Non keratinocytes

theoritical review document

1. NON-KERATINOCYTES






Dr. Bhargavi. V
Post graduate
Narayana Dental College &Hospital

2. CONTENTS
 Introduction
 Langerhans Cells
 Inflammatory Cells
 Merkel Cells
 Melanocytes
 Summary
 Conclusion

3. INTRODUCTION:

 THE PRINCIPAL CELL TYPE OF THE GINGIVAL EPITHELIUM, AS WELL AS OF OTHER
STRATIFIED SQUAMOUS EPITHELIA, IS THE “KERATINOCYTE”.

 IN ADDITION TO THE KERATIN -PRODUCING CELLS WHICH COMPRISE
ABOUT 90% OF THE TOTAL CELL POPULATION, EPITHELIUM ALSO
CONTAINS “NON-KERATINOCYTES”(10%).

 THESE CELL TYPES ARE OFTEN STELLATE AND HAVE CYTOPLASMIC
EXTENSIONS OF VARIOUS SIZE AND APPEARANCE.

 THESE NON-KERATINOCYTES ALONG WITH KERATINOCYTES PLAY AN
IMPORTANT ROLE,IN THE MAIN FUNCTION OF GINGIVA THAT IS THE
PROTECTION OF UNDERLYING TISSUES.

KERATINOCYTES:
AS THE NAME IMPLIES THESE CELLS CONTAIN KERATIN FILAMENTS
(CYTOKERATINS) IN THE FORM OF “TONOFILAMENTS ”.
NON-KERATINOCYTES:
 THESE CELLS DO NOT CONTAIN TONOFILAMENTS AND DESMOSOMES
 THEY DO NOT PARTICIPATE IN THE PROCESS OF MATURATION
EPITHELIUM.
 IN THE HISTOLOGIC SECTIONS THESE CELLS HAVE “CLEAR HALO AROUND
THEIR NUCLEI, AS THEY (EXCEPT MERKEL CELLS) LACK,DESMOSOMAL
ATTACHMENTS TO ADJACENT CELLS, SO DURING HISTOLOGIC
PROCESSING ,THE CYTOPLASM SHRINKS AROUND NUCLEUS TO PRODUCE
CLEAR HALO-THUS THEY ARE NAMED AS “ CLEAR CELLS”. @
TENCATES PAGE 333 ,327
 THEY MIGRATE TO ORAL EPITHELIUM F ROM NEURAL CREST OR FROM
BONE MARROW.
A VARIETY OF CELL TYPES ARE INCLUDED IN NON -KERATINOCYTES
 LANGERHANS CELLS
 LYMPHOCYTES
 MERKEL CELLS
 MELANOCYTES

5. LANGERHAN’S CELLS : @TENCATES,PR GARANT,ORALMICROBIOLOGY AND
IMMUNOLOGY
CELL TYPE LEVEL IN
EPITHELIU
M
SPECIFIC
STAINING
REACTIONS
ULTRA STRUCTURAL
FEATURES
FUNCTION
LANGERHAN’S
CELLS
SUPRA
BASAL
CD1A,CELL
SURFACE
ANTIGEN
DENDRITIC,NO DESMOSOMES
OR TONOFILAMENTS,
CHARACTERISTIC ‘LH’
GRANULES

ANTIGEN
TRAPPING AND
PROCESSING

MERKEL CELLS

BASAL

PAS
STAINING

NON-DENDRITIC,SPARSE
DESMOSOMES,TONOFILAMEN
TS,CHARACTERISTIC
ELECTRON DENSE VESICLES
AND ASSOCIATED NERVE
AXON

TACTILE
SENSORY
CELL.

MELANOCYTES BASAL

DOPA
OXIDASE-
TYROSINASE
,SILVER
STAINS

DENDRITIC,NO DESMOSOMES
OR TONOFILAMENTS;PRE -
MELANOSOMES AND
MELANOSOMES PRESENT

SYNTHESIS OF
MELANIN AND
TRANSFER TO
SURROUNDING
KERATINOCYT
ES

LYMPHOCYTES

VARIABLE

CD3-TCELLS,
CD20-BCELLS

LARGE CIRCULAR
NUCLEUS,SCANT CYTOPLASM
WITH FEW ORGANELLES,NO
DESMOSOMES OR
TONOFILMENTS
ASSOCIATED
WITH
INFLAMMATO
RY RESPONSE

