6. Pulmonary Defense Mechanisms Flashcards
lung defense can be divided into –
2 locations
upper airway/bronchi & alevolar spaces
what defense mechanisms take place in the upper airway & bronchi
anatomic barriers
angulation
cough reflex
mucociliary apparatus
airway epithelium
secretory IgA
dendritic cells, lymphocytes and neutrophils
what defense mechanisms take place in alveolar spaces
alveolar macrophages
type II alveolar cell
surfactant & opsonins
complement
neutrophils & eosinophils
what assists in removal of particulate matter in the resp system
mucus in nose, orpharynx all the way down to bronchi - trap particles
branching of bronchi up prevents particle from getting to ends
what are the sequence of events that lead up to the cough reflex
- deep inspiration
- trapping of air by shutting off its exits (glottis in the case of cough)
- initiation of expiratory effort, raising the intrathoracic P
- build up P
- sudden release of trapped air at high P
what can trigger a cough
chemicals
mechanical stimulation
inflammation
voluntary
what are the physical barriers present in the airway epithelium
cilia/mucociliary escalator
tight jxns
what membrane receptors are found in airway epithelium
adhesion molecules (ICAM-1)
preotease receptors
Toll-like receptors - response to outside threats and secrete beta-defensins
what antimicrobial substances are present in the airway epithelium
beta-defensins
phospholipase A2
SPA & SPD - surfactant
cationic peptides
ROS & RNS
what inflammatory mediators are present in airway epithelium
cytokines, chemokines, leukotrienes, ROS & RNS
what translocates IgA
airway epithelium
-translocate from plasma cell –> across cell –> into airway lumen w/o degradation
what defense molecules does mucus contain
IgA
lysozome
lactoferrin
peroxidases
what are the layers of the mucus blanket
sol layer (aq)
(inbtn = cilia)
mucus layer
what is the mucus elevator
cilia moving thru sol layer striking mucus layer above and then propel it forward
-move mucus up to trigger cough reflex
what can alter mucociliary clearance
asthma, chronic bronchitis, CF
-sol layer becomes less aq & cilia cant move as well so they get stuck in mucus
what is the fxn of the Treg cells
make IL-10 & TGF-beta
keep at immunosuppressive state
what is the fxn of dendritic cells in the airway
extend processes thru tight jxn to sample lumen
present sample to interstial macrophages - make IL-10, TGF-beta & IL-27
what are alveolar (airway) macrophages
first line of defence in alveoli
tissue residents - long lived & self renewing
- plasticity of responses - generally an M2 profile & maintain tolerance
- secrete IL-10 & TGF-beta
what are SPA & SPD
surfactants
- synthesized by type II alveolar cells & Clara cells
- bind pathogens, supress microbial growth, damage bacterial membranes & modulate macrophage phagocytosis
=major opsonin
what are other defense mechanisms of alveolar space
IgA (noninflam- no complement receptor) & IgG (cause inflam)
type II alveolar cells make nonimmune opsonins: surfactant, fibronectin, MBL & C-reactive protein
microbiome
how is tolerance maintained in the airway
alv macrophages provide cytokines
-retnoic acid helps to make/support FOXP3 Treg cells
surfactant
interstitial space immune cells that respond to threat if triggered
what is the acute immune response
activation of immune response by exogenous trigger
influx of inflam cells (neutrophils & macrophages) from caps into air space
deployment of neutrophil nets
how are leukocytes recruited
- activte endothelium by cytokines (which are secreted by resident macrophages & mast cells in periphery)
- acute phase cytokines - IL1, IL6 & TNF upregulated adhesion molecules (P & E selectins)
- leukocytes bind and slow down
- chemokines increase affinity & clustering of integrins
- leukocytes firmly attach, cytoskeleton reorganize & endothelium flattens
Neutrophils and macrophages arrive at different times and respond via different mechanisms- what are they?
neutrophils - hrs –> IL8L receptor on neutrophil responds to IL* & use ICAM1 to go thru membrane
macrophages - days –> CCL2 receptor on macrophage responds to CCR2 & enters via VCAM1
