14. Lung Immunology and Allergic Airway Disease Flashcards
Give an example of an allergic airway disease of the upper airways, bronchi and alveoli
- Upper airways - allergic rhinitis
- Bronchi - asthma
- Alveoli - allergic alveolitis
What is hypersensitivity?
- Exaggerated response
* Immunological (allergy, atopic) or non-immunological (intolerance)
What is an allergy?
• Exaggerated response to a foreign substance
• Inhaled, swallowed, injected, skin/eye contact
• Immunological
- involve early phase (mast cell) and late phase (T cell - Th2) reactions
(mechanism not a disease - but can play a temporary/permanent role in a disease)
• Asthma, drug reactions, food reactions, rhinitis, eczema
What is atopy?
- Hereditary predisposition to produce IgE antibodies against common environmental allergens
- Characterised by infiltration of Th2 and eosinophils
- Allergic rhinitis, asthma & atopic eczema
What is “allergic match”?
Common progression from atopic dermatitis to allergic asthma
What do acute and chronic symptoms of an IgE-mediated allergic reaction result from?
• Acute
- binding of allergen to IgE-coated mast cell
- cell degranulation and histamine release
• Chronic
- interaction of allergen with APCs (becomes an APC)
- involve the release of Th2 cytokines and chemokines
Describe the Th2 responses
- Collaboration between innate and adaptive immune responses
- PAMPs on allergen interact with barrier cells (epithelial airway cells) - secretion of IL-33 and IL-25
- Attract natural helper cells, nyocytes + MPP type 2 cells (differentiate into mast cells, basophils + macrophages)
- These secrete IL-4, IL-5 and IL-13
- Th2 differentiation, B1 cell proliferation and anti-allergen effector functions induced
- Th2 is CD4+ and releases IL-4, IL-5, IL-9 and IL-13
What do the Th2 interleukins do?
- IL-4: IgE synthesis
- IL-5: Eosinophil development (asthma)
- IL-9: Mast cell development
- IL-13: IgE synthesis + airway hyperresponsiveness
Give 4 examples of atopic allergies (IgE mediated)
- Allergic asthma - including occupational
- Allergic rhinitis - including hay fever
- Anaphylaxis - food, insect stings, drugs, latex
- Skin allergies - urticaria, angioedema, atopic eczema
Give 3 examples of non-atopic allergies (IgG mediated/T-cell mediated)
- Contact dermatitis
- Extrinsic allergic alveolitis
- Coeliac disease
What do non-allergic hypersensitivity responses usually involve?
- Usually food intolerance
- Non-immunological
- e.g. enzyme deficiency, migraine, irritable bowel syndrome (IBS), bloating
- Idiopathic environmental intolerance - multiple chemical hypersensitivity, unknown cause
What is allergic rhinitis?
- Blocked/runny nose, sneezing, itching, streaming eyes
- Seasonal allergic rhino-conjunctivitis (hayfever) caused by pollen (commonly grass pollen)
- Milder winters and warmer springs is causing earlier pollination
- Seasonal allergic asthma (wheeziness) can co-exist with rhinitis
- Perennial allergic rhinitis (indoors) - also has similar chronic symptoms (can also be non-allergic e.g. infections/structural abnormalities)
- Allergy to the house dust mite (dermatophagoides) and allergens from animals
What is asthma?
- Chronic disorder characterised by episodes of wheezy breathlessness
- May also present as an isolated cough
- Uncertain aetiology
- Pathology involves inflammation of the large and small airways (bronchi & bronchioles)
- Controlled using inhaled bronchodilators (systemic corticosteroids if severe)
What is the relationship of asthma with an allergy?
• Allergy can trigger an attack in around 75% of asthmatics
• Commonly due to sensitivity to house dust mites and pollen
• Viral infections, exercise, fumes and drugs can trigger
• Food allergens are rarely responsible
• 25% are non-atopic asthmatics
- not sensitised to common allergens
- disorder starts later in life
- more severe
How important is allergy in intermittent/mild asthma, persistent/manageable asthma & chronic/severe asthma?
