Gingival inflammation - Dr Priya Jose

1. GINGIVAL INFLAMMATION

2. INDEX
 General aspects of inflammation
 Steps
 Cells involved
 Factors influencing
 Definition of gingival inflammation
 Studies involved
 Initiation of gingival inflammation
 Steps in gingival inflammation
 Cells involved
 Conclusion
 Reference

3. DEFINITION
 Inflammation is a non specific, localized immune reaction of
the organism, which tries to localized the pathogen agent.
Many consider the syndrome a self-defense mechanism.
 It consist in vascular, metabolic, cellular changes, triggered by
the entering of pathogen agent in healthy tissues of the body.

4. ETIOLOGY
 The causes of inflammation are many and varied:
 Exogenous causes:
 Physical agents
 Mechanic agents: fractures, foreign corps, sand, etc.
 Thermal agents: burns, freezing
 Chemical agents: toxic gases, acids, bases
 Biological agents: bacteria, viruses, parasites
 Endogenous causes:
 Circulation disorders: thrombosis, infarction,
hemorrhage
 Enzymes activation – e.g. acute pancreatitis
 Metabolic products deposals – uric acid, urea

5. CARDINAL SIGNS
 Celsus described the local reaction of injury in terms that have
come to be known as the cardinal signs of inflammation.
 These signs are:
 rubor (redness)
 tumor (swelling)
 calor (heat)
 dolor (pain)
 functio laesa, or loss of function
(In the second century AD, the Greek physician Galen
added this fifth cardinal sign)

6. GENERAL ASPECTS OF INFLAMMATION
 Changes in acute inflammation
 Vascular events
 Haemodynamic changes
 Altered vascular permeability
 Endothelial cell contraction
 Endothelial cell retraction
 Direct endothelial cell injury
 Leucocyte mediated endothelial injury
 Cellular events
 Exudation of leucocytes
 Changes in the formed elements of blood
 Adhesion or rolling
 Emigration
 Chemostasis
 Phagocytosis
 Attachment stage (opsonization)
 Engulfment stage
 Secretion(degranulation stage)
 Killing or degradation stage

10. CELLS OF INFLAMMATION
 Mast cells
 Dermal dendrocytes(histiocytes)
 Peripheral dendritic cells(langerhans cell)
 Neutrophils & monocytes /macrophages
 Lymphocytes
 T cells
 B cells
 Natural killer(NK) cell

11.  Complement
 Transendothelial migration
 Leukocyte function
 Chemotaxis
 Phagocytosis
 Antigen processing & presentation
 Immune responses.

17. DEFINITION
Gingivitis is defined as an inflammation confined to the tissues of
the marginal gingiva.
AAP
Current concept- result of epidemiological studies, analysis of
autopsy and biopsy material , clinical trials and animal experimentation.

18. SOME STUDIES
 Extent of periodontal disease increases with age &
with inadequate oral hygiene.
 Few subjects in each age group suffer from
advanced periodontal destruction.(Loe et al 1986)
 Socransky et al 1984 – periodontitis progresses in
episodes of exacerbation & remission- burst
hypothesis.
 Progression is a continous than episodic &
detaction of burst due to an inadequate resolution
of clinical measurement (Jeffcoat & Reddy 1991)

19. INITIATION OF PERIODONTAL DISEASE
 Micro organism quickly start to colonize clean tooth
surface once an individual abstains from
mechanical tooth cleaning.(Loe et al, 1965).
 Removal of subgingival deposit help in successfully
treating periodontal disease.(Ramfjord et al 1968)
 Long term observation in Beagle dogs concluded
that inflammation occur in animals that accumulate
plaque(Saxa et al 1967)

20. Some imbalance of host –microbe relationship is
occuring in the destructive lesions, which may be unique
to that site and to periodontally susceptible individuals
generally.

21. SOME TERMINOLOGY
 Pristine gingiva-
 State of super health
 Normal gingiva that is free from “ significant “ accumulation of
inflammatory cells histologically .
 Healthy gingiva –
 Clinically similar to pristine gingiva
 Histologically features of inflammatory infiltrate with predominantly
neutrophils associated with junctional epithelium and lymphocytes in
the subjacent connective tisssue.

