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Innate immunity


									   ‫بسم هللا الرحمن الرحيم‬

Atopy and allergy diseases

   Mohamed El-Saeid Suliman

           April 2008

             Allergy/Atopy (Type-I Hypersensitivity)

 Antigen            B-cells         IgE binds     Antigen
                                                              Mast cells
stimulates          release          to mast      binds to
  B-cells             IgE              cells        IgE

                              Allergic reaction                Release
                                                             of mediators
             Allergy/Atopy (Type-I Hypersensitivity)

 Antigen            B-cells         IgE binds     Antigen
                                                               Mast cells
stimulates          release          to mast      binds to
  B-cells             IgE              cells        IgE

 Systemic                     Allergic reaction                 Release
anaphylaxis                                                   of mediators


    Hay fever, Asthma, Atopic dermatitis, Urticaria, Food allergy
                       Allergy/Atopy diseases
• Diseases due to allergic reaction can range from severe reaction (systemic
  anaphylaxis) to localized allergic diseases (hay fever, asthma, atopic
  dermatitis and food allergy).
• Localized allergy occurs when antigen is confined to a particular site based
  on the route of exposure.
• Mast cell degranulation and relaese of mediators is the central mechanism
  of localized reaction.
• "Atopy" refers to localized allergic diseases where there appears to be a
  strong hereditary component, tend to run in families, and often occur
• The genetic basis of atopy is not clearly elucidated.
• However, some studies suggested a link between cytokine genes on
  chromosome 5q and expression of circulating IgE.
• Due to genetic and environmental factors, atopic individuals have higher
  levels of IgE and esonophils.
                         Allergic diseases
• The pathophysiology of allergic diseases divides into two phases.
• Acute phase (the early phase) reaction occurs immediately after
  degranulation and release of mediators.
• This phase can either subside or progress into a "late phase reaction" which
  can substantially prolong the symptoms and result in tissue damage.
• Late phase reaction is due to the migration of eosinophils and other cells to
  the initial site. The reaction is usually seen 2-24 hours after the original
• Release of cytokines plays a role in the persistence of long-term effects.
• The chronic inflammation gets a boost every time a new exposure occurs,
  and it persists even when allergic reaction enters clinical remission.
• Late phase responses seen in allergic asthma are slightly different from
  those seen in other allergic responses, although they are still caused by
  release of mediators, and are still dependent on activity of TH2 cells.
        Types of allergic diseases

• Atopic dermatitis
• Urticaria
• Angioedema
• Food allergy
• Allergic rhinitis
• Allergic conjunctivitis
• Allergic asthma
                         Atopic dermatitis
• Is the most common type of eczema.
• A chronic skin disease characterized by itchy inflamed skin.
• Often occurs together with other atopic diseases (asthma, rhinitis,
• Most common in children and young adults.
• It is a familial and its symptoms can increase or disappear over time.
• Although it is an inherited disease, its primarily aggravated by contact with
  or intake of allergens.
• Atopic dermatitis in older children and adults is often confused with
• The flexural surfaces of the joints (inner sides of elbows and knees) are the
  most commonly affected regions.
Typical sites of atopic dermatitis
                    Atopic dermatitis

Acute atopic dermatitis of the hand
with intense erythema and vesicles.
                                          Subacute lesions of atopic dermatitis
                                          are typically scaly erythematous
                                          papules and plaques.

         (From Logical Images, Inc., Rochester, NY,
                            atopic dermatitis

Severe atopic dermatitis in the popliteal fossae. Note the erythema and oozing of
serous fluid from the most involved areas.
                                               Courtesy of Scott Walsh, MD, FRPCP.
                               Atopic dermatitis

Chronic lesions of atopic dermatitis          Chronic atopic dermatitis with skin
consist of scaly, thickened                   thickening and scaling on the front of the
(lichenified) papules and plaques.            ankle.

 from Williams, W. Atopic Dermatitis. New Engl J Med 2005; 352:2314.
                    Contact dermatitis

dermatitis on the arm and cheek caused by contact with a substance that produced an
allergic reaction (allergen). Contact dermatitis causes redness, itching, and small blisters
    allergic contact dermatitis

Allergic dermatitis caused by hair dye. The skin on the neck is red
(erythematous) and thickened (lichenified).

• Urticaria is also called hives.
• It can be due to local or systemic reactions.
• The release of histamine and other compounds by the cutaneous
  mast cell, in the superficial dermis, and basophils causes the
  appearance of urticaria.
• The usual urticarial lesion is an intensely pruritic, circumscribed,
  raised, erythematous plaque.
• Pruritis is the most common complaint and may cause difficulties
  with sleep or work.
• Individual lesions appear at different locations, may enlarge and
  coalesce, and fade over a few hours without scarring.
             Circumscribed, raised, erythematous plaque

