Lecture B7, B8 Flashcards
salivary glands are ___ that produce ______ which has _____ functions
-exocrine glands
-saliva
-digestive, lubricating and protective
pH of saliva? why?
-6.5-6.9
-buffering function
There are 3 pairs of salivary glands that produce ____: ______
-90% of saliva
-parotid, submandibular, and sublingual glands
Parotid glands, located in _____, are branched acinar glands with exclusively ____ acini that secrete ______ that initiates hydrolysis of carbohydrates and _____
-each cheek near the ear
-serous
-α-amylase
-antimicrobial factors
Submandibular glands, which produce ____ of all saliva, are branched tubuloacinar glands, having primarily _____ acini, but with many ____ tubuloacinar secretory units
-two-thirds
-serous
-mixed/mucus
Sublingual glands, the _____ of the major glands, are also considered branched tubuloacinar glands, and the main product of the gland is _____.
-smallest
-mucus
salivary glands are surrounded by ____
CT capsule
The secretion of each gland is either serous, seromucous, or mucous, depending on _____
-its content of the glycoprotein mucin.
Saliva from the parotids is _____. The submandibular and sublingual glands produce a ______. The saliva of minor glands is mostly ______.
-serous and watery
-seromucous secretion
-mucous
Saliva is modified by the cells of ____ draining the secretory units, with much ______ reabsorbed while _____ are added.
-the duct system
-Na+ and Cl−
-certain growth factors and digestive enzymes
All glands contain ______ (striated duct) and _____ (intercalated ducts)
-ducts of bigger diameter
-branching ducts
The acinar end-pieces are secretory units specialized in a _____
-single type of secretion (serous, mucous or mixed)
myoepithelial cells do what?
provide some contraction to help move saliva from acini
blood vessels & parasympathetic nerves signal ____
saliva & duct production
salivary gland formation general
-epithelial tissue branching into mesenchyme and cleft formation in bud cells to increase SA
stages of salivary gland development
1) initial bud stage
2) pseudoglandular stage
3) cananilcular stage
4) terminal bud stage
initial bud stage of salivary gland
proliferation of simple bud-like structure connected to epithelium by solid stalk and invaginates into mesenchyme
pseudoglandular stage of salivary gland
-formation of main stalk & budding
Cananlicular stage of salivary gland
-branching morphogenesis + myoepithelial cells
Terminal stage of salivary gland
well developed salivary gland
Budding stage requires this signalling pathway: ____
FGF
Pseudoglandular-Canalicular (Duct formation) requires this signalling pathway: ____
WNT (first in mesenchyme,bud)
HH
EGF
Notch
EDA (WNT antagonist)
Terminal differentiation stage requires this signalling pathway: ____
FGF
EGF
BMP
EDA
Signaling from the _____ are all required and interact with one another to regulate salivary gland development. In addition, interactions with ______ are required
-epithelium, basement membrane and mesenchyme
-adhesion proteins and the nervous system
A combination of ______ and _______ is critical to form buds
-strong cells matrix (high B1 integrin) on BM
-weak cell-cell adhesion (E-cadherin) in the middle
Mucous acinar cells descr.
more elongated featuring peripherally compressed basal nuclei due to high mucous production within the cytoplasm
Serous acinar cells descr.
triangular-shaped cells and round nuclei component responsible for secreting a more aqueous secretion
The ductal network contains the ____ that are directly connected to the _______ with a _____ layer
-proximal intercalated ducts
-secretory units (acini)
-single cuboidal epithelial
Then the striated ducts, which are functionally important to the gland for performing _____ through several _____ on their basal side.
- most of the ion exchange between the initial salivary fluid and the extracellular matrix
-membrane folding (striations)
Then a collecting duct (_____) is connected to
______ which is responsible for _____
-stratified epithelial
-all parts of the gland
-carrying the final secretion to the oral cavity
Myoepithelial cells have cellular extensions that are ______ contributing to expelling the salivary content to the ductal network.
-wrapping around the end bud structures and striated ducts,
serous acinar cells with secretory granules have a lot of ____
RER and golgi
Mucous cells vs serous cells under TEM
-mucous cells contain large hydrophilic granules (less electron dense)
-serous cells have small electron dense granules apically
Submandibular gland is a ______ gland with _____ being predominant.
Sublingual gland is a _____gland
-mixed serous and mucous
-serous cells
-mixed but largely mucous
In the intralobular duct system, secretory acini and tubules empty into _____ and several of these ducts join to _____
-short intercalated ducts, lined by cuboidal
epithelial cells,
-form a striated duct
The intralobular/striated ducts have a more columnar duct shape with ______
-many infoldings of their basolateral membrane, all aligned with numerous mitochondria (for ion uptake)
Striated ducts reabsorb _____ from the
initial secretion and their folded cell membranes present a ______, facilitating rapid ion transcytosis and making the secretion ______.
