ALLERGY: AN OVERVIEW

Salwa Hassan Teama

Contents

Allergy

Hypersensitivity

Allergy: IgE Mediated: Type I

Immunopathogenesis

Performed Mediators

Food Hypersensitivity

Laboratory Tests

Prevention

Treatment

Type of hypersensitivity reactions of the immune system. Allergy

may involve more the one type of reaction.

An allergy is a immune reaction to something that does not affect most other people. Substances that often cause reactions are:

Pollen Dust mites Mold spores Pet dander Food Insect stings Medicines …….

Allergy

Risk factor

Host factors; heredity, gender, race, and age.

Environmental factor; infectious diseases during early childhood, environmental pollution, allergen levels and dietary changes.

Allergy

Hypersensitivity (hypersensitivity reaction) refers to

undesirable immune reactions produced by the normal immune system.

Hypersensitivity reactions require a pre-sensitized (immune) state of the host.

Hypersensitivity reactions: four types; based on the mechanisms involved and time taken for the reaction, a particular clinical condition (disease) may involve more than one type of reaction.

Hypersensitivity

Classification of Immunologic Reactions (Gel and Coombs)

Hypersensitivity Reactions

Allergy

Ig E mediated (Type I

hypersensitivity)

Non Ig E mediated

Allergy

Overreaction to an allergen that is contact through skin, inhaled through lung, swallowed or injected.

Triggered by harmless substances such as; pollen, dust, animal danders, food, … can also occur as a result of drug or bee stings or stings from other insects (an allergen).

An allergen; an antigen that causes allergy. Either inhaled, ingested, .. Can be complete protein antigens (Pollen and animal dander) or low molecular weight proteins.

IgE Mediated: Type I

Atopy is the genetic predisposition to make IgE antibodies in response to allergen exposure.

Etiology is unknown but there is strong evidence for a complex of genes with a variable degree of expression encoding protein factors.

Allergic rhinitis, allergic athma, atopic dermatitis are the most common manifestation of atopy. Allergic gastroenteropathy is rara. These manifestation may coexist in the same patients at different times. Atopy can be asymptomatic.

Atopy

Genes Identified to date in Atopy

Proteins Foreign serumVaccinesPlant pollensRye grassRagweedTimothy grassBirch treesDrugsPenicillinSulfonamidesLocal anetheticsSalicylates

FoodsNutsSeafoodEggsPeas, beansMilkInsect productsBee venomWasp venomAnt venomCockroach calyxDust mitesMold sporesAnimal hair and dander

Common allergens associated with type I hypersenstivity

While first-time exposure may only produce a mild reaction, repeated exposures may lead to more serious reactions. Once a person is sensitized (has had a previous sensitivity reaction), even a very limited exposure to a very small amount of allergen can trigger a severe reaction.

Most occur within seconds or minutes after exposure to the allergen, but some can occur after several hours, particularly if the allergen causes a reaction after it is partially digested. In very rare cases, reactions develop after 24 hours.

Mechanism

Immunopathogenesis

Both mast cells and basophils are involved in immunopathogenesis of IgE mediated diseases. Mast cells and basophils have a high affinity IgE cell membrane receptors for IgE.

Immediate hypersensitivity reactions are mediated by IgE, but T and B cells play important roles in the development of these antibodies

Mast cell are abundant in the mucosa of the respiratory, gastrointestinal tracts and in the skin, where atopic reaction localize.

Mast cell release mediator cause the pathophysiology of the immediate and late phases of atopic diseases.

Mast Cell

Mast Cell Activation

Mast cell

Classic Allergic ReactionFlushing

HypotensionIncreased mucus production

PruritusSmooth muscle contraction

Vascular leakage

Late –phase ReactionEosinophil infiltrationNeutrophil infiltration

Fibrin depositionMononuclear infiltration

Tissue destruction

MinutesHours

Histamine: is one well-known mediator. This mediator acts on histamine 1(H1) and histamine 2 (H2) receptors to cause: contraction of smoothmuscles of the airway and GI tract, increased vascular permeability andvasodilation, nasal mucus production, airway mucus production, pruritus,cutaneous vasodilation, and gastric acid secretion.Serotonin: increased vascular permeability and contraction of smoothMuscles.Tryptase: is a major protease released by mast cells; its exact role is uncertain, but it can cleave C3 and C3a. Tryptase is found in all human mast cells but in few other cells and thus is a good marker of mast cell activation.Proteoglycans: include heparin and chondroitin sulfate.Chemotactic factors………………….

Performed Mediators/ Primary Mediators

Performed Mediators/ Secondary Mediators

•Platelet activating factor•Leukotriens •Prostaglandinin•Bardykainin•Cytokines•IL1 ,TNF•IL2,IL3,IL4,IL5,L6

Important Clinical Aspects of Immediate Hypersensitivity

Main organDiseaseMain symptoms

Typical allergens

Route of entery

LungAsthmaWheezing, dyspnea,

tachypnea

Pollens, house dust, animal

danders

Inhalation

Nose and EyesRhinitis, conjunctivitis

Hay fever

Runny nose, redness and

itching of eyes

PollensContact with mucous

membrane

SkinEczema (atopic dermatitis)Urticaria

Pruritic, vesicular lesions

Pruritic, bullous lesions

UncertainVarious foods

Drugs

UncertainIngestionVarious

Intestinal tractAllergic gastroenteropathy

Vomiting diarrhea

Various foodIngestion

SystemicAnaphylaxisShock, hypotension,

wheezing

Insect venom;beeDrugs; penicillinFoods; Peanuts

StingVarious

Ingestion

Food Hypersensitivity

Source: http://www.allergycentre.com.my/index.html

Food Hypersensitivity

Source: http://www.allergycentre.com.my/index.html

Immunopathologic responses into the following 7 categories:Inactivation/activation antibody reactionsCytotoxic or cytolytic antibody reactionsImmune-complex reactionsAllergic reactionsT-cell cytotoxic reactionsDelayed hypersensitivity reactionsGranulomatous reactions

