Periodontology 2000, Vol.
13, 1997, 91-120
Printed in Denmark . All rights reserved
The gingival tissues:
the architecture of periodontal
protection
HUBERTE. SCHROEDER
& MAxA. LISTGARTEN
At a time of rapid advances in molecular biology, the
term architecture may sound somewhat old-fashion-
ed and reminiscent of topographical anatomy.
Nevertheless, architecture implies a structure de-
signed for a particular purpose and to accomplish a
particular task. For the human gingiva, this task is
protection. Gingival tissues are designed in their par-
ticular way because they must provide the frame-
work for peripheral body defense. Both externally
and internally, the human body is protected by a
continuous surface lining, that is, the skin and the
nasopharyngeal and gastrointestinal mucosa. By
erupting through the mucosal lining, deciduous and
later permanent teeth interrupt its continuity, there-
by compromising its protective quality. A sophisti-
cated system for repair, wound healing, is provided
to seal off accidental breaches in this lining. How-
ever, where teeth perforate the lining, the continuity
of the oral mucosa can only be restored by exfoli-
ation or extraction of the teeth. For this reason, the
tissues surrounding the teeth have been designed to
provide a seal around the teeth (via the junctional
epithelium and the epithelial attachment), to with-
stand the frictional forces of mastication and to de-
fend the potential space between the teeth and the
soft tissues against foreign invaders, such as micro-
organisms. These particular goals are achieved
through a structural framework that allows de-
fending cells to traverse various tissue compart-
ments and act without disturbing basic tissue integ-
rity. This chapter reviews and depicts the protective
architecture of the human gingival tissues.
Clinical and histological features
The tissues collectively termed gingiva serve a dual
function: they belong to both the oral mucous mem-
Copyright 0 Munksgaard 1997
PERIODONTOLOGY 2000
ISSN 0906-6713
brane and the periodontium. Ten Cate (197) sug-
gested that an imaginary line running from the al-
veolar crest to the top of the gingival margin could
serve to separate these two parts. However, this is a
theoretical rather than a functional concept that
does not apply to the interdental portion of the gin-
giva. Indeed, there has been a long-standing debate
over the internal boundaries of the gingiva. There is
agreement that, externally, the gingiva extends from
the gingival margin and the tip of the interdental pa-
pillae to the mucogingival junction (Fig. la). How-
ever, internally, the apical line of demarcation can
be drawn to either include or exclude particular
groups of supra-alveolar fibers (see below). We
understand that the gingiva extends apically to in-
clude the dento-alveolar fibers at the entrance of the
periodontal ligament space (95, 166, 167). Therefore,
we consider that the gingival connective tissue in-
cludes the entire supra-alveolar fiber apparatus, al-
though developmentally and histologically, the
dentoalveolar fibers, being attached to both tooth
cementum and bone, could be considered part of
the periodontal ligament as well.
Clinically, the gingiva (or the marginal periodon-
tium) may be regarded as a combination of epithelial
and connective tissues that forms a collar of masti-
catory mucosa around the teeth of the complete de-
ciduous or permanent dentition and is attached to
both teeth and the alveolar process. It covers the al-
veolar crest, the interdental bony septa, and the cor-
onal portion of the alveolar process to the mucogin-
gival junction (Fig. 1, 2) (166, 167). On the vestibular
and lingual aspects, the gingiva borders the alveolar
mucosa; on the palatal aspect, it merges with the
mucosa of the hard palate so that they are clinically
indistinguishable.
The tissues of the gingiva have classically been
subdivided into several topographical portions: free,
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 The gingival tissues: the architecture of periodontal protection
attached and interdental gingiva (41, 42, 95, 140, 166,
167). Biologically, this subdivision is unnecessary
and possibly misleading. Likewise, the term kera-
tinized gingiva is redundant, as the oral surface of
the gingiva, by definition, is lined by keratinizing
epithelium. In fact, the gingiva is an anatomical and
functional unit with variations in shape, contour and
clinical topography that result in part from tissue ad-
aptation to the specific location around fully erupted
teeth.
Along the vestibular and lingual aspects of the al-
veolar ridge, a mucogingival junction demarcates the
normally light pink, firmly bound gingiva from the
dark-red, movable alveolar mucosa or the floor of
the mouth mucosa. These colors may be modified
by various amounts of melanin pigmentation. The
mucogingival junction, particularly on the vestibular
aspect, can be localized (18) functionally (by passive
movement of the lips and cheek (74)), anatomically
(by differences of color and surface characteristics
such as stippling (139)) and histochemically (by ap-
plication of Schiller’s iodine solution to reveal the
glycogen stored in the epithelium of the lining mu-
cosa (53)).Normally, this junction resides about 3-5
mm apical to the level of the alveolar crest. Topo-
graphically, its location remains rather stable with
increasing age, at least in relation to the nasal floor
and the lower border of the mandible (1, 3, 4). The
height (width) of the normal human vestibular gin-
giva, that is, the distance from the mucogingival
junction to the gingival margin surrounding fully
erupted teeth has been determined in primary and
permanent teeth both in children and adolescents
(6, 7, 20, 22). In the anterior region, this height in-
creases from the primary to the permanent den-
tition, more so in the maxilla than in the mandible.
Posteriorly it varies along the dental arches. Maxi-
mum average gingival height (4-6 mm) is found in
the regions vestibular to the maxillary incisors and
lingually to mandibular molars. Differences between
the various reports result in part from using different
methods to determine the position of the mucogin-
gival junction, for example, functional (20) or histo-
chemical (6) ones. A functional method finds the
Fig. 1. Clinical (a) and histological fc) characteristics and
schematic drawing (b) of human, anterior vestibular gin-
giva of a young, clinically healthy subject. ABC: alveolar
bone crest; AEFC acellular extrinsic fiber cementum; AP:
alveolar process; D: dentine; E: enamel; ES: enamel space;
E k epithelial attachment; GM: gingival margin; GS: gingi-
junction to be about 0.5 mm apical to that found
with a histochemical method (18). In general, gingi-
val height in juvenile and early adult life is associ-
ated with growth of the alveolar process (2, 117, 118,
153) and with the position of teeth relative to the
width of the alveolar process. When front teeth are
displaced labially, the gingival height decreases. Gin-
gival height increases when teeth are moved lin-
gually (7, 40, 48). Gingival thickness ranges between
0.5 and 2.5 mm, vestibularly, and is inversely pro-
portional to gingival height (65).
Interdentally, the gingiva adapts its shape to the
form, size and position of adjacent teeth. Therefore,
in the vestibular/oral dimension, the interdental
portion of the gingiva is narrow between front teeth
and broader between premolars and molars. In
young people, the interdental gingiva fills the entire
interdental space vestibularly and orally. Between
the vestibular and oral papillae, which reach about
halfway to the incisal edge (17), the interdental gin-
gival portion forms a concave bridge or col (41, 42).
This interdental col (Fig. 2b) increases both in buc-
colingual width from about 2 to 6 mm, and in verti-
cal depth from about 0.3 to 1.5 mm anteroposterior-
ly (149, 150). The col is lined by the coronally fused
portion of the two junctional epithelia that encircle
the adjacent teeth (Fig. 2a,b). Both the vestibular and
oral as well as interdental portions of the gingiva
normally overlap the enamel by about 2 mm and, in
so doing, follow the often undulating course of the
cementoenamel junction. As this junction runs
about parallel to the crest of the alveolar bone and
the interdental septa by a distance of 1.0 to 2.4 mm
vestibular/oraIly and 0.8 to 1.6 mm interdentally
(1661, the internal, tooth-related part of the gingiva
is about 3 4 mm in height.
