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    Hypersensitivity Rev BW

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    This document discusses the four types of hypersensitivity reactions (Types I-IV). It provides details on: - The mechanisms and defining features of each type, including the roles of antibodies (IgE, IgG, IgM) and T cells. - Examples of conditions that fall under each type, such as allergic rhinitis, asthma, and hemolytic disease of the newborn. - The inflammatory mediators involved in Type I reactions and their effects. - Treatment approaches for different hypersensitivity types, including avoidance, immunotherapy, and anti-IgE therapy.

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    Hypersensitivity Rev BW

    Uploaded by

    Guhan
    123 views34 pages
    This document discusses the four types of hypersensitivity reactions (Types I-IV). It provides details on: - The mechanisms and defining features of each type, including the roles of antibodies (IgE, IgG, IgM) and T cells. - Examples of conditions that fall under each type, such as allergic rhinitis, asthma, and hemolytic disease of the newborn. - The inflammatory mediators involved in Type I reactions and their effects. - Treatment approaches for different hypersensitivity types, including avoidance, immunotherapy, and anti-IgE therapy.

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    This document discusses the four types of hypersensitivity reactions (Types I-IV). It provides details on: - The mechanisms and defining features of each type, including the roles of antibodies (IgE, IgG, IgM) and T cells. - Examples of conditions that fall under each type, such as allergic rhinitis, asthma, and hemolytic disease of the newborn. - The inflammatory mediators involved in Type I reactions and their effects. - Treatment approaches for different hypersensitivity types, including avoidance, immunotherapy, and anti-IgE therapy.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    123 views34 pages

    Hypersensitivity Rev BW

    Uploaded by

    Guhan
    This document discusses the four types of hypersensitivity reactions (Types I-IV). It provides details on: - The mechanisms and defining features of each type, including the roles of antibodies (IgE, IgG, IgM) and T cells. - Examples of conditions that fall under each type, such as allergic rhinitis, asthma, and hemolytic disease of the newborn. - The inflammatory mediators involved in Type I reactions and their effects. - Treatment approaches for different hypersensitivity types, including avoidance, immunotherapy, and anti-IgE therapy.

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    of 34

    Hypersensitivity Reactions

    M. Asghar Pasha, M.D.


    Associate Professor of Medicine and Pediatrics
    Division of Allergy and Immunology
    Department of Medicine
    E-mail: pasham@mail.amc.edu

    OBJECTIVES
    1. To be able to explain the mechanisms of hypersensitivity
    types I-IV and give examples of each.
    2. To be able to explain the distinctive features of the four
    types of hypersensitivity (I-IV).
    3. To be able to list how each hypersensitivity type I-IV is
    treated.

    What is Hypersensitivity?
    Definition, Initiation, & Types
    Definition: An adaptive immune response occurs in an exaggerated or
    inappropriate form to a harmless environmental antigen. Hypersensitivity
    reactions are the result of normally beneficial immune responses acting
    inappropriately, and sometimes cause inflammatory reactions and tissue
    damage.
    Initiation: Hypersensitivity reactions can be provoked by many antigens,
    and the cause of a hypersensitivity reaction will vary from one individual to
    the next. Hypersensitivity is not manifested on first contact with antigen,
    but usually appears on subsequent contact.
    Hypersensitivity Types: There are four types of Hypersensitivity (I, II, III,
    IV). The first three types are antibody-mediated; the fourth is mediated
    mainly by T cells and macrophages.

    Hypersensitivity Type I = Immediate hypersensitivity


    Type I Hypersensitivity: Mediated
    by IgE bound to its Fc receptor on
    mast cells.
    Characterized by an
    allergic
    reaction
    that
    occurs
    immediately following contact with
    antigen referred to as an allergen.
    Allergy: A clinical, immune-mediated
    immediate hypersensitivity reaction to
    a protein antigen (allergen).

    Allergic Rhinitis

    Hypersensitivity Type I: IgE, Heredity, & Common Allergens


    IgE:
    Normal individuals usually
    produce IgE in response to parasitic
    infections. Some individuals have a
    regulatory defect that allows IgE to be
    produced against nonparasitic antigens.
    Atopy: A hereditary predisposition to
    the
    development
    of
    immediate
    hypersensitivity
    reactions
    against
    common environmental antigens. This is
    perhaps the most important determining
    factor.
    Allergen:
    Specifically refers to
    nonparasitic
    antigens
    capable
    of
    stimulating Type I Hypersensitivity.
    Most allergens are small soluble
    proteins; environmental allergens often
    proteases, food allergens heat-stable,
    drugs small chemicals that bind human
    proteins (haptenate) first.

    Hypersensitivity Type I: A Mechanistic Overview


    Mast Cells and Basophils:
    The cells that bind IgE and are
    responsible for the clinical
    manifestations
    of
    Hypersensitivity
    Type
    I.
    Basophils comprise 0.5-1.0% of
    the circulating white blood
    cells. Mast cells are formed in
    the bone marrow and carried
    throughout
    almost
    all
    vascularized tissue where they
    mature.
    The skin contains
    10,000 mast cells/mm3.

