Pulmonary defense Mechanisms Flashcards
what is the purpose of the defense mechanisms in the lung
ensure efficient gas exchange and prevent infection
removal mechanisms are aimed at minimizing inflammation
what are the two locations of lung defense
Upper airway and bronchi:
- anatomic barriers
- angulation
- cough reflex
- Mucociliary apparatus
- airway epithelium
- Secretory IgA
- Dendritic cells, lymphocytes, neutrophils
Alveolar spaces:
- alveolar macrophages
- Type II alveolar cell
- Surfactants and opspnins
- Complement
- neutrophils and eosinophils
removal of particulate matter in the pharynx/oropharynx and also removal in the trachea
in the pharynx/oropharynx/nasal cavity is done by the tonsils and the adenoids
in the trachea removal by mucokinesis and coughing
What are the events of 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 intrathoracic pressure
- build up of pressure
- Sudden release of the trapped air at a high pressure
a cough can be triggered by chemicals, mechanical stimulation, inflammation, or be voluntary
How does the airway epithelium play a factor in the pulmonary defense
Barrier function
Defense function:
- release of bacteriostatic molecules
- regulation of the immune response-contain receptors and produce cytokines
- support the microbiome
Translocate IgA into the airway lumen
how does mucociliary clearance work
Particles larger than 2-3um and smaller than 10 um are deposited on the mucus of the upper airways
The mucus contains defense molecules of IgA, lysozyme, lactoferrin and peroxidases
Mucus blanket is dual layered
- Sol layer (aqueous)
- mucus layer
Cilia move through the sol layer striking the mucus layer above and propel it forward (mucus elevator)
this can be altered in disease states like asthma, chronic bronchitis and cystic fibrosis
what are other mechanisms of the upper airways
Intraepithelial and submucosal lymphocytes
clara cells (club cells): release surfactant to protect the lining
Dendritic cells (antigen presenting cells to naive T cells)
Cytokines (helpful in reqruitment and activation)
Large population of Tregs (modulate the immune response)
what is the first line of defense in the alveoli
Alveolar macrophages -tissue residents -long lived self renewing -Plasticity of responses: generally an M2 profile and maitenance of tolerance
Importance of the two surfactant proteins in the alveoli
Surfactant A (SP-A) and D (SP-D)
synthesized by type II and club cells
both will bind to wide range of pathogens, suppress microbial growth, damage bacterial membranes, and modulate macrophage phagocytosis, regulation of mediator production
what are some other mechanisms of defense in the alveolar space
Immunoglobulins
-IgA and IgG
Nonimmune opsonins:
-surfactant, fibronectin, MBL, and C reactive protein
Microbiome
Complement
how does the Maintenance of tolerance work in the pulmonary tissue
Anti-inflammatory environment of pulmonary tissues
-gets suupport from the microbiome
lots of IL-10 (anti inflammatory response)
-decrease in interleukins
lots of Treg
lots of TGF-B released by alveolar macrophages
what are the events that occur during pulmonary inflammation
Activation of normal immune response and subsequent tissue repair
- Cell proliferation and regeneration
- revascularization
- Tissue remodeling
Recovery
what is the acute Immune response
Activation of immune response by exogenous triggers
- TNF-a
- IL-1
Influx of inflammatory cells from capillaries into the air spaces
- TNF-a
- IL-8
Deployment of neutrophils nets
- release of leukotrienes
- oxidants
- proteases
what is the process of the recruitment of leukocytes
IL-1 and TNF-a increase expression of P and E selectins on endothelium, they bind, detach, bind, rolling of leukocyte to help slow them down, then the leukocytes can respond to the other chemokines (IL-8) to enter cell
IL-8 and ICAM/LFA1 will then bind to pull the neutrophils i (happens within hours)
VLA4/VCAM1 and CCR2/CCL2 help recruit macrophages into the area (happens within days)
What is the inflammatory Exudate and what does it cause
Causes edema: brings proteins into intimate contact with the damaged area
Proteins in the inflammatory exudate:
- Clotting proteins
- Complement (destroy bacteria)
- Kinin cascade (vasodilation to increase peremabillity of the blood vessels and stimulate pain receptors)
- Fibrinolytic protein (degrades the clot when the wound has healed)
