Type III Hypersensitivity

Overview
  • Type III Hypersensitivity is caused by generation of Antibody-Antigen complexes, termed "Immune Complexes", which induce injurious inflammation following deposition in host tissue. The primary feature distinguishing Type III from Type II Hypersensitivity is that in Type III reactions the antibody-antigen complex is pre-formed and circulates prior to deposition whereas in Type II reactions antibody directly binds to antigens which are normal components of the injured tissue.
Pathogenesis
  • Overview
    • Type III Hypersensitivity reactions can be thought of occurring in a number of distinct stages as described below.
  • Formation of Immune Complexes
    • Antigens which induce complex formation can be of endogenous or exogenous origin. Endogenous antigens which frequently cause complex formation with antibodies are host DNA. Exogenous antigens can be pharmacologically administered or due to a microbial source
    • In either case, the antigens bind antibody, resulting in a macro-molecular immune complex which can subsequently precipitate out of plasma and deposit in host tissues.
  • Deposition of Immune Complexes
    • Normally, large immune complexes are cleared by tissue macrophages in the spleen and lymph nodes; however, if the complexes are smaller or macrophages become overwhelmed, the complexes can precipitate out of circulation and deposit in a variety of tissues. Preferred sites of deposition tend to be in the small blood vessels of the kidney, joints, and skin. The glomerulus is one of the most preferred sites of complex deposition since plasma is stringently filtered by the glomerular basement membrane.
  • Inflammatory Reaction
    • Deposited complexes can activate the Classical Pathway of the complement cascade, resulting in the release of C3a and C5a which recruit of neutrophils and macrophages. Additionally, the Fc Region of antibodies within the complex can directly recruit neutrophils and macrophages that in turn cause potent inflammatory damage to the tissue.
Morphology
  • Because circulating immune complexes generally precipitate and deposit within vasculature, the primary histopathological sequelae of Type III Hypersensitivity reactions are found within blood vessels. Generally speaking, a necrotizing vasculitis ensues, dominated by an acute inflammatory picture that ends in fibrinoid necrosis.
Clinical Consequences