    Hypersensitivity Type I: Inflammatory Mediators

    Hypersensitivity Type I: Consequences

    10

    Hypersensitivity Type I: Food/Drug/Hymenoptera Allergy and


    Systemic Anaphylaxis

    Onset within minutes to 2 hours of


    consuming the food
    Hives are commonly seen, skin
    symptoms not always present
    Mild-severe symptoms
    Anaphylaxis is a severe allergic
    reaction that is rapid in onset and
    may cause death
    Two or more organ system
    involvement
    Anaphylaxis can be caused by:
    food allergy
    insect stings
    medications (antibiotics,
    NSAIDs)
    latex

    URTICARIA
    Circumscribed, raised, erythematous and
    pruritic lesions that blanch with pressure
    10-20 % Of general population
    (Sheldon et al; J Allergy 25:525-560)
    (Champion et al; Br J Dermatol 81:588-597)

    0.5-1% persists daily for 6 weeks


    (Zuberbier et al; 2005 EAACI/GA LEN/EDF guideline)

    Common in adults than children


    Female- male ratio

    2-24 hours

    Immediate

    Hypersensitivity Type I:
    Asthma
    Clinical Aspects:
    A common
    disease that effects 5% of Americans
    in the United States. For some
    unknown reason asthma is increasing
    in incidence and severity in the
    United States, especially among
    African-American children in the
    inner-city. The mortality is highest
    among children.

    Congestion
    Edema
    Neutrophils
    T Cells

    Genetics: Atopic individuals are


    most susceptible, but only 10-30%
    get asthma. There appears to be
    multiple genes involved as well as
    environmental factors.
    Environment: A combination of
    cockroach allergy and the presence of
    cockroach allergens has been
    demonstrated to play a role in the
    high incidence of asthma in inner-city
    children. Defects in the public health
    system in these cities has also been
    shown to contribute.
    13

    Hypersensitivity Type I: Skin Prick and Intradermal Test

    Advantages: Low cost screening in a short time.


    High sensitivity.
    Disadvantages: Anaphylaxis (rare), Late phase
    reactions.

    14

    Hypersensitivity Type I: Radioimmunoassay


    Radioimmunosorbent Test: Measures nanogram levels of IgE. IgE is precipitated with anti-IgE
    beads followed by I125-anti-IgE (RIST). This can also be done with allergen-coated beads (RAST).
    RIST

    RAST

    Measures Total IgE

    Measures Allergen-Specific IgE

    15

    Hypersensitivity Type I: Asthma treatment

    16

    Hypersensitivity Type I: Treatment


    Prevention: Currently at equipoise for foods: avoidance or exposure?
    Avoidance: When foods/drugs are involved, strict avoidance. With
    environmental allergens, attempt to minimize exposure to the allergen.

    Subcutaneous Immunotherapy: Injection of Low Dose Ragweed Allergen


    Hyposensitization:
    Repeated
    injections of increasing doses of
    allergen.
    Mechanism: There is a gradual
    switch to higher levels of IgG
    and lower levels of IgE. The
    IgG competes with the IgE for
    allergen forming IgG-allergen
    complexes which are removed
    by phagocytes. A switch from
    Th2 to Th1 cells may also be
    involved.
    17

    IgE-Dependent Release of Inflammatory Mediators

    Allergens

    IgE
    FcRI
    FcRI
    binding site

    Immediate Release
    Granule contents:
    Histamine, TNF-,
    Proteases, Heparin

    Sneezing
    Nasal congestion
    Itchy, runny nose
    Watery eyes

    Over Hours
    Over Minutes
    Lipid mediators:
    Prostaglandins
    Leukotrienes

    Cytokine production:
    Specifically IL-4, IL-13

    Mucus production
    Eosinophil recruitment

    Wheezing
    Bronchoconstriction

    EARLY ALLERGIC REACTION

    LATE ALLERGIC REACTION

    Anti-IgE (Omalizumab)
    FcRI

    IgE

    + Anti-IgE (Omalizumab)

    Allergic Symptomatology

    Hypersensitivity Type II: General


    Description
    Type II Hypersensitivity: Mediated by
    IgG or IgM binding to specific cells or
    tissues.
    Hemolytic Disease of the Newborn (HDNB)

