Defense is resisting an attack; there are numerous protective&nbsp;mechanisms that work in the oral cavity against various insults.&nbsp;Gingiva is constantly subjected to a wide array of mechanical,&nbsp;&nbsp;chemical and antigenic challenges — some of which are&nbsp;transient and others permanent. This review will discuss how&nbsp;the gingiva prepares and safeguards itself via diverse defense&nbsp;mechanisms in the face of this challenging environment

Jhawar, Apurv

Verma, Eshan

English

Atharva Scientific Publications (E-Jounals)

Defense Mechanisms of Gingiva
Journal of Orofacial Research, April-June 2014;4(2):111-114 111
JOFR
ABSTRACT
Defense is resisting an attack; there are numerous protective 
mechanisms that work in the oral cavity against various insults. 
Gingiva is constantly subjected to a wide array of mechani-
cal, chemical and antigenic challenges — some of which are 
transient and others permanent. This review will discuss how 
the gingiva prepares and safeguards itself via diverse defense 
mechanisms in the face of this challenging environment.
Keywords: Gingival defense mechanism, Protective mecha-
nisms in gingiva, Gingival crevicular fluid.
How to cite this article: Verma E, Jhawar A. Defense Mecha-
nisms of Gingiva. J Orofac Res 2014;4(2):111-114.
Source of support: Nil
Conflict of interest: None
InTRoduCTIon
By failing to prepare, you are preparing to fail. Gingiva 
prepares and protects itself from various pathogens, through 
the fine tuning of homeostasis. If this balance is lost, the acti-
vity of gingival tissue becomes abnormal, and this change 
is perceived as periodontal disease.1 Defense mechanisms 
guarding the gingiva can be classified into—nonspeci fic 
and specific mechanisms (Flow Chart 1).2 Nonspecific 
mechanisms include innate immunity and are the first line 
of defense. All infections cannot be prevented by innate 
immunity as microorganisms evolve rapidly.2 To counter 
these changes, specific protective mechanisms of adaptive 
immunity enable the body to differentiate between ‘self’ 
and ‘nonself’.
dISCuSSIon
Nonspecific mechanisms that protect gingiva include host-
microbe symbiosis and tissue resistance. Host-microbe 
symbiosis is a close, prolonged association between two or 
more organisms of different species, regardless of the benefit 
to the members. Most bacteria-host interactions are now 
believed to be nonpathogenic and both the host and bacteria 
benefit from peaceful co-existence.3 Presence of ‘friendly’ 
commensal habitants is essential for mounting a well estab- 
lished host immune system that contributes to a healthy 
periodontium by protecting it from pathogenic microbes. 
The constant ‘appropriate’ innate response of gingiva to 
these commensal microbes (beneficial oral biofilm) thereby 
protects the periodontal tissues.2,3
Tissue resistance (Flow Chart 2) consists of four bar-
riers—anatomical factors, mucous barrier, epithelial barrier 
and local inflammatory barrier. A breach in one or more of 
these can cause disease.6
Anatomy of gingival tissues is designed for effective 
mastication and clearance of food debris.6,8 Any poor 
functional tissue relations lead to plaque accumulation.6 
Stippling is a functional adaptation to provide resistance to 
mechanical trauma.8 Attached gingiva is contoured to allow 
for proper deflection of food and is critical for maintenance 
of gingival health.8 Gingival fibres that brace the marginal 
gingiva firmly against tooth surface, provides necessary 
rigidity to combat forces of mastication and tends to throw 
defense Mechanisms of Gingiva
1Eshan Verma, 2Apurv Jhawar
Review ARticle
10.5005/jp-journ ls-10026-1138
1,2Lecturer
1,2Department of Prosthodontics, Crown and Bridge, Manipal 
College of Dental Sciences, Manipal, Karnataka, India
