15. Lung immunology Flashcards
List 3 allergic airway diseases and the region involved
Upper airways: Allergic rhinitis (hay fever)
Bronchi: Asthma
Alveoli: Allergic alveolitis
Define allergy
an exaggerated immunological response to a foreign substance (allergen) which is either inhaled, swallowed, injected, or comes in contact with the skin or eye. A mechanism (not a disease)
Early and late responding cells in allergy
Early: Mast cells, Basophils
Late: Eosinophils
What are the 2 divisions of hypersensitivity?
Immunological (allergy)
Non-immunological (intolerance, enzyme deficiency, pharmacological)
Define hypersensitivity
Exaggerated response
What is required for an allergic response to arise?
Sensitisation process
Subsequent exposure results in allergic response
Describe the pathophysiology of Seasonal Allergic Rhinitis (SAR)
Nasal epithelium disrupted, allergens enter through mucosa, dendritic cells capture the allergen and migrate towards draining lymph nodes.
Innate cells e.g. ILC2s help DCs mature, prime naïve T cells into Type 2 T cells. These release cytokines: cause immunoglobulin class switch to IgE, sensitise mast cells and basophils in target organ
Following subsequent exposure to allergen, there is degranulation of these cells
Define Atopy
Hereditary predisposition to produce IgE antibodies against common environmental allergens
How can someone be atopic but not allergic?
Have IgE antibodies, but don’t exhibit symptoms when exposed to allergen
List 3 atopic diseases
Allergic rhinitis
Asthma
Atopic eczema
What are allergic tissue reactions in atopic subjects characterised by?
Infiltration of Th2 cells and eosinophils
What is Allergic march?
term describing the common progression of atopic diseases from atopic dermatitis to allergic asthma
Why does seasonal allergic conjunctivo-rhinitis occur?
There are different allergens that appear in different seasons
List 3 common causes of perennial allergic rhinitis and asthma
House dust mite
Cats
Dogs
Nature of asthma
Heterogenous (many phenotypes)
Classifying asthma based on control/ severity
Intermittent, mild: allergy frequently important
Persistent, manageable: allergy often important
Chronic severe: uncontrolled by treatment
Classifying asthma based on endo-type or endo-phenotype
Allergic, atopic or eosinophilic asthma
Neutrophilic asthma
Exercise induced asthma
Define Endotype
A subtype of a condition defined by a distinct pathophysiological mechanism.
Describe the airways of an asthmatic patient
Inflammation due to exposure to allergen (allergic response)
Contraction of smooth muscle
Secretion of mucous by goblet cells
Infiltration of eosinophils and T Cells
List 5 symptoms of asthma
Cough Shortness of breath Wheezing Chest tightness Secretions
How common is extrinsic allergic alveolitis?
Effects 0.1% of the population
What is the mechanisms in Extrinsic Allergic Alveolitis?
Exposure to small allergenic particles that enter alveolus
Captured by antibodies
Various hypersensitivity responses that lead to pro-inflammatory response
List 3 examples of extrinsic allergic alveolitis
Farmer’s lung (mouldy hay)
Bird Fancier’s lung (bird droppings)
Mushroom workers lung (mushroom compost)
3 principle treatments of allergic diseases
Allergen Avoidance
Anti-allergic medication
Immunotherapy (allows desensitisation/hypo-sensitisation)
How common is seasonal allergic rhinitis (SAR)?
Affects 40% of global population
List 4 symptoms of SAR
Runny and itchy nose
Sneezing
Congestion
Sleep deprivation
List 4 treatments for allergic rhinitis
Allergen avoidance
Oral/ local non-sedative H1-blocker
Intra-nasal steroid
Immunotherapy
Which form of allergen immunotherapy is safer and can be taken at home?
Sublingual
Give 2 advantages of allergen-injection immunotherapy
Effective
Produces long lasting immunity
Give 3 disadvantages of allergen-injection immunotherapy
Occasional severe allergic reaction
Time consuming
Standardisation problems
Describe the mechanism underlying allergen-injection immunotherapy
High dose immunotherapy modulates DCs that produce IL-10 and IL-27 (drive T cells towards Type 1 response) Results in induction of interferon gamma and regulatory T cells. Immune deviation (from type 2 to type 1 response). Induction of regulatory responses (T and B cells) Suppresses pro-allergic responses and induction of antibody production e.g. IgG captures allergen and prevents IgE from cross linking high affinity receptors on basophils and mast cells
Describe the anti-inflammatory action of IL-35
IL-35 can supress Type 2 responses, T cell responses, B cell responses (in terms of IgE) and can inhibit mast cell and basophil early phase response
Specific effect of IL-35 on B cells
stimulates B cells to produce IL-10
IL-10 is a suppressive cytokine, dampens immunological response
Describe facilitated antigen presentation in an allergic response
IgE forms complex with allergen, binds to CD23 receptor on B cells.
Complexes internalised and presented to T cells as MHC Class II molecules
Initiates Type 2 response
How does immunotherapy alter the antibody interactions of an allergic response?
Many IgG antibodies, compete with IgE
So complexes don’t form
Avoid activation of Type 2 response
How common is asthma?
Effects 10% of population
