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1.POLARITY- structural and functional differentiationbetween the distal end (toward free surface) and
proximal end (toward CT).
This polarity is evident also in the arrangement of
organelles in the cell interior- the centrosome and
Golgi apparatus being in a supranuclear position. The cell axis, an imaginary line passing through the
centrosome and the center of the nucleus is usually
vertical or perpendicular to the basement lamina.
Oriented parallel to the cell axis and found in greater
numbers in the apical cytoplasm are the long
mitochondria of columnar epithelia.
In stratified squamous epithelia, there is less
evidence of cell polarity.
SPECIALIZATIONS OF EPITHELIAL TISSUE
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Juxta-luminal junctional
complex are sites of low
resistance to ion flow,
providing cell communicationand for coordination of
activities.
The 3 most common kinds of
cell junctions are adhesive
junctions, tight junctions and
gap junctions. Adhesive junctions
(desmosomes,
hemidesmosomes, adherens
junctions) link adjoining cells to
each other and to the ECM.
Although adhesive junctiontypes are similar in structure
and function, they contain
distinct intracellular
attachment proteins and
transmembrane linker proteins.
CELL JUNCTIONS
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The intracellular attachment proteinsform a thick layer of
fibrous material on the cytoplasmic side of the plasma
membrane called a plaque which binds actin microfilaments in
adherens junctions and intermediate filaments in desmosomesand hemidesmosomes.
The transmembrane linker protein is anchored to the plaque by
the cytoplasmic domain and binds the ECM or to the same
proteins on other cells.
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Distribution
of celljunctions in
3 domainsof epithelial
cells.
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ZONULA
OCCLUDENSextends
around the
entire
perimeter ofthe cell, but
typically
located near
the apex.
Also known as
terminal bars, tight or
occluding junctions
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Tight junctions consist of fused
ridges of tightly packed
transmembrane junctional
proteins.
Can be rapidly formed anddisassembled (e.g. during WBCmigration across endothelium).
Epithelia are classified either
as tight or leaky based on
the permeability of the zonula
occludens.
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Tight junctions block
lateral movement of
lipids and membrane
proteins to keep a cellpolarized. They leave
no space between
plasma membranes of
adjacent cells to
prevent the movementof molecules across
cell layers.
Sodium/glucose
symport proteins and
export by glucose
transport proteins onthe basolateral surface
and tight junctions
prevent the lateral
movement of these
transport proteins.
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ZONULA ADHERENS (intermediate junction,
belt desmosomes) is basal to the zonula
ocludens. The adjacent plasma membranes
are separated by a gap of 15-20 nm, filled withan electron dense plaque containing a
glycoprotein localized only in the membrane,
(adherens junction-specific cell adhesion
molecule or A-CAM or E-cadherin).
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Myosin,
tropomyosin,
-actinin, andvinculin, actin-
containing
microfilaments
insert into the
plaque tostabilize the
junction
between
epithelial cells,
fibroblasts,smooth muscle
cells and at
intercalated
discs.
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MACULA ADHERENS or
DESMOSOMES are bipartite
structures of apposing cell
membranes. An attachment
plaque on the cytoplasmic
side anchors tonofilaments
which are intermediate
filaments.
Desmosomes form strong
points of adhesion between
cells in a tissue such that
two adjoining cells are
separated by a thin spaceof 25-35 nm, the
desmosome core, in which
cadherin molecules
mediate cell-cell adhesion.
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The plaques on the inner surfaces of cells joined
by desmosomes have a mixture of intracellular
attachment proteins (desmoplakins andplakoglobin) which interact with the tonofilament
intermediate filaments.
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Adherens junctions called FOCAL ADHESION can join
a cell to the ECM, primarily through fibronectin
receptors.
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HEMIDESMOSOMES connect a cell, through a plaque, to
the basal lamina (ECM) by integrins. As in desmosomes,
hemidesmosomes interact with tonofilament intermediate
filaments. Adherens junctions resemble desmosomes
except two adjoining cells are
separated by a thin space of
20-25 nm and connect to actin
microfilaments
in the cytoplasm.
