Pulmonary defense mechanisms Flashcards
how are foreign particles removed from the airways?
mucus throughout nose to bronchi traps them or they ‘settle out’ in the angling of trachea and branches
what is the sequence of events in the cough reflex?
- deep inspiration
- trapping air by shutting the glottis
- intitian of expiratory effort
- build up of intrathoracic pressure
- sudden release of trapped air at high pressure
what are the roles of airway epithelium?
barrier function- ciliary, tight junctions
defense function- supports microbiome, releases antimicrobial substances, regulates immune response (with receptors and cytokine/chemokine/leukotriene production)
translocates IgA
how does mucociliary clear foreign particles?
particles deposited on mucus of upper airways–>
cilia move thru sole layer striking the mucus layer above it and propelling it forward (known as mucus elevator)
what does the mucociliary consist of?
contains defense molecules- IgA, lysozymes, lactoferrin, and peroxidases
two layers:
- sol layer- aqueous
- mucus layer
what are the adaptive defense cells that are present in airways? what does each secrete?
Tregs- IL-10, TGF-B–> induced by FOXP3
dendritic cells- IL-27, IL -10, TGF-B
clara cells- act like opposins
other cytokines, and intraepithelial and submocosual lymphocytes
what are the first-line defense in the alveoli?
where do they reside?
what type are they?
what is their role and what do they respond to?
macrophages
tissues-for a long time
M2
maintain tolerance (immune suppresion) when responding to TGF-B and IL-10
when threat is presented they instead provoke immune response- respond to T cells and IL-1B
what are the two types of surfactent proteins?
how are they synthesized?
what is theur role?
SP-A and SP-D
made by type II alveolar cells and Clara cells
binds to pathogens, suppress microbial growth thru damging their membranes and macrophage phagocytosis
** able to endocytosis bacteria without immune response (clears pathogens while still maintaining immune suppression)
what are the two anitbodies in the alveolar space?
IgA- non inflammatory
IgG- induces complement (inflammatory)
what are the nonimmune opsonins in the alveolar cpace?
whats another important aspect?
sufactant, fibronectin, MBL, C reactive protein
microbiome- helps maintain tolerance thru balance act
what all does tissue repair (happens after activation of normal immune response) entail?
cell proliferation and regeneration, revascularization, tissue remodeling—-> all lead to recovery
what is overview of the acute immune response of the alveoli?
first line of defense is macrophages–>
they activate neutrophils which then release their NETs—>
hypersecretion of inflammatory cells and increase plasma (increase in permeability) due to injury and because alveoli lie next to capillary, NETs induce clotting of platelets—>
work to capture pathogen
how do the alveolar macrophages induce activation of leukocytes (including neutrophils and more macrophages)?
macrophages secrete cytokines TNF-a, IL-6 and IL-1 and chemokine IL-8 —>
increases expression of P and E selectins on endothelium (2 hours)—>
integrins (on leukocytes) start out with low affinity so intermittent binding of to selectins happens—>
rolling of leukocyte takes place—>
chemokines that continue to be released from inflammatory response increase affinity integrins have for selectons—>
leukocytes firmly attach and flatten on endothelium
neutrophils specifically: express integrin (receptors) IL-8L and LFA-1 that bind to IL-8 (secreted by macrophage) and ICAM1, respectively on endothelium
macrophages: integrins VLA4 and CCR2 bind to VCAM1 and CCL2 respectively on endothelium
what is contained in inflammatory exudate?
what does it cause?
- clotting proteins-stops blood loss
- complement system- stimulates immune response
- kinin cascade-increases permeability of vessels and promotes pain
- fibronolytic prtoein- degrades clot when wound has healed
brings plasma proteins into close contact with damaged area and cuases edema
what will you see on a blood slide when theres actue inflammatory response?
- leukocyte infiltrate
- vascular congestion
- mucus
what is the chronic inflammatory response?
activated T cells (TH1, CTL, TH17) and M1 macrophages continue to be released over time—>
they release chemokines and increase immuno-modulated lipid secretion?—>
causes mucus hypersecretion, substantial remodeling of tissues (fibrosis), and emphysema
in broad terms, what happens when there is dysregulation of immune response?
tissue injury and disease
in type 1 hypersensitivity what is the acute atopic response?
what sx does this produce?
within minutes cross-linking of mIgE happens—>
allergns cause degranulation of mast cells—>
this releases leukotrienes (causes hypermucus), histamine, IL-4 (activates type 2 T helpers) , IL-5 (activates eosinophils) along with cytokines—>
cytokines recruit more inflammatory cells and proteins to area
sx are sneezing, pruritis, rhinnorhea, congestion
in type 1 hypersensitivty what is the late phase chronic atopic response?
mast cells from acute response increase greatly in number with increased expression of FCe receptors—>
in hours: influx of and activaiton of eosinophils, neutrophils, basophils, macrophages, lymphocytes (TH2)
sx are fatigue, myalgia, asthma
what do eosinophils do?
proinflammatory mediators that cuase local tissue damage, sinus infections, chronic hyperplastic eosinophilic sinutisis (CHES)
after acute and chronic immune response phases, what occurs in airway remodeling?
leukotrienes C4, D4, E4 (from lipid mediators) induce broncospasm, vascular permeability (increase mucus production and hyperplasia of goblet cells), mucus production
prostaglandins D2, E2, F2 induce bronchospasm and vasodilation
recruitment of smooth muscle cells and fibroblasts—> lead to deposition of collagen in submucosa
what is the chronic inflammatory repsonse associated with COPD?
neutrophils from innate response activate Th17 cells—>
Th17 cells secrete IL-17 and IL-22—>
induce secretion of IL-8 and G/GM-CSF from airway epithelial cells—>
recruits a bunch more inflammatory macrophages and neutrophils (cast their NETs–> clotting–>damage) to area thats supposed to be immuno suppressed
besides epitelial cells, what other thing does smoking activate?
alveolar macrophages—>
activate Th1 cells and neutrophils—>
Th1 and neutrophils (from both reactions) narrow the airway and destroy alveoli—>
limits airflow
what is the general mechanism of asthma?
type 1 hypersensitiviy
allergens activate ep cells and mast cells—>
activate both Th2 and eosinophils—>
cause bronchoconstriction—>
limits airflow
what are similarities between COPD and asthma?
what are some differences?
similar: hypersecretion of mucus and difficulty breathing
different: immune responses (more lymphocytes in COPD), asthma is reversible and COPD is not
what kinds of damage are associated with ventilator lung injury?
both are iatrogenic
- physical- overinflation and mechanical stress
- biodamage- hyper oxygantion, free radical production, influx of neutrophils (due to activation of endothelium) which cast NETs (clot production)
what are signs of vaping associated lung injury (VALI)?
- present with ARDS
- bilatieral infiltrates on x ray
- absecence of infection
- has recently vaped
what causes lipid pneumonia?
inhalation of lipids (rare)
- vaping CBD/THC (vit E acetate)
- vpaing essential oils
- eating lip gloss (lol)