Normal gingival tissues:
the defense architecture
Structurally, the gingiva is composed of two differ-
ent, stratified epithelia (the junctional and the oral
val sulcus; I P interdental papilla; J E junctional epithel-
ium; OGE: oral gingival epithelium; OSE: oral sulcular epi-
thelium; PL: periodontal ligament. Numbers refer to vari-
ous groups of collagen fibers. Arrows in (a) demarcate the
mucogingival junction. b: reproduced from Schroeder
(1986). c: ~ 2 0bar=
, 1 mm.
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 The gingival tissues: the architecture of periodontal protection
epithelium) and a densely collagenous lamina pro-
pria that includes the supra-alveolar fiber apparatus,
blood and lymphatic vessels and nerves. Over the
last three decades, a distinction has been made be-
tween strictly normal and clinically healthy gingiva,
in adolescents and young adults (100, 163, 166, 198).
Physiologically speaking, the strictly normal gingiva
is an artifact that can be produced under rare experi-
mental conditions. The resulting structural features
display tissues that do not need to defend them-
selves. A keratinized oral epithelium covers the gin-
giva externally up to the gingival margin and the tip
of the interdental papillae (166). A smooth collar of
junctional epithelium is located on the internal part
of the marginal gingiva with its attachment to the
enamel surface (see below). The free surface of the
junctional epithelium is more or less level with the
edge-like gingival margin. The gingival sulcus is ab-
sent. A uniformly dense collagen fiber network char-
acterizes the lamina propria, which lacks all signs of
inflammatory cell infiltration (14,93, 166).Clinically,
this gingiva is pale pink (unless pigmented by mel-
anin) and firm in texture. It has a thin margin, and
the papillae fill the interdental spaces up to the con-
tact points.
The clinically normal gingiva in humans, however,
exists under conditions of low-grade defense, that is,
in the presence of microbial and antigenic chal-
lenges that are compatible with clinical health.
Healthy gingival tissues demonstrate structural and
physiological signs of protection, such as a gingival
sulcus and a junctional epithelium with widened in-
tercellular spaces that harbor elevated numbers of
neutrophilic granulocytes and sulcus fluid. Small
foci of lymphocytes, macrophages and some plasma
cells can be observed in the lamina propria, mostly
along the junctional epithelium. This region also
contains the subepithelial plexus of venules. Clin-
ically healthy, vestibular gingiva consists, on average,
of 4% junctional epithelium, 27% oral gingival epi-
thelium and 69% connective tissue that includes a
Fig. 2. Histological (a), electron microscopic (c) and sche-
matic features (b) of the interdental gingiva as seen in
mesiodistal (a, b) and buccolingual (b) planes of sec-
tioning. The electron micrograph (c) displays the insertion
(left inset) of supra-alveolar fiber bundles (SFB) in ce-
mentum, with collagen fibrils in longitudinal and cross-
section (upper inset). AEFC acellular extrinsic fiber ce-
mentum; AME alveolar mucosa epithelium; D dentine;
E enamel; ES: enamel space; IS: interdental septum; J E
junctional epithelium; O G E oral gingival epithelium; O I P
Fig. 3. Schematic drawing displaying the supra-alveolar
fiber apparatus as seen in a horizontal section through a
lower human jaw. Arrows delineate the tongue and the
vestibular alveolar mucosal surface. Blue: circular and
semicircular fibers; red transseptal fibers; yellow: inter-
gingival fibers.
cellular infiltrate occupying about 3-6% of the gingi-
val volume (171).
The supragingival fiber apparatus
The gingival lamina propria consists mainly of a
dense network of collagen fiber bundles that ac-
count for about 55430% of the connective tissue vol-
ume. This network is called the supragingival fiber
apparatus. On the basis of their preferential orien-
tation, architectural arrangement and sites of inser-
tion, these bundles have been classified as dento-
gingival, dentoperiosteal, alveologingival, circular
and semicircular, transgingival, intercircular, inter-
papillary, periosteogingival, intergingival and trans-
septal fiber groups (Fig. lb, 2b). These fiber bundles
are densely populated by fibroblasts (about
200X 106/cm3of connective tissue (171))and consist
mainly of collagen Type I and I11 (as extractable col-
lagens in a proportion of about 91% to 8% (134,
135)). Collagen Type I represents mainly dense
oral interdental papilla; P L periodontal ligament; VIP
vestibular interdental papilla. Numbers refer to various
groups of collagen fibers: 1: dentogingival fibers (1.1, 1.3);
2 dentoperiosteal fibers; 3:alveologingival fibers; 4 circu-
larlsemicircular fibers; 6 interpapillary fibers; 7: perioste-
ogingival fibers; 8: intercircular fibers; 9: transseptal
fibers. a: rat specimen, ~ 6 0 b; reproduced from Schroe-
der (166); c: human specimen, ~ 9 9 0 0left
; inset: x 19,800,
upper inset: x 103,000.
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 The gingival tissues: the architecture of periodontal protection
fibers; Type 111 is related to loose connective tissue,
subepithelially and around blood vessels (36). Mast
cells are also regular residents (about 17X106/cm3
(17111,whereas lymphocytes, monocytes and macro-
phages vary in number with the need for and degree
of protective activity.
In random tissue sections, discrete fiber bundles
are rarely sectioned along their full length, except for
transseptal and circular or semicircular bundles (Fig.
lc, 2a). Their three-dimensional architecture was re-
constructed first by Feneis (55), and his results were
later confirmed and extended in humans and non-
human primates by several other authors (9, 60, 62,
120, 145).Based on this information, Schroeder (166,
167) produced schematic drawings of the preferen-
tial orientation of these bundles, as expected in a
vestibulo-oral plane through the marginal gingiva
(Fig. lb), in a mesiodistal and a vestibulo-oral plane
through the interdental gingiva (Fig. 2b) and in a
horizontal plane above the interdental septa through
an entire jaw (Fig. 3 ) . These drawings indicate that
the dentogingival, dentoperiosteal, alveologingival
and periosteogingival fiber groups serve to attach
the gingiva to teeth and bone, whereas interpapillary
fibers connect the vestibular and oral interdental pa-
pillae to one another. On the other hand, the circular
or semicircular, transgingival and transeptal fiber
bundles connect adjacent teeth to one another.
These connections are reinforced by intergingival
fiber bundles that merge in part with circular or
semicircular and intercircular fibers and extend in a
mesiodistal direction, buccally and orally, along the
entire dental arch and around the last molars (Fig.
3 ) . In other words, circular or semicircular, intercir-
cular, transgingival, transseptal and intergingival
fiber groups link all adjacent teeth of a fully dentul-
ous jaw into a complete dental arch unit. Transseptal
fibers, first described by Black (241, constitute a
major part of the supra-alveolar fiber apparatus and
are clearly related to mesial drift (148). Normally,
transeptal fibers form a layer of variable thickness
that inserts in the supra-alveolar root cementum of
Fig. 4. Blood supply of human gingival tissues. a. Fluor-
escein angiographic demonstration of subepithelial
blood vessel loops in the papillary body of vestibular
gingiva at lower incisors and accumulation of gingival
sulcus fluid along the gingival margin, 14 to 180 sec-
onds after fluorescein injection. Note density of vascular
loops underneath gingival margin (inset). b. Schematic
drawing of periodontal blood supply from various
sources. c, d. Middle portion of human junctional epi-
the mesial and distal surfaces of adjacent teeth,
using the shortest path between these teeth. This ar-
rangement exists irrespective of tooth rotation. This
means that the formation and insertion of trans-
septa1 and dentogingival fibers is not specific to cer-
tain anatomic surfaces, but is functionally rather
than anatomically determined (88).
