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Principles of Immunology Hypersensitivity and Allergy 4/11/06

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Alpha, beta and gamma chains. Alpha chain. Two Ig like domains; extracellular. Gamma chain. Homodimer; two intracytoplasmic tails ... Fc gamma RIII receptors ... – PowerPoint PPT presentation

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Title: Principles of Immunology Hypersensitivity and Allergy 4/11/06


1
Principles of Immunology Hypersensitivity and
Allergy 4/11/06
  • Education is a progressive discovery of our own
    ignorance.
  • Will Durant

2
Word/Terms List
  • Allergens
  • Atopy
  • Erythroblastosis fetalis
  • Reagin
  • Rhogam
  • Serum sickness
  • Tuberculin skin test

3
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.

4
Four types of Hypersensitivity
  • Type I
  • IgE-mediated
  • e.g.most common allergies
  • Type II
  • IgG-mediated
  • e.g.ABO transfusion reaction

5
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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7
Type I Hypersensitivity
  • Allergens
  • Proteins
  • Low molecular weight, soluble
  • Atopy-Predisposition to type I hypersensitivity
  • Higher levels of circulating IgE
  • Greater numbers of eosinophils

8
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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10
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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12
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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14
Type I Hypersensitivity
  • Clinical manifestations
  • Allergic rhinitis
  • Asthma
  • Food allergies
  • Systemic anaphylaxis

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16
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

17
Type II Hypersensitivity
  • Cell associated antigens
  • Transfusion reactions
  • Hemagglutinins
  • Complement mediated
  • Clinical symptoms include fever, chills, nausea

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20
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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22
Type II Hypersensitivity
  • Drug induced hemolytic anemia
  • Some antibiotics can be antigenic
  • Bind nonspecifically to RBC surface proteins
  • Ab fixes C and lyses RBCs

23
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

24
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

25
Type III Hypersensitivity
  • Arthus reaction
  • Individual is sensitized to antigen
  • Challenge is administered locally
  • Reaction occurs locally
  • Mast cell mediated

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27
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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