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Type 1Type 1
Hypersensitivity:Hypersensitivity:ImmediateImmediate
HypersensitivityHypersensitivityGroup 5:
Garcia, Vixienne GeiaNatividad, Justine
LorenzNicdao, Jan Kevin
BSMT III-A
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OverviewOverviewType I hypersensitivityreactions result from the
binding of antigen toantigen-specific IgE boundto its Fcreceptor,principally on mast cells.
This interaction causes thedegranulationof mast cellsand the release of
inflammatory mediators.
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OverviewOverviewType I reactions are
commonly caused by
inhaled particulateantigens, of which plantpollens are goodexamples. Type I reactions
have effects on varyingseverity, ranging from arunning nose to breathing
difficulties and even deathby asphyxiation.
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OverviewOverview. Type I hypersensitivity
reactions are also
described as immediatehypersensitivity becausethey occur immediately onexposure to antigen.
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Type 1Type 1
HypersensitivityHypersensitivity
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AllergensAllergensSubstances that can give
rise to wheal and flare
responses in the skin andto the symptoms of allergicdisease are derived frommany different sources.
Almost all are protiens10 000 to 40 000 Daltonsfreely soluble in aqueous
solution
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AllergensAllergensBiological functions
(digestive enzymes, carrier
proteins, calycins andpollen recognitionproteins)
Classified by: Source
Route of Exposure
Nature of Specific Protein
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Common sources of allergens
Inhaled Materials
Plant pollensDander of domesticated animals
Mold sporesFeces of very small animals. .,e g house dust mites
Injected Materials
Insect venomsVaccines
DrugsTherapeutic proteins
Ingested Materials
FoodOrally administered drugs
Contacted MaterialsPlant leaves
Industrial products made from plantsSynthetic chemicals in industrial
products
Metals
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AllergensAllergens Atopy a hereditary
predisposition to thedevelopment of theimmediate
hypersensitivityreactions againstcommon
environmentalantigens
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Immunoglobulin EImmunoglobulin EThe B-cell response leading
to production of IgEoccurs
in 2 stages. In the firststage, a resting B-cellswitches from IgD/IgMproduction to
IgEproduction under theinfluence of IL-4. Th2 cellsproduce IL-4 and Th1 cells
produce IFN-y, which hasan opposing effect.
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Immunoglobulin EImmunoglobulin E The ratio of Th1 to Th2 cellsengaged in an immune
response probablydetermines the level ofIgEproduced. The secondstage of IgE response
proceeds when an IgE-producing B cell developsinto a plasma cell. This iscontrolled by cell surface
protein called FcRII orCD23. FcRII links the B-cellsto dendritic cells and soprevents their destruction by
apoptosis.
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Immunoglobulin EImmunoglobulin EThey are thus free todifferentiate intoplasma cells. FcRIIexpression is
regulated by thepresence of IL-4,which stimulates its
production, and byIgE, which suppressits production.
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Mast CellsMast CellsThere are two
populations of mastcells in rodents andhumans: connective
tissue mast cells andmucosal mast cells.
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Mast CellsMast CellsConnective tissue mast cells
arise from precursors in
fetal liver and bonemarrow.
Connective tissue mast cells
contain many uniformgranules and are rich inhistamine and heparin.
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Mast CellsMast CellsMucosal mast cells have
abundant chondroitin
sulphate and littlehistamine in theirgranules.
Mucosal mast cell proliferatein response to IL-3produced by Tcells.
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BasophilBasophilPeripheral blood
basophilsshould not be
considered simply ascirculating mast cells.
They may, however, bepassively sensitized with
IgE, and they will respondto antigen in a mannerapparently similar to that
of mast cells.
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IgE binding FcIgE binding Fc
ReceptorsReceptors The reaginic activity of
IgE depends on its ability
to bind to a receptorspecific for the Fcregion ofthe heavy chain. Thereare 2 types of IgE receptor:
high affinity (FcRI) andlow affinity (FcRII orCD23).
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IgE binding FcIgE binding Fc
ReceptorsReceptorsHigh affinity receptor(FcRI)
Low affinity receptor(FcRII or CD23)
Mainly found on mastcells and basophils, where
there are from 10^4 to10^5 per cellMultichain receptorconsisting of one alphachain (45-65 kDa) that
binds IgE, and beta chain(32 kDa), and 2 disulfidelinked y chains (20 Kda)that are required forsignal transduction
Found on NK cells,macrophages, dendritic
cells, eosinophils andplateletsIs as selectin and is thusthe only known Abreceptor that do not
belong to theimmunoglobulinsuperfamily
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IgE CrosslinkageIgE Crosslinkage
Initiates DegranulationInitiates DegranulationThe biochemical events that
mediate degranulation of
mast cells and bloodbasophils have manyfeatures in common.
Although mast cells
degranulation generally isinitiated by allergencrosslinkage of bound IgE, anumber of other stimuli can
also initiate the process,including the anaphylatoxins(C3a, C4a and C5a) andvarious drugs.
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ReceptorReceptor
CrosslinkageCrosslinkage IgE-mediateddegranulation begins
when an allergencrosslinks IgE that isbound (fixed) to the Fc
receptor on the surfaceof a mast cell orbasophil. In itself, the
binding of IgE toFcRIapparently has noeffect on a target cell.
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ReceptorReceptor
CrosslinkageCrosslinkageIt is only after allergen
crosslinks the fixed IgE-
receptor complex thatdegranulationproceeds.The importance of
crosslinkage isindicated by theinability of
monovalentallergens,which cannot cross linkthe fixed IgE, to trigger
degranulation.