In conclusion, the supragingival fiber apparatus
not only attaches the gingiva to teeth and bone but
also provides a dense framework that accounts for
the rigidity and biomechanical resistance of the gin-
giva. Thus, gingival turgor, that is, the resilience and
pliability of the attached gingiva as measured during
micro-compression, is significantly smaller than that
of the adjacent alveolar mucosa (125). For this rea-
son, the gingiva is able to withstand frictional forces
and pressures that result from mastication. The fiber
apparatus also controls the positioning of teeth
within the dental arch. In addition to contributing
to tooth positioning and biostability of the gingival
tissues, the supragingival fiber apparatus also pro-
tects the very sophisticated cellular defenses located
at the dentogingival interface (166). Maintenance of
this fibrous complex is facilitated by a connective
tissue turnover rate that is much faster than that of
skin (135, 187). Consequently, postinflammatory re-
pair of the fiber apparatus is completed within 40 to
60 days (92, 122).
Vascular distribution
The human gingival lamina propria is highly vascu-
larized. The primary blood supply in the maxilla is
derived from the posterior and anterior superior al-
veolar (dental) arteries and the major palatine arter-
ies. In the mandible, it is provided by the inferior
alveolar (dental), buccal, sublingual and mental ar-
teries. Branches of these arteries reach the gingiva
from three sites, that is, the interdental septa, the
periodontal ligament, and the oral mucosa (Fig. 4b)
(33, 158). Venous vessels are assumed to follow the
course taken by the arterioles and arteries.
thelium (JE) and subepithelial plexus of postcapillary
venules (BV), as seen with light (c) and electron micro-
scopy (d). Note enamel space (ES), connective tissue
(CT) and neutrophilic granulocytes (NG). a: reproduced
from Schroeder (166), courtesy of W. Mormann, Zurich,
Switzerland. b: reproduced from Schroeder (166) as
adapted from Castelli (33). c: reproduced from Schroe-
der (166), x600. d reproduced from Schroeder (1661,
x4500. Inset: courtesy of W. Mormann.
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 The gingival tissues: the architecture of periodontal Drotection
Within the gingival lamina propria, terminal blood
vessels form two networks underneath the oral gin-
gival epithelium, including the gingival margin and
along the junctional epithelium. Both networks exist
prior to tooth eruption. Numerous studies of the lo-
cal gingival vasculature (166) in rats, cats, dogs, non-
human primates and humans have provided strong
evidence for the existence of these two anatomically
distinct networks.
Underneath the oral gingival epithelium, the lam-
ina propria is anatomically divided into a papillary
and a reticular component. The papillary compon-
ent consists of intraepithelial connective tissue pap-
illae, with a density of about 120+30/mm2 gingival
surface (82, 167).Each of these papillae carries a ter-
minal capillary loop, with an ascending arterial and
a descending venous limb (56, 801, that becomes vis-
ible clinically after an intravenous injection of flu-
orescein (129) (Fig. 4a). The average density of clin-
ically visible loops, that is, 50-60/mm2 (80) or even
100-130/mm2 (132),may be lower than the anatom-
ical loop density, as not all of these are patent and
carry erythrocytes at the time of observation. The re-
ticular component encompasses the remaining por-
tion of the lamina propria.
The vascular network under the oral gingival epi-
thelium, as observed clinically by fluorescein angio-
graphy, videomicroscopy or laser-Doppler flowmetry
(15, 37, 38), appears to increase in density with age,
although vessels exhibiting active blood flow seem
to decrease with age. These changes may reflect
merely a change in the number of patent vessels
(112). From a pathophysiological point of view, this
vascular network is concerned with gingivo-mucosal
surface activity rather than with periodontal defense.
The other vascular network located lateral to the
rather smooth junctional epithelial collar is designed
very much differently. Architecturally, this internal
network is like a thin vascular basket, rich in ana-
stomoses. It has been termed the gingival plexus
(Fig. 4b). This plexus consists mainly of postcapillary
venules (Fig. 4c,d) and extends from the coronal to
the apical termination of the junctional epithelium,
both vestibularly and orally as well as interdentally.
With developing inflammation, the basket-like net-
work becomes more prominent as the capillary
loops increase in size and number. Under these con-
Fig. 5. Postcapillary venules (BV) under the junctional epi-
thelium (JE) with emigration of neutrophilic granulocytes
(NG). Within the gingival sulcus, neutrophilic granulo-
ditions, the postcapillary venules assume the typical
character of high endothelial venules (208).High en-
dothelial venules are absent in gingival health but
are typically seen in the paracortical regions of
lymph nodes and tonsils, where they facilitate
lymphocyte emigration (73). The development of
high endothelial venules during early experimental
gingivitis may occur in response to various lympho-
kines or other mediating molecules released during
inflammation. The presence of high endothelial ven-
ules during plaque-induced gingival inflammation
as well as in delayed-type hypersensitivity reactions
(59) may indicate that a selective homing and mi-
gration of lymphocytes occurs in the gingiva (208),
at least in early lymphocyte-dominated gingivitis in
children and adolescents. In addition, these postcap-
illary venules or some of them express the endo-
thelial cell leukocyte adhesion molecule- 1 (ELAM-I),
the intercellular adhesion molecule- 1 (ICAM-l),and
the leukocyte function-associated antigen (LFA-3),
both in health and, more intensely, during develop-
ing gingivitis (44, 130, 199).Furthermore, as is typical
for high endothelial venules (32, 1931, some of the
venules of this gingival plexus also express the vas-
cular cell adhesion molecule-1 (VCAM-l),while all
terminal vessels express the platelet endothelial cell
adhesion molecule-1 (PECAM-l), the latter being an
endothelial cell marker (199). ELAM-1 binds neutro-
philic granulocytes selectively and, together with the
non-cell-specific binding of the ICAM- 1 molecule, is
responsible for the adhesion and facilitated emi-
gration of these cells from postcapillary venules (Fig.
5b). On the other hand, ICAM-1 and VCAM-1 selec-
tively bind to the integrins LFA-1 and VLA-4 of
mononuclear blood cells, in particular T-lympho-
cytes, that enter into the inflammatory infiltrate and
the junctional epithelium (Fig. 5a) (182). It is poss-
ible that the venules of the gingival plexus, even in
the healthy gingiva, are functionally specialized to
constitutively express ELAM-1 and ICAM-1 in order
to facilitate leukocyte traffic (130). As neutrophilic
granulocytes emigrate even in an artificially normal-
ized gingiva, the particular molecules that facilitate
their emigration might also be expressed in the total
absence of inflammation. On the other hand, high
endothelial venules-like venules seem to be absent
in health (207).It is not clear, therefore, whether high
cytes phagocytize bacteria (inset, arrow). C T connective
tissue; L intraepithelial lymphocyte. Magnification:
a: ~ 6 5 0 0b:
; ~ 5 0 0 0 inset:
; X8000.
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 The gingival tissues: the architecture of periodontal protection
endothelial venules-CAM molecule expression is
characteristic of all venules of the gingival plexus or
only of these added during inflammation. The in-
creasingly dense terminal vasculature associated
with the lining of periodontal pockets also exhibits
an high endothelial venules-character, an obser-
vation that suggests that such vessels serve preferen-
tially for emigration of neutrophilic granulocytes
(209).
The junctional epithelium and the gingival sulcus
The junctional epithelium is the most interesting
part of the gingiva. It is normally formed from the
reduced enamel epithelium when the crowns of
teeth of limited eruption emerge in the oral cavity.