    Enlarged liver and spleen and elevated bilirubin


    20

    Hypersensitivity Type II: Transfusion Reactions


    Mechanism: An individual with one allelic form of blood group antigen can
    recognize other allelic forms as foreign when transfused with them. Binding of
    antibodies to red blood cells activates complement leading to massive intravascular
    hemolysis. Antibodies are due to normal exposure to bacterial antigens similar to
    those on red blood cells.
    Isohemagglutinins: Antibodies to the A,B,O blood groups, usually of the IgM subclass.
    Immediate: A,B,O related. Triggered by IgM antibodies.
    Within hours free hemoglobin is detected in plasma.
    Symptoms include: fever, chills, nausea, blood clotting,
    lower back pain, and hemoglobin in urine.
    Delayed: Usually involves IgG responses to blood group
    antigens other than A,B,O (Rhesus, Kell, Kidd, Duffy),
    following repeated transfusions.
    IgG-dependent
    complement-mediated lysis is less efficient and lysis tends
    to occur at extravascular sites. Thus hemoglobin is not
    usually detected in plasma or urine. Symptoms include:
    fever, low hemoglobin, increased bilirubin, mild jaundice,
    and anemia.
    Treatment: Termination of
    transfusion and diuretics to
    maintain urine flow.

    22

    Hypersensitivity Type II: Hemolytic Disease of The Newborn


    Mechanism: HDNB is caused by maternal IgG antibodies to fetal blood group antigens
    which cross the placenta and destroy fetal red blood cells.
    Erythroblastosis Fetalis: Severe HDNB most commonly occurs when the mother is Rh- and the fetus is Rh+.

    Clinical Manifestations: Mild to severe anemia can develop and become fatal.
    Bilirubin can accumulate in the brain and cause brain damage.

    (24-48 h after delivery)

    Treatment:
    Transfusions until
    or after delivery.
    UV
    light
    to
    remove bilirubin.

    23

    Hypersensitivity Type III: General Description


    Type III Hypersensitivity: Mediated by immune complexes which
    persist and are deposited in a range of tissues and organs. This then
    results in complement and effector-cell-mediated damage.
    Examples (antigen):
    Systemic lupus erythematosus (DNA, nucleoproteins)
    Poststreptococcal glomerulonephritis (streptococcal cell wall antigens)
    Serum sickness (various proteins, i.e. drugs)
    Arthus reaction (various proteins, i.e. mold)

    24

    Hypersensitivity Type III:


    The Arthus reaction
    Clinical Manifestations:
    Insect Bites: In sensitive individuals initially a
    Type I reaction may occur at the site. Four to
    eight hours later, a typical Arthus reaction also
    develops at the site, with pronounced erythema
    and edema.
    Farmers Lung: An intrapulmonary Arthustype reaction which develops after inhalation of
    thermophilic actinomycetes from moldy hay.
    Results from
    Pigeon Fancier s Disease;
    inhalation of a serum protein from pigeons in
    dust derived from pigeon feces.

    25

    Hypersensitivity Type IV: General Description


    Type IV Hypersensitivity: Takes more than 12 hours to develop, and
    involves cell-mediated immune reactions rather than humoral (antibodymediated) immune reactions.
    Classical T cell-mediated inflammatory reaction is called delayed-type
    hypersensitivity (DTH), which is an injurious cytokine-mediated
    inflammatory reaction resulting from the activation of T cells.

    27

    Type IV hypersensitivity reation (Immune response in allergic contact dermatitis)


    Haptens
    Afferent limb

    Efferent limb

    LC

    LC

    IFg

    IL-2
    Th1

    IFNg
    Blood
    vessel

    LC

    GM-CSF

    Th0
    Beltrani et al, Contact dermatitis: Ann
    Allergy Asthma Immunol 1997:78:160-75

    Lymph Node

    Th1
    sensitized
    Th1

    unsensitized

    Hypersensitivity Type IV: The Allergens

    Note: This response is designed to eliminate parasites and intracellular pathogens.


    Problems arise when the response is prolonged as a result of failure to eliminate the
    pathogen.

    29

    Hypersensitivity Type IV: Contact dermatitis


    Contact Dermatitis: This results from small molecules which are not normally immunogenic
    complexing with skin proteins forming a hapten-carrier-like complex. These complexes are then
    presented by professional antigen presenting cells (Langerhan's cells) to TDTH cells.
    Contact Dermatitis-Inducing Agents: Formaldehyde,
    trinitrophenol, nickel, turpentine, cosmetics, hair dye,
    poison oak, and poison ivy.

    Type IV hypersensitivity
    Allergic reaction to
    Rubber gloves
    (Carba Mix
    &
    Thiuram Mix)

    30

    Type IV hypersensitivity reactions


    Diagnosis:
    Patch test for the diagnosis of allergic contact dermatitis

    Treatment:
    Topical steroids
    Systemic steroids

    Penicillin may elicit Hypersensitivity reactions I-IV

    Wheal and Flare


    (Type I)

    Arthus (Less definedType III)

    Red Induration (Hardening)


    (Type IV)

    32

    Hypersensitivity Types I-IV:


    Summary of Distinguishing Features

    33

    Hypersensitivity Reactions

    Thank you!
    M. Asghar Pasha, M.D.
    Associate Professor of Medicine and Pediatrics
    Division of Allergy and Immunology
    Department of Medicine
    E-mail: pasham@mail.amc.edu

    34

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