6 TOB Epithelial Specialization
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What are six epithelial specializations?
- 1. Bind cells together (zona adherens, desmosomes)
- 2. Bind epithelial sheets to lamina propria (hemidesmosomes, basal lamina)
- 3. Seal epithelium (zona occludins, tight junctions)
- 4. Synchronize epithelial activity (gap junctions)
- 5. Promote absorption, secretion and diffusion (microvilli, outfolding, infolding)
- 6. Protection (Glycocalyx, Cilia [also promotes reproduction and hearing])
- goblet cells
- glandular simple columnar epithelial cells whose function is to secrete mucin, which dissolves in water to form mucus
- they use merocrine exocytosis for secretion
respiratory epithelium contains:
goblet cells, mucus cells, ciliated cells
cilia and flagella
- motile projections from a cells’ apical surface
- found in the epithelial lining of trachea, fallopian tubes, & spermatozoa flagella
- (can be visualized with light microscope)
What are cilia and flagella made of?
- they're composed of MICROTUBULES arranged as 9 outer doublets & 2 central singlets
- associated accessory structures include a central sheath, radial spokes, nexin linkages, & dynein arms
- as a whole, the cohesive bundles are called the axoneme
- the cytoskeletal (microtubule) inner core of cilia and flagella
- they're surrounded by plasma membrane and anchored at their proximal ends to a basal body (modified centriole) in the apical cytoplasm of the cell
What is each part of the axoneme composed of?
- doublet/singlet microtubules?
- peripheral linkage?
- inner & outer arms?
- doublet/singlet microtubules: tubulin
- peripheral linkage: nexin
- inner & outer arms: dynein
What particles build and maintain the cillium?
IFT (intra flagellar transport) particles
describe the movement of flagella
symmetrical planar waves for propulsion of single cells (eg. spermatozoa)
describe the movement of cilia
- asymmetrical, 3-dimensional waves for moving fluids over surfaces (eg. as mucus in trachea, or ovum in oviduct)
What specifically causes movement in microtubule structures?
- dynein ATPase: it generates active sliding between adjacent doublet fibers which bends the axoneme
- immotile cilia LACK dynenin or other components essential for force generation
- non-motile cilia that usually occur one per cell
- specialized primary cilia can be found in human sensory organs such as cone and rod cells in the retinal epithelium, or hair cells in the cochlea
primary ciliary dyskinesia (PCD)/immotile ciliary syndrome/Kartagener Syndrome (KS)
- AR genetic disorder that causes a defect in the dynein of cilia that manifests as uncoordinated or absent beating
- main consequence of impaired ciliary function = reduced/absent mucus clearance from the lungs and therefore susceptibility to chronic recurrent respiratory infections (eg. sinusitis, bronchitis, pneumonia, and otitis media)
- when accompanied by situs inversus, chronic sinusitis, and bronchiectasis --> Kartagener syndrome
Why is infertility common in those with primary ciliary dyskinesia?
because of defective transport of the ovum by ciliary action in females and immotile spermatozoa resulting from defective flagellar motility in male
- cell surface projections found on many cells that serve to increase the absorptive surface area of the cell
- found on epithelia that lines the SMALL INTESTINE & proximal convoluted tubule of the KIDNEY
- brush/striated border are composed of lots of microvilli
What's the structure of microvilli?
