-Week26:Inflammatoryairwaydiseases(AsthmaandCOPD) - Heterogeneous disease: This means many dif f erent forms (phenotypes) of asthma exist -Phenotypesinclude:Allergic,non-allergic,late-onset,withfixedairflowlimitation, with obesity - 300 million af f ected worldwide - Lung structural cells: - Airway smooth muscle: Smooth muscle f i bres surround the larger airways throughout the lung, Evolved to prevent inhaling noxious gases, contains numerous receptors Including numerous GPCRs which control the contraction and relaxation - Asthmatic ASM remodelling: Hypertrophy - Increased cell volume, Hyperplasia - Increased cell number - Epithelial cell: f i rst point of contact for allergens, pollution and other irritants, and pathogens, but also inhaled therapies - Epithelial cilia beat in a synchronised pattern to clear mucus and irritants - Myof i broblast: shows characteristics of both smooth muscle cells and f i broblasts, Within the asthmatic lung the myof i broblasts produce large amounts of Extracellular matrix (Collagen, actin vimentin desmin) - Epithelium & basement membrane undergoes structural changes - ie. unsynchronised cilia, coupled with goblet cell hyperplasia and mucus gland hypertrophy causes an accumulation of airway mucus, The epithelial cells can lose their ciliated physiology or slough of f leading to local lung remodelling, source of a largenumberofpro-inflammatorycytokines/chemokinesandotherinflammatory mediators - Bronchoconstriction, Remodelling -Inflammation: - Mast/basophil cell: mast cell degranulation causes bronchoconstriction, Histamine, Cysteinyl-leukotrienes and Prostaglandins - T-lymphocyte: T helper2 (Th2 imbalance in asthma) - B-lymphocyte: Th2 cytokines (particularly IL-4 and IL-13) promotes the isotype switch of B cells to produce IgE, IgE is strongly associated with asthma and allergy - Eosins work in gangs, help destroy parasites. During the late asthmatic reaction eosinophilsinfiltratetheairwaysanddegranulatecausinginflammation - Eosinophil degranulation products: Eosinophil cationic protein (ECP) - Also known as Ribonuclease 3. Eosinophil-derived Neurotoxin (EDN) - aka Ribonuclease 2 or RNaseA. - Major basic protein (MBP) - aka Proteoglycan 2 (PGR2) - Eosinophil peroxidase - Neutrophilic lung diseases: severe asthma and copd - COPD: emphysema and chronic bronchitis -Smallairwaysdiseaseandparenchymaldestructionleadstoairflowlimitation - Emphysema: damage and destruction of alveolar sacs in lung - Chronic bronchitis: results in respiratory passages to be swollen and irritated, increases the mucus production and damages the lungs. The increased mucus production along with dysfunctional cilia results in increasing thick mucus blocking the airways and thereby reducing the capacity of the lung
- Exacerbations: Dysnea, increased sputum purilence or volume, cough, wheezing, cold, nasal discharge or sore throat - Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) Treatment is by corticosteroids/glucocorticoids, Selective B2-adrenoceptor agonists (short acting vs long acting), smoking cessation Rhinovirus (RV) Respiratory syncytial virus [RSV) Human metapneumovirus (HMV) Influenta vines Viruses Bacteria Mycoplasma pneumoniee Chlamydia pneumoniae Fungi Tree, Weed and grass pollen Indoor allergens House dust mite. Cockroach Allergen Occupational Animal exposures Chemical exposures Airway pollutants Cigarette smoke Irritants Aspirin Exercise Cold air Other Healthy airway With asthma Asthma attack Normal airway Airway smooth muscle Increased airway smooth muscle Mild/Moderate Asthma Eosinophils ++ Macrophages+ CD4+ T-Lymphocytes (Th2) Mast cells L Constricted airway during an asthma attack · Contracted airway smooth muscle Severe Refractory Asthma Neutrophils+ Macrophages CD4+T-Lymphocytes (Th2) CD8+ T-Lymphocytes (Tc1)
Input Output Antigen specific/ Adaptive Antigen +