allergy & hypersensitivity hajeer

8/7/2019 allergy & hypersensitivity Hajeer

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Allergy and Hypersensitivity

Ali Hajeer


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What is Hypersensitivity or Allergy?

Hypersensitivity: is an excessive immuneresponse which leads to tissue or organ

damage or dysfunction.The trigger is often an innocuous antigen.

Allergy: is a hypersensitive response to anenvironmental antigen. Such as asthma, hay

fever, dermatitis and anaphylaxis.


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Four types of

hypersensitivity

Type I hypersensitivity: Immediate hypersensitivity,IgE mediated.

Type II hypersensitivity: Cytotoxic hypersensitivity,IgG mediated.

Type III hypersensitivity: Immune complex mediatedhypersensitivity.

Type IV hypersensitivity: Delayed typehypersensitivity, cell mediated (Th1)


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Four Types ofHypersensitivities


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Impact ofallergic diseases

Allergic condition Estimated number

affected (million) USA

Allergic rhinitis 19.6

Chronic sinusitis 32.5

Contact dermatitis & eczema 5.8

12Skin rashes

Asthma 9-12

Anaphylaxis 1-2


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Immunobiology defines allergy as an IgE

response to innocuous antigens (i.e., a type Ihypersensitivity)

Others define all hypersensitivities as allergies(i.e., types I to type IV)

An antigen that causes allergy is an allergen


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Hypersensitivity

Excessive immune response in a sensitized individual(atopic) leading to tissue damage.

Types of Hypersensitivity:

Types I, II, III Immediate, Antibody-mediated.

Type IV Delayed, T cell-mediated.


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Type I hypersensitivity

It is the most common type

It is mediated by IgE

It occurs immediately and disappear rapidly The major problem is functional disorder

rather than tissue damage

The main components are: Allegens Allergen and Antibody (IgE) complex

FcIER on mast cells

FcEIRI on basophils

Eosinophils


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The mechanisms of type I hypersensitivity

1. Allergy induced period

2. Allergy stimulated period

3. Effector period


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Allergy induced period

Allergen entry

Allergen is recognized by BCR on nave Blymphocytes

B cell activation by Th2 cells through IL-4

Production of IgE antibodies

IgE binds to FcIRI on mast cells and basophils


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Allergy stimulated period second exposure

Antigen binding to the IgE on mast cells

Cross-link the FcRI on mast cell

Mast cell activation

Release of mast cell mediators (degranulation) Existing mediators such as histamine Newly synthesized mediators such as leukotrines,

prostaglandins and cytokines.


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Mast cell degranulation by antigen (allergen)

cross-linking ofFcIR-bound IgE

Eosinophils and basophils

may also participate


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Effector period

Is the effect of the mediators

Leukotrines: Increase vascular permeability, vasodilationand smooth muscle contraction

Cytokines e.g. TNF : IL-3 activates eosinophils

IL-4 stimulates T helper

TNF promotes inflammation

Histamine: Increase vascular permeability and smooth

muscle contraction

Chemokines: attracts macrophages

Platelet activating factor: platelet activation

Proteases: cause tissue damage (last step)


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Early phase reaction: occurs within minutes mainly byhistamine, increase vascular permeability,vasodilation and smooth muscle contraction

Late phase reaction: occurs within hours induced bythe synthesis and release of leukotrines,prostaglandines, cytokines, chemokines from theactivated mast cells, inflammation and eosinphils, Tcells and neutrophils infiltration.

Effector period continued


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Compounds Released fromMast Cells upon activation

[antigen (allergen) binding on the surface IgE]

Pre-formed and

in granules

Synthesized

upon mast cell

activation


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Sensitization against allergens andtype-I hypersensitivity

B

cell

Histamine,

tryptase,kininegenase,

ECFA

Leukotriene-B4, C4, D4,

prostaglandin D, PAFNewly

synthesized

mediators

TH2

Mast cells

Plasma

cellIgE


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Allergy (type I hypersensitivity mediated by IgE on mast cells)


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Why? Normally IgE responses are associated with

worm infestations. These responses help evacuate the

places where the worms often live.

Mast cell activation (degranulation) has many effects

Mast cells are most common near

epithelial surfaces (e.g., skin, lungs,gut). Most IgE is on mast cells, not in

the blood


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DustMite

fecal pellet


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The enzymatic activity ofa dust mite fecal protein allows it to

penetrate epithelial tight ju

nctio

ns and indu

ce a TH2 respo

nse


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What are the characteristics ofallergens?

It is not fully understood howor

why, but these type ofantigens

tend to stimulate IL-4production; Il-4 production

tends to lead tomore IL-4

production. IL-4 favors class

switching toIgE (cause allergy)


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Both Genetics and the Environment play a significant roles

in determining who has allergies and which kind ofallergy.

Certain allergies and autoimmunity can be mapped to specific gene loci.


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GeneticsGenetics and EnvironmentEnvironment are important for the development ofallergies

Susceptibility genesSusceptibility genes for asthma (certain alleles make

individuals more susceptible to allergies)


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The hygiene hypothesishygiene hypothesis

ofallergy induction

contends that too clean of

an environment and lackof

infections during childhood

(along with a geneticsusceptibility) promote a

bias of the immune system

toward TH2 and IgE

GeneticsGenetics and EnvironmentEnvironment are important for the development ofallergies

Atopy: a increased

tendency toward type I

hypersensitivity (IgE

allergies)


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Allergy symptoms depend on route ofallergen entry

Can be fatal.Allergy to insect

venom, drugs,

foods and


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Type I hypersensitivity because IgE-mediated

TH2-mediated chronic

airway obstruction

Type IV hypersensitivity

because TH2 involvement

(asthma)


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Allergy treatments

make IgG response

to compete with IgE

desensitizationReverse TH1/TH2 balance(2006)

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