The slow process of transformation has been de-
scribed histologically and cytologically both in non-
human primates and humans (64, 133, 169). How-
ever, the junctional epithelium can also be formed
de novo, for example, after gingivectomy, by dividing
basal cells of the oral gingival and other oral epi-
thelia and the epidermis (25, 57, 58, 94, 96). A fully
regenerated junctional epithelium is practically
identical to its original. This is also true for the junc-
tional epithelium surrounding implants (67, 70, 99,
119, 192).
Under conditions of clinical health, the junctional
epithelium forms a collar that surrounds the erupted
tooth. Apically, it follows the cementoenamel junc-
tion and extends from there to the gingival margin
(Fig. lb,c). Interdentally, the junctional epithelia of
adjacent teeth fuse coronally to form the lining of
the interdental col (Fig. 2a,b). In humans, this collar
is about 2 mm in height and up to 100 pm thick. It
tapers in an apical direction. Basically, this collar is
a stratified squamous epithelium composed of two
layers (strata), a basal layer and a suprabasal layer.
Basal cells are somewhat cuboidal and suprabasal
cells extremely flattened, elongated and oriented
parallel to the tooth surface (Fig. 4c, 6a,c). Along its
interfaces with both the tooth surface and the con-
nective tissue, the junctional epithelium forms a
Fig. 6. Human junctional epithelium (JE) as seen with
light (a, b) and electron microscopy (c).For morphometric
analysis of leukocyte content, the junctional epithelium is
subdivided along its axis into 100-pm intervals (b) and a
double-lattice test system is superimposed at a 20” angle
on every single 100-pm portion. For the example given in
(b), 20 cross-points of heavy lines fall on epithelial tissue,
and 62 cross-points of light lines fall on leukocytes. This
basal lamina, the internal lamina being part of the
epithelial attachment (Fig. 6c). The free surface of
this collar forms the bottom of the gingival sulcus
surrounding each tooth.
Based on its ultrastructural and cytochemical fea-
tures, the junctional epithelium is a so-called simple,
nondifferentiating and nonkeratinizing tissue (133,
165, 166). Basal cells but also some of those directly
facing the tooth (cells directly attached to enamel)
(141, 156) are capable of synthesizing DNA and di-
viding. All cells of the junctional epithelium are very
much alike ultrastructurally (116, 165, 170). In con-
trast to the oral gingival epithelium, they contain
only few cytoplasmic filaments. These are composed
of keratins 5, 13, 14 and 19; the latter, possibly a
“neutral” keratin (190), is a marker for simple epi-
thelia (54, 61, 78, 128).In addition, all junctional epi-
thelial cells express N-acetyl-lactosamine (104, 1911,
epidermal growth factor (194) and the intercellular
adhesion molecules ICAM- 1 and LFA-3 on their sur-
face (44, 61). Lysosomal bodies are encountered in
cells facing the tooth surface and those near the sul-
cus bottom (57, 89, 90, 165). Membrane-coating
granules are absent, an observation suggesting that
the junctional epithelium lacks a diffusion barrier.
A characteristic feature of the junctional epithel-
ium is its exceptionally high rate of cellular turnover.
In primates this turnover time was found to be 4.6
to 10.9 days and in mice 3 to 5 days (47, 81, 185).
Consequently, the junctional epithelium is com-
pletely restored within about 5 days in primates (25,
195). This high turnover rate is characterized by a
constant flux of coronally migrating daughter cells as
well as a high rate of cell exfoliation into the gingival
sulcus (see below). The high rates of cell migration
and exfoliation are facilitated by the relatively small
number of desmosomes and gap junctions that con-
nect junctional epithelial cells (71, 155, 157, 169,
170).Because of the low density of intercellular junc-
tions, the intercellular spaces between junctional
epithelial cells can vary considerably in size, with
larger spaces observed in the presence of subclinical
or slight gingival inflammation than in its absence.
amounts to 12.4%for the leukocyte volume. The neutro-
philic granulocyte content of the junctional epithelium
portion shown in (c) amounts to 9.5%. C T connective
tissue; ES: enamel space; ICS: intercellular space; MA:
mast cell. a: X640; b: reproduced from Schroeder (160),
x 590; c: reproduced from Schroeder & Miinzel-Pedrazzoli
(170), X1800.
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Schroeder & Listgarten
Fig. 7. Leukocyte content of the junctional epithelium.
Individual (numbers 17-23, a) and average (n=19,
+standard deviation) percentage volume (WV,,, b) of all
leukocytes residing in random light microscopic sections
of human junctional epithelium of clinically slightly in-
flamed gingiva, as determined in 100-pm steps (see Fig.
These spaces account for at least 2-5% of the junc-
tional epithelial volume (165) and can be labeled
with ruthenium-red or lanthanum-nitrate (169).
However, a variable proportion of these intercellu-
lar spaces can be occupied by both, transmigrating
neutrophilic granulocytes and infiltrating mono-
nuclear cells such as macrophages and lymphocytes,
in various phases of activation (160, 161). Under
noninflammatory conditions all such cells occupy
about 1 2 %of the space (165), while with slight in-
flammation, that is, with defense being activated,
that percentage may rise to 30% or higher (160, 161).
Because the junctional epithelium has a high con-
tent of mononuclear cells, at least during a period of
time following tooth eruption, it has been compared
with a tonsillar crypt epithelium (161). As such, it
may function as a reticular epithelium, which pro-
vides a favorable environment for local immune rec-
ognition processes (146). These and other functions
may be regulated by intraepithelial innervation. At
least in rats, the junctional epithelium has been
shown to include numerous nonmyelinated, delicate
axons that react immunohistochemically with anti-
bodies to substance r: the calcitonin gene-related
peptide and the protein gene product 9.5 (30, 31,
109).
The free surface of the junctional epithelium
forms the bottom of the gingival sulcus. The latter
has been defined as the shallow groove (up to 0.5
mm in depth) between the tooth surface and the
marginal gingiva (160). The gingival sulcus results
from the particular anatomical relationship of epi-
102
-1ol
@2OOSp600 ‘1000’1400’1800’22002 6 0 0 ~
6b). S, marks the average depth of the gingival sulcus.
Note that the maximum leukocyte volume is just below
the sulcus bottom and decreases toward the apical ter-
mination of the JE. Biopsy 17 (Fig. 8) is an exception.
Source: adapted from Schroeder (161).
thelia at the gingival margin. It may be absent under
strict “normal” conditions induced experimentally
(with the junctional epithelium extending to or be-
yond the level of the gingival margin), but will de-
velop under conditions of clinical health and in-
creasing gingival inflammation, with sulcular depth
fluctuating between 0.2 and 0.7 mm (207). The epi-
thelia lining the sulcus are the junctional epithelium,
which forms the sulcus bottom, and the oral sulcular
epithelium, which lines the lateral sulcus wall, ves-
tibularly and orally (Fig. Ib,c). Exfoliation of worn-
out epithelial cells occurs from both of these sulcular
walls. Sulcular depth may increase when the mar-
ginal gingiva swells as a result of edema.
All of the gingival tissue structures described so
far contribute to the framework for defense that are
discussed in the following section.
