Epithelium Surface Specializations

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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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