Dr. P. Poornima,

First Year Postgraduate

NON-KERATINOCYTES/ CLEAR CELLS

•Histologic sections - clear cells.

•10% of the population in the epithelium

•Depending on the position of clear cells in the epithelium. They

are further divided into:

low level clear cells (Melanocytes & Merkel cells) and

high level clear cells (Langerhans cells)

MELANOCYTE

•Melanocytes - basal layer of epithelium.

•Only cells that synthesize the pigment melanin, which is

packaged in, Melanosomes.

•Oral mucosal melanocytes are present in unipolar,

bipolar, or multiple-dendritic forms, with marked

variation in cell size and complexity of dendritic

systems.

History:

•Becker in1927 - dendritic cells - basal layer of oral epithelium.

•Oral Mucosal Melanocytes - gingival - Landlaw & Cahn in

1932.

Origin:

•From the neural crest.

•Number of melanocytes in the oral epithelium is the same

regardless of racial/ethnic origin.

•The colour of oral mucosa is determined by several factors:

•Number, size, and distribution of melanosomes

•Type of melanins,

•Masking effect of heavily keratinized epithelium.

•Degree of vascularization of tissues and by level of

haemoglobin in blood

Embryonic development of melanocytes:

Influenced by a number of signaling molecules produced

by neighbouring cells:

•Wnt,

•ET‐3,

•BMPs,

•SF & c‐Kit ligand,

•HGF

•Cadherins

The keratinocyte-melanocyte unit

•The ratio of melanocytes to keratinocytes ranges from 1:10 to

1:15.

•Each unit consists of one melanocyte and a group of about 36

keratinocytes.

Melanosome

•Is membrane‐bound organelle in which melanin

biosynthesis & storage take place

Melanosome biogenesis: 4 morphologic stages

Melanosomal transport:

Within melanocytes:

•Melanosomes are transferred from cell centre -melanocytes

dendrites - through microtubules

•The transport is controlled by 2 classes of

microtubules‐attached motor proteins kinesins & dyneins.

•Centrifugal movement by kinesin, Centripetal movement

by dynein

To keratinocytes:

1)Exocytosis

2)Cytophagocytosis

3)Fusion of melanocyte & keratinocyte plasma membrane

4)Shedding of melanosome‐filled vesicles followed by

phagocytosis of the vesicles by keratinocytes

Regulation of melanocyte function:

UV irradiation

Functions of melanocytes:

•Determines the colour of skin, hair and eyes

•Provides protection from stressors

•Capacity to sequester metal ions and to bind certain drugs

and organic molecules

Langerhans cell

Langerhans cells (LC) are dendritic, antigenpresenting cells

(APC), function as the “outermost arm” of the immune

system.

located suprabasally, constitute 2-8%

History:

•Paul Langerhans in 1868.

•In 1961,ultra-structural characteristics - Birbeck.et.al.

•The Birbeck‘s granule serves as element for

morphological identification of the LCs.

Origin:

•From bone marrow

Location

Ultrastructure:

•12 microns, cleaved or folded nucleus, absence of

tonofilaments and desmosomes.

•Birbeck granules – size- 100 nm to 1 μm - “tennis racket”

•seen in continuity with the cytoplasmic membrane and are

often clustered near the Golgi apparatus.

•Two hypotheses explaining their origin:

•Arise from the Golgi apparatus.

•Arises from invaginations of the cytoplasmic

membrane.

•The Birbeck granules seem to be specific markers of LCs.

•Based on electron microscopy, two types of LCs:

•Type – I

•Type – II

Life cycle of Langerhans cell

Merkel cell

folded nucleus, a clear, organelle-rich cytoplasm with

peripheral protrusions among the epithelial cells, few

desmosomal attachments

found in basal and spinous layer of epithelium, concentrated

at base of retepegs.

History:

In 1875, Friedrich Sigmund Merkel, in base

of rete pegs of the epidermis of pig snout

skin called -‘Tastzellen’ (touch cells).

