This document provides an overview of inflammation and the immune system. It discusses the signs and steps of inflammation, as well as the cells involved in immunity and inflammation, including mast cells, dendritic cells, neutrophils, macrophages, and T and B cells. It also covers the different types of inflammation, such as immediate, acute, and chronic inflammation. Toll-like receptors and the complement system are also summarized.

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INFLAMMATION OF
PERIODONTIUM
Dr Mushahida Anjum
Dental College Azamgarh

2. Introduction
Immunity
Inflammation
Signs of inflammation
Steps of inflammation
Types of inflammation
Inflammation of gums
Cells of immunity &
inflammation
Toll like receptor
Complement system
Tissue destruction
Conclusion
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3.  Survival of all organisms requires they eliminate:
1. foreign invaders (infectious pathogens: viruses, bacteria, fungi)
2. damaged tissues.
 Achieved via a complex mechanism called
“inflammation”
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4.  The term immunity refers to the body’s specific
protective response to an invading foreign agent or
organism.
 The human body has the ability to resist almost all
types of organisms or toxins that tend to damage the
tissues and organs. The capability is called immunity.
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5.  1. Natural (Innate) immunity
 2. Acquired (adaptive) immunity
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6. NATURAL IMMUNITY ACQUIRED IMMUNITY
1. Is a nonspecific
immunity present at birth
2. responses to a foreign
invader are very similar
from one encounter to
the next.
1. Specific immunity
develops after birth
2. Increases in intensity
with repeated exposure
to the invading agent.
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7.  is a protective response
 eliminate the initial cause of cell injury
 diluting, destroying and neutralizing the harmful
agent
 remove the damaged tissue
 generate new tissue
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8. Inflammation is a protective response
intended to eliminate the initial cause of cell injury as
well as the necrotic cells and tissues resulting from
the original insult
Inflammation is observable alteration in tissue
associated with changes in vascular permeability &
dilation
(carranza)
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9.  Although inflammation helps clear infections and
other noxious stimuli and initiates repair
 The inflammatory reaction and the subsequent repair
process can cause a considerable harm.
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Cardinal signs are
 Heat (calor)
 Redness (rubor)
 Swelling (tumor)
 Pain (dolor)
1 additional sign seen in acute inflammation
 Loss of function (functio laesa)

11. 5R’s
1. Recognition of injurious agent
2. Recruitment of leukocytes
3. Removal of agent
4. Regulation of the response
5. Resolution
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12. EXOGENOUS ENDOGENOUS
 Mechanical
 Physical
 Chemical
 Biological
 Circulatory disorder
 Hypoxia
 Endogenous protease
release
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 Immediate inflammation
 Acute inflammation
 Chronic inflammation

14.  Among the most important resident leukocyte are
mast cells, peripheral dendritic cells, & monocyte
derivative such as dermal dendrocyte .
 These resident leukocyte transmit information that
initiate process of immediate inflammation.
 It lasts upto several hours
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16.  Characterized by an influx of neutrophils to the area
 Rapid response to injury or microbes and
other foreign substances that is designed to deliver
leukocytes and plasma proteins to sites of injury.
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18. transient vasoconstriction
for 3-5 sec
arteriolar vasodilation
increased viscosity & slowing of circulation
Stasis
Migration
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20. vascular and cellular reactions that characterize acute
inflammation are reflected in the morphologic
appearance of the reaction
serous inflammation
fibrinous inflammation
suppurative inflammation
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serous inflammation- outpouring of a watery
relatively protein-poor fluid
fibrinous
occurs as a consequence of more severe injuries,
resulting in greater vascular permeability that allows
large molecules (such as fibrinogen) to pass the
endothelial barrier

22.  manifested by the presence of large amounts of
purulent exudate consisting of neutrophils, necrotic
cells, and edema fluid
 Abscesses are focal collections of pus that may be
caused by seeding of pyogenic organisms into a tissue
or by secondary infections of necrotic foci.
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Inflammation of prolonged duration (weeks to months
to years) in which active inflammation, tissue injury,
and healing proceed simultaneously.

25.  Infiltration with mononuclear cells (macrophages,
lymphocyte, plasma cell)
 Tissue destruction by inflammatory cells
 Repair involving new vessels proliferation
(angiogenesis, fibrosis)
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26. 1. T lymphocyte –mediated immune responce
(called delayed - type Hypersensitivity)
2. Immune-mediated inflammatory diseases
3. Autoimmune diseases
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27. Gingivitis
Periodontitis
Gingivitis is reversible inflammatory condition of
marginal gingiva,
Periodontitis is a destructive, non reversible condition
resulting in loss of tooth connective tissue attachment
to bone, ultimately leads to loss of involved teeth.
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28.  Primary colonizers
yellow complex
purple complex
bacteria independent of defined complex
 Secondary colonizers
red complex
orange complex
green complex
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29.  First line of host defense in periodontal region is
junctional epithelium that hinders bacterial invasion
into periodontal tissue.
 Along with this GCF flow, JE is efficient inhibitor of
bacterial colonization.
 JE contains natural antimicrobial peptide such as
defensins, cathelicidine, calprotectins.
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hBDs expressed in GCF, saliva & gingival epithelium.
Calprotectins expressed in gingival keratinocyte,
neutrophils monocytes.
 JE cells stimulate complement system & facilitate
cytokine release to express chemotaxins (IL-8,C5a)
while comes in contact with micro-organisms.
 JE cells actively facilitate leukocyte recruitment to
site of inflammation by chemotaxins.

