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Respiratory System > 14. Lung Immunology and Allergic Airway Disease > Flashcards

14. Lung Immunology and Allergic Airway Disease Flashcards

1
Q

Give an example of an allergic airway disease of the upper airways, bronchi and alveoli

A
  • Upper airways - allergic rhinitis
  • Bronchi - asthma
  • Alveoli - allergic alveolitis
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2
Q

What is hypersensitivity?

A
  • Exaggerated response

* Immunological (allergy, atopic) or non-immunological (intolerance)

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3
Q

What is an allergy?

A

• 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

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4
Q

What is atopy?

A
  • Hereditary predisposition to produce IgE antibodies against common environmental allergens
  • Characterised by infiltration of Th2 and eosinophils
  • Allergic rhinitis, asthma & atopic eczema
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5
Q

What is “allergic match”?

A

Common progression from atopic dermatitis to allergic asthma

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6
Q

What do acute and chronic symptoms of an IgE-mediated allergic reaction result from?

A

• 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

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7
Q

Describe the Th2 responses

A
  • 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
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8
Q

What do the Th2 interleukins do?

A
  • IL-4: IgE synthesis
  • IL-5: Eosinophil development (asthma)
  • IL-9: Mast cell development
  • IL-13: IgE synthesis + airway hyperresponsiveness
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9
Q

Give 4 examples of atopic allergies (IgE mediated)

A
  • Allergic asthma - including occupational
  • Allergic rhinitis - including hay fever
  • Anaphylaxis - food, insect stings, drugs, latex
  • Skin allergies - urticaria, angioedema, atopic eczema
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10
Q

Give 3 examples of non-atopic allergies (IgG mediated/T-cell mediated)

A
  • Contact dermatitis
  • Extrinsic allergic alveolitis
  • Coeliac disease
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11
Q

What do non-allergic hypersensitivity responses usually involve?

A
  • Usually food intolerance
  • Non-immunological
  • e.g. enzyme deficiency, migraine, irritable bowel syndrome (IBS), bloating
  • Idiopathic environmental intolerance - multiple chemical hypersensitivity, unknown cause
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12
Q

What is allergic rhinitis?

A
  • 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
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13
Q

What is asthma?

A
  • 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)
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14
Q

What is the relationship of asthma with an allergy?

A

• 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

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15
Q

How important is allergy in intermittent/mild asthma, persistent/manageable asthma & chronic/severe asthma?

A
  • Intermittent/mild asthma - allergy very important
  • Persistent/manageable asthma - allergy sometimes important
  • Chronic/severe asthma - allergy less important (infection is important)
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16
Q

What is extrinsic allergic alveolitis (EAA)?

A
  • 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
17
Q

Give 5 examples of extrinsic allergic alveolitis and the cause

A
  • 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
18
Q

Explain the prevalence of extrinsic allergic alveolitis

A
  • 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
19
Q

Describe the histology of extrinsic allergic alveolitis

A 
• Lymphocytic infiltrate
• Predominance of:
- CD8+ lymphocytes
- "foamy" alveolar macrophages
- granulomas
• Consistent with non-specific interstitial pneumonia
20
Q

How is extrinsic allergic alveolitis treated?

A
  • Oxygen
  • Oral corticosteroids (may not affect the long-term outcome)
  • Favourable prognosis if intervention undertaken before pulmonary fibrosis
21
Q

What is general anaphylaxis?

A
  • 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
22
Q

Allergic airway disease statistics

A
  • 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)
23
Q

How are allergic airway diseases a social and economic burden?

A
  • 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
24
Q

What is the hygiene hypothesis?

A
  • 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
25
Q

What microbial and non-microbial factors are associated with allergy/asthma prevalence?

A

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)
26
Q

What are the principles of treatment of allergic diseases?

A
  • Allergen avoidance
  • Anti-allergic medication
  • Immunotherapy
27
Q

What does anti-allergic medication involve?

A
  • Antihistamines (rhinitis symptoms)
  • Histamine 1-receptor antagonists - less sedative and more selective than old antihistamines
  • Topical corticosteroids (anti-inflammatory)
28
Q

What does immunotherapy involve?

A
  • 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)
29
Q

What are the advantages and disadvantages of immunotherapy?

A 
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

Respiratory System (18 decks)

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