Type 1 Hypersensitivity

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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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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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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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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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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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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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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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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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Type 1 Hypersensitivity

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