Allergy Flashcards

1
Q

allergy

A

Immediate hypersensitivity (Type I) = the combined immediate and late-phase reactions
=Immediate ->Begins rapidly (min)
-Has Hypersensitivity (pathology consequences)
-Also includes, late-phase reaction (more slowly developing inflammatory component characterized by the accumulation of neutrophils, eosinophils and macrophages

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2
Q

allergens

A

the antigens that elicit immediate hypersensitivity. most them are common environmental proteins, animal products, and chemicals that can modify self proteins

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3
Q

common features shared between all allergic reactions

A

production of IgE antibody, dependent on activation of IL-4 T helper cells (strong IL-4-producing helper T cells responses and produce IgE on exposure to these allergens)
-Requires a priming of the immune response (allergies require sensitization= Previous T cell-dependent allergen-specific IgE production by B cells and binding of IgE to mast cells) mast cells are now sensitive to the antigen and ready to be activated on antigen encounter
-TH2 mediated disease (pathologic features triggered by TH2 cytokines)
-IL-4, IL-5, IL-13 secreted by Th2, TFH, type 2 ILCs and other cells (DTH is type I)
allergic reaction Manifests in different way depending on tissues affected

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4
Q

what is the typical sequence of events in immediate hyper-sensitivity

A
  1. exposure to an antigen
  2. activation of lymphocytes (TH2 cells, IL-4 producing follicular helper T cells and B cells) specific for the antigen
  3. production of IgE antibody
  4. binding of antibody to Fc receptors on mast cells (sensitization)
  5. triggering mast cells by re-exposure to the antigen
  6. results in the release of mediators (vasoactive amines, lipid mediators and cytokines) from mast cells and the subsequent pathologic reaction/late phase reaction
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5
Q

Different mediators initiated by IgE-mediated mast cell activation cause:

A

Vascualr and smooth muscle reactions (immediate)

Recruitment of leukocytes (delayed late-phase)

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6
Q

The amount of IgE produced is directly related to

A

an individuals ability to generate allergen-specific Tfh cels because these cells produce cytokines IL-4 and IL-13 which stimulate B cell class switching to IgE

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7
Q

importance of IgE antibody is that it is the isotype that contains the

A

epsilon heavy chain which binds to specific Fc receptors on mast cells

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8
Q

two important characteristics or allergens (proteins or chemicals bound to proteins)

A
  1. individuals are exposed to them repeatedly
  2. unlike microbes, they do not generally stimulate the innate immune response associated with macrophage and DC secretion of TH1- and TH17-inducing cytokines
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9
Q

The development of allergic disease begins with

A

the differentiation of IL-4–, IL-5–, and IL-13–producing CD4+ helper T cells in lymphoid tissues. (but the development of these cells is not completely known)

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10
Q

the result of the differentiation of IL-4–, IL-5–, and IL-13–producing CD4+ helper T cells in lymphoid tissues is:

A
  • Secretion of IL-25, IL-33 and thymic stromal lymphopoietin
  • Causes DCs to migrate to lymph nodes
  • Drives naïve T cells toward IL-4, IL-5 and IL-13-producing Th2 and Tfh cells
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11
Q

Effector cells of Allergy:

A

Mast cells
Bsaophils: blood granulocytes that have structural and functional similarities to mast cells
Eosinophils
* each have cytoplasmic granules that contain preformed amines and enzymes
*all three produce lipid mediators and cytokines that induce inflammation

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12
Q

how are mast cells activated ?

A

activated by cross-linking of FcεRI molecules

-occurs by binding of multivalent antigens to the IgE molecules that are attached to the Fc receptors on mast cells

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13
Q

Activation of mast cells cells results in 3 types of biological responses:

A
  1. secretion of preformed granule contents by exocytosis (degranulation):
    =activated PKC phosphorylates the myosin light chain component of actin-myosin complexes located beneath the plasma membrane, leading to disassembly of the complex. exocytosis process mediated by members of SNARE protein family
  2. synthesis and secretion of lipid mediators (vascular/smooth muscle response/ immediate reaction)
    - controlled by enzyme PLA2
  3. synthesis and secretion of cytokines (leads to inflammation/late phase reaction)
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14
Q

mediators(molecules released from the activated cells) derived Mast Cells and Eosinophils: two types

A
  1. Performed mediators
    A) Vasoactive amines-histamine (act on blood vessels and smooth muscle) *can cause vasodilation/vascular leak
    B) Granule macromolecules-neutral serine proteases (tryptase/chymase) *contribute to tissue damage and immediate hypersensitivity reactions
  2. Newly synthesized
    A) Lipid mediators (prostaglandin D2)
    B) Cytokines-many
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15
Q

Immediate Reaction

A

demonstrated by the wheal and flare reaction to the intradermal injection of an allergen
-reaction is dependent on IgE and Mast cells (their cytoplasmic granules have been discharged)
wheal= vasodilation and congestion (middle)
flare= leakage of plasma fluid and protein (edema)

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16
Q

Late-Phase Reaction

A

Neutrophils, eosinophils, basophils, and helper T cells
2-4 hours after immediate reaction
-accumulation of inflammatory leukocytes:
Neutrophils, eosinophils, basophils, and helper T cells
-can occur without a detectable preceding immediate hypersensitivity reaction

17
Q

treatment of asthma/bronchioconstriction

A

mediators: mast cell derived leukotrienes and PAF
therapy: reduce mast cell activation with inhibitors (cromolyn-blocks vasoconstriction)
- corticosteroid therapy used to inhibit cytokine synthesis bc it blocks the recruitment of leucocytes

18
Q

Allergy suscepibility

A

Genetic component
Many genes identified by GWAS
Genes in cytokine gene cluster (IL-4, IL-5, IL-13), CD14,β2-adrenergic receptor
Not important to know them…

Environment component
“Building tolerance”
Hygiene hypothesis
Certain viral infections predipose, so…
Too little isn’t good, but too much isn’t good either!