Immediate Hypersensitivity: Mechanisms, Manifestations, Management

Question 1

What factors contribute to allergic disease?

Answer 1

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

Question 2

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

Answer 2

TH1 –> TH2

Question 3

What are the 3 types of immediate hypersensitivity reactions?

Answer 3

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

Question 4

Describe Immunologic Non-IgE mediated reactions

Answer 4

• 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

Question 5

What are examples of non-immunologic reactions?

Answer 5

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

Question 6

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

Answer 6

1. Oral allergy syndrome, anaphylaxis, urticaria
2. eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, atopic dermatitis
3. protein-induced, enterocolitis, protein-induced, enteropathy, dermatitis, herpetiforms

Question 7

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

Answer 7

• CD40

- IL-4

Question 8

Describe IgE-mediated reactions:

Answer 8

• 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

Question 9

Describe IgE:

Answer 9

• 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)

Question 10

CT Mast Cell vs. Mucosal Mast Cell:

Answer 10

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

Question 11

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

Answer 11

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

Question 12

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

what various outcomes result from their release?

Answer 12

• 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

Question 13

What does histamine do?

Answer 13

• 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

Question 14

effects of histamine on:

• skin
• eye
• nose
• lung

Answer 14

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

Question 15

What does PAF (platelet activating factor) do?

Answer 15

-life-threatening manifestations of immediate hypersensitivity (lethal)

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

Question 16

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

Answer 16

• PAF: directly correlates (more of this is bad news)

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

Question 17

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

Answer 17

histamine, prostaglandins, PAF, LTC4, LTD4

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

Question 18

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

Answer 18

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

outcome: attract and activate neutrophils and eosinophils

Question 19

List manifestations of immediate hypersensitivity:

Answer 19

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

Question 20

Common allergens:

Answer 20

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

Question 21

What are the 3 types of anaphylaxis?

Answer 21

• uniphasic
• biphasic
• protracted