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Microbiology Week 11 Lecture

Hypersensitivity reactions are classified into four types, with types I, II, and III being humoral and mediated by antibodies, while type IV is cell-mediated. Type I hypersensitivity is characterized by IgE production in response to allergens, leading to mast cell and basophil degranulation and the release of mediators like histamine, which cause various physiological effects. The document also discusses the roles of primary and secondary mediators, including leukotrienes and cytokines, in the clinical manifestations of type I hypersensitivity.

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15 views14 pages

Microbiology Week 11 Lecture

Hypersensitivity reactions are classified into four types, with types I, II, and III being humoral and mediated by antibodies, while type IV is cell-mediated. Type I hypersensitivity is characterized by IgE production in response to allergens, leading to mast cell and basophil degranulation and the release of mediators like histamine, which cause various physiological effects. The document also discusses the roles of primary and secondary mediators, including leukotrienes and cytokines, in the clinical manifestations of type I hypersensitivity.

Uploaded by

FATIMA SALEEM
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© © All Rights Reserved
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Hypersensitivity

Classification

• Coombs proposed a classification scheme in which hypersensitive


reactions are divided into four types.
• Three types of hypersensitivity occur within the humoral branch and are
mediated by antibody or antigen-antibody complexes: IgE-mediated (type
I), antibody-mediated (type II), and immune complex–mediated (type III).
• A fourth type of hypersensitivity depends on reactions within the cell-
mediated branch, and is termed delayed-type hypersensitivity, or DTH
(type IV).
• Each type involves distinct mechanisms, cells, and mediator molecules.
IgE-Mediated (Type I) Hypersensitivity
• A type I hypersensitive reaction is induced by certain types of antigens referred to as
allergens.
• What distinguishes a type I hypersensitive response from a normal humoral response
is that the plasma cells secrete IgE.
• This class of antibody binds with high affinity to Fc receptors on the surface of tissue
mast cells and blood basophils.
• Mast cells and basophils coated by IgE are said to be sensitized.
• A later exposure to the same allergen cross-links the membrane-bound IgE on
sensitized mast cells and basophils, causing degranulation of these cells (Figure).
• The pharmacologically active mediators released from the granules act on the
surrounding tissues.
• The principal effects—vasodilation and smooth-muscle contraction—may be either
systemic or localized, depending on the extent of mediator release.
There Are Several Components of Type I Reactions

• As depicted in Figure several components are critical to development of type I


hypersensitive reactions.
• Section will consider these components first and then describe the mechanism of
degranulation.
ALLERGENS

• The majority of humans mount significant IgE responses only as a defense against
parasitic infections.
• After an individual has been exposed to a parasite, serum IgE levels increase and
remain high until the parasite is successfully cleared from the body.
• Some persons, however, may have an abnormality called atopy, a hereditary
predisposition to the development of immediate hypersensitivity reactions against
common environmental antigens.
• The IgE regulatory defects suffered by atopic individuals allow nonparasitic antigens to
stimulate inappropriate IgE production, leading to tissue damaging type I
hypersensitivity.
• The term allergen refers specifically to nonparasitic antigens capable of stimulating
type I hypersensitive responses in allergic individuals.
General mechanism underlying a type I hypersensitive reaction. Exposure to an allergen activates B cells to form
IgE secreting plasma cells. The secreted IgE molecules bind to IgE specific Fc receptors on mast cells and blood
basophils. (Many molecules of IgE with various specificities can bind to the IgE-Fc receptor.) Second exposure to the
allergen leads to crosslinking of the bound IgE, triggering the release of pharmacologically active mediators, vasoactive
amines, from mast cells and basophils. The mediators cause smooth-muscle contraction, increased vascular
permeability, and vasodilation.
Common allergens
associated with type I
hypersensitivity
Several Pharmacologic Agents Mediate Type I Reactions

• The clinical manifestations of type I hypersensitive reactions are related to the


biological effects of the mediators released during mast-cell or basophil degranulation.
• These mediators are pharmacologically active agents that act on local tissues as well
as on populations of secondary effector cells, including eosinophils, neutrophils, T
lymphocytes, monocytes, and platelets.
• When generated in response to parasitic infection, these mediators initiate beneficial
defense processes, including vasodilation and increased vascular permeability, which
brings an influx of plasma and inflammatory cells to attack the pathogen.
• On the other hand, mediator release induced by inappropriate antigens, such as
allergens, results in unnecessary increases in vascular permeability and inflammation
whose detrimental effects far outweigh any beneficial effect
Cont.…
• The mediators can be classified as either primary or secondary (Table).
• The primary mediators are produced before degranulation and are stored in the
granules.
• The most significant primary mediators are histamine, proteases, eosinophil
chemotactic factor, neutrophil chemotactic factor, and heparin.
• The secondary mediators either are synthesized after target-cell activation or are
released by the breakdown of membrane phospholipids during the degranulation
process.
• The secondary mediators include platelet-activating factor, leukotrienes,
prostaglandins, bradykinins, and various cytokines.
• The differing manifestations of type I hypersensitivity in different species or different
tissues partly reflect variations in the primary and secondary mediators present.
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HISTAMINE
• Histamine is a major component of mast-cell granules, its biological effects are
observed within minutes of mast-cell activation.
• Once released from mast cells, histamine initially binds to specific receptors on various
target cells. Three types of histamine receptors—designated H1, H2, and H3—have
been identified;
• These receptors have different tissue distributions and mediate different effects when
they bind histamine.
• Most of the biologic effects of histamine in allergic reactions are mediated by the
binding of histamine to H1 receptors.
• This binding induces contraction of intestinal and bronchial smooth muscles, increased
permeability of venules, and increased mucus secretion by goblet cells.
• Interaction of histamine with H2 receptors increases vaso-permeability and dilation and
stimulates exocrine glands. Binding of histamine to H2 receptors on mast cells and
basophils suppresses degranulation; thus, histamine exerts negative feedback on the
release of mediators.
Leukotrienes and Prostaglandins

• As secondary mediators, the leukotrienes and prostaglandins are not formed until the
mast cell undergoes degranulation and the enzymatic breakdown of phospholipids in
the plasma membrane.
• An ensuing enzymatic cascade generates the prostaglandins and the leukotrienes.
• It therefore takes a longer time for the biological effects of these mediators to become
apparent.
• Their effects are more pronounced and longer lasting, however, than those of
histamine.
• The leukotrienes mediate bronchoconstriction, increased vascular permeability, and
mucus production.
• Prostaglandin D2 causes bronchoconstriction.
CYTOKINES

• Adding to the complexity of the type I reaction is the variety of cytokines released from
mast cells and eosinophils.
• Some of these may contribute to the clinical manifestations of type I hypersensitivity.
• Human mast cells secrete IL-4, IL-5, IL-6, and TNF- These cytokines alter the local
microenvironment, eventually leading to the recruitment of inflammatory cells such as
neutrophils and eosinophils.
• IL-4 increases IgE production by B cells. IL-5 is especially important in the recruitment
and activation of eosinophils.
• The high concentrations of TNF- secreted by mast cells may contribute to shock in
systemic anaphylaxis.

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