22. FEATURES OF CLINICALLY HEALTHY GINGIVA
 Infiltrate of inflammatory cells(PMN) in JE &
lymphocyte in CT.
 Very early stage collagen depletion is noted.
 Exudative & transudative fluid & plasma protein
arrive –GCF
 Infiltrate 5 % of CT
 Recruitment of PMN by chemoattractant action ( IL-
8,C5a, leukotriene B4, LPS, formyl methionyl leucyl
phenylalanine)
 Later leukocytes arrive( Attstrom 1971)
 Cytokines & adhesion molecules

23. DEFENSIVE FACTOR
 Regular shedding of epithelial cells into the oral
cavity.
 Intact epithelial barrier.
 Positive fluid flow of gingival crevice
 Antimicribial effect of antibody
 Phagocytic function of neutrophil & macrophage
 Detrimental effect of complement

24.  Weakening host factors seen during
 Hormones –puberty & pregnancy
 Drugs-cyclosporin
 Systemic infection
 Neutrophil depletion or dysfunction

25. HOST –PARASITE INTERACTION
Microbial
virulence
factors
Host defense
factors

26. MICROBIAL VIRULENCE FACTORS
 Either can directly injure host cells & tissues or activate immune
systems
 Microbial invasion
 Enzymes- Host protein& other molecule
 Protease
 Waste products- Ammonia, indole, hydrogen sulphide & butyric acid.
 Endotoxin- Leukotoxin
 LPS, LTA & proteins- activate chemical mediators
 Immunodominant molecules

27. HOST DEFENCE FACTORS
 Innate ( Non- specific ) response
 Adaptive (Specific ) response.
 Tailored to offending pathogen.

28. INNATE DEFENSE SYSTEMS
 Physical barrier
 Vascular response
 Cellular response
 Epithelial surface
 Produce /release cytokine
 Release IL-1 enhance immune response
 GCF
 Saliva
 Toll like receptors on epithelium- LPS & defensin-
attach to particular microbe

29. VASCULAR RESPONSE
 5 cardinal signs
 RED- ness
 Swelling
 Temperature
 Pain
 Loss of function- Mobility

31. CELLULAR –MOLECULES, CELLS & PROCESS
 Proteinases
 Proteinase inhibitors
 MMP
 Cytokines
 Proinflammatory cytokines
 Prostaglandins
 PMN
 Elastase
 Lactoferrin

32. ADAPTIVE IMMUNITY
 Humoral immunity
 IgG
 IgA
 Cellular immunity
 Mainly T helper cell

33. CELLS INVOLVED
 Antigen presenting cell
 TCR
 T cell mediated process
 B cell mediated process

41. STAGE IN THE PATHOGENESIS OF GINGVAL
INFLAMMATION
 Page & Schroeder -1976- depending according to clinical & histo
pathological evidence.
 Stage I- initial lesion
 Stage II- Early lesion
 Stage III-Established lesion
 Stage IV- Advanced lesion
-STATE OF PROGRESSION OF GINGIVITIS TO PERIODONTITIS

42.  Mostly non-human experiment.-( animal biopsy &
some young adolescent)
 A new classification is outlined.

44.  Within 10-20 days of plaque accumulation , clinical
signs of gingivitis are established.

45. INITIAL LESION
Clinical Within 24 hours
Subclinical gingivitis – not apparent
Histological Changes in microvascular plexus-dialation of arteriole,
capillary & venules of dentogingival plexus.
Hydrostatic pressure inc ,intercellular gap formed, fluid
& protein exuded.
GCF inc( washing)-plasma proteins defense action
PMN cell migration –adhesion molecules
Leukocyte migrate up cytokineretained longer help of
CD 44 receptor- diapedesis.
Perivasular connective tissue matrix –exudation &
deposition of fibrin
Cellular response is well established. Help of cytokine

47. STAGE II –EARLY LESION
Clinical After 1 week
Detected clinically- second week
Subgingivally located biofilm is formed
Gingiva becomes erythematous –proliferation of
capillary
No clear cut dividing line
GCF flow reach maximum in 6 -12 days after clinical
gingivitis
Histology Vessels remain dialated,number increase
Lymphocytes ( 75
5 % T cells & PMN are predominant two to three fold
.Few plasma cells are seen
15% volume
Fibroblast degenerate –more infiltration
Collagen destruction occur(70%).
Main fiber affected are circular & dento gingival fibers
Basal cells of JE & SE proliferated
Epithelial rete pegs invading coronal portion of lesion.