Corresponding Author: Apurv Jhawar, Lecturer, Department 
of Prosthodontics, Crown and Bridge, 702, Kirthi Samrath 
End Point Road, Manipal-576104, Karnataka, India, Phone: 
+91-9740727216, e-mail:  apurvjhawar01@gmail.com
Flow Chart 2: Tissue resistance
Flow Chart 1: Classification of defense mechanism in gingiva
Eshan Verma, Apurv Jhawar
112
out any foreign material into the sulcus.4,6,8,9 This expul-
sion is aided by the movement of teeth and gingival tissues 
during function of dentition and pulse beats.9
Mucus barrier is formed by saliva, washing the gingival 
surface and gingival crevicular fluid (GCF), flowing through 
junctional epithelium (JE) into the gingival sulcus.2,6 
Saliva is the muco-serous secretion contributed by salivary 
glands.2,6,7 Glycoproteins and mucoids in saliva, coat the 
gingival surface providing lubrication and physical protec-
tion.1,6,7,10,11 Salivary flow influences calculus formation 
and thus gingival health.7 This flow cleanses the gingival 
surface by cleaning debris and bacteria.6,7 Bicarbonates 
and phosphates act as antacids neutralizing acidic bacte-
rial products.7 Coagulation factors VIII, IX and X, plasma 
thromoboplastin antecedent, Hageman factor in saliva, 
speed up coagulation and protect wounds from bacterial 
invasion.7 Host defense molecules found in saliva including 
the host’s innate and acquired immune responses, such as 
antimicrobial peptides, chemokines, cytokines, etc. have a 
major role in determining microbial balance and bacterial 
colonization.3,6,10
Antimicrobial peptides (Flow Chart 3) are early respon-
ders of innate immunity that ‘search and destroy’ the inva-
ding pathogens.10 Cationic peptides may be bactericidal 
or bacteriostatic.10 While no activity has been reported 
against Candida albicans, adenomedullin has shown to 
protect against Gram positive and Gram negative bacteria 
suggesting that it contributes to the mucosal host defense 
system.10 Alpha-defensins5,10 (human neutrophil pep-
tides1-4) and Beta defensins3,5,10,12 (hBD1, hBD2, hBD3) 
expressed in the gingival epithelium act as broad spectrum 
antibacterials, binding to or inserting into the bacterial cell 
membrane causing cell lysis. Also, Cathelicidin,10 a precur-
sor of antimicrobial peptide LL-37 ligates to and neutra-
lizes lipopolysaccharides in Gram negative bacteria and 
C. albicans. Salivary-5-histatin10,13,14 involved in genera-
tion of reactive oxygen species also binds to fungal cell 
membranes and enters the cytoplasm targeting the mito-
chondria inducing non-lytic cell death. Statherin,10 another 
antimicrobial peptide, inhibits growth of anaerobic bacteria, 
and prevents crystallization of calcium phosphate thereby 
inhibiting calculus formation. Bacterial agglutination and 
adhesion proteins include mucin-7, salivary agglutinin and 
surfactant protein-A that are involved in bacterial binding 
and agglutination thus promoting bacterial clearance.10 
According to recent studies, they also block HIV from 
entering into host cells.10 Proline rich proteins (PRP) are 
unique, since they may be both beneficial and harmful as 
the larger proteins promote the attachment of bacteria to the 
pellicle and thus induce plaque formation while the smaller 
ones inhibit their attachment.1,10 Proline rich proteases in 
commensal bacteria degrade PRP and the end products limit 
bacterial adhesion.10 Fibronectin reduces bacterial adhesion 
to oral surfaces by causing bacterial agglutination. It also 
inhibits the fimbrillin-induced expression of inflammatory 
cytokines in macrophages by directly binding to the fimbril-
lin from P. gingivalis.10
Metal ion chelators, e.g. calgranulin A and B and lacto-
ferrin are cation scavengers that inhibit bacterial growth. 
