Immediate Hypersensitivity: Mechanisms, Manifestations, Management Flashcards Preview

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Flashcards in Immediate Hypersensitivity: Mechanisms, Manifestations, Management Deck (21):

What factors contribute to allergic disease?

-changes in lifestyle: hygiene hypothesis
-occupational exposures
-certain medications


Urban lifestyles are more hygienic and cause a shift from ___ to ___ phenotype.

TH1 --> TH2


What are the 3 types of immediate hypersensitivity reactions?

1. Immunologic: IgE-mediated
2. Immunologic: Non-IgE-mediated (substance works directly on mast cells)
3. Non-immunologic


Describe Immunologic Non-IgE mediated reactions

-substance acts directly on mast cells to cause degranulation
-IgE not required
-no prior exposure necessary (sensitization not necessary)
-ex: drugs: muscle relaxants, antibiotics, RCA (contrast agents), protamine, ASA, NSAIDs


What are examples of non-immunologic reactions?

-compliment mediated: C3a, C5a
-reactions to blood products
-reactions to dialysis membranes


1. IgE-mediated:
2. Intermediate:
3. Non-IgE mediated:

1. Oral allergy syndrome, anaphylaxis, urticaria

2. eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, atopic dermatitis

3. protein-induced, enterocolitis, protein-induced, enteropathy, dermatitis, herpetiforms


What signals from T helper cells (Th) to B cells result in IgE production?



Describe IgE-mediated reactions:

-requires prior exposure (initiates IgE isotype switch)
-allergen-specific IgE produced by plasma cells, released to circulation
-binds high affinity receptors on mast cells + basophils
-next exposure to allergen results in mast cell degranulation


Describe IgE:

-binds Fc receptors on basophils and mast cells
-half-life: few days
-protected from proteases by binding to these cells
-sensitization can lasts for months (bound to cells)
-detected by skin prick test or radioallergosorbant test (RAST)


CT Mast Cell vs. Mucosal Mast Cell:

CT Mast cell:
-ubiquitous-long lived >40 days
-3x10^4 IgE receptors
-high histamine content
-heparin and high levels of tryptase

Mucosal Mast cell:
-gut and lung
-T cell dependent
-short lived <40 days
-25x10^5 IgE receptors
-lower histamine content
chondroitin sulphate
-lower tryptase


Describe the order of IgE-dependent release of mediators from mast cells:

Immediate release: histamine, TNF-a, proteases, heparin --> sneezing, nasal congestion, itchy/runny nose, watery eyes, wheezing, bronchoconstriction

Minutes: lipid mediators, prostaglandins, leukotrienes (wheezing, bronchoconstriction)

hours: cytokines produced: IL-4, IL-13--> mucus production, eosinophil recruitment


What are the 3 classes of mediators derived from mast cells?

what various outcomes result from their release?

-preformed, stored in granules (histamine)
-newly formed: leukotrienes, prostaglandins, platelet activating factor
-cytokines produced by activated mast cells/basophils: TNF, IL3, IL4, IL5, IL13, chemokines

-smooth m. contraction, mucus secretion, bronchial spasm, vasodilation, vascular permeability, edema


What does histamine do?

-non-life-threatening aspects of allergic reaction
-inc vascular permeability--> edema
-constricts bronchial sm. m.
-stimulates secretion from nasal, bronchial, gastric glands
-hives, conjunctivitis, rhinitis


effects of histamine on:

-skin: wheal, erythema, pruritis
-eye: conjunctivitis, erythema, pruritis
-nose: nasal discharge, sneeze, pruritis
-lung: bronchospasm of sm. m.


What does PAF (platelet activating factor) do?

-life-threatening manifestations of immediate hypersensitivity (lethal)

-increased vasc. permeability
-impaired myocardial contractility


How do PAF and PAF-AH correlate with anaphylaxis/fatality?

-PAF: directly correlates (more of this is bad news)
-PAF-AH: inverse correlation (less of this is bad news, <20nmol/min/ml)


list the mast cell mediators of the acute phase and outcome:

histamine, prostaglandins, PAF, LTC4, LTD4

Outcome: urticaria, angiodema, pruritis, sm. m. contraction, increased vasc perm. , cramps, diarrhea


list the mast cell mediators of the late phase and outcome:

cytokines (IL4, IL5, TNFa, IL8), LTB4, eotaxin

outcome: attract and activate neutrophils and eosinophils


List manifestations of immediate hypersensitivity:

-abdominal cramps
-pruritic rashes
-laryngeal edema


Common allergens:

-mite feces (digestive enzymes)
-cockroach feces
-animal danders
-insect stings (venom components)
-food proteins


What are the 3 types of anaphylaxis?