6.  A DENDRITIC CELL OF INTERSTETIAL SPACES OF MAMMALIAN EPIDERMIS
AND MUCOSA THAT FUNCTIONS AS ANTIGEN PRESENTING CELL ,WHICH
BINDS ANTIGEN ENTERING THROUGH THE SKIN/MUCOSA AND
TRANSPORT IT TO LYMPH NODES.
 LOCATED AMONG THE KERATINOCYTES AT ALL SUPRA BASAL LEVELS.
 NAMED AFTER GERMAN ANATOMIST AND PHYSICIAN “PAUL
LANGERHANS” WHO DESCRIBED IT WHEN HE WAS A MEDICAL
STUDENT.?(1868 )( VIRCHOWS ARCH PATH ANAT PHYSIO)
 THEY BELONG TO RETICULO-ENDOTHELIAL SYSTEM AS MODIFIED
MONOCYTES AND DERIVED FROM BONE MARROW.
 THEY ACT AS SENTINELS IN EARLY DETECTION OF FOREIGN ANTIGENS.
 THEY ARE FOUND IN ORAL EPITHELIUM,NORMAL GINGIVA AND SMALLER
AMOUNTS IN SULCULAR EPITHELIUM.THEY ARE PROBABLY A BSENT
FROM JUNCTIONAL EPITHELIUM OF NORMAL GINGIVA.
ORIGIN:
 IT IS A CELL OF HEMATOPOETIC ORIGIN. THEY ARE DERIVED FROM THE
BONE MARROW PRE -CURSORS.
 A SPECIFIC TYPE OF MONOCYTE PROLIFERATES AND DIFFERENTIATES
TO FORM LANGERHAN’S CELLS.
 COLONY STIMULATION FACTOR(CSF) IS NECESSARY FOR
TRANSFORMATION.
 THEY ENTER THE BLOOD STREAM FROM BONE MARROW,CIRCULATE AND
LEAVE THE BLOOD STREAM TO ENTER LAMINA PROPRIA BEFORE
PENETRATING THE BASAL LAMINA TO ENTER
EPITHELIUM.(BERKOVITZ,HOLLAND G.R, BJ. MOXHAN ).
 SUCH MIGRATION MAY RELATE TO CERTAIN CHEMOKINES(MONOCYTE
CHEMOATTRACTANT PROTEIN 1) RELEASEDBY KERATINOCYTES WITH
SURFACE RECEPTORS ON LANGERHAN’S CELLS
 THEY APPEAR IN THE EPITHELIUM AT THE SAME TIME OR JUST BEFORE
MELANOCYTES,AND CAPABLE OF DIVISION WITHIN THE EPITHELIUM.

7. STRUCTURE:
 THEY ARE DENDRITIC - WITH LONG IRREGULARPROCESSES.
ULTRASTRUCTURE :
 THEY LACK TONOFILAMENTS AND DESMOSOMAL ELEMENTS TO
SURROUNDING CELLS.
 THERE IS CLEAR HALO AROUND NUCLEUS - SO THEY ARE CALLED AS
“CLEAR CELLS”.
 THE NUCLEUS IS CONVULUTED.
 THEY ALSO CONTAINS SMALL ROD/FLASK SHAPED GRANULESCALLED
“BIREBECK GRANULES” NAMED AFTER PERSON WHO FIRST DESCRIBED
THEM.(1961)
STAINING OR IMMUNOHISTO CHEMISTRY :
 GOLD IMPREGNATION IS THE CLASSICAL TECHNIQUE USED BY
LANGERHANS 100 YEARS AGO,BUT IT REQUIRES DILIGENT PREPARATION.
 THEY ARE FREE OF MELANIN - SO THEY DOES NOT STAIN IN DOPAMINE
REACTION AS MELANOCYTES.
 THEY EXPRESS FC RECEPTORS, CD1A CELL SURFACE ANTIGEN MARKER,
MHC-II PROTEINS ON THEIR SURFACE, WHICH SERVES VARIOUS PU RPOSES
DURING ANTIGEN PRESENTATION AND IMMUNE REACTIONS.
 THEY ALSO HAVE MARKED ATP ACTIVITY AND CAN BE LOCALISED DUE
TO PRESENCE OF ATPASE.
FUNCTION:
 BECAUSE OF THEIR EFFICIENT ANTIGENIC TRAPPING PROPERTY AND
THEIR CAPACITY TO GENERATE STRONG CO-STIMULATORY
SIGNALS.THEY HAVE AN IMPORTANT ROLE IN IMMUNE REACTION AS
“ANTIGEN PRESENTING CELLS ” FOR LYMPHOCYTES.

8.  FOLLOWING UPTAKE OF ANTIGEN, THESE CELLS MIGRATE INTO MORE
CENTRAL LOCATION SUCH AS REGIONAL LYMPHNODES,WHERE THEY
STIMULATE ANTIGEN SPECIFIC T-CELL PROLIFERATION.
LANGERHAN’S CELLS INGEST ANTIGEN BY MACROPINOCYTOSIS AND VIA A
VARIETY OF CELL SURFACE RECEPTOR (TOLL LIKE RECEPTORS)

THEN THEY LEAVE THE EPITHELIUM

ENTER LYMPHATICS AND TRAVEL TO PARA CORTEX OF
LYMPHNODE.

