ALLERGY: AN OVERVIEW

SUBDIVISI HEMATOLOGI

Contents
Allergy

Hypersensitivity
Allergy: IgE Mediated: Type I Immunopathogenesis Performed Mediators Food Hypersensitivity Laboratory Tests Prevention Treatment

Allergy

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.

Hypersensitivity

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.

Classification of Immunologic Reactions (Gel and Coombs)

Hypersensitivity Reactions

Allergy

Ig E mediated (Type I hypersensitivity)

Allergy
Non Ig E mediated

IgE Mediated: Type I

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.

Atopy

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.

Genes Identified to date in Atopy

Common allergens associated with type I hypersenstivity

Proteins
Foreign

Foods
Nuts Seafood Eggs Peas, Milk

serum Vaccines Plant pollens Rye grass Ragweed Timothy grass Birch trees Drugs Penicillin Sulfonamides Local anethetics Salicylates

beans

Insect products
Bee

venom Wasp venom Ant venom Cockroach calyx Dust mites Mold spores Animal hair and dander

Mechanism

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.

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

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 Activation

Mast cell

Minutes
Classic Allergic Reaction Flushing Hypotension Increased mucus production Pruritus Smooth muscle contraction Vascular leakage

Hours

Late phase Reaction Eosinophil infiltration Neutrophil infiltration Fibrin deposition Mononuclear infiltration Tissue destruction

Performed Mediators/ Primary Mediators

Histamine: is one well-known mediator. This mediator acts on histamine 1 (H1) and histamine 2 (H2) receptors to cause: contraction of smooth muscles of the airway and GI tract, increased vascular permeability and vasodilation, nasal mucus production, airway mucus production, pruritus, cutaneous vasodilation, and gastric acid secretion. Serotonin: increased vascular permeability and contraction of smooth Muscles. 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/ Secondary Mediators

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

Important Clinical Aspects of Immediate Hypersensitivity

Main organ
Lung

Disease
Asthma

Main symptoms
Wheezing, dyspnea, tachypnea Runny nose, redness and itching of eyes Pruritic, vesicular lesions Pruritic, bullous lesions Vomiting diarrhea Shock, hypotension, wheezing

Typical allergens
Pollens, house dust, animal danders Pollens

Route of entery
Inhalation

Nose and Eyes

Rhinitis, conjunctivitis Hay fever Eczema (atopic dermatitis) Urticaria

Contact with mucous membrane Uncertain Ingestion Various

Skin

Uncertain Various foods Drugs

Intestinal tract Systemic

Allergic gastroenteropathy Anaphylaxis

Various food Insect venom;bee Drugs; penicillin Foods; Peanuts

Ingestion Sting Various Ingestion

Food Hypersensitivity

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

Food Hypersensitivity

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

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

Immunopathologic responses into the following 7 categories: Inactivation/activation antibody reactions Cytotoxic or cytolytic antibody reactions Immune-complex reactions Allergic reactions T-cell cytotoxic reactions Delayed hypersensitivity reactions Granulomatous 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

Allergic Hypersensitivity: Non IgE Mediated

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.

Comparison of Allergy with other Responses

Result Disease Prophylaxis Antigen source Foreign Foreign Mechanism Immunologic Immunologic Disease Allergy Immunity

Disease
Disease

Self
Foreign

Immunologic
Toxic

Autoimmunity
Toxicity

Laboratory Diagnosis

Skin Tests
IgE-Mediated Allergies

Blood Tests

Skin Tests
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

Laboratory 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.

Nasal smear/ Spirometry

Nasal smear Elevated eosinophil levels can be consistent with

allergic rhinitis. Spirometry or pulmonary function tests offer an objective means of assessingasthma. Peakflow meters can also be used for this and can be used by patients at home to monitor their status

Standardized diagnostic allergens are not available for drugs

Penicillin is the only drug for which a standardized diagnostic allergen exists. While nonstandardized skin

tests can be performed for the minor determinants in

penicillin or for other drugs (ie, by pricking the skin where drug solution has been placed), these tests are only useful if findings are positive.

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

First Generation Antihistamines

Easily cross the bloodbrain barrier.

Sedative and anticholinergic effects (sedating

antihistamines). Short half-lives. Limited use in the treatment of allergic symptoms. Still widely used, mainly as over-the-counter products, often in combination with other drugs

Second Generation Antihistamines

Highly effective treatments for allergic disease Do not cross blood-brain barrier Lack significant CNS & anticholinergic effects

Long half life

Among the most frequently prescribed and

safest drugs - expensive

Other treatments
Nasal steroids must be given before season

relieve nasal blockade Antihistamines combined with anti-leukotriene drugs Avoidance -mattress covers, specialised Hoovers, wood floors,

References &Further Reading

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: 978-0838563007 ISBN-10: 0838563007 Anaphylaxis 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: 978-0838563007 ISBN-10: 0838563007 Adkinson NF Jr. Middletons 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#a0104 Sell S, Rich RR, Fleisher TA, et al, eds. Clinical Immunology: Principles and Practice. ed. St. Louis, Mo: Mosby-Year Book; 1996:449-77

Image Citation

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