Protection against infection
Protection against gingival and periodontal infection
is provided by extrinsic and intrinsic defense sys-
tems. Extrinsic protection is derived from the secre-
tions of major and minor salivary glands. The latter
are located in the mucosa of the upper and lower
lips, cheeks and the soft palate. Their orifices face
the erupted crowns of teeth and the gingiva. These
secretions contain relatively high concentrations of
secretory immunoglobulin A (IgA). At night, when
the major glands reduce their production or cease to
function, tooth surfaces and gingiva are flooded with
 The gingival tissues: the architecture of periodontal protection
Fig. 8. Portion of heavily leukocyte-infiltrated human
junctional epithelium (JE) (see Fig. 7a, No. 19) as seen
with light (a) and electron microscopy (b, c). Neutrophilic
granulocytes (NG) reside mainly on the tooth-related as-
pect of the junctional epithelium (a), while lymphocytes
secretory IgA-rich secretions. These counteract bac-
terial colonization, as do some other salivary muco-
proteins (26, 46).
Some protection against mechanical injury of the
gingiva is due to the mechanical resistance and stiff-
ness of the gingiva, which is provided by the supra-
alveolar fiber apparatus and the stratum corneum of
the oral gingival epithelium. Shielded by these struc-
tures, intrinsic protection operates within and be-
neath the epithelial dento-gingival junction, close to
tooth surfaces. The various arms of the intrinsic de-
fense system and the architectural tissue compart-
ments utilized for its operation are discussed in the
following sections.
(L) predominate on the connective tissue (CT) side (a to
c). ES: enamel space; ML: medium-sized lymphocyte;
MC: macrophage; S L small lymphocyte. Magnification:
a: ~ 8 0 0 b,
; c: X4000.
Pathway of exudation and cellular emigration
When Brill & Krasse (29) first described the passage
of gingival tissue fluid (crevicular or sulcus or pocket
fluid) from gingival blood vessels to the gingival
margin, and when Brill (28) summarized these find-
ings, the gingival architecture, in particular the junc-
tional (cuff) epithelium and the extent of the gingival
sulcus or crevice were still not well known. Neverthe-
less, these authors recognized gingival fluid as part
of a defense system which contributed to flushing
out the crevice. Later, Sharry & Krasse (1811, Egelberg
(511, Klinkhammer (84, 851, Schiott & Loe (1591, Atts-
trom (10) and Attstrom & Egelberg (12, 13) showed
103
Schroeder & Listnarten

Fig. 9. Cross-sectionsof the coronal portion of the human gingival sulcus (SU) and the apical termination of supra-
junctional epithelium (JE)from a clinically slightly in- gingival, bacterial plaque (BPI. Sections a and b are taken
flamed gingiva (insets in a, b). The sections include the from the same gingival margin at a distance of about 3

104
 The gingival tissues: the architecture of oeriodontal orotection
Fig. 10. Coronal portion of junctional epithelium (JE) with
numerous neutrophilic granulocytes emigrating towards
and covering a small focus of supragingival bacterial
plaque (a). In this condition, junctional epithelium cells
contain numerous lysosomal bodies (LB in c) and phago-
cytized bacteria in membrane-bounded vesicles (b, inset,
that leukocytes, in particular neutrophilic granulo-
cytes, were a consistent component of that fluid, at-
tracted by chemotactic gradients of bacterial origin
(196). Consequently, Attstrom (11) considered these
cells as the most important arm of the gingival de-
fense systems.
mm. Note the sharp demarcation line between the junc-
tional epithelium and the oral sulcular epithelium (OSE),
with the epithelial attachment extending up to the sulcus
bottom. There is no pocket. C T connective tissue; E: en-
amel; VE: subepithelial postcapillary venule. Reproduced
from Schroeder et al. (174). Magnification: a: X600, b
x600; insets: X50.
arrow). BL: basal lamina; DC: dental cuticle; ES: enamel
space; ICT infiltrated connective tissue; SU: gingival sul-
cus. b, c: reproduced from Lange & Schroeder (89). Magni-
fication: a: x 120; b: ~ 8 0 0 0 ;c: x 13,800; upper inset:
X44,OOO; lower inset: ~ 7 0 , 0 0 0 .
Today, it is well established that in clinically healthy
or even slightly inflamed gingiva, the pathway of fluid
exudation and neutrophilic granulocyte emigration is
the coronal portion of the intact junctional epithel-
ium rather than the potential or real space between
epithelium and the tooth surface, postulated by Waer-
haug (202). In fact, this is the preferential pathway for
the inflammatory exudate, since neither the oral sul-
cular epithelium nor the oral gingival epithelium
serve that purpose (Fig. 9a,b). Gingival fluid as well as
neutrophilic granulocytes originate from the vessels
of the gingival plexus.
Gingival fluid is of an exudative nature and is ab-
sent when the gingiva is virtually free of inflam-
mation, as is the case in experimentally induced nor-
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106
 The gingival tissues: the architecture of periodontal protection
ma1 gingiva (14,39, 52). Fluid flow requires increased
vascular permeability that is readily induced by
slight mechanical trauma (such as probing or inser-
tion of a filter paper strip) and other initiators of in-
flammation (39). Within the junctional epithelium,
gingival fluid passes through the intercellular spaces
that can be distended to variable degrees. In a
slightly inflamed gingiva, fluid may accumulate in
the enlarged spaces. Ultrastructurally, enlarged in-
tercellular spaces have been shown to be filled with
electron-dense material, probably serum proteins
(Fig. 11). Such enlargements occur mainly in the cor-
onal half of the junctional epithelium, particularly in
its central portion (173, 174). However, moderately
enlarged intercellular spaces do not appear to inter-
fere with epithelial integrity, as the tooth-related and
connective tissue-related epithelial portions retain
their integrity and their basal lamina connections
(Fig. 6a, 11, 12).
The ability of the junctional epithelium and ad-
jacent parts of the sulcus to serve as fluid reservoirs
explains two clinical observations. First, during gin-
gival fluid collection, the first sample at a particular
site will often be considerably larger than sub-
sequent samples (68, 147). This is due to removal of
the accumulated fluid and is not considered to be
representative of the rate of fluid flow (34, 84). Sec-
ondly, the large spaces filled with fluid serve as a
diffusion pathway for chemotactic, antigenic and
other substances to enter the gingival connective
tissue from the outside, and for antibodies, comple-
ment components, mammalian cell enzymes and
various mediators of inflammation to move in the
opposite direction (39).
In addition, neutrophilic granulocytes utilize the
intercellular spaces of the junctional epithelium as a
preferential pathway for emigration (Fig. 9a). Upon
leaving the plexus of normal or high endothelial ven-
ules (Fig. 5b), they pass through the extravascular
connective tissue (Fig. 4d) to enter the junctional epi-
thelium via the external basal lamina. In response to
chemotactic gradients, they move by active loco-
motion through the intercellular spaces (Fig. 612, 9a,
Fig. l l . Electron micrograph of the sulcus bottom and ad-
jacent, most coronal portion of the junctional epithelium
(JE). Serial section from that illustrated in Fig. 9. Apical to
the sulcus bottom, the junctional epithelium is attached
to the enamel (E) surface by a basal lamina and hemides-
mosomes. A patch of dental cuticle (DC) material is inter-
posed between the enamel surface and the junctional epi-
12) until they reach the sulcus bottom (Fig. 11). They
usually migrate preferentially along the central and
tooth-related portions of the junctional epithelium
(Fig. 12).When single bacteria are encountered, neu-
trophilic granulocytes phagocytize and remove them
from the intraepithelial pathway (89, 154) (insets Fig.
5, 13). Cells of the junctional epithelium contain lys-
osomal bodies with a full battery of enzymes (89,901
that participate in the elimination of bacteria (Fig. 10).
