Immediate Hypersensitivity: Mechanisms, Manifestations, Management Flashcards Preview

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Flashcards in Immediate Hypersensitivity: Mechanisms, Manifestations, Management Deck (21):
1

What factors contribute to allergic disease?

-genetics
-environment-pollution
-changes in lifestyle: hygiene hypothesis
-occupational exposures
-certain medications

2

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

TH1 --> TH2

3

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

4

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

5

What are examples of non-immunologic reactions?

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

6

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

7

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

-CD40
-IL-4

8

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

9

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)

10

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

11

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

12

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

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

13

What does histamine do?

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

14

effects of histamine on:
-skin
-eye
-nose
-lung

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

15

What does PAF (platelet activating factor) do?

-life-threatening manifestations of immediate hypersensitivity (lethal)

-hypotension
-increased vasc. permeability
-impaired myocardial contractility
-bronchospasm
-coagulopathy

16

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)

17

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

18

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

19

List manifestations of immediate hypersensitivity:

-nausea
-diarrhea
-vomiting
-abdominal cramps
-pruritic rashes
-hives
-angiodema
-asthma/rhinitis
-laryngeal edema
-anaphylaxis

20

Common allergens:

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

21

What are the 3 types of anaphylaxis?

-uniphasic
-biphasic
-protracted