49. STAGE III- ESTABLISHED LESION
Clinically More edematous swelling
Chronic gingivitis 2 – 3weeks after plaque –
Anoxemia, blood flow stasis, slightly bluish in color
Extravasation of erythrocytes
histologically Increased fluid exudation & leukocyte migration into tissue
Dominated by plasma cells- situated primarly in coronal CT &
vessels
Predominant Ig is Ig G 1 & Ig G 3
Collagen loss both lateral & apical loss-leukocytic inflitration
JE proliferate & rete pegs extend deeper-epithelial integreity &
barrier
JE is changed – not closely attached
Pocket epithelium- heavy leukocyte infiltrate
Basal lamina may be destroyed
JE more permeable- underlying CT –necrosis
Elevated levels of acid & alkaline phosphatase, beta –
glucuronidase, beta glucosidase, cytochrome oxidase,esterase
Neutral mucopoltsaccharide are dec

50.  Two types
 One remains stable-not progessing for months or years
 Second –Active –progressive & destructive advanced
lesion.

51.  Proportion of T cell decrease,B cell increase
 Change in microbial flora or infectiopn of gingival
tissues.

53. STAGE IV – ADVANCED LESION
Clinical Phase of periodontal breakdown.
Formation of periodontal pocket, suppuration,
mobility, migration & tooth exfoliation
Histological As pocket deepens –apically migration of JE
Destructive episode
Flourishes anaerobic niche
Infiltrate extend laterally & apically
Features of established
Except- alveolar bone loss, fiber damage
extensive,JE migrate apically, wide spread
manifestation of inflammatory & immuno
pathological tissur damage.
No longer localized .
Plasma cell domination
Areas of temporary ulceration.

54. GINGIVAL INFLAMMATION ASSESSMENT:
IMAGE ANALYSIS
 non-index method to measure gingival condition.
 the quantitative analysis of gingival swelling and
color characteristics of gingiva by digital images
before and after treatment of individual patients.
 Image analysis using using Serif photo pluse-6
software.
 (MATLAB software) would give more precise
readings
Journal of Indian Society of Periodontology - Vol 16, Issue 2, Apr-Jun 2012

55. CONCLUSION
 Gingival inflammation has two components- Acute
& chronic .
 Each gingival region can have varying amounts of
acute & chronic component.
 Those with acute inflammatory changes – there is
dramatic change in treament.
 The more inflamed a gingival unit appear clinically,
the better the chances of therapeutic measures
resulting in a return to normal gingivak health.

56. REFERENCES
 Carranza’s Textbook of Periodontology-10th &11th edition
 Clinical periodontology and implant dentistry –Jan
Linde-5 th edition
 Textbook of Periodontology and Oral implantology-
Nayak-First edition
 Loe H, Theilade E, Jensen SB (1965) Experimental
Gingivitis in Man.J Periodontol 36: 177–187
 Eberhard J, Reimers N, Dommisch H, Hacker J, Freitag
S, et al. (2005) The effect of the topical administration of
bioactive glass on inflammatory markers of human
experimental gingivitis. Biomaterials 26: 1545–155
 Li Y, Lee S, Hujoel P, Su M, Zhang W, et al. (2010)
Prevalence and severity of gingivitis in American adults.
Am J Dent 23: 9–13

57.  Thank you

58. CELLS OF INFLAMMATION
 Mast cells
 Dermal dendrocytes(histiocytes)
 Peripheral dendritic cells(langerhans cell)
 Neutrophils & monocytes /macrophages
 Lymphocytes
 T cells
 B cells
 Natural killer(NK) cell

60. TRANSENDOTHELIAL MIGRATION

61. CHROMOSOME INVOLVED IN AGGRESSIVE
PERIODONTITIS
 Chromosome 6 –TNF alpha gene polymorphism.
 IL-10 gene polymorphism- chromosome 1
 Cathespin C gene polymorphism.
 IL-1 gene polymorphism-chromosome 2

62. Interleukin-1 Intrabony defects
Influence of IL-1 gene polymorphism on clinical and
radiographic healing outcomes of GTR therapy did not
reveal any statistically significant differences between IL-
1 + and IL-1 – patients.
Interleukin -4 Evaluation of IL-4 gene polymorphisms in the intron 2 and
in the promoter
region (PP +and IP+) showed no association with
periodontal disease
susceptibility.
Interleukin-2 It is established that – 330 (T→G) polymorphism in IL-2
gene is associated with
severity and active role in pathogenesis of periodontal
disease
Tumor necrosis factor -α Research to investigate 4 polymorphisms in TNF- α gene
which were all transitions from G to A, 3 in the promoter
positions: – 376, – 308, – 238 and at position + 489, could
not be identified as susceptibility or severity factors in
periodontitis.

