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
Functions of resident dendritic cells
phagocytosis of inhaled particles, migrates to lymph nodes, activates adaptive immunity in presence of PAMPs
What is the trimolecular complex
APC’s MCH + Ag + T cell receptor on T cell
initiation of granulomatous response
Step 1-triggering of CD4+ T cells by APCs, Step 2-release of Th1-type cytokines (IL-2, IFN-g, and TNF-a), Step 3-accumulation of immunocompetent cells at the site of disease activity
Granulomatous lung disease pathogenesis
Antigen causes alveolitis and granuloma formation which leads to lung injury and possibly lung fibrosis
Bronchoalveolar lavage in sarcoidosis
Dramatic increase in the number of CD4+ and/or CD8+ T cells in the lungs of patients with granulomatous lung disease. Percentage of lymphocytes can range from 5-95% of alveolar cells, depending on the severity of the alveolitis. CD4:CD8 ratio > 3-15:1
What do activated T cells express
IL-2R- IL-1 and IL-2 attract blood T cells to the site of inflammation.
Mechanisms of T cell increases in lungs
influx of Ag-specific T cells from blood or Local T cell proliferation
Th1, Th17 and Th2 functions
Th1: intracellular pathogens, cell mediated immunity. Th17: Clearance of bacterial pathogens, autoimmunity. Th2: humoral immunity, helminths, atopy, allergic disease
Function of TGF beta in T cell development
inhibits differentiation into Th1 and Th2