Calprotectin, a dimer of calgranulin A and B, chelates 
with manganese and zinc ions.10 Lactoferrin binds with 
two ferric ions along with a bicarbonate ion and acts on 
bacteria, viruses, fungi and parasites, killing A. actinomy-
cetemcomitans, inhibiting the growth of P. ginigivalis and 
inhibiting the adhesion of P. intermedia, P. nigrescens and 
A. actinomycetemcomitans to fibroblasts.1,10 
Generated by the host and bacteria, proteolytic enzymes 
in saliva initiate and contribute to the progression of perio-
dontal diseases. Their action on target tissues is inhibited 
by Protease inhibitors.10 Cystatins C and S are cysteine 
protease inhibitors that inhibit the growth of P. gingivalis.10 
Secretory leukocyte protease inhibitor, an antibacterial and 
anti-inflammatory protein, inhibits the action of bacterial 
serine protease enzyme.10 Elafin has anti elastase activity.10 
Lactoperoxidase and myeloperoxidase belonging to heme 
peroxidise family form a major part of peroxidase system 
of saliva that catalyzes the oxidation of thiocyanate forming 
hypothiocyanite, and oxidation of chloride and iodide ions 
forming bactericidal end products.1,10
Another group of proteins are the ones which act against 
the bacterial cell walls. Lysozyme hydrolyses the (1,4)-beta 
linkages between NAM and NAG residues in peptidog-
lycans, mainly in the gram positive bacterial cell walls, 
making them more permeable.1,10 Peptidoglycan recognition 
Flow Chart 3: Subclasses of antimicrobial proteins
Journal of Orofacial Research, April-June 2014;4(2):111-114
Defense Mechanisms of Gingiva
113
JOFR
proteins1,3,4 present in saliva are bactericidal for pathogenic 
and non-pathogenic Gram positive bacteria by binding to 
the peptidoglycan. However, unlike lysozymes, they do not 
permeate the cell walls.10
Gingival crevicular fluid (GCF), another component of 
the mucosal barrier,2,6 is an altered inflammatory exudate 
that flows into the oral cavity from the gingival crevice.2,5,7,11 
However, compared to saliva, the non-specific antibacterial 
mechanism offered by GCF consists of a more complex 
array of immune components.1 GCF is derived from the 
gingival capillary bed as well as the resident and migrating 
inflammatory cells.1,5,7 GCF flow increases during inflam- 
mation and thus may be considered as a way of throwing 
out the toxins and bacteria from the gingival sulcus.5,7,9 It 
lubricates foreign materials to facilitate their expulsion.9 It 
contains antimicrobial proteins, similar to those found in 
saliva.1,3,5,7,10,12,15 It also contains inflammatory immune cells 
that contribute to local immune regulation through many 
mediators, including prostaglandin, leukotrienes, IL-1, IL-6, 
TNF and IL-8 and humoral antigenic activity.1,2,4,5,7,9,15-17
The epithelial barrier is a continuous epithelial sheath 
consisting of gingival, sulcular and junctional epithelium 
through which crowns of teeth protrude into the oral 
cavity.2,6,10,12-14,16,17,19 An intact epithelium prevents frank 
bacterial invasion of periodontal tissues and is also effective 
against penetration of metabolic and bacterial components 
under normal health conditions.2,4-7,9-11,16 Turnover rate, 
the rate at which all the cells in the tissue can be replaced 
is high at 41 to 57 days for gingival, 10 to 14 days for 
sulcular and 4 to 6 days for junctional epithelium, which 
allows for the rapid replacement of cells and tissues that 
are injured by pathological microorganisms.2,4-7,9,10,11,16,18 
Desquamation, the process wherein the dehydrated and 
flattened cells of the superficial layers are lost and replaced 
by cells of the underlying layers, limits the colonization of 
epithelial surface by pathogenic microorganisms, removes 
the bacteria that have already colonized and regenerates an 
intact epithelial barrier.2,4-6,8-11,16,18
A protective surface coverage is provided by the outer 
barrier of keratinized gingival epithelium and an inner bar- 
rier of epithelial attachment.2,4-6,8-11,16,18 Epithelial attach-
ment, formed by superficial flattened layer of JE in contact 
with the tooth surfaces and the inner basal lamina, together 
provide the attachment of gingiva to the tooth surfaces 
thereby preventing the growth and apical migration of bacte-
rial plaque into gingival connective tissues.2,4-6,8-11,16,18  This 
attachment is reinforced by gingival fibers, referred to as 
dentogingival unit.14 The JE allows bidirectional movement 
of various compounds between the gingival connective tis-