- Intermittent/mild asthma - allergy very important
- Persistent/manageable asthma - allergy sometimes important
- Chronic/severe asthma - allergy less important (infection is important)
What is extrinsic allergic alveolitis (EAA)?
- aka hypersensitivity pneumonitis
- non-IgE, cell mediated inflammatory disease
- affects the alveoli and interstitium
- occurs in susceptible people following repeated inhalation of certain antigens
- typically bacterial or fungal microorganisms, or bird antigens
- some antigens that cause asthma (mold, alternaria) can induce EAA
Give 5 examples of extrinsic allergic alveolitis and the cause
- Farmer’s lung - mouldy hay
- Bird fancier’s lung - bird droppings
- Air conditioner lung - air conditioner moulds
- Mushroom workers lung - mushroom compost
- Hot tub lung - bacterial contamination
Explain the prevalence of extrinsic allergic alveolitis
- Varies
- Related to to the particular antigen and the host immune response
- Minority of individuals exposed develop disease
- Cytokine gene polymorphism in the TNF-alpha promoter region appear to be a host susceptibility factor
Describe the histology of extrinsic allergic alveolitis
• Lymphocytic infiltrate • Predominance of: - CD8+ lymphocytes - "foamy" alveolar macrophages - granulomas • Consistent with non-specific interstitial pneumonia
How is extrinsic allergic alveolitis treated?
- Oxygen
- Oral corticosteroids (may not affect the long-term outcome)
- Favourable prognosis if intervention undertaken before pulmonary fibrosis
What is general anaphylaxis?
- Systemic manifestation of an allergic reaction
- Dizziness, arrhythmia, vomiting, urticaria, bronchoconstriction, laryngeal oedema
- Caused by drugs, foods, insect stings and latex
- Treated with an EpiPen
Allergic airway disease statistics
- 5.7m diagnosed with asthma
- 1/15 diagnosed with allergic rhinitis
- 117% increase in peanut allergies (2001-2005)
- 7x increase in hospital admissions due to anaphylactic shock (1990-2000)
How are allergic airway diseases a social and economic burden?
- Makes social interactions difficult - everyday activities pose a major risk
- Anxiety - impairs quality of life
- Large part of health care cost
- Allergy-related work absences - large cost to the economy
What is the hygiene hypothesis?
- Taking away stimuli for the immune system
- Not exposed to a basic/low level of the stimuli (that can stimulate Th2 cells)
- Full exposure can cause allergic response
What microbial and non-microbial factors are associated with allergy/asthma prevalence?
Microbial
• Water sanitation
• Food quality (lack of fermenting bacteria, more processed foods)
• Poverty (higher asthma rates)
• Medical interventions (antibiotics and vaccinations)
Non-microbial • Pollution • Diet and nutrition (lack of vitamin D, fish oil, trace elements etc.) • Obesity (chronic inflammation) • Climate change • Stress • Genetics (chromosome predispositions)
What are the principles of treatment of allergic diseases?
- Allergen avoidance
- Anti-allergic medication
- Immunotherapy
What does anti-allergic medication involve?
- Antihistamines (rhinitis symptoms)
- Histamine 1-receptor antagonists - less sedative and more selective than old antihistamines
- Topical corticosteroids (anti-inflammatory)
What does immunotherapy involve?
- Administering increasing concentrations of allergenic extracts over long periods of time
- Encouraging a Th1 (T-reg) response (IgG, IL-10)
- Discouraging a Th2 response (IgE, mast cells)
What are the advantages and disadvantages of immunotherapy?
Advantages • Effective • Long lasting immunity Disadvantages • Risk of developing anaphylaxis • Time consuming • Standardisation problems - pre-treatment of allergen extracts sometimes required - this reduces immunogenecity and decreases IgE binding
