Pulmonary Defense Mechanisms Flashcards
Airway clearance mechanisms
- Mucous is projected towards the pharynx by the beating of cilia on epithelial cell
- Cleared by coughing, sneezing and/or swallowing
Ciliary function and causes of reduced clearance
- 10-15 beats per second
- 200 cilia per cell
- Coordinated movement
- Particle movement
–Small airways 0.5-1.0 mm/min
–Large airways 5-20 mm/min
•Examples of reduced clearance
–Air pollution/ozone –Viral infection –Cigarette smoke
Contents of airway epithelial fluid & fxn
- Antimicrobial peptides and proteins
- Antioxidants
- Antiproteases
- IgA
- Contribute to maintenance of airway structure and function
Innate Immune System function @ lungs
–Provides early host defense against virus, fungi, and bacteria
–Relies on recognition of pathogen-associated molecular patterns (PAMPs)
–PAMPs are recognized by secreted, cell surface, or intracellular pattern recognition receptors (PRRs) –Engagement of PRRs results in recruitment of phagocytes, killing of microbes, and inflammation
Adaptive immune system fxn @ lung
–B and T cells
–Provides antigen specificity
–Upon re-exposure, immunological memory allows for a more rapid and augmented secondary immune response
Immune system fxn in airway clearance
- Smaller particles (<5 µm) deposit in the lower airways
- Ingested by resident alveolar macrophages (AM) and/or dendritic cells
- Bind to lung collectins and surfactant protein A and D (i.e., secreted PRRs) that bind to PAMPs
- Leads to opsonization and phagocytosis by AM and dendritic cells
Role of macrophages in host defense of lung
- Suppression of adaptive immune responses
- Clearance of particles, bugs and cell debris
- Clearance of apoptotic cells
- Elicit an inflammatory response
- Transport particles and bugs to lymph nodes
- Clear alveolar surfactant
Bronchoalveolar lavage procedure & normal cell differential
- bronchoscope into airways ==> fluid squirted into lung ==> fluid collected and analyzed
- •Normal cell differential
- 90-95% macrophages
- < 5% lymphocytes
- < 1% eosinophils
- < 1% neutrophils
- •In smokers, dramatic increase in the number of macrophages
- •Normal CD4:CD8 ratio-2:1
Consequences of TLR stimulation
- proinflammatory response.
- •Bridge between innate and adaptive immunity.
- Activates/enhances oxidative burst from macrophage, neutrophils, eosinophils.
- Induces cytokines from tissue monocytes & dendritic cells
- Enhances NK cell activation for killing and IFN-γ production
- Activation of DCs (Migration to T cell areas of lymphoid tissue)
- §Induction of type 1 IFN from either infection itself or from TLR stimulation
Summary of lung innate immunity [fxn of resident macrophage, monocytes, and DCs]
BAL 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
Activation of adaptive immune response
- The main response occurs in the lymph nodes.
- Sampling by APCs occurs @ lungs
- APCs (dendritic cells) take up antigen, processes it, puts proteins in its MHC Class 2, which present to CD4’s
- It also puts it in MHC 1 which presents to CD8 cells
- DCs ==> lymph nodes, presents, and activates the adaptive response (activates T cells, proliferation of T cells, etc).
Activation of T Cells @ lungs
- Following presentation of Ag by APCs, T cells are activated and express IL-2R
- IL-1 and IL-2 attract blood T cells to the site of inflammation
- T cells in the lung are increased by 2 potential mechanisms:
–Influx of Ag-specific T cells from the blood
–Local T cell proliferation
