Principles of Immunology Hypersensitivity and Allergy 4/11/06

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Principles of ImmunologyHypersensitivity and
Allergy4/11/06

• Education is a progressive discovery of our own
  ignorance.
• Will Durant

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Word/Terms List

• Allergens
• Atopy
• Erythroblastosis fetalis
• Reagin
• Rhogam
• Serum sickness
• Tuberculin skin test

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Hypersensitivity and Allergy

• Hypersensitivity-An exaggerated immune response
  that may cause damage to the host. The trigger is
  often an innocuous antigen
• Allergy-A hypersensitive response to an
  environmental antigen. Often presents as hay
  fever, asthma, dermatitis or anaphylaxis.

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Four types of Hypersensitivity

• Type I
• IgE-mediated
• e.g.most common allergies
• Type II
• IgG-mediated
• e.g.ABO transfusion reaction

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Four types of Hypersensitivity

• Type III
• Immune-complex mediated
• e.g.serum sickness
• Type IV
• T cell-mediated delayed type
• e.g.tuberculin reaction

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Type I Hypersensitivity

• Allergens
• Proteins
• Low molecular weight, soluble
• Atopy-Predisposition to type I hypersensitivity
• Higher levels of circulating IgE
• Greater numbers of eosinophils

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Type I Hypersensitivity

• Mechanism
• Allergen is recognized by naïve B cell
• B cell stimulated by T helper cell through IL4
• IgE specific for allergen is recognized by mast
  cell
• Cross linkage of IgE on mast cells
• Mast cell degranulates

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Mast Cell Degranulation

• Leukotrienes
• Smooth muscle contraction vascular permeability
• Platelet activating factor
• Activates platelets
• Histamine
• Vascular permeability smooth muscle contraction
• Cytokines
• IL4- Stimulates T helper response
• IL3- Activates eosinophils
• TNF- Promotes inflammation
• Chemokines
• MIP- Attracts macrophages

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Mast Cell Receptors

• Fc epsilon RI
• Ig superfamily
• Alpha, beta and gamma chains
• Alpha chain
• Two Ig like domains extracellular
• Gamma chain
• Homodimer two intracytoplasmic tails
• ITAMs
• Cross linkages activates PTKs
• Cell signaling leads to degranulation

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Type I Hypersensitivity

• Clinical manifestations
• Allergic rhinitis
• Asthma
• Food allergies
• Systemic anaphylaxis

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Prausnitz-Kustner Reaction

• Described in 1921
• Injected allergen caused specific local reaction
  (Wheal and flare)
• Called reagins
• Later identified in 1960s to be new class of
  antibody
• Rabbit Ab against serum from ragweed sensitive
  individuals could neutralize allergic reaction

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Type II Hypersensitivity

• Cell associated antigens
• Transfusion reactions
• Hemagglutinins
• Complement mediated
• Clinical symptoms include fever, chills, nausea

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Type II Hypersensitivity

• Erythroblastosis fetalis
• Rh fetus born to Rh- mother
• First pregnancy sensitizes
• Subsequent pregnancies result in anti Rh Ab
• Mild to severe anemia in fetus
• Rhogam

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Type II Hypersensitivity

• Drug induced hemolytic anemia
• Some antibiotics can be antigenic
• Bind nonspecifically to RBC surface proteins
• Ab fixes C and lyses RBCs

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Type III Hypersensitivity

• Soluble antigens complexed with Ab
• Deposit in tissue or on walls of blood vessels
• C activation
• Mast cell binds Fc degranulates
• Fc gamma RIII receptors
• Neutrophils drawn to area release of lytic
  enzymes cause type III reaction

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Type III Hypersensitivity

• Serum Sickness
• Response to foreign protein in serum,e.g horse
  serum (tetanus antitoxin)
• Deposition of immune complexes systemically
• Systemic reactions
• Fever, vasculitis, arthritis, nephritis

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Type III Hypersensitivity

• Arthus reaction
• Individual is sensitized to antigen
• Challenge is administered locally
• Reaction occurs locally
• Mast cell mediated

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Type IV Hypersensitivity

• T cell mediated
• T helper 1 cells
• Effector response is through macrophages not T
  cytotoxic cells
• Cytokine mediated
• IL3 Hematopoiesis
• Interferon, TNF, IL 1 Extravasation
• MCAF Attracts macrophages
• MIF Retains macrophages

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