THERE THEY DIFFERENTIATE INTO MATURE DENDRITIC CELLS.

THEY ACTIVATE NAIVE T —LYMPHOCYTES (LYMPHOCYTES THAT HAVE
NEVER ENCOUNTERED THEIR SPECIFIC ANTIGEN) BY MHC II PATHWAY AND
RELEASE A VARIETY OF CYTOKINES.
MHC MOLECULE :
 MAJOR HISTOCOMPATIBILITY COMPLEX IS A GROUP OF 6 GENES LOCATED
ON THE SHORT ARM OF CHROMOSOME6, THEY PRODUCE ANTIGEN
CALLED HUMAN LEUKOCYTIC ANTIGEN (HLA) WHICH WILL BE PRESENT
ON THE CELL MEMBRANES.
 AS THESE CAN BE RECOGNISED AND IDENTIFIED BY THE IMMUNE
SYSTEM CELLS,THE NAME “ANTIGEN” IS GIVEN TO THEM.
 THESE MOLECULES PRESENT ANTIGENIC PIECES OF MICROBES TO T -
CELLS AND ARE CALLED AS MAJOR HISTOCOMPATIBILITY COMPLEX
MOLECULES(MHC)/HUMANLEUCOCYTE ANTIGEN(HLA).

9. TWO TYPES OF MHC-HLA MOLECULES.
MHC-I: FOUND IN ALL NUCLEATED CELLS, BUT ALSO ON PLATELETS
MHC-II: FOUND IN SPECIALISED ANTIGEN PRESENTING CELLS DENDRITIC
CELLS,MACROPHAGES, B CELLS
 THE DISTRIBUTION IS NECESSARILY DIFFERENT SO AS TO DIRECT T -CELL
(TC & TH CELLS) TO CARRY OUT THEIR APPROPRIATE FUNCTION.
 FOR PEPTIDES TO ASSEMBLE WITH HLA MOLECULES AND PRESENT ED TO
LYMPHOCYTES THEY NEED TO BE PROCESSED BY INTRACELLULAR
ENZYMES.
 TWO DIFFERENT PROCESSING PATHWAYS EXIST FOR THESE TWO MHC
MOLECULES TO DISPLAY THE MICROBIAL PEPTIDES FOR T -CELL
RECOGNITION.
 THEY ARE
1) ENDOGENOUS PATHWAY AND
2) EXOGENOUS PATHWAY
WHICH INTURN DETERMINED BY MODE OF ENTRY OF INVADING MICROBES.
ENDOGENOUS PATHWAY :
 VIRUS WHICH ENTER CELL , PRESENT IN CYTOSOL AND ARE PROCESSED
BY CTOPLASMIC ENZYMES,VIRAL PEPTIDES ARE ASSEMBLED WITH HLA –I
MOLECULES.
EXOGENOUS PATHWAY:
 FOR MICROBES WHICH ARE TAKEN BY PHAGOCYTOSIS AND PEPTIDES
FORMED BY PROCESSING OF LYSOSOMAL ENZYMES ARE ASSEMBLED
WITH HLA-II MOLECULES.
 AS ANTIGENPRESENTING CELLS HAVE MHC -HLA-II MOLECULES ON THEIR
SURFACE THEY USE EXOGENOUS PAT HWAY TO PRESENT ANTIGENS TO
LYMPHOCYTES.

10.  BY MHC-II PATHWAY CD4+T LYMPHOCYTES (IMMATURE TH HELPER T -
CELLS) ARE ACTIVATED,
 THESE TH CELLS ON ACTIVATION PRODUCE,CYTOKINES LIKE IL -2, INF-Γ,
WHICH ACTIVATE OTHER T -CELLS LIKE CYTOTOXIC T -CELLS , T-
SUPPRESSOR CELLS.
 THE CYTOTOXIC T-CELLS KILL THE PATHOGENIC ORGANISM, SUPPRESSOR
T-CELLS PREVENT THE EXCESIVE DESTRUCTION OF HOST OWN CELLS.
 AFTER ACTIVATION OF LYMPHOCYTES FEW CELLS BECOME MEMORY T -
CELLS WHICH REACT IMMEDIATELY FOLLOWING SECOND EXPOSURE.
PERIODONTAL IMPLICATIONS:
 HUTCHENS AND CO WORKERS SUGGESTED DIRECT RELATIONSHIP
BETWEEN LANGERHAN’S CELLS AND DEGREE OF KERATINISATION
(J.INVEST DERMATOL 56:325 1971) NEWCOMB ET AL(JCP 1982 9:197)
EXAMINED THE ATTACHED GINGIVA AS PLAQUE WAS ALLOWEDTO
ACCUMULATE LANGERHANS CELLS APPEARED TO BECOME MORE
DENDRITIC IN SHAPE AFTER 8 DAYS OF PLAQUE ACCUMULATION THAN AT
DAY 0. AT 21 DAYS THE SAME MORPHOLOGIC APPEARANCE WAS NOTED
AS AT 8 DAYS. AS DENTAL PLAQUE ACCUMULATED ADJACENT TO AND ON
THE ATTACHED GINGIVA, THERE W AS A STATISTICALLY SIGNIFICANT
INCREASE IN LCS IN THE STRATUM SPINOSA
 INVESTIGATORS FELT THAT THE INCREASE IN LYMPHOCYTES AND
LANGERHANS CELLS WAS IN RESPONSE TO EXTERNAL ANTIGENIC
CHALLENGE.( BOS AND BURKHARD(1980 -81))
 REDUCTION IN LANGERHAN’S CELLS AFTER NON –SURGICAL
PERIODONTAL THERAPHY WAS OBSERVED