Some of the
transmembrane
glycoproteins are
cadherins.
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Hemidesmosomes
occur at most basal
surface of stratifiedsquamous epithelia
where the
superficial layer lack
junctional
complexes, and the
basal cells are
exposed to the
underlying CT.
They serve mainly as sites of
attachment for the actin-based
contractile system of the
cytoplasm.
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GAP JUNCTIONS (NEXUS)
separate cells by 2-3 nm and
allow direct electrical andchemical communication.
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The nexus is a site where there is no actual fusion of
membranes, and the gap is bridged by a connexon. These are
tightly packed 7 nm wide hollow cylinders in two adjacent cellmembranes that form a 3 nm thin hydrophilic channel that
allows the passage of small molecules and ions.
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The connexons of each membrane link to form
continuous pores that bridge the intercellular gap,
allowing passage of ions, cyclic AMP, amino acids andother small molecules.
As sites of electronic coupling (reduced resistance to
ion flow), it is the only type of junction mediating flow
of current between cells important in intercellular
communication and coordination.
An influx of calcium ions results in the closure of their
channels, preventing spread of damage to other cells.
Also found between osteocytes, astrocytes, cardiac
muscle cells, smooth muscle cells, & endocrine cells. Cancer cells generally do not have gap junctions, so
that cells fail to communicate their mitotic activity to
each other, which may explain their uncontrolled
growth.
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CELL SURFACE MOLECULESSurface
glycoproteinsthat bind to
other cells, or
to components
of theextracellular
matrix; play a
role in mutual
recognition ofsimilar cell
types
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1. Cadherins- a family of single-pass transmembrane
glycoproteins which stick embryonic cells together in the
presence of calcium (E-cadherin are found in epithelial tissues,N-cadherin occurs in neural tissue).
Cadherin tails are anchored to actin bundles in the
cytoskeleton by a complex called catenins (F-catenin, a
component of the Wnt signaling pathway provides a potential
link between cell signaling & cell association).
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2.Cell adhesion molecules
(CAMs)- single-pass
transmembrane glycoproteinswhich do not require calcium
to bind to other cells.
N-CAMs are a large family of
proteins formed by alternative
splicing Expression of low sialic acid
N-CAM molecules on adjacent
cell surfaces promote junction
formation on the adjacent cell
membranes.
When the polysialic acid
residues are removed, the two
cells can adhere.
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Three glycoproteins that mediate Ca+2-dependent
cell adhesion (desmoglein I, desmocollin I & II) and 4
nonglycosolated proteins located in the attachmentplaque (desmoplakin I & II, pakoglobin & a basic
polypeptide) have been identified as desmosome
components.
Abundant in stratified squamous epithelium, which
are sites of attachment of the cytoskeleton to the
free surface
Although sites of cell to cell adhesion, they do not
hamper the flow of substances between cells.
Bullous pemphigold is an autoimmune disease inwhich antibodies against desmosomal proteins are
formed. This results in widespread skin & mucous
membrane blistering as desmosomal proteins fall
apart.
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3.Integrins (ICAMS)- cell
surface glycoproteins
that require (Ca+2 orMg+2), to interact with
ECM components
(fibronectin, laminin and
collagens). Important in epithelial
cell cohesion and
attachment to substrate
& cell migration during
tissue repair.
Bound integrins prevent
transcription of genes
that specify apoptosis.
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Binding of integrins to ECM also activatessignal transduction pathways.
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1.MICROVILLI
Closely packed, finger-
like projections of
cytoplasm that increase
surface area of the cell.
Number and shape on
cell surface correlate
with absorptivecapacity.
Can be seen under LM
(brush border or
striated border).
Usually present onsurface of microvilli is
an amorphous cell coat
of glycoprotein
glycocalyx.
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Contain a core of actin
filaments, which are
anchored to villin at tip.
Actin extends downwardinto apical cytoplasm
where it attaches to the
terminal web which is a
horizontal network of
actin filaments lying justbelow base of microvillus.
These actin filaments are
stabilized by spectrin.
Spectrin anchors terminal
web to apical membraneof cell.