63. Interleuin-10 Three single-nucleotide polymorphisms (SNPs) in the
IL10 gene at positions – 1087, a G to A substitution, –
819, a C to T substitution and – 592, a C to A substitution
have been associated with altered synthesis of IL10
HLA Genetics The MHC genes are the most polymorphic genes present
in the genome of every species.
Studies suggested that patients with HLA-DRB1*1501-
DQB1*0602 genotype may have accelerated T cell
response and increased susceptibility to periodontitis
FcγReceptor polymorphisms, When one or several of FcγR-mediated leukocyte
functions are less or over
efficient due to polymorphisms, it is conceivable that
susceptibility for or severity of periodontitis is seen.
Vitamin D receptor (VDR)
polymorphisms
Studies demonstrated vitamin D receptor (VDR) gene is
localized in chromosome 12 with a cluster of
polymorphisms: BsmI, ApaI and TaqI and relationship
between TaqI VDR gene polymorphisms and periodontitis
Matrix
metalloproteinases(MMP)
polymorphisms
A single nucleotide polymorphism in the promoter region
of - 1607 bp of MMP-1 gene a, 5’-GGA-3’, instead of 5’-
GAT-3’ has been found to be associated

64. MICROBES

66.  The “red-complex organisms” – Porphyromonas
gingivalis, Tannerella forsythia, and Treponema
denticola
 Inhibition of the chemokine IL-8
 Modulation of signalling in “lipid rafts” - between TLR2
and CXC-chemokine receptor 4 (CXCR4) after they are
recruited to a lipid raft inresponse to P. gingivalis fimbriae.
 Directly antagonizing TLR4 through production of Lipid
A

67. DIAGNOSTIC METHOD TO ASSESS
INFLAMMATION
 Genetic analysis
 Clinical method
 Bleeding on probing
 Probes
 Gingival temperature
 Biochemical analysis
 Microbiological analysis
 Image Analysis

68. PROTEOLYTIC HYDROLYTIC
Collagenase
Elastase
Cathepsin – G
Cathepsin – B
Cathepsin – D
Dipeptidylpeptidases
Tryptase
Aryl Sulphatase
 -Glucuronidase
Alkaline Phosphatase
Acid Phosphotase
Myeloperoxidase
Lysozyme
Lactoferrin

69. FACTORS THAT MAY MODIFY THE INFLAMMATORY
RESPONSE
 Mechanical
 Calculus
 Caries
 Restorations *overhangs will increase plaque
 Prosthesis
 Tooth Anatomic Factors
 Systemic
 Uncontrolled diabetes *most common cause of perio disease – if you have diabetes
you are more prone to periodontal disease. Glucose control and periodontal disease
are linked.
 Obesity = more prone to perio disease; overweight means you hae more fat and fat
cells produce cytokines, these produce inflammatory mediators. More cytokines
than normal  more risk of perio problems.
 PMN defects
 Hematological
 Pregnancy
 Puberty
 Immune disturbances
 HIV/AIDS *a person can have this from birth, we don’t have a lot of statistics on this
topic.
 Medications
 Nutritional deficiencies

70.  Genetic
 Agranulocytosis
 Cyclic neutropenia *lack of PMN’s – no first responders to the
inflammation.
 Other neutropenias
 Lazy leukocyte syndrome
 Leukoctye adhesion deficiency (LAD)
 Down’s syndrome
 Papillon-Lefevre syndrome
 Hypophosphatasia *prepubertal patients tend to have these problems.
 Chediak-Higashi syndrome
 Ehlers-Danlos syndrome
 Habits: smoking,
 Systemic disorders: HIV and Diabetes

71.  Innate and Adaptive Immunity
 Immune Cells
 *the vast majority of the immune cells are neutrophils –
these are the first responders
 *they have a 48 hour lifespan in the blood with migration to
sites for phagocytosis.
 Monocytes are on the scene – in the tissue these become
macrophages.
 Cytokines
 Definition: soluble, locally active polypepties: regulate cell
growth, differentiation, function
 Produced by cells of the immune system
 Specific cytokines may have different biologic properties
depending on their concentration, the cells producing
them, the cells being acted upon, and the extracellular
matrix.

72. October 30–November 2, 1999, the International Workshop for a Classification of Periodontal Diseases and Conditions

73. TOLL LIKE RECEPTOR
 First identified as fruit flies-Drosophila spp.-Christiane
Nüsslein-Volhard -1985
 The first reported human TLR was described by
Nomura et al. in 1994 , and mapped to a chromosome
by Taguchi et al. in 1996
 TLR cause APC to upregulate the co-stimulatory B7
molecules.
 Leads to T-cell proliferation.

