L6- Asthma pathology

Question 1

What is the definition of hypersensitivity?

Answer 1

Immunologically driven host damaging or tissue irritating process

Question 2

How does Type 1 hypersensitivity occur in asthma and allergy?

Answer 2

• Dendritic cell detects and presents foreign antigen
• Th2 cells are activated and produce cytokines
• IgE class switching occurs in B cells
• B cells produce IgE antibodies which bind to surface of mast cells and sensitise them
• When antigen encountered again it binds to IgE on mast cells, crosslinking of two IgE cause degranulation of mast cell

Question 3

What cytokines do Th2 cells release?

Answer 3

• IL-13- mucus hypersecretion
• IL-5- eosinophil activation
• IL4,IL5,IL13- IgE class switching in B cells

Question 4

What is inside mast cell storage granules?

Answer 4

• Histamine causes increased vascular permeability and smooth muscle contraction and vasodilation
• Tryptase causes tissue remodelling and increased mucus secretion
• De novo synthesis of prostaglandins, leukotrienes and cytokines causing similar effects

Question 5

What are other mediators of type 1 hypersensitivity?

Answer 5

• Basophils
• Cytokines
• Eosinophils

Question 6

What are the main characteristics of allergens?

Answer 6

• Individuals are repeatedly exposed to them

* They do not induce macrophage/dendritic cell responses that drive Th1/Th17 responses like microbes

Question 7

What are the main types of allergens?

Answer 7

• Inahled= pollens, spores, dust mites
• Ingested= peanuts, eggs, fruits
• Venoms= bee, wasp, snake
• Drugs= antibiotics, chemotherapeutics

Question 8

What allergens are associated with asthma?

Answer 8

Indoor= Arthropods (dust mites), animal dander
Outdoor= Fungi, pollen

Question 9

How does type 4 hypersensitivity work?

Answer 9

• Delayed inflammation, antibody independent
• Cytokine-mediated inflammation
• T- cell mediated cytotoxicity

Question 10

What is the difference between asthma and COPD pathology?

Answer 10

• Equal inflammation
• More smooth muscle build up in airway walls in asthma
• Thicker basement membrane in asthma
• Greater fibrosis in COPD
• Greater alveolar destruction in COPD

Question 11

What is the difference in the nature of COPD and asthma diseases?

Answer 11

• Asthma is variable in its severity and symptoms and is impacted heavily by exacerbations
• COPD is more stable and progressive

Question 12

What are the clinical differences between asthma and COPD?

Answer 12

• Asthma symptoms more variable while COPD are persistent and worse in exertion
• Asthma in childhood, COPD over 45’s
• COPD patients usually always smoke
• Asthma treated well by bronchodilators and steroids but not in COPD
• Asthma caused by allergens

Question 13

What is the pathophysiology of COPD?

Answer 13

• Smoke triggers damage to epithelial cells and activates alveolar macrophages
• Macrophages stimulate neutrophils that produce proteases which cause mucus hypersecretion, lung alteration and destruction
• CD8+ T cells activated and cause damage

Question 14

What are the different asthma phenotypes?

Answer 14

• Allergic asthma
• Non-allergic asthma
• Late-onset asthma
• Asthma with obesity
• Severe asthma

Question 15

What are the main features of asthma?

Answer 15

• Variable airway narrowing- airflow obstruction that is reversible
• Non-specific airway hyperresponsiveness to innocuous stimuli leading to bronchoconstriction
• Mucosal inflammation and airway remodelling

Question 16

What are the types of inflammation in asthma?

Answer 16

• Allergic eosinophilic (Th2, eosinophilic)
• Non-allergic eosinophilic
• Mixed granulocytic (Th17, neutrophils)
• Paucigranulocytic

Question 17

What are the pharmacological options for asthma?

Answer 17

• Bronchodilators (selective b2 adrenoreceptor agonists) that can be long/short acting and inhaled
• Anticholinergic/muscarinic receptor antagonists
• Inhaled corticosteroids targeting inflammation
• Biologics