Also contains myosin II
and tropomyosin
filaments, which allows
microvillus to contract.
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2.STRIATED/BRUSH
BORDER
Delicate vertical striationsseen in a refractile border
of columnar epithelia.
Plasma membrane-
covered microvilli
extensions 80-90 nm indiameter and 1-2 Qm long.
Non-contractile, and have
a purely supportive
function.
Cytoplasm shows parallelbundles of actin micro-
filaments anchored in a
dense mat of filaments in
the terminal web.
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Prominent in cells whose
principal function is to
enhance the surface area
of membranes exposedto substances for
absorption and digestion
Biochemical analysis
show that they containdigestive enzymes in
their glycocalyx.
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3.STEREOCILIA- long
pyriform tuft of slender
processes projecting intothe lumen.
Seen in the epithelium
lining the epididymis and
the hair cells of the inner
ear. Individual processes are
not true cilia but are non-
motile, very long microvilli.
Amplify the cell surface in
absorptive epithelium. In the inner ear they
generate an electrical
signal that is conveyed to
the CNS.
In the testes, theyconcentrate the seminal
plasma during its
passage through the
epididymal duct
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4.CILIA- numerous motile
processes larger than microvilli
Arranged in parallel rows
projecting from the free surfaces
of some epithelial cells.
Cilia moving in waves and
sweeping over the epithelial
surface serve to propel fluid or
a coating of mucus towards the
exterior.
At the base of each cilium is a
dense elongate granule called
the basal body.
They arise de novo, developing around small bodies
called deuterosomes or procentriole organizers.
These organizer lengthen by polymerization of tubulin to
form the 9 ciliary triplet microtubules; serve as templates
during ciliogenesis.
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Ciliary motion depends on
ATP-dependent dynein-
generated sliding of
doublet microtubules. Kartageners syndrome, a
rare disorder in which
dynein arms are lacking,
result in situs inversus
(organ reversal due tofailure of cells to migrate
properly during
embryogenesis),
recurrent
sinus/pulmonaryinfections (inability to
move mucous), and
sterility in males (retarded
sperm movement)
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1.BASEMENT MEMBRANE
(membrane propia, basal lamina)-
present in all epithelia except:
follicular epithelium of the thyroid
gland, the olfactory neuro-
epithelium and the transitional
lining epithelium of the excretory
passages of the kidney.
2.Functions:
Attachment of the basal cells of the epithelium,
providing stronger anchorage of the tissue
Form a barrier between epithelium & connective tissue
Under normal conditions, lymphocytes may pass the
basal lamina during immune surveillance
In cancer, neoplastic cells may pass the basal lamina
as a scaffolding during malignant invasion
A passive molecular sieve or ultrafilter.
A scaffolding in regeneration or wound healing
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It is a thin, homogeneous or fibrous layer composed
of type IV collagen (exclusive only to the basal
lamina), laminin (adherent to specific membranereceptors, and to collagen of the lamina densa) and
proteoglycans (heparan sulfate, fibronectin).
Under EM, 2 zones are distinguishable: the lamina
lucida adjacent to basal cell membranes, and the
lamina densa, an outer zone exposed to theunderlying CT.
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The lamina increases in density at its outer zone,
where small units of collagen and reticular fibers are
found.
It is believed to be a product of the epithelium, while
the outer dense layer of reticular fibers is a product of
CT fibroblasts.
The polysaccharide content of the basal lamina can
be well shown by the PAS technique; due to thereticular fibers, it stains + in silver dyes
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2.TUNICA or LAMINA PROPRIA
All epithelia possess a
tunica propria.
Maybe areolar or fibro-
reticular CT located
immediately beneath the
basement membrane.
Serves as a support to the epithelium, and as avascularized CT bed containing the blood vessels,
lymph vessels and nerves.
The blood vessels do not penetrate the basement
membrane, while nerve fibers do.
CT papillae are outgrowths of the tunica propiatowards the deep surface of thick epithelium such as
stratified squamous epithelium of the skin.
This facilitates nutrition by increasing surface area
thru which diffusion can take place.
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