2) INFLAMATORY CELLS:

11.  INFLAMATORY CELLS ARE THE CELLS ACCOMPANIED BY OR TENDING
TO CAUSE INFLAMMATION.
 WHEN SECTIONS OF EPITHELIUM TAKEN FROM CLINICALLY NORMAL
AREAS OF MUCOSA ARE EXAMINED MICROSCOPICALLY, A NUMBER OF
INFLAMATORY CELLS OFTEN CAN BE SEEN IN NUCLEATED CELL
LAYERS.
 A FEW INFLAMMATORY CELLS ARE COMMON PLACE IN ORAL
EPITHELIUM AND CAN BE REGARDED AS A NORMALCOMPONENT OF
NON-KERATINOCYTE POPULATION.
 THESE ARE TRANSIENT AND DO NOT REPRODUCE THEMSELVES IN
EPITHELIUM AS OTHER NON -KERATINOCYTES DO.
 THE CELLS MOST FREQUENTLY SEEN ARE LYMPHOCYTES ALTHOUGH
PMN’S AND MAST CELLS ARE NOT UNCOMMON.
 LYMPHOCYTES ARE ASOCIATED WITH LANGERHAN’S CELLS, WHICH ARE
ABLE TO ACTIVATE T-LYMPHOCYTES,AS MENTIONED ABOVE.
 LYMPHOCYTES CELL OUT LINES ARE FAIRLY REGULAR WITH
OCCASIONAL SURFACE PROJECTIONS.
 CYTOPLASM IS HOMOGENOUS WITH PLENTIFUL FREE RIBOSOMES AND
MODEST MITOCHONDRIA BUT LITTLE RER, SER, AND FEW LYSOSOMES
OR SECRETORY GRANULES (WHEELER’S FUNCTIONAL HISTOLOGY PAGE
198)
 HAVE SMALL ROUND NUCLEI AND CONDENSED CHROMATIN,CLUMPED
AROUND PERIPHERY.
3) MERKEL CELLS:
 ONE AMONG THE NON -KERATINOCYTE CELL POPULATIONS,SPECIALIZED
, AND FORMS PART OF DIFFUSE NEURO - ENDOCRINE SYSTEM .
(WINKELMANN.R.K)
 A CELL THAT OCCURS IN THE BASAL PART OF EPIDERMIS AND MUCOSA
 THEY WERE FIRST DESCRIBED BY MERKEL(1875) AS A SPECIALIZED
EPITHELIAL CELL FOUND AT OR NEAR THE TIPS OF RETE RIDGES. THEY

12. ARE USUALLY ADJACENT TO A NERVE CELL, AND MAY FUNCTION AS
TOUCH RECEPTOR CELLS (PATRIZI AND MUNGER, 1966;MUNGER, 1975).
 IN MOUTH THEY ARE PREDOMINANTLY LOCATED IN GINGIVA,BUCCAL
MUCOSA AND HARD PALATE. (FORTMANN.GT; WINKELMANN.R.K; TACHI
BANA.T; NAVATI.)
 PRESENT IN MASTICATORY MUCOSA BUT ABSENT IN LINING MUCOSA
(ORBANS ORAL HISTOLOGY AND EMBRYOLOGY)
ORIGIN : THESE CELLS ARISE FROM THE DIVISION OF AN EPITHELIAL CELL
(KERATINOCYTES).
ULTRA STRUCTURE:
 UNLIKE OTHER NON -KERATINOCYTES THEY CONTAIN FEW TONO
FILAMENTS AND DESMOSOMES LINKING TO ADJACENT CELLS.AS A
RESULT MERKEL CELLS DOEN NOT ALWAYS RESEMBLE OTHER CLEAR
CELLS.
 THEY DEVELOP A CLOSE CONTACT TO INTRA EPITHELIAL NERV ENDINGS
TO FORM MERKEL CELL-NEURITE COMPLEX.
 THE MERKEL CELLL-NEURITE COMPLEX FUNCTION AS SLOW ADAPTING
MECHANO-RECEPTOR WITH A RELATIVELY SMALL RECEPTOR
FIELD(TYPE SA-1).
 MERKEL CELLS AND THEIR ASSOCIATED NERVE ENDINGS EXPRESS
RECEPTORS FOR EPIDERMAL GROWTH FACTOR, BUT THEY DO NOT MAKE.
 THE EGF IS EXPRESSED BY ADJACENT KERA TINOCYTES SUGGESTING
THAT THEY CONTROL DIFFERENTIATION OF MERKEL CELLS VIA A
PARACRINE-EPIDERMAL GROWTH FACTOR EFFECT.
 SURVIVAL OF MATURE MERKEL CELL IS ALSO DEPENDENT ON
NEUTROTROPHIC FACTORS SECRETED FROM THE ASSOCIATED NERVE
ENDINGS.
 SEVERENCE OF AΒ FIBERS SUPPLYING MERKELCELL -NEURITE COMPLEX
LEADS TO ATROPHY OF MERKEL CELL.

