Hypersensitivity can be defined as an exaggerated response of the immune system leading to host tissue damage.
HYPERSENSITIVITY
Hypersensitivity can be defined as an
exaggerated response of the immune system leading to host tissue damage.
However, some of the immune responses described in the hypersensitivity
classification below are, in some circumstances, appropriate responses to
invading antigen. For example, a component in what is an appropriate immune
response to tissue transplant rejection can be defined as a type II
hypersensitivity reaction.
The highly influential Gell and Coombs
classification scheme defines four categories of hypersensitivity:
• Type I—immediate hypersensitivity
This is also called anaphylactic or acute
hypersensitivity. It involves IgE antibody and is mediated via degranulation of
mast cells leading to release of preformed factors which promote an influx of
immune cells to the site of mast cell activation and initiation of a rapid
inflammatory reaction. In the extreme case the inflammatory response extends
beyond the localized site of initiation and affects systemic tissues leading to
life-threatening anaphylactic reactions such as those documented to penicillin,
to peanut antigen, or to bee-sting antigen. Examples of localized type I
hypersensitivity include hay fever. The term ‘allergy’ has become synonymous
with type I hypersensitivity.
• Type II hypersensitivity—antibody-mediated cytotoxicity
This is caused by
antibodies that are directed against cell surface antigens. IgG and IgM are the
key antibodies involved that direct cytotoxic events against the cell surface
with which they interact. The cytotoxic events include activation of the
classical complement pathway leading to the formation of a MAC, and the
attraction and activation of killing cells such as NK cells or phagocytes which
can bind to the antigen–antibody complex via receptors for antibody Fc domains
or complement C3b. Type II hypersensitivity disorders include blood transfusion
reactions arising from mismatch of the blood ABO antigens between donor and
recipient, or haemolytic disease of the newborn. Autoimmune disorders such as
myasthenia gravis, Goodpasture’s syndrome and autoimmune haemolytic anaemias
are initiated by autoantibodies reacting against ‘self ’ tissue.
• Type III hypersensitivity—complex-mediated
This involves the formation of large
antigen–antibody complexes that circulate in the blood, are usually coated by
complement proteins and are removed by phagocytosis. If this process is
compromised for any reason then the antigen–antibody complexes will be
deposited in tissue capillary beds, with kidney deposition being clinically the
most important site. This deposition of high molecular weight antigen–antibody
complexes in the glomerular capillaries of the kidney can lead to a condition
termed glomerulonephritis which involves disruption of the glomerular basement
membrane, destruction of glomeruli and ultimately renal failure which may
necessitate organ transplantation. Systemic lupus erythematosus is a condition
where autoantibodies are directed against the host’s DNA and RNA with
subsequent complement coated immune complexes deposited throughout systemic tissues
such as in the kidney, skin, joints and brain.
• Type IV hypersensitivity—cell-mediated
This results from inappropriate accumulation
of macrophages at a localized site, and may or may not involve the presence of
antigen. Under conditions of ongoing localized infection or inflammation,
macrophages release proteases, which destroy infected or otherwise damaged
tissue. However, with the inappropriate recruitment and/or activation of
excessive numbers of macrophages, continuing damage to normal tissue may
result, leading to chronic inflammation. The recruitment and activation of
macrophages in type IV hypersensitivity is augmented by the activity of helper
T-lymphocytes (specifically the TH1 subpopulation). Examples of type IV
hypersensitivity include granuloma formation and contact dermatitis. Granulomas
are initiated and maintained by the recruitment of macrophages into the site of
a persistent source of antigen or toxic material. A granuloma is a fibrotic
core of tissue composed of tissue cells and macrophages surrounded by
lymphocytes and then further surrounded by layers of calcified collagenous
material. Sarcoidosis is a granulomatous disease of unknown cause but
characterized by granuloma nodule formation in the lung and skin, among other
sites.
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