Asthma & COPD Word Scramble
|
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Question | Answer |
Characteristics of Asthma and COPD | Chronic inflammation condition, airflow limitation, tissue remodelling |
Causes | allergic disease/ tobacco smoke and irritants |
Outcomes | Reversible airflow obstruction/ incompletely reversible airflow limitation, resulting in progressive decline of lung function |
Classical pathlogies | asthmatic airways show CD4+ lymphocytes, eosinophil and macrophage immune response/ CD8+ T cell, neutrophils and macrophage |
However, in severe/ sudden onset fatal asthma | neutrophilic (IL-17A) |
in acute exacerbation of COPD (frequently triggered by viral infection) | eosinophilic |
Inflammatory response in asthma | Predominance of Th2 cytokines: IL-4, IL-5, IL-13 and chemokines: RANTES, eotaxins, monocyte chemoattractant-1 |
Inflammatory response in COPD | Th1-dominated responses: IFNgmma, IL-8 (neutrophil chemoat.) leukotriene B4, IL-1 and TNFa (which induce asthma via IL-4, IL-5 and IL-13) |
Pathological changes in the airways are similar | Inflammatory characteristics of asthma and COPD are interchangeable during exacerbation and infection, due to the association with the similar cytokine profiles and levels |
Asthma pathology | Notion: imbalance Th1/Th2 allergic inflammatory response which polarises Th2 cell pathway |
Asthma - initiation | professional APCs present fragment of antigen on MHCII molecule to naive T cells, directing them in favour of Th2 cell phenotype |
Asthma - T cell co-stimulation | T cell upregulates expression of genes including IL-3, IL-4, IL-5, IL-9, IL-13 and GM-CSF, which involved in a) isotype switching of B cell, b) recruitment of mast cell and c) maturation of e-phil and b-phil. |
More recently | CD25+ FOXP3+ T cell is suggested to control Th2 through IL-10 and TGFbeta |
Central mediator of allergic response (atopic form asthma) - IgE | Upon exposure to allergen, along with Th cytokines, B cells produce and release IgE. IgE binds to FceR1 on mast cell, e- and b-phils, thereby sensitizing these cells to antigen resposne |
Upon subsequent antigen exposure | cross-linking of adjacent IgE-FceR1 complexes trigger the a) deregulation of cytoplasmic vesicles containing histamine and b) the de novo formation of eicosanoids and reactive oxygen species, resulting SM contraction, mucous secretion and vasodilation. |
Then move on the the later allergic response (6-72 hrs later) | The release of cytokines/ chemokines that recruit macrophages, e- and b-phils that comprise the late allergic response |
Eosinophil | prominent in allergic airway disease, linked asthma severity |
Eosinophil activities | 1)release of pre-stored granular proteins e.g. e- cationic proteins and e-peroxidase, which are cytotoxic 2)synthesis and release of oxygen radicals and lipid mediators as well as numerous cytokines 3)role in airway remodelling: fibrogenic cytokines |
IL-5 is the most important cytokines associated with eosinophil | produced by Th2, mast cell and eosinophil, regulate most aspects of eosinophil behaviour |
Airway remodelling - resulting in airway hyper-responsiveness and mucous secretion | 1)collagen 2)fibronectin deposition 3)thinkness of subepithelial basement membrane 4)goblet cell hyperplasia 5)increased ASM mass and size 6)angiogenesis 7)fibrosis |
Airway remodelling - pathology | imbalance of matrix metalloproteinases and their inhibitors, also increase in ASM content, along with change in the phenotype of fibroblasts cause permanent reduction of airway caliber, which is steroid insensitive |
Airway remodelling - associated cytokines | TGF-beta, PDGF, IL-6, IL-11, IL-13, IL-17 and IL-25 |
Immunomodulation - IL-10 actions | 1)on eosinophil survival by prevent the release of chemoattractants 2)downregulation of IL-4, which induces isotype switching of B cell, 3)inhibit IFNgamma and IL-2,4)interfere with function of mono and Macro, 5) MHC expression on APCs |
Chemokines | class CC, target T cells, monocytes and eosinophils. Eotaxin and RANTES, acting in synergy with IL-5, chemoattractant in allergic inflammation, induce A4 and B1 integrin expression on eosinphil- firm adhesion to epitheilium and tranmigration |
Therapies - 1 | Inhaled corticosteroids e.g. beclomethasone binds GR in the cytosol, leading to the dissociation of hsp complex and translocation, transsupression and transactivation |
Transsupression action | interacts with co-activators with HAT activity, which activate pro-in transcription factors wuch as NFkB and AP1 |
Transactivation action | IL-10 and IkB-alpha |
Ineffective in virus-induced exacerbation and COPD | IL-2 and IL-4 induce p38 MAP kinase which phosphoylates GR/ HDAC2 is reduced |
Therapies - 2 | B-adrenoceptor agonists (short/long-acting) e.g. salbutamol/salmeterol, rapid relif of asthma symptoms |
actions | Gs-adenylate cyclase-cAMP-PKA PKA mediates SM relaxation through P myosin light-chain kinase and by opening of KCa ch. |
Therapies - 3 | Immunotherapy, increase the production of IgA and IgG, Treg cell (TGFbeta adn IL-10), reduction in the recruitment of Macro B and E-phil |
Therapies - 4 | IgE, direct neutralization by IgG antibodies e.g. Omalizumab |
Therapies - 5 | inhibitors of mast cells (e.g. sodium cromoglicate), inhibit Cl- flux in mast cell and epithelial cell to increase the threshold of actication; KCa ch. can also be targeted since it mediates mast cell chemotaxis/ activation |
Therapies - 6 | Cytokines-based-5 sites of actions:signal transdution, transcription, translation process, soluble and receptor e.g. increase IL-10 and IL12(Th1 differentiation), dicrease IL-4, IL-5, IL-9, IL-13 and IFNs e.g.suplatast tosilate inhibits Th2 cell+cytokine |
COPD initiation | Inhaled cigarette smoke and other irritants activates epithelial cells and Macrophage to release chemotactic factors |
COPD chemokines | CCL2 on CCR2 monocytes, CXCL1 and CXCL8 on CCR2 neutrophils and monocytes, CXCL9, CXCL10, CXCL11 on CCR3 Th1 and Tc1 cells |
COPD - pathology | protases-antiprotase imbalance, such as matrix metalloproteinase which cause elastin degradation and emphysema |
COPD - Epithelial cells and Macrophages | release TGFbeta, which stimulates fibroblast proliferation, resulting in fibrosis in small airways |
Therapy | B2 agonist theophylline (PDE inhibitor, increasing cAMP) Muscarinic receptor antagonist |
other approaches for both | B cell inhbition, NKkB pathway inhibition, chemokine receptors, Th17 |
Created by:
JonLai
Popular Medical sets