Pulmonary Defense Mechanisms Flashcards
How does the gross structure of the airway serve as a mechanical defense?
angulation helps particulates settle out
What is the cough reflex?
- a type of mechanical defense
- sudden release of trapped air at an increased pressure
-triggered by chemicals, mechanical stimulation, inflammation, or can be voluntary
What defense characteristics are present on the surface of airway epithelial cells?
- cilia
- tight junctions
-adhesion molecules and TLR’s (ICAM-1, VCAM, selectins) that can be upregulated d/t threats
What secretory products do airway epithelial cells use as defense?
- defensins and cathelicidins
- Surfactants A & D
- cytokines, chemokines, and leukotrienes
Which immunoglobulin is associated with airway epithelial cells?
IgA
-airway epithelial cells translocate IgA
True or False: airway epithelial cells support the microbiome
True
What are the two layers of the airway mucus?
sol layer (closest to epithelium) gel layer (on top of sol layer)
What are the characteristics of the sol layer of mucus?
- thin, aqueous, closest to epithelium
- produced by serous cells
- cilia are in this layer
In certain pathologies, the sol layer is less aqueous. How would this affect the pulmonary defense mechanisms?
-if the sol layer is less aqueous, the cilia can’t move well
What are the characteristics of the gel layer of mucus?
- on top of the sol layer
- cilia draws back and strikes the mucus layer
- mucus moves upward to trigger cough
- produced by goblet cells
What immune molecules are present in the mucus?
- IgA
- defensins
- cathelicidins
What are defensins and cathelicidins?
-small, antimicrobial peptides that can also fxn as opsonins
What types of cells form the majority of immune cells in the airway?
T-reg cells
What are the main cytokines secreted by immune cells in the airway?
IL-10
TGF-beta
(the “shut-it-down-o-kines”)
keep the airway in a state of tolerance
In addition to T-reg cells, what other immune cells are present in the airway?
- dendritic cells
- interstitial macrophages
- alveolar macrophages
What are alveolar macrophages?
- mainly an immunosuppressant, Type II macrophage profile, but can respond if threatened
- tissue-resident, self-renewing
What surfactant proteins are present in the airway?
Surfactant Protein A
Surfactant Protein D
What are the characteristics of Surfactant Proteins A & D?
- function as a major opsonin
- don’t cause inflammation
- synthesized by Type II pneumocytes and Clara cells
What products are present in the airway that can initiate the complement system?
- IgG
- mannose-binding lectin
What types of immune cells migrate into the airway from the capillaries?
- macrophages
- neutrophils
What do macrophages secrete to aid in pulmonary defense?
leukotrienes, that cause mucus hyper secretion
What do neutrophils do to aid in pulmonary defense?
-NET deployment and fibrin deposition
What fills the alveolar space during pulmonary defense?
protein-rich edema fluid
What is the mechanism to slow the rolling of leukocytes during an adaptive immune response in pulmonary defense?
IL-1 and TNF increase expression of P & E selectins
What signals neutrophils to enter into pulmonary defense?
IL-8
What types of cells are the first to respond in adaptive immunity?
neutrophils, they arrive only a few hours
When do macrophages respond in adaptive immunity?
a few days later, following CCR2
What is the purpose of edema, in regards to the inflammatory exudate?
it brings the plasma proteins into intimate contact w/ the damaged area
What is the purpose of the kinin cascade, in reference to its presence in inflammatory exudate?
- vasodilation
- increase blood vessel permeability
- stimulates pain receptors
What is the purpose of fibrinolytic protein, in regards to inflammatory exudate?
-degrades clots when the wound is healed
What products and/or processes are present in the airway d/t inflammatory exudate?
- edema
- clotting proteins
- complement
- kinin cascade
- fibrinolytic protein
What are the consequences of chronic inflammation in the airway if the pulmonary threat isn’t cleared?
- infiltration of activated T-cells and M1 macrophages
- -macrophages secrete leukotrienes
- –mucus hypersecretion
-remodeling of tissues leads to fibrosis
What happens within the first several minutes of a Type I Hypersensitivity?
- cross-linking of membrane-bound IgE
- degranulation of Mast Cells
- -IL-4, IL-5, leukotrienes
- -sneezing, pruritis, rhinorrhea
What is the role of IL-4 secreted by a Mast cell in a Type I hypersensitivity?
recruit Type II helper cells
What is the role of IL-5 secreted by a Mast cell in a Type I Hypersensitivity?
recruit eosinophils
What is the role of leukotrienes secreted by Mast cells in a Type I Hypersensitivity?
- mucus hypersecretion
- bronchospasms
What happens within the first few hours of a Type I Hypersensitivity?
-influx and activations of Type II helper cells, eosinophils, basophils and neutrophils
Symptoms: fatigue, myalgias, asthma
What are some characteristics of an eosinophil response to a Type I Hypersensitivity?
-eosinophils are pro-inflammatory mediators
-eosinophils can cause local tissue damage
-eosinophils can cause sinus infections
(Chronic Hyperplastic Eosinophilic Sinusitis)
What immune molecules are active in chronic asthma-related airway remodeling?
- leukotrienes C4, D4, and E4
- prostaglandins D2, E2, and F2
What are the physical consequences of leukotrienes being active during chronic asthma-related airway remodeling?
- bronchospasms
- vascular permeability
- mucus hypersecretion
What are the physical consequences of prostaglandins being active during chronic asthma-related airway remodeling?
- bronchospasm
- vasodilation
In chronic asthma-related airway remodeling, the recruitment of smooth muscle cells and fibroblasts leads to what?
-collagen deposition in the submucosa
What is the treatment for chronic asthma-related airway remodeling?
- corticosteroids
- leukotriene antagonists
What is the mechanism of disease of COPD?
- epithelial cells secrete IL-8 which recruits neutrophils
- neutrophils secrete IL-17 and IL-22
-IL-17 and IL-22 recruit inflammatory macrophages and more neutrophils
What triggers asthma versus what triggers COPD?
asthma: allergens
COPD: cigarette smoke
What types of innate immune cells are responsible for acting in asthma versus in COPD?
asthma: Mast cells
COPD: alveolar macrophages
What adaptive immune cells are active in asthma versus in COPD?
asthma: CD4 (Th2 cells)
COPD: CD8 (Th1 cells)
What types of leukocytes are responsible for acting in asthma versus in COPD?
asthma: eosinophils
COPD: neutrophils
What is the main end action of asthma versus COPD?
asthma: bronchoconstriction
COPD: alveolar destruction
Are the consequences of asthma reversible or irreversible?
reversible
Are the consequences of COPD reversible or irreversible?
irreversible
Clinical: Ventilator-Associated Lung Injury
-physical damage: over-inflation, mechanical stress
- biodamage: hyperoxygenation leads to free radicals
- -influx of neutrophils leads to NET’s
- –platelet activation and clotting
Clinical: Vaping-Associated Lung Injury
- presents w/ acute respiratory distress syndrome
- b/l infiltrates on chest x-ray
- -but w/o infection
- vaping use within the previous 90 days
Clinical: Lipoid PNA
- caused by inhalation of lipids (vaping CBD)
- -vitamin E acetate (a lipid)
- -essential oils (castor oil, mineral oil, etc.)
- macrophage + lipid = foam cells
What is the treatment for Lipoid PNA?
- supportive care
- steroids
- antibiotics for secondary complications