74.  These germline-encoded receptors, collectively
known as pattern-recognition receptors (PRRs),
can detect and respond to conserved and generally
distinct microbial structures that are shared by
related groups of microorganisms (1).
 These microbial structures are referred to as
pathogen-associated molecular patterns (PAMPs),
and include bacterial lipopolysaccharides,
peptidoglycan, lipoproteins, bacterial DNA, and
double-stranded RNA.
 Upon interaction with these PAMPs, TLRs activate
the innate immune cells through intracellular
signaling pathways.

75.  With IL 1 - “Interleukin-1 Receptor/Toll-Like
Receptor Superfamily”
 Three subgroups of TIR domains exist
 Subgroup 1 TIR domains are receptors for interleukins
and all have extracellular immunoglobulin (Ig) domains.
 Subgroup 2 TIR domains are classical TLRs, and bind
directly or indirectly to molecules of microbial origin.
 A third subgroup -consists of adaptor proteins that are
exclusively cytosolic and mediate signaling from
proteins of subgroups 1 and 2

76. STRUCTURE
 TLRs are transmembrane glycoproteins possessing
varying numbers of extracellular N-terminal leucine-rich
repeat (LRR) domain, followed by a cysteine-rich region,
a transmembrane domain and a C-terminal cytoplasmic
Toll/IL-1R (TIR) domain .
 The LRR domain is important for ligand binding and
associated signaling, and is a common feature of PRRs.
 The TIR domain is important in protein- protein
interaction and is typically associated with innate
immunity.

79.  Toll-like receptors (TLRs 1, 2, 4, 5 and 6) that
recognize extracellular microbial structures are
expressed on the host cell surface.
 Toll-like receptors (TLRs 3, 7, 8 and 9) specifically
detecting viral or bacterial nucleic acids are
expressed intracellularly on endocytic vesicles

80. TOLL LIKE RECEPTORS AND IMMUNE CELLS

83. Journal of Oral Science, Vol. 53, No. 3, 263-271, 2011

84.  Continuous model (1900-1950’s)
 Continuous through life at the same rate of loss (i.e.,
everyone gets periodontal disease)
 Progressive model (1940-1960-2)
 Progressive loss over time of some sites
 No destruction in others.
 Time of onset and extent vary among sites.
 (e.g., Periodontal disease affects mainly the posterior
teeth)

85.  Random burst model (1970-2000’s)
 Activity occurs at random at any site
 Some sites show no activity
 Some sites have one or more burst of activitiy
 Cumulative extent of destruction varies among sites
 i.e., periodontitis is different in various sites in the same
individual and it is difficult to predict attachment loss
 Asynchronous Burst
 Asynchronous multiple burst model (1970s-
2000s)
 Several sites have one or more burst of activity
during one period of life
 Prolonged period of inactivity; remission.
 This is similar to random burst but it takes into
account the risk factors of overhangs, smoking,
diabetes, etc.

86. OBESITY & PERIODONTAL DISEASE
 In 1977, Perlstein et al. observed histopathologic changes
in the periodontium in hereditary obese Zucker rats.
 In 1998, Saito et al. analyzed 241 healthy Japanese
individuals and showed, for the first time, an association
between obesity and periodontal disease in humans.
 Genco et al. analyzed National Health and Nutrition
Examination Survey (NHANES III) data and demonstrated
that BMI was positively correlated ; they found that this
relationship is modulated by Insulin resistance.

87.  Suggesting that periodontitis might impact diabetes with topical
antibiotics improves HbA1c by reducing hs-CRP, which may
relate to amelioration of insulin resistancein type 2 diabetic
patients with periodontal disease.
 It has been suggested that the secretion of TNF-α by adipose
tissue triggered by LPS from periodontal gram-negative
bacteria promotes hepatic dyslipidemia and decreases insulin.
 Type 2 diabetes and decreased insulin sensitivity are
associated with the production of advanced glycation end
products (AGE), which trigger inflammatory cytokine production,
thus predisposing to inflammatory diseases such as
periodontitis.

88.  Adipose-Tissue-Derived Hormones and Cytokines
(Adipokines) Inflammatory Markers
 Adipose tissue secretes proinflammatory cytokines such as tumor
necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).
 Leptin-
 pleiotropic cytokine, secreted by adipocytes
 “lipostat” –regulate adipose tissue mass
 Decreased leptin levels –increasing pocket pocketing depth.
 Adiponectin, Resistin and other Adipose- Tissue-Derived
Cytokines
 Apidonectin- reduced levels in obesity, insulin resistance or type 2
diabetes
 Resistin
 Visfatin- insulin like effects
 Serum – retinol- binding protein4 (RBP4)

91. PHAGOCYTOSIS