Inflam & Lung Disease Flashcards
What immune mediated cells sit in the lamina propria?
Mast cells + macrophages
Lamina propria = loosely connected area of tissue under basement membrane
What happens to the immunity in the inflamed airway?
Lamina propria becomes swollen + expands as other inflam cells recruited + more mucus produced
What is COPD?
- Emphysema + bronchitis
- Progressive + irreversible airflow limitation
- Primary cause = abnormal inflam. in response to noxious gases + particles
Define asthma
Reversible airflow limitation
Associated with allergy
What effect do carbon particles have on airway epithelium?
Activate macrophages + irritates epithelium = produces cytokines
Summarise the COPD inflam mechanisms
Macrophage activation > neutrophil + monocyte recruit > proteases > alveolar destruction, damage to cilia, mucus hyper-secretion > air trapping, increased infection, increased obstruction + reduced air flow
Epithelial cell activation > fibroblast prolif + CD8 & CTC recruit > collagen deposition scar, alveolar destruction (emphysema) > increased obstruction, reduced airflow + gas exchange
What anti-inflam therapies are used for COPD?
Corticosteroids
- inhibits multiple inflam pathways
- increased risk pneumonia
- steroid resistance = problem
PDE4 inhibitors
- inhibits cAMP production in macrophages, neutrophils + eosinophils
Summarise the asthma inflam mechanisms
Dendritic cells recognise allergens > CD4 + TH2 cell activation
> B cells secrete allergen specific IgE > mast cell activation by allergens > inflam lipids + cytokines + histamine > inflam cell recruitment + vasodilation increased permeability + SM contraction > inflam airway narrowing, bronchoconstriction
> Eosinophil recruit, airway activation > Cytotoxic proteins > Damage to epithelium > increased infection, increased sensitivity pollutants, tissue remodelling, membrane thickening, increased goblet and mucus
What anti-inflam therapies are used for asthma?
Na cromoglicate/Nedocromil Na
- inhibits mast cell histamine release
Corticosteroids
Leukotriene receptor antagonists
- relax smooth muscle
Anti-IgE antibodies
- prevents IgE interaction with mast cells
- pt with severe persistent allergic disease
What is cystic fibrosis?
- SNPs in Cl- anion channels CFTR = impaired
- Thick mucus in lungs + GI
- Impaired mucociliary action + neutrophil function = chronic infection + inflam
How do neutrophils kill bacteria?
- Oxidative mechanisms - produce ROS - target bacteria lipids + proteins within phagosome
- Non-oxidative mechanism - proteases (e.g. elastase + MMPs) - target bacterial proteins within phagosome
What are the consequences of excess protease activity?
- Degrade structural proteins
- Impaired ciliary function
- Increased protease expresion
- Impaired innate defense
- Pro-inflam
What is the difference in the amount of macrophages and neutrophils in acute and chronic inflam response?
High levels of macrophages in acute
Longer duration of neutrophils in chronic
What causes the yellow/green colour of sputum?
Myeloperoxidase = heme containing protein in neutrophils
Indicates inflam
Greener sputum = more neutrophils
What are the anti-inflam therapies for CF?
Corticosteroids - alleviate wheezing
Ibuprofen