IgE-mediated reactions to contact allergens, medications, stinging insects,
foods and food additives, parasitic infections, and blood products can all
cause acute urticaria.
• Acute urticaria are characterized by a rapid onset and resolution
  within several hours and they can be recurrent.
• Chronic urticaria is defined by the presence of hives, usually on
  most days of the week, for a duration of longer than six weeks.
• The clinical appearance of the lesions of acute and chronic urticaria
  are usually identical.
• About 40 percent of patients with chronic urticaria have associated
                      Allergic angioedema
• It is self-limited, localized swelling, which
  results from extravasation of fluid into interstitial
• It affects the skin and mucosal tissues of the face,
  lips, mouth, and throat, larynx and genitalia.
• typically occurs within minutes to a few hours
  following exposure to foods, drugs, or the stings
  of various insects.
• Urticaria is commonly present in this setting.
• It is most often seen in patients with other
  allergic conditions.
• Allergic angioedema is dependent upon the
  presence of IgE molecules specific to proteins in
  the causative agent.
Angioedema of the uvula
                           Food allergy
• Food allergy refers to an immediate, often dramatic reaction to food
• Caused by intake of certain food (peanuts, eggs, fish, etc).
• Mast cell degranulation and release of mediators leads to localized
  smooth muscle contraction and vasodilatation.
• Often causes nausea, vomiting, abdominal pain and diarrhea.
• Due to increased permeability of mucous membrane of GIT, the
  allergen can absorbed into blood causing skin reaction, such as
  urticaria or asthma.
• Food-induced anaphylaxis: refers to a serious allergic reaction
  following the ingestion of a food, which is generally rapid in onset
  and may progress to death.
• Food-dependent, exercise-induced anaphylaxis: refers to an IgE-
  mediated food-induced anaphylactic reaction that develops only
  when exercise is undertaken within a few hours of ingesting a food.
                      Food intolerance
• Food intolerance is a digestive system response rather than an
  immune system response.
• It occurs when something in a food irritates digestive system
  or when a person is unable to properly digest or breakdown the
• Intolerance to lactose (found in milk) is the most common
  food intolerance.
                            Allergic Rhinitis
• Commonly known as “hay fever”
• It is classified as seasonal if symptoms typically occur at a particular time
  of the year
• Caused by airborne allergens (pollen, grass) that react with IgE-sensitized
  mast cells in the nasal mucosa, respiratory mucosa and/or conjuctiva and to
  basophils in the peripheral blood.
• The release of histamine increases capillary permeability, causes mucus
  secretion, localized vasodilatation leading to congestion and tissue edema
• the symptoms include: sneezing, rhinorrhea, itching of the nose, and palate,
  nasal obstruction, and coughing.
• Once allergic reactions begin, mast cells appear to amplify such reactions
  by releasing also cytokines and induce inflammation (late phase).
                    Allergic Rhinitis

Pollen in the sinus leads to acute bacterial infection and then to
chronic sinusitis
                                                Allergic nasal reactions

                                                   Schematic showing pathways
                                                   (including cells and cytokines)
                                                   underlying early (left) and late
                                                   (right) phase nasal reactions.

Reproduced from deShazo, RD. In: Cecil Textbook of Medicine, 5th ed, Goldman (Ed), 2002.
                      Allergic conjunctivitis
• The signs and symptoms include itching, tearing, conjunctival edema,
  hyperemia, watery discharge, burning sensation, and photophobia.
• Eyelid edema is also common.
• Symptoms are usually bilateral; however, one eye can be affected more
  than the other.
• Allergic conjunctivitis can be subdivided into three specific conditions:
• Acute : a sudden-onset reaction caused by environmental exposure, usually
  to a known allergen, such as cat dander. characterized by intense episodes
  of itching, hyperemia, tearing, chemosis, and eyelid edema.
• Seasonal : pollens and grass.
• Perennial: is a mild, chronic, allergic conjunctivitis related
   to exposure to allergens (usually indoor), such as dust and
   animal danders.
                         Allergic asthma
• Is triggered by allergen induced activation of submucosal mast cells in
  lower respiratory tract.
• Within seconds, leads to bronchial constriction and increase of mucous
  secretion making difficulty in breathing.
• It is commonly caused by the same allergen causing allergic rhinitis and
• The late phase of allergic asthma can evolve into chronic inflammation,
  characterized by presence of TH2 cytokines and eosinophils.
• The presence of TH2 cytokines and eosinophils induces the development of
  metaplasia and secretion of mucous.
• The presence of these cells and chemokines cause airway remodling due to
  thickning of airway walls by hyperplasia and hypertrophy of the smooth
  muscles and mucous glands, and eventually fibrosis.
                     Allergic asthma
• Two main mechanisms have been identified that underlie airway
  obstruction in asthma.
• Type I hypersensitivity, is principally an antibody-mediated reaction that
  mediated by IgE, which produced by activated B cells by IL-4.
  Crosslinking stimulates the release of various mediators and cytokines,
  which together elicit three airway changes that contribute to obstruction,
  airway hyper-responsiveness, goblet-cell metaplasia with mucus
  overproduction and mucosal oedema (see the figure).
• Type IV hypersensitivity, also crucially involves TH2 cells. Recently
  recognized through studies of immunoglobulin-deficient mice and is
  mediated through the TH2 cytokines IL-4 and IL-13 which are present on
  target tissues of the lung, such as smooth muscle and the airway epithelium,
  to elicit airway obstruction more directly.
Pathophysiology of allergic asthma

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