In the rhesus monkey, the emigration time of neutro-
philic granulocytes from blood vessels to the sulcus
was reported to be about 20-30 min (175, 176).Similar
results were reported for the dog (12). Shortly after
their arrival in the gingival sulcus, close to 80% of
these neutrophilic granulocytes are vital (87, 175, 184,
205) and at least 50% of them are nitro blue tetrazoli-
um positive, indicating a high degree of enzyme activ-
ity (35,871.All of them are as able to phagocytize and
produce superoxide as peripheral blood neutrophilic
granulocytes (35,206),although their mobility may be
somewhat impaired (177).Furthermore, neutrophilic
granulocytes passing through the junctional epithel-
ium carry normal receptors for C3b and the Fc region
of IgG and kill microorganisms effectively (35, 205).
These observations support the statement that neu-
trophilic granulocytes kill bacteria with almost equal
efficiency under aerobic or anaerobic conditions
(188,204).
The number of emigrating neutrophilic granulo-
cytes can be enhanced by topical application at the
gingival margin of chemotactic agents such as casein
(66) and extracts of microbial plaque (72). Neutro-
philic granulocyte-emigration increases spon-
taneously with increasing degrees of gingival in-
flammation (10, 12, 13, 84, 85, 86). Irrespective of
the clinical state and even under normal conditions,
neutrophilic granulocytes account for about 95% of
all leukocytes sampled by smears or washings from
the gingival sulcus. Mononuclear cells such as
lymphocytes and monocytes/macrophages account
for fewer than 5% of all leukocytes (10,12).The same
is true for salivary leukocytes (151, 152). These data
suggest that neutrophilic granulocytes actively mi-
thelium. The boundary between the junctional and the
oral sulcular epithelium (OSE) is demarcated by a white
line. Junctional epithelial cells desquamate at the sulcus
bottom. Dilatations of the intercellular spaces contain
slightly electron-dense material (SF sulcus fluid) and
neutrophilic granulocytes (NG). Reproduced from Schroe-
der et al. (1731, ~ 2 1 0 0 .
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Schroeder & Listnarten

108
 The gingival tissues: the architecture of periodontal protection
grate through the junctional epithelium into the oral
cavity, even under conditions of gingival health, and
serve as the first line of peripheral defense. They also
help to explain the differential volume occupied by
leukocytes within the junctional epithelium (Fig.
6a,b) (161).The average volume occupied by neutro-
philic granulocytes is 32+18% (range 8-61%) as
compared with lymphocytes and monocytes, which
occupy 68218% (range 39-91%) of the total intra-
epithelial leukocyte volume. Occasionally, mast cells,
plasmablasts (Fig. 13a,b) and even Langerhans cells
(79) are encountered in junctional epithelium, al-
though the latter are not always present (45, 136).
The highest concentration of leukocytes is found be-
neath the sulcus bottom, in the most coronal part
of the junctional epithelium, and decreases apically
(160, 161) (Fig. 7a,b). Inside the junctional epithel-
ium, the ratio of neutrophilic granulocytes to mono-
nuclear leukocytes is, on average, 1:3.6, instead of
95:5 as reported in sulcular washings (161, 164).
However, there is no correlation between the num-
ber of leukocytes in the junctional epithelium and
the degree of inflammation of the gingival connec-
tive tissue (160). Since a limited number of neutro-
philic granulocytes transmigrate the junctional epi-
thelium, even in the experimentally normalized gin-
giva, when gingival fluid flow is undetectable, it may
be concluded that neutrophilic granulocyte-trans-
migration and fluid exudation are separate, unre-
lated phenomena, that may occur concomitantly
(14, 39, 86, 160, 161). It is remarkable that constant,
moderate transmigration of neutrophilic granulo-
cytes, that is, when neutrophilic granulocytes ac-
count for less than 30% of the junctional epithelial
volume, does not result in epithelial disintegration.
The pathway remains intact, both structurally and
functionally. This is in line with results from in uitro
experiments showing that neutrophilic granulocytes
migrating through a monolayer of kidney cells, did
not affect epithelial permeability (123, 124).
Epithelial infiltration with mononuclear
leukocytes
In the clinically healthy or slightly inflamed gingiva
of children and adolescents, as well as of young
Fig. 12. Middle portion of the junctional epithelium (JE)
with numerous emigrating neutrophilicgranulocytes (NG)
in widened intercellular spaces that contain a slightly
electron dense material indicative of sulcus fluid (SF). The
dogs, the junctional epithelium serves not only as a
pathway for the transmigration of neutrophilic gran-
ulocytes and for gingival fluid exudation but also as
a compartment that accommodates mononuclear
leukocytes (83, 103, 160, 161, 164, 171,200). As these
cells appear in only very small proportions in wash-
ings of the gingival sulcus (see above), they are con-
sidered transient rather than transmigrating cells.
Those arriving at the gingival sulcus appear to be
passively carried into the sulcus. Based on electron
microscopic observations, this population of mono-
nuclear leukocytes consists of small lymphocytes, T-
and B-lymphoblasts, as well as monocytes/macro-
phages (103, 160, 161) and, rarely, mast cells (Fig. 1,
8b,c). The exact proportion of each cell class is un-
known and appears to vary unpredictably over time.
Within the junctional epithelium, these cells reside
most often in the basal and parabasal cell layers,
tightly squeezed within the intercellular spaces (Fig.
8a,b, 13a,b). In exceptional cases, they may account
for up to 80-90% of the total intraepithelial leukocyte
volume (161) and, together with transmigrating neu-
trophilic granulocytes, seem to contribute to the lo-
calized, focal disintegration of the junctional epithel-
ium (Fig. 8a). Their volumetric contribution to the
total population of leukocytes that momentarily re-
sides in the junctional epithelium does not correlate
with that of the neutrophilic granulocytes. This is re-
flected by an extreme variability of the ratio of
mononuclear to polymorphonuclear cells (161). Nor
is there a correlation between the proportion of
intraepithelial mononuclear leukocytes and the clin-
ical state of gingival health (160, 161). Thus, volume
fractions of mononuclear cells in the junctional epi-
thelium are similar in size in clinically healthy and
slightly inflamed gingiva. On the other hand, mono-
nuclear cell infiltrations of pocket epithelium in
periodontitis are dominated by plasma cells (131).
In the juvenile gingiva, the heavily infiltrated junc-
tional epithelium (Fig. 8a-c) strongly resembles the
crypt epithelium of the human palatine tonsil (146,
161). As in the latter, infiltration of the junctional
epithelium is often patch-like and variable and in-
cludes small lymphocytes, B- and T-lymphoblasts,
monocytes and macrophages, but with a predomi-
nance of lymphocytes. As in the tonsil, the infiltrated
subepithelial connective tissue (CT) exhibits a dense ac-
cumulation of lymphocytes and emigrating neutrophilic
granulocytes. Specimen derived from slightly inflamed
gingiva. Magnification: X 2200.
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Schroeder & Listgarten

110
 The gingival tissues: the architecture of periodontal protection
junctional epithelium is adjacent to a lymphocyte-
dominated connective tissue compartment. A ques-
tion that remains to be answered is how the cellular
composition of the connective tissue compartment
is related to that of the junctional epithelium (200).
The connective tissue compartment of the gingival
defense system
Beneath the junctional epithelium, the gingival lam-
ina propria provides another compartment that is
indispensable for gingival defense. This compart-
ment may be restricted to the coronal aspect of the
junctional epithelium (Fig. 9), or it may extend more
apically. Like the junctional epithelium, it encircles
the tooth. It varies considerably in width and may
not always be readily identifiable.