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Pharmacologic AgentsPharmacologic Agents
that Mediate Type Ithat Mediate Type I
ReactionsReactionsHistamine
Most of biologic effects
of histamine in allergicreactions are mediatedby the binding of
histamine to H1receptors. This bindinginduces contraction ofintestinal and bronchial
smooth muscles,increased permeabilityof venules, andincreased mucussecretion by goblet
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Pharmacologic AgentsPharmacologic Agents
that Mediate Type Ithat Mediate Type I
ReactionsReactionsHistamine
Interaction of histamine
with H2 receptorsincreasesvasopermeabilityand
dilation and stimulatesexocrine glands.Binding of histamine toH2 receptors on mast
cells and basophilssuppressesdegranulation; thus,histamine exertsnegative feedback on
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Pharmacologic AgentsPharmacologic Agents
that Mediate Type Ithat Mediate Type I
ReactionsReactionsLeukotrienes and
Prostaglandins As secondary mediators,
they are not formed untilthe mast cell undergoesdegranulation and the
enzymatic breakdown ofphospholipids in theplasma membrane
An ensuing enzymatic
cascade generates theprostaglandins and theleukotrienes. It thereforetakes a longer time for
biological effects of thesemediators to become
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Pharmacologic AgentsPharmacologic Agents
that Mediate Type Ithat Mediate Type I
ReactionsReactionsLeukotrienes and
ProstaglandinsTheir effects are more
pronounced and longerlasting, however, thanthose of histamines.
Leukotrienes mediatebronchoconstriction,increased vascularpermeability, and mucus
production. Prostaglandin D2 causes
bronchoconstriction
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Pharmacologic AgentsPharmacologic Agents
that Mediate Type Ithat Mediate Type I
ReactionsReactionsCytokines
Human mast cells
secrete IL-4, IL-5, IL-6,and TNF-a. Thesecytokines alter the local
microenvironment,eventually leading tothe recruitment ofinflammatory cells such
as neutrophils andeosinophils.
IL-4 increases IgE
production by B cells
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Pharmacologic AgentsPharmacologic Agents
that Mediate Type Ithat Mediate Type I
ReactionsReactionsCytokines
IL-5 is especially
important in therecruitment andactivation of
eosinophils.The high concentration
of TNF-a secreted bymast cells may
contribute to shock insystemic anaphylaxis.
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Clinical Manifestations OfClinical Manifestations Of
Type I HypersensitivityType I HypersensitivityAll of the clinical signs of
type I hypersensitivity
relate to the release ofvasoactive molecules frommast cells and basophils.
The severity of these
clinical signs depends onthe number and location ofthe mast cells stimulated,
and this in turn dependson the amount and routeof antigen administration.
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Clinical Manifestations OfClinical Manifestations Of
Type I HypersensitivityType I HypersensitivityIf the rate of release of
vasoactive molecules is
greater than the bodysability to respond to rapidchanges to its vascularsystem, the patients
suffers from acuteanaphylaxis oranaphylactic shockand
may die.
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Clinical Manifestations OfClinical Manifestations Of
Type I HypersensitivityType I HypersensitivityIf, on the other hand,
antigen is administered
either locally in smallquantities or slowly, thenthe clinical signs ofhypersensitivity will be
much less severe, sincethe individual will havetime to compensate for the
vascular changes provokedby the mast-cell-derivedmolecules.
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Allergy (HayAllergy (Hay
Fever/Allergic rhinitis)Fever/Allergic rhinitis)Hay fever or allergic
rhinitis this results from
the reaction of airborneallergens with sensitizedmast cells in theconjunctivae and nasal
mucosa to induce therelease ofpharmacologically active
mediators from mast cells;these mediators thencaused localizedvasodilation and increased
capillary permeability.
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Allergy (HayAllergy (Hay
Fever/Allergic rhinitis)Fever/Allergic rhinitis)The symptoms include
watery exudation from the
mucus membranes of theupper respiratory tract andconjunctivae, the naturalconsequence of which
include violent and oftenprotracted sneezing, nasaldischarge, and lacrimation.
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Allergy (Asthma)Allergy (Asthma)Asthma. Airborne or blood-
borne allergens, such as
pollens, dust, fumes, insectproducts, or viral antigens,trigger an asthmatic attack(allergic asthma); in other
cases, an asthmatic attackcan be induced by exerciseor cold, apparently
independently of allergenstimulation (intrinsicasthma).
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Allergy (Asthma)Allergy (Asthma)Asthma is triggered by
degranulation of mast cells
with release of mediators,but instead of occurring inthe nasal mucosa, thereaction develops in the
lower respiratory tract.Airways edema, mucussecretion and
inflammation contribute tothe bronchial constrictionsand to airway obstruction.
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Allergy (FoodAllergy (Food
Allergy)Allergy)Food allergy.The local
reactions to antigens in the
intestine causes smoothmuschleconstriction andeffusion of fluid. This resultsin the intense discomfort
and diarrhea. The allergensmay be absorbed and causemast cell degranulation
elsewhere in the body.
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Allergy (FoodAllergy (Food
Allergy)Allergy)Thus local reactions in the
skin can cause the
development of edematouslesions commonly calledhives or urticaria.Respiratory symptoms such
as asthma may also developas a result of food allergies.
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Allergy (AtopicAllergy (Atopic
Dermatitis)Dermatitis)Atopic dermatitis (allergic
eczema) is an inflammation
disease of skin that isfrequently associated with afamily history of atopy. Thedisease is observed mostfrequently in young children,
often developing duringinfancy. Serum IgElevels areoften elevated. The allergicindividual develops skin
eruptions that areerythematousand filled withpus.
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