13.  THERE IS ALSO EVIDENCE OF RECIPROCAL STIMULATION,MERKEL CELLS
MAY ACT AS TARGET CELLS SECRETING SUBTANCES THAT ATTRACT
AFFERENT SENSORY AXONS TOWARDS THEIR LOCATION IN EPITHELIUM.
(CHENG CHEW S.B, LEUNG)
 THESE CELLS CONTAIN MANY DENSELY STAINED GRANULES 50 -140NM IN
DIAMETER SURROUNDED BY LIMITING MEMBRANE.(GARANT ETAL)
 MOST GRANULESARE CONCENTRATED BETWEEN THE GOLGI COMPLEX
AND THE PLASMA MEMBRANE THAT ABUTS THE ADJACENT NERVE
TERMINAL.
 THE GRANULES ORIGINATE FROM THE GOLGI APPARATUS AND ARE
SECRETORY IN NATURE
 NEUROPEPTIDE (HISTIDINE, LEUCINE,VASOACTIVE INTESTINAL
POLYPEPTIDE)HAVE BEEN LOCALIZED IN MERKEL CELL GRANULES BY
IMMUNOCYTOCHEMISTRY.
 RELEASE OF NEUROPEPTIDE IN THE IMMEDIATE VICINITY OF NERVE
ENDINGS KEEP THE RECEPTOR IN THE HEIGHTENED STATE OF
RESPONSIVENESS. EXPERIMENTS HAVE SHOWN THAT DEPLETION OF
MERKEL CELL GRANULES LEADS TO DECREASES RESPONSIVENESS OF
NEURITE
 THE MERKEL CELL PLA SMA MEMBRANE FACING THE NERVE ENDING
APPEARS TO HAVE SYNAPTIC SPECIALIZATION.
 THE MERKEL CELL NEURITE CONTAINS NEUMEROUS MITOCHONDRIA
INDICATING THAT IT HAS HIGH METABOLIC ACTIVITY.
 MERKEL CELLS HAVE MANY SPINY CYTOPLASMIC PROCESSES THAT
PROJECT INTO ADJACENT INTER CELLULAR SPACES AND INDENT THE
CYTOPLASM OF A ADJACENT KERATINOCYTE (GARANT)
 THESE RIGID SPINES CONTAIN CYTOPLASMIC FILAMENTS THAT
INTERCONNECT WITH LARGER FILAMENT NETWORK IN CYTOPLASM.
 THE FUNCTION OF THESE SPINY PROJECTIONS IS UNCLEAR HOWEVER
THEY APPEAR SUITED FOR DETECTING AND AMPLIFYING THE