Origin:

Two hypotheses concerning origin of MCs:

(1)Neural crest origin hypothesis and

(2)Epidermal origin hypothesis

Evidence from experiments, in birds -neural crest derived,

in mammals - epidermal origin.

Merkel’s cell located in the

region of the stratum basale,

associated with nerve axon

Ultrastructure:

•In stratum basale of the epithelium.

•approximately 10 μm in diameter.

•specialized neural pressure sensitive receptor cell.

•commonly seen in masticatory mucosa, but absent in

lining mucosa.

•MCs differ from other non-keratinocytes – not dendritic.

High numbers in the lip, anterior hard palate and gingiva.

The regions richer in MCs are involved in tactile

perception.

In oral mucosa in recognition of particle size and texture

during mastication.

More numerous in the sun-exposed skin than in covered

skin.

• MCs shows lobulations or spine-like protrusions –

microvilli, upto 50, 2.5 mm in length.

•The spine-like protrusions of highly variable length

attached to the neighboring keratinocytes by

relatively few, small desmosomes

Ultrastructure:

•Dense-core secretory granules.

•Granules measures about 80-120 nm or100-140 nm in

diameter.

•Cytoplasm shows loosely arranged intermediate

filament cytoskeleton.

•possesses a characteristic intranuclear rodlet

•make contact with nerve terminals to form

MC-neurite complexes.

Electron micrograph of Merkel cell in the basal layer of oral epithelium.

The cytoplasm of this cell is filled with small, dense vesicles situated

close to an adjacent unmyelinated nerve axon. Arrowheads point to the

site of the basal lamina.

Basal Lamina

It is the interface between epithelium and the connective

tissue.

•Basal lamina is made up of :

• Lamina lucida: 20 – 40 nm thick –BP 180,integrins,

laminin-5

•Lamina densa: 20 – 120 nm thick- Type IV collagen,

laminins, perlecan, nidogen

•Lamina fibroreticularis:Collagen Type VII

Functions of basament membrane:

•Scaffold for tissue organization and template for tissue

repair.

•Selective permeability barrier.

•Physical barrier

•Firmly link an epithelium to its underlying matrix

•Regulate cellular functions.

Lamina densa is constructed of type IV collagen molecules

assembled to form a meshwork

Laminin-1 also undergoes self assembly to form a

meshwork.

The two networks combine through the interaction of

nidogen bridges to create a scaffold

The biochemical bond formed between integrins and

laminin-5 in tha basal lamina densa

•Type VII collagen forms special anchoring fibrils

•Looplike formations of Type VII collagen fibrils originate

and terminate in the lamina densa

•Collagen types VI and XV are also localized to the

basement membrane zone

Constituents of Basal lamina includes:

• Collagens: Type IV and Type VII

• Cell surface proteoglycans : Syndecan and Epican

• Noncollagenous components: Laminins, Nidogen,

Perlecan

Type IV Collagen:

•Type IV collagen is a nonfibrillar collagen

•Type IV procollagen molecules are heterotrimers

•Each chain–collagenous domain – about 1400 aminoacids

•Several short, non collagenous segments that impart

flexibility

•Made up from two α1 (IV) chains and one α2 (IV) chain.

•Connected to perlecan, nidogen, and BPAG-2.

Type VII Collagen

•Composed of three identical α chains

•Type VII collagen is made by epithelial cells and by

fibroblasts of the lamina propria.

Cell surface proteoglycans

Syndecan

syndecan – 1 is capable of forming attachments to

fibronectin, collagen types I, III, and V and tenascin

Noncollagenous components of Basal lamina

Nidogen

Perlecan

•Main producers – Fibroblasts

•Binds to fibronectin, nidogen and laminin

Laminins

•Primary organizer of the sheet structure, and early in

development, basal laminae consist mainly laminin.

•Large, flexible, extracellular, cross shaped adhesion proteins

consisting of three long polypeptide chains ( α, β, and γ).