-Na+ ions
-large surface area with ion transporters
-slightly hypotonic
Salivary glands contain several pools of ______ able to self-renew, proliferate and give rise to differentiated ______
-undifferentiated progenitors
-acinar and ductal cells
_____ is a “master regulator” of acinar formation
-SOX2
salivary gland: Genetic removal of SOX2 inhibits ______
formation of acinar cells but no effect on ductal cell formation
Expansion of SOX2 expressing cells in salivary gland during development requires _____
-innervation by peripheral nerves
salivary gland acinar and duct lineages are maintained separately during _____ but after injury, ______
-homeostasis
-cellular plasticity allows those lineages to restore damaged function
Current regeneration approaches for salivary gland dysfunction
-Exogenous delivery of cells or genes
-Endogenous reactivation of resident stem cells or tissue components
xerostomia aka _____
dry mouth
main function of lungs
-exchange of O2 and CO2 to and from the blood
respiratory system has two parts: _____ respiratory tract
upper and lower
Histologically and functionally, the respiratory system has a conducting portion, which ______, and a respiratory portion, where ______, consisting of _______
-consists of all the components that condition air and bring it into the lungs
-gas exchange actually occurs
-respiratory bronchioles, alveolar ducts, and alveoli in the lungs
Respiratory system includes the ____(3)
trachea, airways, and distal alveoli
Respiratory system link to the ____ to accomplish gas exchange
cardiovascular system
The epithelial lining of the trachea and bronchi is _____ containing which cells?
-pseudostratified
-basal cells, club cells and ciliated cells with a small number of neuroendocrine cells and goblet cells
_____are the basic functioning units of the lungs that perform gas exchange
-Alveoli
There are ______ alveoli in adult and total surface area of alveoli is ____ square meters
-~300-700 million
-78-100
conducting portion of RS consists of _____
-nasal cavities, pharynx, larynx, trachea, bronchi
(Gr. bronchos, windpipe), bronchioles, and terminal bronchioles
respiratory portion of RS consists of _____
respiratory bronchioles, alveolar ducts, and alveoli
Alveoli are the cellular sites of the ______ between
inspired air and blood
-exchange of O2 and CO2
Alveoli are _______ structures.
-small, airfilled, saclike
lung comes this germ layer?
foregut endoderm
Lung endoderm specification begins on _____ of the _____ foregut endoderm where initiation of ____ expression commences
-the ventral side
-anterior
-Nkx2.1
lungs: low Nkx2.1 expression = ____
trachea
lungs: high Nkx2.1 expression = _____
budding lungs
lungs: Sox2+, TP63 expression = ____
trachea + proximal airways/progentiors
lungs: Sox9+, Id2+ expression = ____
distal airways/progenitors
alveolarization stage of lungs happens when?
-start in utero in humans, but after birth in mice
lungs: Early Nkx2.1 progenitors is surrounded by mesenchyme that provides these paracrine signals for lung development: ______ (2)
- Wnt2 promotes expression of Nkx2.1 via βCatenin
- Fgf10 which is essential for branching morphogenesis
progenitors of lungs expresses ____
Nkx2.1
lungs: Proximal Progenitors are all found within _____. Distal progenitors populate _____
-the conducting airways
-the alveoli
proximal progentiors differintiates in _____
neuroendocrine and non- neuroendocrine cells, which then forms secretory, goblet and cilliated cells
FGF10 expression in distal progenitors does what?
direct direction of branches
BMP and SHH expression in distal progenitors does what?
restrict FGF10 signal
Branching morphogenesis is finite as ___ are lost after birth
Sox9 progenitors
cells of upper respiratory epithelium
-goblet cells
-ciliated cells
-basal cells
-neuroendocrine cells
-club/clara cells
lungs: goblet cells descr.
-basal nuclei and apical domains have granules of mucin glycoproteins and play a role in innate immunity
lungs: ciliated cells descr.
-majority of cells
-columnar cells with beating cilia to remove debris, microorganisms out of lungs
-200-300 cilia per cell on apical surface
lungs: basal cells descr.
-stem cells
-mitotically active cells
lungs: neuroendocrine cells descr.
-secrete serotonin and peptides to regulate rate of mucous secretion, cilia beating, and contraction smooth muscle cells
lungs: club/clara cells descr.
-exocrine cells secrete surfactant to protect epithelium
-produce glycoproteins and microbial peptides
-can self renew and produce ciliated cells
____ signalling control the balance of cells in upper RS
- NOTCH
mucous layer of RS is ___ thick
5 um
mucosciliary escalator (def.)
cilia all beat in same direction at about 12 beats per sec
If debris gets into the alveoli, then what happens?
it is engulfed by macrophages
submucosal gland descr.