The principal component of this compartment is
the ring-like gingival plexus, a network of postcapil-
lary venules described previously. As soon as anti-
gens and other immunogenic substances enter the
connective tissue via the highly permeable junc-
tional epithelium, these venules assume the charac-
teristics of high endothelial venules which serve for
homing and entry of (T-)lymphocytes into the con-
nective tissue (208). For that purpose, gingival high
endothelial venules express ELAM-1, ICAM- 1, LFA-3
and VCAM-1 that bind to T-cell surface receptors
(such as selectins and integrins), especially CD4+
memory cells (182). Whether additional adhesion
molecules, unique to the oral mucosa or gingiva, are
present in or become expressed by these vessels is
still unknown. However, the fact that the venules of
the gingival plexus are present at this particular site
and that they develop into high endothelial venules
that proliferate under challenge suggests that selec-
tive homing and entry of lymphocytes is provided by
the gingival plexus.
Following tooth eruption, in clinically healthy and
slightly inflamed gingiva of children and adoles-
cents, leukocytes accumulate around these vessels,
thus giving rise to the compartment described
above. The development and composition of these
Fig. 13. Coronal (a) and middle (b) portion of the junc-
tional epithelium (JE) with numerous neutrophilic gran-
ulocytes (NG, upper inset) emigrating through its coronal
portion (a) and with mast cell (MA) and lymphocyte (L)
infiltration in the connective tissue-related part of its
middle portion (b),as seen by light (a) and electron micro-
scopy (b). The apical continuation of the area outlined in
leukocyte accumulations have been studied by a var-
iety of methods, including light and electron micro-
scopy for general morphological descriptions and
the use of monoclonal antibodies for specific label-
ing of leukocyte surface receptors. Based on a
stereological analysis at the electron microscopic
level, such cell accumulations in the buccal gingiva
of recently erupted premolars in 9- to 14-year-old
adolescents averaged 13X lo6 fibroblasts, 362X 10'
small and 282X lo6 medium-sized lymphocytes,
17x10' T-blasts, 14X106 plasma cells and 28X106
mast cells per cm3 of tissue (171). Thus, about 78%
of all cells were lymphocytes. Many of the fibro-
blasts, in direct contact with small lymphocytes, ex-
hibited cytopathic disintegration, that is, chromatin-
poor nuclei, swollen mitochondria, enlarged and di-
latated cisternae of the rough endoplasmic retic-
ulum and a distended vacuolated cytoplasm (171,
172, 183). Later, using buccal gingival biopsies of 3-
to 8-year-old children, Longhurst et al. (102, 103)
confirmed these data by differential cell counting
using light and electron microscopy. The data offer-
ed by Hinge et al. (831, following 4 days of experi-
mental gingivitis in 11- to 13-year-old adolescents,
suffered from difficulties in cell identification at the
light microscopic level. However, in a series of
studies using histochemical markers and mono-
clonal antibodies, Seymour et al. (178, 179), Armitt
(81, Gillett et al. (63) and Walsh et al. (203) confirmed
that leukocyte accumulations in the gingiva around
deciduous teeth are comprised of up to 80% T-
lymphocytes, including natural killer cells, all of
them HLA-DR+ and -DQ', that is, activated but not
proliferating cells. Fewer than 5% were interleukin
(1L)-2 and transferrin receptor positive (203).Among
T-lymphocytes, helper and inducer (CD4+) cells out-
numbered suppressor and cytotoxic (CD8+) cells by
a ratio of 2.1:l. The same was true in peripheral
blood (138). Many of these cells were clustered
around small blood vessels (high endothelial ven-
ules), with occasional natural killer cells (203). Acti-
vated macrophages, that may include functionally
different subsets (201), accounted for 7-16% of the
(a) is enlarged in (b). Next to the mast cells, plasmablasts
(PB) are also found in the junctional epithelium. The
connective tissue (CT) exhibits a dense accumulation of
lymphocytes (b). BP: bacterial plaque; E: enamel; M:
phagocytized microorganisms. Magnification: X 2200;
upper and lower insets: X4500.
Iff
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112
 The gingival tissues: the architecture of periodontal protection
cells, whereas B-lymphocytes and plasma cells ac-
counted for only a small fraction of the entire cell
population. These cells reside mainly around blood
vessels, at the periphery of the accumulated cell
mass, which also contains occasional dendritic Lan-
gerhans cells (203). These data were recently corro-
borated by Alcoforado et al. (5) and Tonetti et al. (200)
for the very slightlyinflamed gingiva of deciduous and
permanent teeth in children and young adolescents.
Electron microscopically,blast-forming T- and B-cells
are seen (Fig. 14b,c), although they represent fewer
than 10% of all cells present (168). Not infrequently,
macrophages contain large heterolysosomal bodies
filled with cellular debris and lysosomes of neutro-
philic granulocyte origin (Fig. 14a) (162).
These characteristics of leukocyte accumulations
in the defense domain of human gingiva are unique
to children and young adolescents. They are typically
associated with the absence of a gingival pocket and
its pocket epithelium and found irrespective of the
gingival health status. Chronic inflammatory lesions
characterizing experimentally induced or spon-
taneous gingivitis and periodontitis in adults display
a distinctly different type of leukocyte accumulation,
always dominated by B-lymphocytes and plasma
cells (76, 105, 106, 107, 180), with some variations in
size, density and composition “over relatively short
distances along the soft tissue wall of the periodontal
pocket” (77).
The early gingival lesion:
a sign of immune recognition?
The type of alterations seen in the various defense
compartments of the gingiva in children and young
adolescents have been termed the early gingival
lesion, emphasizing its inflammatory nature (143).
This lesion was originally interpreted as representing
the beginning of destructive disease and as an inter-
mediate step between the initial acute phase of gin-
givitis and the established lesion of clinically overt
chronic gingivitis (143). Based on more recent clin-
ical investigations and the evidence discussed here,
this view must be revised.
Fig. 14. Lymphocyte-dominated leukocyte accumulation
in the connective tissue of a clinically slightly inflamed
gingiva of an adolescent. Along the junctional epithel-
ium (JE), this accumulation is composed of altered
fibroblasts (FI), numerous small (SL) and medium-sized
lymphocytes (ML), macrophages (MC) as well as typical
Clinically the gingiva around deciduous teeth is
rarely inflamed, although the adjacent tooth surfaces
are covered with microbial plaque. Gingival fluid
flow is minimal (186). At the same level of plaque
accumulation, the gingiva of children is comparably
less inflamed than that of adolescents and adults
(115). When the experimental gingivitis model (101)
is applied to children, microbial plaque accumulates
rapidly but fails to induce clinical signs of inflam-
mation; rates of gingival fluid flow and emigration of
neutrophils do not increase (108, 113, 127). More-
over, the amount of plaque accumulating on decidu-
ous teeth does not correlate with the size of the
leukocyte-dominated gingival connective tissue. The
latter persists irrespective of whether the gingiva is
clinically normal or not (21, 23, 108, 178).This is also
true for the gingiva around recently erupted perma-
nent teeth (83, 91). Gingival tissues in young adoles-
cents that underwent several weeks of professional
oral hygiene still presented with a lymphocyte-domi-
nated defense-domain, although they were clinically
healthy and, histologically, contained relatively few
blood vessels (91). Thus, even in young adolescents,
a leukocyte accumulation resembling the early
lesion exists in the absence of vasculitis, that is,
acute inflammation. This finding refutes the hypo-
thesis that a relatively thick marginal gingiva around
deciduous teeth masks the inflammatory reaction
prevailing underneath (21, 23). Matsson (114), who
came to a similar conclusion, pointed out that nei-
ther the amount of plaque nor a sudden shift in its
composition, except for gradual age-related changes
until puberty, could explain the relatively mild gingi-
val reaction in children and young adolescents. Simi-
lar thoughts were expressed by Bimstein & Ebersole
(19).
