ALLERGY: AN OVERVIEW

Salwa Hassan Teama

 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  Foods
 Foreign serum  Nuts
 Vaccines  Seafood
 Plant pollens  Eggs
 Rye grass  Peas, beans
 Ragweed  Milk
 Timothy grass  Insect products
 Birch trees  Bee venom
 Drugs  Wasp venom
 Penicillin  Ant venom
 Sulfonamides  Cockroach calyx
 Local anethetics  Dust mites
 Salicylates  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

Hours
Minutes
Classic Allergic Reaction
Flushing Late –phase Reaction
Hypotension Eosinophil infiltration
Increased mucus production Neutrophil infiltration
Pruritus Fibrin deposition
Smooth muscle contraction Mononuclear infiltration
Vascular leakage 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 Disease Main Typical Route of entery
symptoms allergens
Lung Asthma Wheezing, Pollens, house Inhalation
dyspnea, dust, animal
tachypnea danders
Nose and Eyes Rhinitis, conjunctivitis Runny nose, Pollens Contact with
Hay fever redness and mucous
itching of eyes membrane
Skin Eczema (atopic Pruritic, Uncertain Uncertain
dermatitis) vesicular Various foods Ingestion
Urticaria lesions Drugs Various
Pruritic, bullous
lesions
Intestinal tract Allergic Vomiting Various food Ingestion
gastroenteropathy diarrhea
Systemic Anaphylaxis Shock, Insect venom;bee Sting
hypotension, Drugs; penicillin Various
wheezing Foods; Peanuts 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 Antigen source Mechanism Disease

Disease Foreign Immunologic Allergy

Prophylaxis Foreign Immunologic Immunity

Disease Self Immunologic Autoimmunity

Disease Foreign Toxic 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. Peak-
flow 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
 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. 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#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
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http://en.wikipedia.org/wiki/File:The_Allergy_Pathway.jpg
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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