14. MOVEMENT OF ADJACENT EPITHELIUM,POSSIBLY BY DEFORMING
STRETCH ACTIVATED CATIONIC CHANNELS.(TAZAKI.M, SUZUKI.T).
 IT HAS BEEN SPECULATED THAT MECHANICAL DISPLACEMENT OF
EPITHELIUM,AMPLIFIED BY SPINES OF MERKEL CELLS,LEADS TO
DISCHARGE OF NEURO TRANSMITTOR GRANULES AND ACTIVATIONOF
ADJACENT NERVE ENDING.
 IN HUMANS AND PRIMATES THESE CELLS ARE HIGHLY CONCENTRATED
IN SKIN OF FINGER TIPS.
 NEURO-PHYSIOLOGIC STUDIES OF FINGER TIP MERKEL CELL NERVE
COMPLEX HAVE LED TO THE CONCLUSION THAT THEY PROVIDE
TACTILE INFORMATION FOR THE SHAPE AND TEXTURE
PERCEPTION.(BLAKE D.T,JOHNSON.K,HSIAO S.S..)
 BECAUSE OF THEIR RELATIVELY SMALL RECEPTIVE FIELDS THE SA-
1NERVE ENDINGS ALSO PROVIDE FOR TWO POINT DICRIMINATION.
 IT IS PROPOSED THAT MERKEL-CELL NERVE COMPLEXES OF ORAL
MUCOSA PLAY A SIMILAR TACTILE SENSORY FUNCTION IN
RECOGNITION OF PARTICLE SIZE AND TEXTURE DURING MASTICATION.
STAINING:
 MERKEL CELLS ARE DIFFICULT TO DISTINGUISH FROM KERATINOCYTE S
BY ROUTINE LIGHT MICROSCOPY. BUT CAN READILY BE IDENTIFIED BY
ELECTRON MICROSCOPY. THEY CONTAIN DENSE -CORE GRANULES
TYPICAL OF ALL NEUROENDOCRINE CELLS, AND ARE ASSOCIATED WITH
NERVES IN THE BASAL OR SUPRABASAL CELL LAYERS OF ORAL
EPITHELIA. (FORTMAN AND WINKELMAN, 1977).

 MERKEL CELLS HAVE ALSO BEEN IDENTIFIED BY FLUORESCENCE AFTER
INJECTION OF ANIMALS WITH THE DYE QUINACRINE (NURSE ET AL., 1983),
WHICH IS SPECIFICALLY TAKEN UP INTO NEUROENDOCRINE GRANULES,
AND BY ANTISERUM TO NEURON -SPECIFIC ENOLASE (GUET ET AL., 1981).

15.  RECENTLY, A MONOCLONAL ANTIBODY (LK2H10) HAS BEEN PREPARED
TO NEUROENDOCRINE GRANULES (LLOYD AND WILSON, 1983). THIS
ANTIBODY STAINS ALL NEUROENDOCRINE CELLS, AND HAS ALSO BEEN
USED TO IDENTIFY MERKEL CELL TUMORS.
 THEY ARE IDENTIFIED BY STAINING OF ANTIBODIES TO KERATINS -18, 19,
20.
 IDENTIFICATION OF MERKEL CELLS IN ORAL EPITHELIU M USING
ANTIKERATIN AND ANTINEUROENDOCRINE
MONOCLONAL ANTIBODIES (K.H. NESS, T.H. MORTON AND B.A. DALE J DENT RES
1987; 66;1154)
 CHROMOGRANIN A - A MATRIX COMPONENT OF MERKEL CELL GRANULES
NEURAL ADHESION MOLECULE (GALLEG, ,GARCIA,MOLL.R,MOLL.L,FRANK
W.W)
4) MELANOCYTES :
 AN EPIDERMAL CELL THAT PRODUCES A PIGMENT CALLED
MELANIN,ALSO SEEN IN ORAL MUCOSA.
 THESE ARE DENDRITIC CELLS, SITUATED IN THE BASAL LAYER OF ORAL
EPITHELIUM AND EPIDERMIS.
 THEY ARE FIRST IDENTIFIED IN ORAL EPITHELIUM BY BECKER IN 1927,
THEY WERE ISOLATED FROM SAMPLES OF GINGIVAL TISSUE BY
LAIDLOW AND CAHN.
 THEY PRODUCE A PIGMENT CALLED AS “MELANIN”,IT IS A NON-
HEMOGLOBIN DERIVED BROWN PIGMENT AND IS RESPONSIBLE FOR
NORMAL PIGMENTATION OF SKIN,GINGIVA AND ORAL MUCOSA
 THE REGION OF ORAL MUCOSA WHERE MELANIN PIGMENTATION IS
SEEN MOST COMMONLY CLINICALLY ARE GINGIVA, BUCCAL
MUCOSA,HARDPALATE AND TONGUE.
 MELANIN FUNCTIONS TO ABSORB U.V LIGHT AND SCAVENGING SOME
CYTOTOXIC COMPOUNDS.

