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Objectives

After working through this module, you should

be able to:

Differentiate the terms: hypersensitivity,allergy, anergy and atopy.

Explain the immunological mechanismsunderlying type I hypersensitivity reaction.

Describe the principal causes and symptomsassociated with each type of type I

hypersensitivity reaction. Discuss current approaches to the

prevention or relieve of type Ihypersensitivity response.

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Introduction

Definition:

Hypersensitivity

Term used when an immune

response results inexaggerated or inappropriate

reactions harmful to

the host

Allergy

Term which is often equated with

hypersensitivity

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Introduction

Definition:

Anergy

Term used for a state of

unresponsiveness which isspecific for a specific epitope

AtopyTerm used for a strong familialpredisposition for

immediate-hypersensitivity reactions

and is

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Introduction

The immune system is a destructiveorganization in the human body whichconstantly destroys invadingmicroorganisms from the environmentusing mechanisms such as complementfixation, ADCC, cytotoxic T cells, andreactions involving many othercytotoxic factors.

Some of the immune reactions maymayactually damage host tissuesactually damage host tissues due to anover response to certain antigensresulting in hypersensitivity.

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Introduction

Many reactions in hypersensitivityappear to have no apparent beneficialeffect on the human body.

There are 4 different types of hypersensitivity reactions, namelytypes I,II,III and IV; each type carries a

unique mechanism that can causetissue damage.

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HYPERSENSITIVITY REACTIONS

A hypersensitivity reaction may bedefined as:

an immune or inflammatory

response that occurs in anexaggerated or inappropriate form,or in an inappropriate situation

Occurs only following second orsubsequent contact with a particularantigen

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Characteristics of 4 types of hypersensitivity

Type Name Response

I Allergy Ab-mediated (IgE)

II Cytotoxic Ab-mediated (non-IgE, to cell

surfaces)

III Immune complex Ab-mediated (non-IgE, tosoluble molecules)

IV Delayed T cell mediated

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Type I Hypersensitivity

Type I hypersensitivity, also knownas the immediate typehypersensitivity

Is the most common form of theallergic reaction

The response occurs shortly after theexposure of an antigen to the bodywhich had previously been sensitizedto that specific antigen.

Type I hypersensitivity may result in

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TYPE I HYPERSENSITIVITY

An immediate response =anaphylaxis, allergy

Allergens – food, medicines, dust etc.

Basis of Type I response is productionof IgE instead of other antibodyisotypes, regulated by cytokines

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Mechanism of Type IHypersensitivity

antigen

IgE

Mast Cell

Degranulation

Mediators

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Mechanism of Type IHypersensitivity

IgE attaches via the Fc portion toFcε receptor on mast cell and theircirculating counterpart the basophil.

Cross-linking of IgE by the antigenstimulates the mast cell todegranulate and release the

mediators

2 types of mediators

- preformed

- newly synthesized

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PreformedMediators Function Antagonist

Histamine

HeparinProtease

Contraction of smooth muscle

AnticoagulantActivation of kinin andcomplement

Antihistamine

ProtaminenProteaseinhibitor

Eosinophil.Chemotactic.Factor of

anaphylaxis.

Chemotaxis Unknown

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Mediators Function Antagonist

Prostaglandin Inhibitdegranulation

IndometachinAspirin

Leukotrienes Contraction of smoothmuscle

Indometachin

Thromboxane Plateletaggregation

Indometachin

Platelets

activation

Platelet

aggregation

Phospholipas

e

• Newly synthesize mediators

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Clinical examples of type I hypersensitivity. Asthma

Urticaria

Anaphylaxis

How do you diagnose allergies?

Skin testingIgE levels

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i i i

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Principle of treatment with reference tothe stages of type I hypersensitivity

i. Avoidance of the allergen

ii. Medication to relieve symptomsantihistamines, topical nasal steroids,sodium cromoglycate

iii. Immunotherapyallergy immunization or desensitization

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Current approaches to the prevention ofhypersensitivity responses.

Immunotherapy

i. Desensitizationincrease IgG decrease

IgE

ii. recombinant cytokinesbalance Th1 /Th2 activity

f

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References

Roderick Nairn and Matthew Helbert. Immunology

for Medical Students. Elsevier Mosby. 2003.

Stites DP, Terr Al and Parslow TG. MedicalImmunology. 10th Edition, Appleton & Lange,Prentice-hall International Inc. 2001.

Roitt I, Brostoff J and Male D. Immunology. 6th Edition, Gower Medical Publishing, London. 2001

Cedric Mims, Hazel M. Dockrell, Richard V.Goering,Ivan Roitt, Derek Wakelin and Mark Zuckerman.Medical Microbiology. 3rd Edition, Elsevier Mosby.2004.

Marjorie Kelly Cowan and Kathleen Park Talaro.

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