sue and oral cavity.2,4-6,7,9-11,16 It is nonkeratinizing, being 
undifferentiated even in the coronal layers.4,5,8,18 The lack 
of extensive intercellular connections and the presence of 
fewer intercellular adhesions and gap junctions provide 
it with abundant intercellular spaces. These spaces act as 
a GCF reservoir, becoming larger during inflammation 
and getting infiltrated with neutrophils, monocytes and 
lymphocytes. This prevents bacteria from penetrating the 
epithelium and producing a diffusion barrier to microorgan-
isms, bacterial enzymes, metabolic by-products and other 
antigenic substances.2,4-6,8-11,16 These spaces also produce 
a diffusion pathway for GCF and its constituents. Another 
special protective role of JE that has been recently reported 
is its endocytic capacity, similar to that of macrophages and 
neutrophils.2,5,8,19 These cells are found to contain lysozyme 
like bodies and they engulf bacteria.2,5,8,19 Epithelial cells 
have also been found to express antimicrobial peptides 
like beta-defensins, catheliciden, c-c motif chemokine 28, 
calgranulin A and B, lactoferrin, peptidoglycan recognition 
proteins 3 and 4.3,4,5,7,10,15
Local inflammatory response is the most significant and 
final barrier to penetration of connective tissue by bacteria 
and their toxins.2,6 This response is stimulated by tissue 
injury and infection.2 A series of reactions brings about local 
changes like increased vascularization leading to increased 
fluid collection and cellular exudation that eventually causes 
accumulation of serum proteins and phagocytic cells in the 
affected area.2,16
Keratinocytes, no longer considered as passive by-
standers, play an active role in the activation of inflam-
mation within the gingival tissues.4,5,8 They synthesize a 
number of cytokines, adhesin molecules, growth factors and 
enzymes.4-7,10 They also produce Interleukin 1, TNF, prosta-
glandin E2, matrix metalloproteinases, that diffuse through 
JE, enter the gingival connective tissue and initiate the cel-
lular immune reaction.4-7,10 Recruitment of neutrophils into 
the JE is mediated by antigen presenting cells (Langerhans 
cells), and adhesion molecules secreted by keratinocytes, 
promoting diapedesis of neutrophils along the chemical 
gradient.5-7,10,19  Fibroblasts in the connective tissue are also 
involved in bringing about local inflammatory response.1
Neutrophils and macrophages are the two most impor-
tant phagocytes that consume bacteria to protect the host 
tissues.2,4-7 Neutrophils, the most predominant inflamma-
tory cells in periodontal sulci, are important in maintaining 
the health of periodontium.2,4,5 PMNs adhere to the host 
substrate, migrate to the site of infection along the chemical 
gradient, recognize the bacteria, and bring about phagocy-
tosis.2,5 Cytoplasmic processes or pseudopodia engulf and 
integrate the pathogen forming a phagosome.5 Phagosomes 
then fuse with lysosymes to form phagolysosome wherein 
digestion and destruction of pathogen takes place. PMNs 
also undergo degranulation and allow extracellular killing of 
pathogens which is considered a principle mode of reducing 
bacterial count in the gingival crevice. The granules found 
Journal of Orofacial Research, April-June 2014;4(2):111-114
Eshan Verma, Apurv Jhawar
114
in PMN consist of primary (azurophilic) and secondary 
(specific) granules.5 These can bring about oxygen depend-
ant or independent plaque reduction.5
Macrophages have two protective roles — as phagocytes, 
and as antigen presenting cells.2,5 The former engulf foreign 
material while the latter present the antigens on their cell 
surface thereby activating T-cells and providing cellular 
immunity.
Specific mechanisms: The body produces antibodies 
specific to a particular antigen. These antigens have ‘flags’ 
(specific amino-acid sequences) that help the immune sys-
tem to recognize the ‘non-self’.2 After the lymphocyte gets 
exposed for the first time to the antigen, the lymphocyte 
memorizes the antigen encountered so that a consequent 
exposure will result in a faster secondary response of to the 
antigen.2 Saliva and GCF contain immunoglobulin G, M 
and A that are synthesized locally as they bind exclusively 
to the strains of bacteria native to the mouth. IgA, IgG 
and IgM along with complements and PMNs bring about 
opsonization.2,4-7
ConCluSIon
The proper course of action, when under attack is usually to 
counterattack. The oral cavity is well equipped to counter-
attack any adverse condition that may harm the gingiva. 