16. ORIGIN: (ORBANS ORAL HISTOLOGY)
 DURING INTRA-UTERINE LIFE, PRE-CURSORS OF MELANOCYTES THAT IS
MELANOBLASTS, MIGRATE FROM NEURAL CREST TO EPIDERMIS AND
HAIR FOLLICLES, BECOME DIFFERENTIAITED INTO DENDRITIC CELLS.
 HEAD AND NECK IS THE FIRST PART OF THE BODY WHERE
MELANOCYTES APPEAR AROUND 11WEEKS OF GESTATION PERIOD.
 IN EPITHELIUM THEY DIVIDE AND MAINTAIN THEMSELVES AS A SELF
REPRODUCING POPULATION.
STRUCTURE:
 MELANOCYTES ARE LONG BRANCHING PROCESS THAT EXTEND
BETWEEN KERATINOCYTES OFTEN PASSING THROUGH SEVERAL
LAYERS OF CELLS.
 CROSS OR OBLIQUE INTERSECTIONS OF CYTOPLASMIC PROJECTIONS OF
ACTIVE MELANOCYTES WERE FREQUENTLY ENCOUNTERED BETWEEN
BASAL AND IN SUPRABASAL KERATINOCYTES THE WIDTH OF THE
PROJECTIONS VARIED RANGING FROM 0.23 TO 3.40 MICRONS.
 THERE WAS A REVERSE RELATIONSHIP BETWEENTHE NUMBER OF
PREMELANOSOMES AND MEIANOSOMES,AND THE APPROXIMATE
SURFACEAREA OF THE INTERSECTED CYTOPLASMIC PROJECTIONS
.NORMALLY, THE GINGIVA AS WELL AS THE SKIN EXHIBITS AT LEAST
THREE TYPES OF MELANIN CONTAINING CELLS WHICH CONSTITUTE
ONTOGENETIC SYSTEM OF SYNTHESIS,PHAGOCYTOSIS AND
DEGRADATION OF MELANIN
a) MELANOCYTES (MELANIN SYNTHESIS),
b) KERATINO CYTES (MELANIN PHAGOCYTOSIS) AND
c) CONNECTIVE TISSUE CELLS SUCH AS FIBROBLASTS
(MELANIN PHAGOCYTOSIS)
ULTRA STRUCTURE AND FUNCTION:

17. THE NORMAL MELANOCYTES OF ORAL MUCOSA HAVE A SMALL ROUND
NUCLEUS AND A SMALL AMOUNT OF CLEAR CYTOPLASM WITH A SLENDER
DENDRITES EXTENDING BETWEEN KERATINOCYTES.
TWO TYPES OF STRUCTURAL LY DIFFERENT MELANOCYTES COULD BE
DISTINGUISHED:
INACTIVE AND ACTIVE CELLS.
THE INACTIVE MELANOCYTE:
HAD A NUCLEUS VARYING: FROM OVOID, ROUND TO SLIGHTLY INDENTED
OUTLINES. THROUGHOUT THE CYTOPLASM, DELICAT FILAMENTS WERE
PRESENT, WHICH WERE LESS ELECTRON DENSE THAN THOSEOF
KERATINOCYTES. THE NORMAL SET OF ORGANELLES APPEARED POORLY
DEVELOPED. WITH A FEW EXCEPTIONS, AND THERE WERE NO MELANOSOMES AS
WELL. PREMELANOSOMES WERE FOUND, REPRESENTED BY
ROUND,MEMBRANEBOUND ORGANELLES (APPROXIMATELY0.2 MICRON IN
DIAMETER) REVEALING A GRANULAR INNER STRUCTURE OF VARYING DENSITY.

ACTIVE MELANOCYTES :
HAVE DIFF ERENTLY SHAPED NUCLEI GENERALLY REVEALED A MOST
PROMINENT GOLGI APPARATUS.PREMELANOSOMES IN ALL DEVELOPMENTAL
STAGES AND FULLY MELANIZED MEIANOSOMES CUT AT AL POSSIBLE
PLANESWERE NUMEROUS. IN ELECTRON MICROGRAPHS(N=6) SHOWING
ENTIRELY CROSS, SECTIONEDCEL LS, 40 TO 130 PREMELANOSOMES AND
MEIANOSOMES COULD BE COUNTED. ABOUT ONE QUARTERTO ONE THIRD OF
THESE WERE FULLY MELANIZED,EXTREMELY ELECTRON DENSE MEIANOSOMES.
( HUBERT E. SCHHOEDER J.PERIODOM. RES. 4: 1-18. 1969)
STRUCTURE AND DEVELOPMENTAL STAGES OF PREMELANOSOMES
 WITHIN THE CYTOPLASM OF ACTIVE MELANOCYTES, 2 TYPES OF
STRUCTURALLY DIFFERENT PREMELANOSOMES COULD BE
DISTINGUISHED.
 BOTH TYPES OF PREMELANOSOMES WERE MEMBRANE BOUND
ORGANELLES OF OVOID SHAPE.

