Pulmonary defense mechanisms Flashcards
Problems in host defense
host defects: alcoholism, genetic abnormalities and diversity. Lung defects: conducting airways and gas exchange portions. Environmental agents: air pollution, viral infections, smoke
How does alcohol impair pulm defense
- Oropharynx: bacterial colonization, poor dentition. Glottis: decreased cough, increased aspiration. Airways: decreased mucociliary function. Innate immunity: decreased macrophage and neutrophil function. Adaptive immunity: decreased T cell and cytokine production, decreased B cells and airspace IgG
- Oropharynx: bacterial colonization, poor dentition. Glottis: decreased cough, increased aspiration. Airways: decreased mucociliary function. Innate immunity: decreased macrophage and neutrophil function. Adaptive immunity: decreased T cell and cytokine production, decreased B cells and airspace IgG
When should asthmatics exercise
Early in morning when ozone is lowest
Airway clearance mechanisms
- Air turbulence created by nasal passages, trachea and large airways. Large particles (>10 µm) deposited on mucous-coated surfaces of these airways. Mucous is projected towards the pharynx by the beating of cilia on epithelial cell. Cleared by coughing, sneezing and/or swallowing
- Air turbulence created by nasal passages, trachea and large airways. Large particles (>10 µm) deposited on mucous-coated surfaces of these airways. Mucous is projected towards the pharynx by the beating of cilia on epithelial cell. Cleared by coughing, sneezing and/or swallowing
Causes of reduced clearance by cilia
air pollution, viral infection, cigarette smoke
Constituents of Airway Epithelial Fluid
Antimicrobial peptides and proteins (e.g., β defensins, cathelicidin, lysozyme and lactoferrin), Antioxidants, Antiproteases, IgA
Antimicrobial peptides and proteins (e.g., β defensins, cathelicidin, lysozyme and lactoferrin), Antioxidants, Antiproteases, IgA
General - innate immunity
Early host defense. Pattern recognition receptors (secreted, intracellular, cell surface) recognize PAMPS, and recruit phagocytes, induce inflammation
How are small particles cleared from airway
Smaller particles (<5 µm) deposit in the lower airways and are Ingested by resident alveolar macrophages (AM) and/or dendritic cells. Also can Bind to lung collectins and surfactant protein A and D (i.e., secreted PRRs) that bind to PAMPs which Leads to opsonization and phagocytosis by AM and dendritic cells
Role of macrophages
Suppress adaptive immune response, clearance of particles, bugs, cell debris, apoptotic cells, elicit inflammation, transport particles to lymph nodes, clears alveolar surfactant. Activated by PAMPs
Normal WBC differential in bronchoalveolar lavage
90-95% macrophages, < 5% lymphocytes, < 1% eosinophils, < 1% neutrophils, CD4:CD8 is 2:1
How does smoking affect WBC differential
Dramatic increase in number of macrophages
Where are TLR’s located
Plasma membrane bound, endosome bound
What does TLR stimulation do
Induces proinflammatory response and forms a bridge btw innate and adaptive immunity. Activates macrophages, neutrophils, eosinophils, induces cytokine release from monocytes, enhances NK activation (killing and IFN-gamma), epithelial cell activation, dendritic cell activation (cytokin production, migration),
Major antigen presenting cell in lung
dendritic cell
functions of lung monocytes
differentiates into macrophages or DCs, is activated by PAMPs
