Lecture 27; Hypersensitivities I Flashcards
what is a hypersensitivity
Exaggerated, inappropriate or prolonged immune response to antigen
What are two phases of hypersensitivity reactions
- Sensitization
- Effector
Hypersensitivity reactions are recognized based on
- Type of immune response causing tissue injury
- Location of the target antigen
Type I hypersensitivity rxn
Immediate hypersensitivity (IgE)
Type II hypersensitivity rxn
Cytotoxic hypersensitivity IgM or IgG
Type III hypersensitivity reaction
Immune complex mediated cytotoxicity (IgM or IgG)
Type IV hypersensitivity reaction
Delayed type, T cell mediated
Type I immediate hypersensitivity is an inappropriate secretion of
IgE
Which hypersensitivity type is often genetic
Type I
What is the hygiene hypothesis
Prevalence of atopic disorders increases as the environment becomes more hygienic due to lack of microbial diversity
During type I sensitization phase first exposure to antigen activates what Th cells
Th2
What does activation of Th2 cells stimulate
Class switching to IgE via IL-4 and IL-13
When are mast cells considered sensitized
IgE binds FCeRs on surface of mast cells
Where do matura mast cells reside
Connective tissue throughout body
The effector phase occurs during repeat exposure to same allergen that causes cross linking of what
IgE bound FcERs on mast cells
Mast cell activation in effector phase results in
Release of granular contents and synthesis and release of lipid mediators and cytokines
What do mast cell granules contain
Preformed histamine and proteases
What is the major mediated in granule contents
Preformed histamine
Is histamine an early or late phase reaction
Early
What are the biologic effects of histamine
Vasodilation, increased vascular permeability, non-vascular smooth muscle contraction and increased mucus production
What lipid mediators do mast cells release
prostaglandins and leukotrienes
Are lipid mediators part of early or late phase reaction
Early
What are the biologic effects of prostaglandins and leukotrienes
PG’s- amplify pain
LT’s- vasodilate (redness) and increased vascular permeability
What cytokines released from mast cells cause inflammation
TNF and IL-6
What cytokines promote Th2 and IgE
IL-4 and IL-13
What cytokine recruits eosinophils
IL-5
Are cytokines part of late or early phase reaction
Late
What are the biologic effects of eosinophils
Release cytotoxic granules, release lipid mediates and cytokine secretion
What cytokines do eosinophils secrete
IL-12, IL-31 and TNF
Inflammatory responses produce by cytokines recruit what two cell types
Eosinophils and neutrophils
Recruitment of eosinophils and neutrophils can result in damage to what
Tissue
Corticosteroids are used to prevent ____
Damaging inflammation
What is anaphylaxis
Acute, hypersensitive allergic reactions to an antigen
Anaphylactic reactions manifest in different ways depending on ___
Location
Localized anaphylaxis
Local release of mediators, specific clinical manifestations are dependent on site of allergen exposure and location of mast cell activation
What is systemic anaphylaxis
Systemic release of mediators, result from allergen in/spread through bloodstream
Allergic rhinitis and allergic conjunctivitis activate mast cells where
URT and eyes
What are clinical signs of allergic rhinitis and allergic conjunctivitis
Itchy, watery eyes, sneezing, runny nose
What are some treatment options for allergic rhinitis and allergic conjunctivitis
Antihistamines, corticosteroids and antimicrobials if infectious
Allergic asthma activates mast cells where
Lower respiratory tract
What does allergic asthma cause
Bronchoconstriction and increased mucus secretion
What are some symptoms of allergic asthma
Coughing, wheezing, open mouth breathing, and or gasping for breath
What are some treatments for allergic asthma
Bronchodilators (fast acting) and corticosteroids (prevent late phase response)
Atopic dermatitis and urticaria activate mast cells where
Skin
What are some clinical signs of atopic dermatitis and urticaria
Red, dry, itchy, inflamed skin lesions
Treatments for atopic dermatitis
Corticosteroids, antihistamines, cyclosporine A, lokivetmab, and olacitinib
Food allergies cause activation of mast cells where
GI tract
Clinical signs of food allergies
Vomiting, diarrhea, gas
Which allergens often become systemic and can manifest in skin and respiratory tract
Food allergies
What are some common systemic allergens
Drugs, vaccines, food venoms
Systemic anaphylaxis is a medical emergency and the following should be done
Remove inciting substance, stabilize, treat with epinephrine, add adjunctive tx- antihistamines, IV fluids, bronchodilators, corticosteroids
What does epinephrine cause
Vasoconstriction, relax bronchial smooth muscle, increase HR and BP, inhibit mast cell degranulation
How can you test for allergies
Intradermal allergies or immunoassays to measure IgE
How doe allergic immunotherapy work
Administration of low dose of antigen to alter the immune response
AIT results in induction of Tregs to suppress
Mast cells, basophils, eosinophils, Th2 cells, IgE production, tissue inflammation and mucous production, inflammatory Dc’s (make DC’s tolerogenic