18.  ONE TYPE: EXHIBITED AN INNER STRUCTURE OF LOOSE SPIRAL COILS
RUNNING PARALLELOR SLIGHTLY CURVED TO THE LONG AXIS OF THE
ORGANELLE . BECAUSE OF IRREGULARITIES IN ITS COURSE AND
APPEARANCE, THE PERIODICITY OF THE SPIRAL COILS COULD NOT
ACCURATELY BY MEASURED .
 THE INNER STRUCTURE OF THE SECOND TYPE OF PREMELANOSOME
APPEARED AS A SINGLE OR COMPOSITE STRIATED BAR(S) RUNNING
PARALLEL TO THE LONG AXIS OF THE ORGANELIE WHICH OTHERWISE
WAS GRANULAR OR APPARENTLY ELECTRON LUCENT. FREQUENTLY, THE
STRIATED BAR(S) ALMOST FILLED THE MEMBRANE BOUND ORGANELLE.
 MELANIN IS SYNTHESISED WITHIN MELANOCYTES IN A SMALL
STRUCTURE CALLED MELANOSOMES.
 THEY CONTAIN TYROSINASE WHICH HYDROXYLATES TYROSINE TO
DOPA WHICH IN TURN IS PROGRESSIVELY CONVERTED TO MELANIN.
 THE MALANOSOMES ARE INOCULATED INTO CYTOPLASM OF ADJACENT
KERATINOCYTES BY THE DENDRITIC PROCESS.
 MELANOSOME IDENTIFIED UNDER LIGHT MICROSCOPE IN
HEAVLYPIGMENTED TISSUE, STAINS WITH HEMATOXYLIN AND
EOSIN,THEY ARE REFERRED AS “MELANIN GRANULES”.
 LIGHT AND DARKLY PIGMENTED INDIVIDUALS HAVE SAME NUMBER OF
MELANOCYTES IN ANY GIVEN REGION OF SKIN AND ORAL
MUCOSA,COLOUR DIFFERENCE RESULT FROM RELATIVE ACTIVITY OF
MELANOCYTES IN PRODUCING MELANIN AND THE RATE FROM WHICH
MELANOSOMES ARE BROKEN DOWN IN KERATINOCYTES.
 IN HEAVILY PIGMENTED INDIVIDUALS MELANOCYTES ARE SEEN IN
CONNECTIVE TISSUE,THEY ARE PROBABLY MACROPHAGES THAT
HAVE TAKEN UP BY MELANOSOMES,THEY ARE CALLED AS
“MELANOPHAGES”.
LABELLING OF MELANOCYTES :
 3,4 DI HYDROXY PHENYLALANINE A SUBSTRAT FOR TYROSINE

19.  ARGENTIFFINIC MELANIN LABELLING TECHNIQUE-MASSAN
FONTANAN STAIN IS USED,INACTIVE MELANOCYTES DOES NOT STAIN
WITH THIS METHOD.
IMMUNO-HISTOCHEMISTRY:
 S100 ANTIGEN IS THE MOST COMMON MARKER.IT APPEARS TO BE
STRONGER IN MELANOCYTES LACKING PIGMENT.
 HMB-45- A MONOCLONAL ANTIBODY DIRECTED AGAINST A
MELANOSOMAL GLYCOPROTEIN CAN ALSO BE USED FOR I
DENTIFICATION.
MELANIN IS OF DIFFERENT TYPES:
EU MELANIN: BROWN BLACK MELANIN
PHEO MELANIN : REDDISH
NEURO MELANIN: IN NEURAL TISSUE
SUMMARY
NON-KERATINOCYTES THOUGH THEY ARE NOT INVOLNED IN MATURATION OF
EPITHELIUM,THEY PLAY AN IMPORTANT ROLE IN PROTECTION AT BODY
SURFACES
LANGERHAN’S CELLS: STIMULATE DEFENCE MECHANISM.
MERKEL CELLS ARE TACTILE RECEPTORS
MELANOCYTES : PIGMENT PRODUCING CELLS,PROTECT THE SKIN FROM
U.V RAYS
CONCLUSION:
 CLEARLY THE ASSOCIATION BETWEEN KERATINOCYTE AND NON-
KERATINOCYTES IN SKIN AND ORAL MUCOSA REPRESENT A SUBTLE

20. AND FINELY BALANCED INTER-RELATIONSHIP IN WHICH CYTOKINES ARE
CONTROLLING FACTORS.
 KERATINOCYTES PRODUCE CYTOKINES THAT MODULATE THE
FUNCTION OF LANGERHAN CELLS.INTURN, LANGERHAN CELLS PRODUCE
CYTOKINES SUCH AS IL-1 WHICH CAN ACTIVATE T-LYMPHOCYTES, SO
THAT THEY ARE CAPABLE OF RESPONDING TO ANTIGENIC CHALLENGE.
 IL-1 ALSO INCREASES NUMBER OF RECEPTORS TO MELANOCYTE
STIMULATING HARMONE IN MELANOCYTES AND SO CAN EFFECT
PIGMENTATION.
 THE INFLUENCE OF KERATINOCYTES EXTEND TO ADJACENT
CONNECTIVE TISSUE, WHERE CYTOKINES PRODUCED IN EPITHELIUM
CAN INFLUENCE FIBROBLAST GROWTH AND FORMATION OF FIBRILS
AND MATRIX PROTEIN.