bundles of actin MICROFILAMENTS form a core which is surrounded at the distal end by plasma membrane and at the proximal end attached/embedded in the terminal web
- terminal web
- filamentous structure found at the apical surface of epithelial cells that anchor microvilli to the apical cell membrane
- composed primarily of actin filaments stabilized by spectrin
- ATPase activity of myosin explains the ability of the terminal web to contract, which spreads apart the microvilli & therefore increases absorption
- a cell surface coat consisting of complex carbohydrates associated with proteins
- using a light microscope it looks like a fuzzy coating on cell surfaces
- long modified microvilli found in the male reproductive system (epithelium of epidydmis and ductus deference) as well as the sensory hair cells of the inner ear
- purpose is for reabsorption
- terminal bar
- a junctional complex that attaches adjacent epithelial cells to each other on their lateral surfaces
- it's found at the apical cell boundaries of certain epithelial cells & is composed of 3 structures
- 1. zonula occludens [tight junctions] (TJ)
- 2. zonula adherens (ZA)
- 3. desmosome (D)
zonula occludens (tight junctions)
- areas in which the membranes of two cells join together forming a virtually impermeable barrier to fluid
- tetraspan transmembrane proteins claudins & occludins interact homophilic and mediate membrane connections
- these proteins themselves associate with intracellular adapter proteins such as ZO-1, ZO-2, and ZO-3 found in the actin cytoskeleton
- tracer = black
- depending on which side (apical or basal) it's added to it will show where the tight junction is located based on the tracer not being able to move and stain past a certain point
- a cell junction located BELOW the zonula occludens whose cytoplasmic face is linked to the actin cytoskeleton
- they serve to structurally reinforce the tight junctions
- this junction is mainly responsible for adhesion between cells mediated by homophilic interactions between E-cadherins
- single pass transmembrane proteins responsible for mediating zonula adherens between cells
- they themselves are linked to the actin/actomyosin cytoskeletal systems via adapter proteins catenins, actinins & vinculins
- desmosome (macula adherens)
- snap-fastener or button between cells (macula = spot) that help resist shearing forces
- adhesion is mediated by homophilic interaction between desmoglein & desmocolin (cadherins)
- these are linked to cytoskeletal intermediate filaments network via plakoglobin and desmoplakin (adapter proteins)
- blue = zonula adherence
- green = intermediate filaments
- areas where blue meets blue = gap junctions
pemphigus (desmosome clinical correlate)
- an autoimmune disease in which patients produce antibodies against proteins in DESMOSOMES which hold epithelial cells in the skin together
- this results in severe blistering of the skin due to the leakage of fluids into the loosened epithelium
gap junction (or nexus or macula communicans)
- metabolic coupling (allow passage of ions and small water soluble metabolite)
- chemical coupling (allow passage of 2nd messengers to coordinate responses to extracellular signals)
- electrical coupling- allows synchronous function of group of cells- heart beats, peristalsis, vision
- their cytoplasms are connected by a connexon channel, each cell contributing 6 connexin subunits (half a channel each) to form the junction
- (synapse is another name for gap junction)
- half desmosomes found at the basal surface of some epithelial cells that make "contact" with the basal lamina to prevent detachment of the epithelium from the underlying tissue
- they associate with the basement membrane using heterophilic interactions
What does the hemidesmosome heterophilic interaction consist of?
- the adhesive component of the desomosome is a heterodimer of alpha6 beta4 integrin associated with Collagen XVII
- inside the cell this complex associates with the cytoskeletal network of intermediate filament via the adapter proteins p-lectin and B230
- Outside the cells it interacts with laminin to anchor the basal surface of the epithelium to the basement membrane
Epidermolysis bullosa simplex (EBS)
- defective tonofilaments
- a blistering disease formed by mutation in genes encoding the intermediate filaments keratin 5 and keratin 14 (they interact w/ hemidesmosomes to form a continuous cytoskeletal network that reinforces the epithelium)
Junctional epidermolysis bullosa (JEB)
- defective hemidesmosomes or anchoring filamentsa
- blistering disease due to autoimmunity against collagen type XVII
- destruction of collagen XVII results in the detachment of the epithelium from the basal lamina - BAD
collagen type XVII
- component of hemidesomosomes that links the adhesion complex (heterodimer) to the basal lamina
- it prevents detachment of the epithelium from the basal lamina
- (17 attaches epith --> to basal lamina)
collagen type VII
- anchoring fibrils that anchor the basal lamina to the underlying connective tissue and prevent detachment of the basal lamina + any overlying epithelium FROM the connective tissue
- (7 attaches epith + basal lamina --> to CT)
Dystrophic epidermolysis bullosa (DEB)
- a blistering disease formed by defective collagen type VII
- destruction of collagen VII results in the detachment of the epithelium & basal lamina from the underlying connective tissue
- functions as structural support to epithelia and a selective barrier between epithelial and connective tissue
- (secreted by the epithelium; forms a two-dimensional dense layer; consists of a very fine meshwork of fibrils called the lamina densa)
What are the main components of the basal lamina?
- type III collagen (recticulum), laminin, enactin and proteoglycans such as perlacan (heparan sulfate proteoglycan)
- collagen type IV & laminin associate to from two-dimension networks linked to one another vial small adapter proteins nidogen and pelican
How is the basal lamina attached to the connective tissue?
by anchoring fibrils made out of type VII collagen
What is unique about the basal lamina in the lung alveoli and renal glomerulus?
- the basal lamina of adjacent epithelial layers fuse to form structures specialized for air filtration in the lung, and blood filtration in the kidney
Where in the body might a discontinuous basal lamina be found?
in sinusoids, to allow for passage of medium and large proteins from capillary vessels
What are two specializations of the basal surface lamina?
1. epithelial apposition (fusion of the basement membrane that serves to filtration material passing through)
- 2. infoldings (invagination of the basement membrane facilitates ion transport)
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