Based on the still inconclusive and fragmentary
evidence discussed here, the T-lymphocyte-domi-
nated defense domain, together with the mono-
nuclear infiltration of the junctional epithelium, in
clinically healthy and slightly inflamed gingiva of
children and young adolescents may represent an
immune reaction, involving initial recognition and
later a defense reaction, against immunogenic sub-
immunoblasts (IB, b and left inset) and plasmablasts
(PB, c and right inset). The low-power electron micro-
graph (a) is reproduced from Schroeder et al. (171).
Magnification: a: X2000; b: ~ 6 7 0 0 ;c: X9600; upper in-
set: x7200; left lower inset: ~ 3 6 , 5 0 0 ;right lower inset:
~54,600.
113
Schroeder & ListKarten
stances that leak through the highly permeable (164,
189) junctional epithelium, as soon as the tooth
starts to erupt. In monkeys as well as conventional
and germ-free rats, the first accumulation of leuko-
cytes was detected at the very stage when oral and
dental epithelia fuse and the teeth started to emerge
(110, 111). Such leukocyte accumulations were also
reported by Listgarten & Heneghan (97, 98) in germ-
free dogs.
Despite their defense functions, the junctional
epithelium and the most internal zone of the lam-
ina propria remain structurally and functionally in-
tact, apart from the fact that fibroblasts are ad-
versely affected in the connective tissue-domain.
This results in a temporary net loss of collagen
fibers and space for leukocyte accumulation (75,
143, 171). It is conceivable that antigens and other
immunogenic molecules that enter the intercellular
spaces of the junctional epithelium by passive dif-
fusion are met by macrophages (and Langerhans
cells?) which present them to T-lymphocytes inside
or outside the LFA-3 and ICAM-1 positive junc-
tional epithelium, as is the case in the tonsillar
crypt epithelium (27, 43). Initially, during tooth
eruption, this would require the presence of naive
(CD45RAf) T-lymphocytes. Later, while the recog-
nition process persists or even subsides, memory
(CD45RO+)T-lymphocytes could enter (via high en-
dothelial venules) and populate the defense domain
without dividing (2001, ready to help activate B-
lymphocytes in case of need. For example, such
need could arise when bacteria grow subgingivally,
a gingival pocket develops and the junctional dif-
fusion pathway breaks down. As long as the latter
remains intact, the defense alert (91) is maintained,
even in the temporary absence of gross microbial
plaque at the gingival margin. Acute inflammatory
episodes, triggered by bacterial invasion, may be
superimposed on this otherwise quiescent state.
Therefore, the early gingival lesion may represent
a transient lymphoid tissue, rather than a leukocyte
infiltration, as most if not all components typical for
such a tissue are present, including various T-cell
subsets, high endothelial venules, antigen-present-
ing cells such as activated macrophages and possibly
interdigitating cells. Consequently, the leukocyte ac-
cumulation in junctional epithelium and the inner-
most connective tissue of the gingiva in children and
young adolescents should not be regarded unequi-
vocally as a first step toward severe gingivitis and
periodontitis, but rather as a normal constituent of
the host defense system, not associated with a de-
structive process.
114
Successful versus compromised
periodontal defense
The various gingival tissue compartments specifi-
cally used for peripheral defense of the periodon-
tium function with astonishing efficiency in most
people, not only in children and adolescents but also
later in life. However, this defense system can be in-
terfered with, both from without as well as from
within the human body.
Interference from without may result from thera-
peutic intervention. For example, restorative pro-
cedures that permanently damage the tissues of the
gingival margin, while contributing to dental plaque
accumulation, create an environment that is more
prone to chronic injury and more difficult to protect
by means of the defense activities described.
More importantly, host-intrinsic factors render a
person more susceptible to disease. Such factors are
becoming more numerous and their relationships
and functions better understood as the result of on-
going research. Intrinsic risk factors have been de-
tected that affect every line of defense. There is now
general agreement that one of the first lines of peri-
odontal defense is provided by neutrophilic granulo-
cytes emigrating along the pathway described above
(69,126,137,142, 144,205).Failure of these cells to re-
sist bacterial colonization and tissue invasion results
in clinical symptoms of inflammation, that is, gingi-
vitis (69, 126, 205). According to Offenbacher et al.
(1371,the second line of peripheral gingival defense is
formed by the combined antibody and neutrophil
axis, while the last and third defense line is provided
by the monocyte and lymphocyte axis that, in ad-
dition, modulates the inflammatory response. This
modulation apparently derives from various T-cell ac-
tivities, with T-helper 2-cells (that are IL-4, IL-5, IL-6
and IL-10 positive) abrogating and T-helper 1-cells
(that produce IL-2, interferon gamma and tumor ne-
crosis factor+) enhancing inflammatory disease ac-
tivity, that is, destruction (49, 50). Offenbacher et al.
(137) refers to a noninflammatory (MO-/Thelp) and
hyperinflammatory (MOf/Tinfl),that is, an up- or
downregulated inflammatory response. Functional
defects or decreased numbers of cells could occur at
any of these defense levels as the result of genetic
traits that regulate disease development, that is, suc-
cessful or compromised host defense (69, 121, 126).
But even in the absence of such interference, pe-
ripheral periodontal defense may depend on an
early and prolonged phase of local antigen recog-
nition, followed by challenges of great antigenic di-
versity, over a period of time. Thus, the local
 The gingival tissues: the architecture of periodontal protection
immunogenic activity in gingival tissue compart-
ments around erupting and newly erupted teeth,
both deciduous and permanent, may be conceived
as indispensable for the development of a long last-
ing successful defense system. This does not in any
way underestimate the pathogenic potential of vari-
ous oral microorganisms. However, the mere pres-
ence of certain bacteria does not necessarily indicate
periodontal disease (69).
Conclusion
The gingival tissues, with their specialized relation-
ship to the tooth surface, constitute the major pe-
ripheral defense against microbial infections that
may lead to periodontal disease. Both the epithelial
and connective tissue components play major roles
in this defense.
Although the keratinized oral gingival epithelium
provides effective protection against both mechan-
ical trauma and bacterial invasion, the nonkeratiniz-
ed junctional epithelium is only partly effective in its
protective role, because its attachment function to
the tooth is incompatible with good resistance to
trauma. However, with the assistance of leukocytes
residing in the intercellular spaces and its high turn-
over rate, it provides a fairly effective barrier to bac-
terial penetration. The protective function of the gin-
gival epithelia against infection is enhanced by the
action of salivary secretions that physically cleanse
and lubricate the epithelial surfaces and provide
antimicrobial protection through various constitu-
ents that are directly toxic to bacteria or interfere
with their ability to colonize the mucosal surfaces.
The lamina propria, with its fibrous and cellular
constituents, provides the major anchorage of the
gingiva to the tooth. It also houses the cellular mech-
anisms necessary to protect the host against bac-
terial invasion and promote tissue regeneration and
repair. Gingival inflammatory cell infiltrates, particu-
larly in the young individual, serve an important
protective function and do not necessarily indicate
progressive or even future disease. Current infor-
mation on various inflammatory cell types indicates
that cellular infiltrates observed in children and in
adults with periodontitis may differ qualitatively as
well as quantitatively. Likewise, observations on
populations in rural Africa (16) suggest that, even in
the presence of a heavy plaque and calculus load,
the inflammatory reaction is primarily protective
and may not necessarily lead to progressive tissue
destruction.
Acknowledgments
We thank S. Munzel-Pedrazzoli for competent help
in designing and producing the illustrative plates
and R. Kroni for processing the manuscript and pro-
viding the reference list.
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