Pulmonary Defense Mechanisms Flashcards
Lung defense can be divided into two anatomical locations, what are they?
Upper airways and bronchi : conduction of air –Anatomic barriers –Angulation –Cough Reflex –Mucociliary apparatus –Airway epithelium –Secretory IgA –Dendritic cells, lymphocytes, neutrophils
Alveolar spaces : exchange of gases –Alveolar macrophages –Type I/ II / III alveolar cells –Clara cells (club cells) –Surfactants and opsonins –Complement –Neutrophils and eosinophils
What are the sequence of events involved in the cough reflex?
- Deep inspiration
- Trapping of air by shutting off its exit (glottis in the case of cough)
- Initiation of expiratory effort, raising the intra-thoracic pressure
- Build up of pressure
- Sudden release of the trapped air at a high pressure
*Note: A cough can be triggered by chemicals, mechanical stimulation, inflammation, or be voluntary
What are the functions of airway epithelium?
•Barrier function
•Defense function
–Release of bacteriostatic molecules
–Regulation of the immune response- contain receptors
and produce cytokines
–Support microbiome
•Translocate IgAhow does mucociliary clearance work?
Particles larger than 2-3 μm and smaller than 10 μm are deposited on the mucus of the upper airways
The mucus contains defense molecules- IgA, lysozyme, lactoferrin and peroxidases
Mucus blanket: dual layer–Sol Layer – aqueous –Mucus layer
Cilia move through the sol layer striking the mucus layer above and propel it forward (mucus elevator)
Mucociliary clearance is altered in disease states such as asthma, chronic bronchitis, and cystic fibrosis
What are some other mechanisms of defense in the airways?
- Intraepithelial and submucosal lymphocytes
- Dendritic cells
- Cytokines
- Large population of Tregs
What is the first line defense in the alveoli?
-Airway macrophages
•Tissue Residents •Long lived self renewing •Plasticity of responses –Generally an M2 profile –Maintenance of tolerance
Why are surfactants important in airway defense?
Because of surfactant Protein A (SP-A) and D (SP-D) : opsonins
- Synthesized by type II alveolar and Clara cells.
- Both SP-A and SP-D bind to a wide range of pathogens, suppress microbial growth, damage bacterial membranes, and modulate macrophage phagocytosis.
Explain the acute inflammatory response.
IL-1 and TNF increase expression of adhesion molecules on endothelium and leukocytes. End result is neutrophils slow down, bind to endothelium and follow chemokine IL-8. Monocytes (macrophages) enter in second wave.
Explain inflammatory exudate.
Edema
–Brings plasma proteins into intimate contact with the
damaged area.
Proteins in the inflammatory exudate include:
• Clotting proteins:
•forms blood clots to prevent further loss of blood
• Complement:
•stimulate immune responses and destroy bacteria
• Kinin cascade:
•vasodilation, increase the permeability of blood
vessels and stimulate pain receptors
–Fibrinolytic protein:
•degrades the clot when the wound has healed
What happens in the acute immune response in bronchioles?
- Activation of immune response by exogenous triggers
- Influx of inflammatory cells from capillaries into air spaces
- Deployment of neutrophils nets
What happens when there is a chronic inflammatory response?
Over time:
•Infiltration of activated T cells and M1 macrophages
•Mucus hyper-secretion
•Substantial remodeling of tissue leading to fibrosis
What happens in the early phase (immediate) acute atopic response?
Minutes:
•Cross-linking of mIgE
•Degranulation of Mast cells
•Sneezing, pruritis, rhinorrhea, congestion
•Preformed Mast cell cytokines and inflammatory proteins recruit inflammatory cells to the area
What happens in the late phase chronic atopic response?
Hours: 4 - 12
•Influx and activation of eosinophils, neutrophils, basophils and lymphocytes (Th2)
•10-fold increase in Mast cells present in area & increased expression of Fce receptors
•Eosinophils:
–Proinflammatory mediators
–Local tissue damage
Systemic symptoms: fatigue, myalgias, asthma
Describe chronic asthma related airway remodeling?
Leukotrienes C4, D4, & E4 induce bronchospasm, vascular permeability and mucus production
Prostaglandins D2, E2, F2 induce bronchospasm and vasodilation
Recruitment of smooth muscle cells and fibroblast leading to deposition of collagen in the submucosa
Explain Th17 Mediated inflammation in COPD.
- Th17 cytokines induce IL-8 secretion from airway epithelial cells –IL-17, IL-22
- Recruitment of large population of inflammatory macrophages and neutrophils.
