HYPERSENSITIVITY
HYPERSENSITIVITY
BY YUNDZIR FURQANHYPERSENSITIVITYUndesired/ exaggerated immune
reaction produce by normal immune system due to repeated exposure
to antigenThe cause of this reaction is idiopathic but some has
asserted that it may be a genetic factorAntibody plays an integral
role in forming a cascade of reaction into producing an adverse
effect on its surrounding tissues, forcing an unfavourable
inflammation
HYPERSENSITIVITYDivided into 4 types:
Classification of Immunologic Reaction (Gell And Coombs)
TYPEMEDIATORREACTION1IgEImmediate2IgG, IgM
(Cell-Ag)Cytotoxic3Ag-Ab ComplexImmune complex4T
cellCell-mediatedType 1 (Immediate) HypersensitivityRapid IgE and
mast cell mediated reaction.Reaction presented can be systemic
(systemic anaphylaxis) or localized (asthma, allergy,
rhinitis).Occurs in genetically susceptible individuals upon
exposure to antigen (allergen) through ingestion, inhalation,
injection or direct contact.Allergen may be of a vast variety of
metals, drugs, dust, pollen etc which normally would be harmless to
the body.
Type 1 (Immediate) Hypersensitivity
Type 1 (Immediate) Hypersensitivity
Type 1 (Immediate) Hypersensitivity
Type 2 (cytotoxic) HypersensitivityResult of antibodies direct
reaction towards antigen (self or non-self) on surface of a cell or
tissuesIgG or IgM mediated which activated the complement system2
types : antibody-dependent cytotoxicity and antibody-dependent cell
cytotoxicity (ADCC)Causing either 3 plausible outcome, which
is:Inflammation,Opsonization and phagocytosis, orFunctional
derangements
Type 2 (cytotoxic) HypersensitivityInflammationAntibody(IgG or
IgM) bounds to cell or tissue activated complementProducts of
complement activates macrophageOnce macrophage is activated,
pro-inflammatory mediators, lysosomal enzymes and reactive oxygen
species are releasedNeutrophils are activated in the same timeThis
causes inflammatory reaction
Type 2 (cytotoxic) HypersensitivityOpsonization and
Phagocytosis
Plasma cells start producing antibodies errantly directed
against circulating cells such as blood cellsThese circulating
cells will be opsonized and targeted for destruction by macrophage
(phagocytosed)Type 2 (cytotoxic) HypersensitivityFunctional
derangement
Antibdy may act as an antagonist or competitive antagonist for
variety of receptorThis could be disastrous, particularly if the
receptor is involved in endocrine or neuromuscular signalingFor
example, Pernicous Anaemia:
Type 3 (Immune complex) HypersensitivityOccurs when the immune
complexes form is not completely cleared from the circulationMostly
arise from intermidiate to small sized immune complexed which are
deposited in the vascular wallsThis desposition bring about
inflammatory response which then affects the vascular wallsType 3
(Immune complex) HypersensitivityFactors which increase the risk of
complexes causing disease are: Large excess of antibody for
particular circulating antigenPersistent complexesFast deposition
of complexes into tissues
Antigen-Antibody Complex formed in the blood vesselType 3
(Immune complex) HypersensitivityFactors which influenced Ag-Ab
Complex deposition:Size: Small and medium sized, longer-lived
complexesAb-Ag affinity: higher affinity complexes, dissociates
longer, thus having more time to be lodged in tissueHaemodynamics:
high pressured vascular bed favours complex deposition
Type 3 (Immune complex) HypersensitivityInduced inflammatory
response:Ag-Ab Complex activates the complement systemChemical
mediators releasedIncreased vascular permeabilityChemotaxis of
neutrophils and monocytesMacrophage proceed to phagocytosis and
releasing pro-inflammatory mediators which degrade basement
membrane and extracellular matrix of vascular wall
Type 4 HypersensitivityThe only hypersensitivity that is not
antibody mediated but is cell mediated.It is an excessive immune
reaction by T- cells.Starts hours after contact with antigen and
often last for days. Thus the name delayed hypersensitivity.Divided
into 2 types: Delayed and Cell- mediated hypersensitivityType 4
HypersensitivityDelayed type hypersensitivityActivated Th-1
secretes interferon gamma which stimulates macrophages.Macrophage
produce pro-inflammatory mediators and increase growth factor (GF)
production.GF stimulates proliferation and differentiation of
fibroblast.Resulting in fibrosis and granulomatous
inflammation.
Type 4 HypersensitivityCell-mediated hyspersensitivityBegin with
the activation of CD8+ cytotoxic T cells.Cytotoxic T cell release
enzyme responsible for cell apoptosis signaling.This T cell also
release INF-gamma which influence the recruitment and activation of
macrophagesChronic reaction will result in severe fibrosisThis
reaction plays a major role in organ transplant.