While the innate immunity acts primarily against any 
foreign invader, the specific immunity takes a more com-
plex targeted approach to protect the gingiva. Right from 
its superficial epithelial layer to the innermost connective 
tissue, there is a line of defense that acts in harmony with 
other oral structures to maintain homeostasis to revert any 
imbalance that would otherwise shift the equilibrium to the 
diseased state.6
REfEREnCES
 1. Kornman W. Immune response in periodontal diseases. Fun-
damentals of periodontics. Quintessence Publishing Co, Inc. 
p.131-134.
 2. Eley BM, Soory M, Menson JD. Host-parasite Interaction. 
Periodontics. 6th ed. Churchill Livingstone Elsevier. p. 27-35.
 3. Jin L. An update on innate defense molecules of human gingiva. 
Periodontol 2011 Jun;56(1):125-142.
 4. Bartold PM, Walsh LJ, Narayan AS. Molecular and cell biology 
of the gingiva. Periodontol 2000-2000. p. 24-28.
 5. Delima AJ, Dyke TEV. Origin and function of the cellular 
components in the gingival crevice fluid. Periodontol 2000; 
2003. p. 31-55.
 6. Macphee T, Cowlet G. The environment of the tooth. Essentials 
of periodontology and periodontics. 3rd ed. Blackwell Scientific 
Publications. p. 19-28.
 7. Newman, et al. Defense mechanism of gingiva. In: Carranza 
FA, editor. Carranza’s Clinical Periodontology. 10th ed. St 
Louis, Saunders, 2006. p. 334-354.
 8. Newman, et al. The gingiva. In: Carranza FA, editor. Carranza’s 
Clinical Periodontology. 10th ed. St Louis, Saunders, 2006. p. 
46-67.
 9. Ramfjord SP, Ash MM. Physiology and defense mechanism 
of the gingival sulcus. Periodontology and Periodontics WB 
Saunders Company, 1979. p. 65.
 10. Gorr SU. Antimicrobial peptides of the oral cavity. Periodontol 
2000;2009;(5).p.152.
 11. Schluger: The normal periodontium. Periodontal diseases, basic 
phenomenon, clinical management and occlusal and restorative 
interrelationships, 1977. p. 48-51.
 12. Krishnakarnkit S, Winberg A, Perez CN, Dale BA. Expression 
of peptide antibiotic human β-defensin 1 in cultured gingival 
epithelial cells and gingival tissues, Infection and Immunity 
1988 Sep;66(9):4222.
 13. Edgeton M, et al. Salivary Histatin-5 and its similarities to 
other antimicrobial proteins in human saliva. Adv Dent Res 
2000 Dec; 14:16. 
 14. Kavanagh K, et al. Histatins: antimicrobial peptides with 
therapeutic potential. J Pharm Pharmacol 2004 Mar;56(3):285.
 15. Schenkein HA, Genco RJ. Gingival fluid and serum in peri-
odontal diseases. J Periodontal 1977 Dec;48(12):772.
 16. Grant DA, Stern IB, Listgarten MA. Defense mechanism of the 
gingiva. Periodontics in the tradition of Gottlieb and orban, 6th 
ed. The CV Mosby company. 1988. p. 48.
 17. Rose LF, et al. Immunoinflammatory response in periodontal 
diseases. Periodontitis, Medicine, Surgery and implants, China, 
Mosby 2004. p. 85.
 18. Nanci A. Oral Mucosa. Ten cate’s oral histology, development, 
structure and function, 7th ed. Mosby, 2007. p. 323-325.
 19. Cho MI, Garant PR. Development and general structure of the 
periodontium. Periodontol 2000 Oct;24:9-27.
Journal of Orofacial Research, April-June 2014;4(2):111-114


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