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Allergy: An Overview
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 than one type of reaction. An allergy is a 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 …….
• Mechanisms of tissue injury are the same as the effector
mechanisms of defense against infectious pathogens • The problem is that these reactions are poorly controlled
Allergy
Risk factor Host factors; heredity, gender, race, and age HLA and non-HLA genes
Environmental factor; infectious diseases during early childhood, environmental pollution, allergen levels and dietary changes.
Allergy
Allergens
• Allergens are nonparasite antigens that can stimulate an hypersensitivity response.
• Allergens bind to IgE and trigger degranulation of chemical mediators.
Characteristics of allergens • Small 15-40,000 MW proteins. • Specific protein components
• Often enzymes. • Low dose of allergen • Mucosal exposure. • Most allergens promote a Th2 immune.
Epidemiologists began to notice differences between the immune systems of city kids and farm kids. Farm kids were less likely to have allergies. David Strachan, an epidemiologist at St. George’s University of London, hypothesize that bacteria were the key to proper develop our immune system.
The Hygiene Hypothesis
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 (Gell and Coombs)
Hypersensitivity Reactions
Allergy
Ig E mediated (Type I hypersensitivity)
Non Ig E mediated
Allergy
Overreaction to an allergen that is contacted through skin,
inhaled through lung, swallowed or injected. Individuals must be previously sensitized
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 serum Vaccines Plant pollens Rye grass Ragweed Timothy grass Birch trees Drugs Penicillin Sulfonamides Local anethetics Salicylates
Foods Nuts Seafood Eggs Peas, beans Milk Insect products Bee venom Wasp venom Ant venom Cockroach calyx Dust mites Mold spores Animal 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
Phases of immediate hypersensitivity reactions
Phases of immediate hypersensitivity reactions. A, Kinetics of the immediate and late-phase reactions. The immediate vascular and smooth muscle reaction to allergen develops within minutes after challenge (allergen exposure in a previously sensitized individual), and the late-phase reaction develops 2 to 24 hours later. The immediate reaction (B) is characterized by vasodilation, congestion, and edema, and the late-phase reaction
(C) is characterized by an inflammatory infiltrate rich in eosinophils, neutrophils, and T cells.
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
Fc Receptor structure
Signal transduction pathway mediated by Antigen binding to IgE
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/ 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 organ Disease Main
symptoms Typical
allergens Route of entery
Lung Asthma Wheezing, dyspnea,
tachypnea
Pollens, house dust, animal
danders
Inhalation
Nose and Eyes Rhinitis, conjunctivitis
Hay fever
Runny nose, redness and
itching of eyes
Pollens Contact with mucous
membrane Skin Eczema (atopic
dermatitis) Urticaria
Pruritic, vesicular lesions Pruritic,
bullous lesions
Uncertain Various foods
Drugs
Uncertain Ingestion Various
Intestinal tract Allergic gastroenteropathy
Vomiting diarrhea
Various food Ingestion
Systemic Anaphylaxis Shock, hypotension,
wheezing
Insect venom;bee
Drugs; penicillin Foods; Peanuts
Sting Various
Ingestion
Type II Hypersensitivity
If plasma cells start producing antibodies that are errantly directed against circulating cells such as RBCs or platelets, these circulating cells can be opsonized. This opsonization targets the cells for destruction by neutrophils and macrophages, eliminating them in the spleen.
Type IV Hypersensitivity Mechanisms of T cell–mediated (type IV)
hypersensitivity reactions. A, CD4+ TH1 cells (and sometimes CD8+ T cells, not shown) respond to tissue antigens by secreting cytokines that stimulate inflammation and activate phagocytes, leading to tissue injury. CD4+ TH17 cells contribute to inflammation by recruiting neutrophils (and, to a lesser extent, monocytes). B, In some diseases, CD8+ cytotoxic T lymphocytes (CTLs) directly kill tissue cells. APC, Antigen-
presenting cell.
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
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 • Anaphylaxis: epinephrine (vasoconstriction,
bronchospasm resolution), oxygen (intubation sometimes required), anti-histamine, glucocorticoids
• Urticaria: anti-histamine, adrenergic agonists • Allergic rhinitis: anti-histamine, adrenergic agonists,
glucocorticoids, Immunotherapy • Asthma:
• Quick relief: ß-adrenergic agonists to release bronchospams • Long-term control: glucocorticoids
Treatment
