • Type III – Immune-complex deposition
  • Type IV – Delayed Type Hypersensitivity
• Type I hypersensitivity:

  • Antigens encountered at cutaneous or mucosal surface
  • Can be local or systemic response (anaphylaxis)
  • High levels of antigen specific IgE formed which binds to Fc receptors on mast cells and basophils
  • Subsequent encounters mean the antigen binds to IgE bound to mast cells in tissue and triggers degranulation. Mast cell degranulation occurs very quickly triggering inflammation
  • Bronchoconstriction (contraction of smooth muscle)
  • Itching (pruritis)
  • Recruitment of inflammatory cells (eosinophils and macrophages) takes longer
• Type II hypersensitivity:

  • Sensitisation to antigen expressed on surface of a cell
  • Antibody production
  • IgG or IgM mediated destruction of cell
  • Via complement
  • Via phagocytosis
  • Examples
  • Blood transfusion reactions
  • Basis of some autoimmune disease
• Type III hypersensitivity:

  • Formation and deposition of immune complexes
  • Antibody excess:
  • High concentration of IgG following repeated sensitisation
  • Following repeat exposure antigen rapidly binds and deposition locally to antigen exposure site
  • Inflammation of tissue as result of complement activation
  • Antigen excess:
  • Moderate concentration of IgG
  • High concentration of antigen on subsequent exposure binds and circulates
  • Deposits in small capillaries e.g. glomerulus
  • Inflammation of tissue as result of complement activation
• Type IV hypersensitivity:

  • Cell-mediated, delayed type hypersensitivity (days)
  • Sensitisation:
  • Th1 cells generated in response to antigen
  • Subsequent exposure:
  • Reactivation of T-cells and migrate to site of antigen exposure
  • Attract other inflammatory cells such as macrophages and pro-inflammatory cytokines