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Narrative Review

Vol. 1 No. 1 (1995)

Immune-Mediated Tissue Injury (Hypersensitivity Reactions)

  • Gerald J Prud'homme
November 12, 2020


Hypersensitivity is synonymous with immune-mediated tissue injury. Hypersensitivity reactions occur in several forms and give rise to numerous conditions including allergies, autoimmune disease, allograft rejection, granulomatous inflammation, and a variety of acute or chronic inflammatory disorders (vasculitis, glomerulonephritis, arthritis, pneumonitis, encephalitis, etc.). While hypersensitivity is usually detrimental, in some cases it represents a normal response to a pathogen (e.g., the granulomatous inflammation of tuberculosis).

Several years ago, Gell and Coombs divided hypersensitivity states into four basic types (1), and this classification remains useful today (Table 1). Type I hypersensitivity reactions result from IgE-dependent degranulation of mast cells or basophils. Type II, or "cytotoxic" hypersensitivity, results from the binding of IgG or IgM antibodies to cell membranes or fixed tissue antigens, causing activation of the complement system. Type III, or "immune-complex" hypersensitivity, results from the formation of immune complexes that precipitate in tissues (or form in situ), also with activation of complement. Type IV, or "cell-mediated" reactions, can be subdivided into two basic types: type IV-A is synonymous with delayed-type hypersensitivity (DTH) and usually occurs in response to soluble antigens; type IV-B results from the direct killing of target cells by cytotoxic T lymphocytes (CTL). Stimulation of cells by anti-receptor autoantibodies (such as the anti-TSH receptor antibodies of Graves' disease) has been designated as type V hypersensitivity by some authors. In addition, there are syndromes caused by massive cytokine release that are not usually referred to as hypersensitivity reactions, although (in accord with the definition) they should be included in that category. Examples are anti-CD3 mAb therapy, superantigen- (superAg) induced diseases (toxic shock syndrome, scalded skin syndrome), and shock caused by endotoxins (gram negative septicemia).

Despite the occurrence of tissue injury, it should be understood that hypersensitivity mechanisms evolved as a means of fighting infectious agents. The mechanisms underlying these hypersensitivity states will be described and some clinical examples will be mentioned. In particular, the important role of cytokines, which is an area where considerable progress has occurred in recent years, will be emphasized.


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