-Lined by goblet and serous cells
-Enter airway via single duct
-Secrete mucin, host defense, innate immune proteins, antimicrobial peptides, electrolytes
-Provide rapid response to irritants or neural stimulation via regulation of secretory activity
Trachea / bronchi description of cells
-pseudostratified columnar epithelia with ciliated cells
-Club/Clara cells and goblet cells
High numbers of the basal cells (stem cells) decrease in number as _____
you move towards bronchioles and alveolar cells
Bronchioles have ______ cells which are _____ and are thought to function as _____
-neuroendocrine
-innervated
-airway sensors
Bronchial wall: the epithelial lining of bronchi is _____
-mainly pseudostratified ciliated columnar cells with a few goblet cells
-lamina propria contains layer of smooth muscle around the bronchus
-submucosa has supporting cartilage
-the adventitia includes blood vessels & nerves
Bronchioles size
very variable
bronchioles cell descr.
larger bronchioles: pseudostratified columnar epithelium with cilia
very small bronchioles: cuboidal epithelium with cilia
elastin in smooth muscle
Ciliated cuboidal cells remove substances via ______
-coordinated cilia movement
The last parts of the air conducting system before the sites of gas exchange appear are called the _____
terminal bronchioles
terminal bronchioles cell descr.
-club cells (exocrine) and have apically granules.
-secretes surfactant to reduce surface tension to prevent collaspe
-some SC that can regenerate all cells of bronchioles
Terminal bronchioles branch into _____, which then branch further into _____ and individual ____.
-respiratory bronchioles
-alveolar ducts
-alveoli
Respiratory bronchioles are similar to terminal bronchioles except for the _______ along their length.
-presence of scattered alveoli
bronchioles parallels ____
pulmonary blood vessels
There are two types of cells in the lining of the alveoli: _____ + descr.
-Type I alveolar cells cover most of the wall: they are thin and flat (squamous; 80 nm) to allow gas
exchange.
-Type II alveolar cells are interspersed among them. These are plump and secrete surfactant, a phospholipid-rich material that forms a film on
the free water surfaces, which reduces ST, making it easier to re-inflate even if they collapse.
alveolar pores are formed by ___
the fusion of type 1 alveolar cells in the middle
respiratory membrane consisted of ____
alveolar epithelium, fused basement membrane of alveolar epithelium and the capillary endothelium (not fenestrated)
Surfactant contains protein -lipid complexes synthesized initially in _____
-the ER and Golgi apparatus
Further processing and storage of surfactant occurs in large organelles called ______
-lamellar bodies (100-400 nm)
In surfactant-producing cells the _____ are added to the lamellar bodies.
-vesicles in multivesicular bodies
Surfactant is secreted continuously by_____ and forms an oily film containing _______
-exocytosis
-phospholipids and surfactant proteins
Type II alveolar cells ultrastructure
-cuboidal cells bulging into the air space, interspersed among the type I alveolar cells
-bound to AEC1 via tight junctional complexes
cells from highest capacity for self-renewal/regeneration
-(highest- constant renewal, stem, progenitor cell pop’n) intestine, hematopoiesis, hair follicle
-(fairly quiescent as adult, can regenerate after injury)lung, liver, pancreas
-(lowest-quiescent as adult, can’t really respond well after injury) heart, brain
The lung has _____ turnover in the adult, and can _____ in response to injury
-very slow but continuous
-regenrate
different progenitors of lungs
-Basal stem cell (BSC) - can make secretory and ciliated epithelia in trachea/bronchi, can make alveolar epithelium after extreme injury
-Neuroendocrine cell - can make secretory and ciliated epithelia after injury (limited)
-Bronchioalveolar stem cell (BASC) between bronchiolar and alveolar region- activated after injury
-AEC2- can self renew/forms AEC1 during homeostasis/after injury
BSC is marked by ______
Trp63+/K5+
BASC is marked by ______
Sftpc+/Scgb1a1+
Alveolar progenitor is marked by ______
Sftpc-/Itgb4+
Components of lung epithelial stem cell niche (7)
-intraepithelial signalling
-cell-cell adhesions
-cell-matrix adhesions
-biophysical forces
-inflammatory and immune signals
-nervous innervation
-epithelial-stromal interactions
lung: Differentiation of either ESCs or iPSCs into specific tissue lineages can be guided by adding combinations of _____to the media at specific times during culture
-growth factors or small molecules (CHIR)
BALO (def.)
a “mini lung” model to study cell–cell interactions
BALO is formed by ____
BASC were cultured with macrophages and mesenchymal cells in Matrigel-based environments
BALO was used to study ____
SARS-CoV-2 effect of lungs