This system accounts for the fact that multiple components of the immune system can be involved in various types of hypersensitivity reactions. For example, T cells play an important role in the pathophysiology of allergic reactions . In addition, the term immediate hypersensitivity is somewhat of a misnomer because it does not account for the late-phase reaction or for the chronic allergic inflammation that often occurs with these types of reaction. References & more: http://emedicine.medscape.com/article/136217-overview#a0104

References: Sell S, Rich RR, Fleisher TA, et al, eds. Clinical Immunology: Principles and Practice. ed. St. Louis, Mo: Mosby-Year Book; 1996:449-77

Immunopathologic Response Classification System Proposed by Sell et al., 1996

Hypersensitivity pneumonitis involves inhalation of an antigen. This leads to an exaggerated immune response (hypersensitivity). Type III hypersensitivity and type IV hypersensitivity occur in hypersensitivity pneumonitis.

Allergic contact dermatitis.

…

Allergic Hypersensitivity: Non IgE Mediated

ResultAntigen sourceMechanismDisease

DiseaseForeignImmunologicAllergy

ProphylaxisForeignImmunologicImmunity

DiseaseSelfImmunologicAutoimmunity

DiseaseForeignToxicToxicity

Comparison of Allergy with other Responses

Laboratory Diagnosis

IgE-Mediated Allergies

The cutaneous test (prick test, puncture test epicutaneous test)

Routine diagnosis in diseases (atopic or anaphylactic). A single drop of concentrated aqueous allergen extract placed

on the skin which is then pricked lightly with a needle point at the center of the drop. After 20 minutes the reaction is graded and recorded

Skin Tests

IgE levels may be elevated in patients who are atopic, but the level does not necessarily correlate with clinical symptoms.

The tryptase level can be elevated, which is indicative of mast cell degranulation. False-negative results can occur.

An elevated eosinophil count may be observed in patients with atopic disease.

RAST/CAP RAST/CAP FEIA (fluorenzymeimmunoassay):

measures antigen-specific IgE.

Laboratory Tests

Nasal smear

Elevated eosinophil levels can be consistent with allergic rhinitis.

Spirometry or pulmonary function tests

offer an objective means of assessingasthma. Peak-flow meters can also be used for this and can be used by patients at home to monitor their status

Nasal smear/ Spirometry

Standardized diagnostic allergens are not available for drugs

Prevention

Avoid triggers such as foods and medications,…… that have caused an allergic reaction, even a mild one. This includes detailed questioning about ingredients when eating away from home. Ingredient labels should also be carefully examined.

A medical ID tag should be worn by people who know that they have serious allergic reaction.

If any history of a serious allergic reactions, carry emergency medications (such as diphenihydramine and injectable epinephrine.

Do not use your injectable epinephrine on anyone else. They may have a condition (such as a heart problem) that could be affected by this drug.

Treatment

Allergic diseases: in Medical Immunology .eds ( Tristram G.Parslow, Daniel P. A Stites, Abba I.Terr.and John B. Imboden), 814 pages tenth edition. McGraw-Hill/Appleton & Lange; 10 edition 2001)(March 23, ISBN-13: 978-0838563007ISBN-10: 0838563007Anaphylaxis and Urticaria: in Medical Immunology .eds ( Tristram G.Parslow, Daniel P. A Stites, Abba I.Terr.and John B. Imboden), 814 pages tenth edition. McGraw-Hill/Appleton & Lange; 10 edition 2001)(March 23, ISBN-13: 978-0838563007ISBN-10: 0838563007Adkinson NF Jr. Middleton’s Allergy: Principles and Practice. 6th ed. Philadelphia, Pa: Mosby; 2003.Rakel RE. Textbook of Family Medicine. 7th ed. Philadelphia, Pa: WB Saunders; 2007. Miriam K Anand, Michael A Kaliner, et al., Advances in Immunology. N Engl. J.Med,. vol. 344, No.1. January4, 2001. Available from.http://emedicine.medscape.com/article/136217-overview#a0104Sell S, Rich RR, Fleisher TA, et al, eds. Clinical Immunology: Principles and Practice. ed. St. Louis, Mo: Mosby-Year Book; 1996:449-77

References &Further Reading

SariSabban. Allergy Pathway. 1September 2011The http://en.wikipedia.org/wiki/File:The_Allergy_Pathway.jpg

Wolfgang Ihloff. Allergy skin.30.1.2008. testing. http://en.wikipedia.org/wiki/File:Allergy_skin_testing.JPG

Mast cell. Http://en.wikipedia.org/wiki/File:Mast_cells.jpg Wenliang Zhang. Universty of Geogorgia. Immunology. The immune system..

http://wenliang.myweb.uga.edu/mystudy/immunology/ScienceOfImmunology/Hypersensitivitydiseases.html

Dr. M. Yadav. Food Hypersensitivity. http://www.allergycentre.com.my/index.html

Image Citation