Week 10 Part 2 - Asthma and Allergies Continued Flashcards
Allergy Clinical Tests - Skin Prick
Small amounts of potential allergens introduced at skin sites
If allergic, mast cells degranulate
Wheel and flare reaction within 15 minutes
Late phase reaction can occur 6 hours later
Allergy Clinical Tests - Serum Levels of IgE Specific for Allergen
Allergen coupled to an ELISA plate -> serum added -> specific IgE binds allergen -> anti-IgE antibody tagged with a label which can be quantitated
Allergy Clinical Tests - Serum Levels of Total IgE
Anti-IgE coupled to an ELISA plate -> serum added -> second anti-IgE antibody tagged with a label which can be quantitated
Anaphylaxis
Anaphylaxis can be fatal: triggered by allergen introduced into blood or gut or skin
Occurs rapidly: type I hypersensitivity reaction from IgE-mediated release of inflammatory mediators from mast cells and basophils
Plasma histamine is a critical mediator: rises after 5 mins and remains elevated 30-60 mins
-> Massive edema, shock and bronchiole constriction
Plasma Histamine Effects during Anaphylaxis
Increased vascular permeability -> urticaria (hives) and angioedema (skin swelling, mucosa, submucosa)
Increased heart rate, coronary artery vasospasm
Contraction of bronchial tract and GI tract -> wheezing, shortness of breath, nausea, vomiting, diarrhoea
What is the Drug of Choice for Anaphylaxis?
Epinephrine/adrenaline
- relaxes smooth muscle and stops vascular permeability
- improves cardiac output, stopping vascular collapse
Food Allergy Clinical Consequences
Mast cell mediators lead to localised smooth muscle contraction and vasodilation
Vomiting and diarrhoea
Atopic Dermatitis Clinical Consequences
Loss of skin barrier function: filagrin mutations
Allergens enter the skin -> Th2 response
Mast cells induce chemotaxis of inflammatory cells
Mostly eosinophils -> inflammatory skin lesions
Eczema -> increased risk of allergic rhinitis and asthma
Treatment: corticosteroid creams
Allergic Rhinitis Clinical Consequences
Allergens diffuse across mucous membranes of nasal passages
Activate mucosal mast cells
Local edema and nasal discharge of mucus rich in eosinophils
Irritation due to histamine release
Treatment: anti-histamines or intra-nasal corticosteroids
Asthma
Chronic disease of the lower airways, episodes of reversible airflow limitation
Airway hyper-reactivity (wheeze) due to late phase reactions: IL-13, histamine, leukotrienes
- IL-13 stimulates mucus secretion
- bronchial contraction by non-specific stimuli (e.g. histamine)
Late Phase Reactions in Asthma
Eosinophils lead to chronic inflammation of bronchial mucosa
IL-5 essential for development and proliferation of eosinophils
IL-5, IL-4, IL-13 and eotaxin regulate eosinophil accumulation in tissues
Mucus build-up, edema, sloughing of epithelium
-> Occlusion of bronchial lumen
Features of Inhaled Allergens that Promote Priming of the Th2 Cells that Drive the IgE Response
Molecular type - proteins, because only they induce T cell responses
Function - many allergens are proteases
Low dose - favours activation of IL-4 producing CD4 T cells
Low molecular mass - allergen diffuses out of particle into mucus
High solubility - allergen is readily eluted from partcile
High stability - allergen survives in desiccated particle
Contains peptide that bind host MHC class 2 - necessary for T cell priming
Asthma Allergic vs Non-Allergic
Non-allergic asthma: exposure to air pollution, cigarette smoke, diesel particles, infection
Innate lymphoid cells (ILCs)
- cells that parallel types of T cells in adaptive immunity
- however, ILCs lack antigen-specific receptors and react to a wide range of innate signals
ILC2s: non-allergic asthma
- secrete large quantities of IL-5, IL-13 and have receptors for IL-33 and IL-25
- function similar to Th2 cells
Non-Allergic Asthma Overview
Irritant or infection acts on lung epithelium
Triggers release of IL-33
Activates ILC2s through IL-33 receptors -> type 2 cytokines IL-5 and IL-13
Induce inflammatory cell infiltration, mucus production and airway hyper-responsiveness