31. According to page & schroeder, in 1976
 Initial lesion
 Early lesion
 Established lesion
 Advanced lesion
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Initial Lesion
response of resident leukocyte & endothelial
cell to bacterial biofilm.
No sign of clinical inflammation, but changes in the
tissue can be observed histologically.
Metabolic products of bacteria trigger JE cells to
produce cytokines & stimulate neutrons to produce
neuropeptides leads to vasodilatation.

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Early Lesion
 increased no of neutrophils in CT tissues &
appearance of macrophages, lymphocytes, plasma
cells & mast cells.
 epithelium proliferate to form rete pegs observed
histologically, & bleeding can be seen clinically.
GCF increased.
 Complement proteins are activated.

34. Cell of immune system that are important in
inflammation & host defenses include mast cells,
dermal dendrocytes, peripheral dendritic cells,
neutrophil, monocyte/macrophage, T cells, B cells,
natural killer cells, leukocyte, basophils, eosinophils,
& plateletes.
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Effect on resident cells

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37.  The distribution places the mast cell in a sentinel
position between environmental antigens and the host
for a variety of acute and chronic inflammatory
conditions.
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39.  Activation – release of preformed contents of
granules
histamin
proteoglycans
proteases
cytokines – TNFα and IL-4, IL-5, IL-6
 Stimulation
synthesis – cytokine
-chemokines
 increase Monocytes and macrophages by
releasing GM-CSF
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40.  3 distinct subpopulation
Myeloid lineage- langerhanse cell, dendritic cells
Lymphoid lineage- plasmacytoid
(don’t express MHC classII)
Resident cells present in basal & supra-basal layer of
epithelium & C.T. that function as sentinel of innate
immune system.
DC express TLR-9, able to recognize antigens.
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order of langerhans cells
very responsive to plaque,
non keratinized mucosa of soft palate ˃ ventral surface of
tongue˃ lip & vestibule ˃ gingiva ˃ hard palate
more recently dermal & plasmacytoid dendritic cells
identified in oral mucosa
Lysosome-bearing dermal dendritic cells infiltrate
lamina propria during bacterial infection.

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 DC have unique capacity to initiate T cell immune
response.
(act as link b/w innate & acquired immune system)
Mature DC present antigen in a MHC classII- peptide
complex as well as can produce cytokines, co-
stimulatory molecules (CD-40, CD-54, CD-80, CD-
86) that induce activation of T lymphocyte.
Myeloid dendritic cells can polarize effector response
toward Th1 or Th2 depending on the stimulant.
(endotoxins & LPS)
Plasmacytoid tend to favor Th2 response, it activated in
the presence of IL-3 & CD40 ligand.

43.  First to be exposed to PAMPs
 Express TLR-2, TLR-9
 Produce IL-8, MMPs, ICAMs
expression of both ICAM-1 & IL-8 are down regulated
by P. gingivalis LPS.
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44.  Endothelial cells may be stimulated by IL-8 &
directly by LPS through TLR-4, ultimately leading to
activation & increased adhesion of monocyte.
 Activated endothelial cells induce production of IL-2,
IL-4, INF-β by both naive & memory T cells.
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45.  Gingival fibroblast & PDL fibroblast possess distinct
phenotypes.
 PDL fibroblast present alkaline phosphatase activity
 Gingival fibroblast can produce pro-inflammatory
cytokines & express adhesion molecules in respone to
PAMPs, including LPS, PGN & CpG DNA.
 Express OPG, OPN (by cementoblast also)
 Macrophage also resident antigen presenting cells
produce MMP-1, nitric oxide
 osteoblast also sensitive to PAMPs
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Effects on non-resident cells

47.  produce potent vasoactive mediators
 prostaglandins
 leukotriens IL1 and TNF
 platelet activating factors (PAF)
 inflammatory cytokines
 growth factors
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48. Dominant cell of chronic inflammation
derived from circulating blood monocytes
act as filters for particulate matter, microbes, and
senescent cells, as well as acting as sentinels
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Together these cells comprise the so called
mononuclear phagocyte system, also known by the
older name of reticuloendothelial system
Macrophage highly efficient resident presenting cells
produce cytokines (e.g.IL-23) stimulated by
CpG DNA, LPS. Produce biologic mediators-(MMP-1,
NO)
scattered in most connective tissues

51. 3 types distinguished on the basis of receptors for
antigens.
T-cells, B-cells, natural killer cells
Mobilized to the setting of any specific immune
stimulus as well as non-immune mediated
inflammation
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53. Participate in adaptive immune response
Recognize & kill certain tumor & virally infected cells,
contains antigen receptors.
Recognize glycolipid antigen associated with antigen
presenting molecule CD1+ instead of MHC
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54. To obtain a specific immune response T cells must
interact with APC.
T cell recognize antigen on APC, receive co-
stimulation, activate receptors & produce cytokines.
T cells contain 3000-50,000 TCR on their surface to
recognize antigen.
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T helper -1
associated with stable lesion, release IL-12, IFNγ.
By controlling altered cells & intracellular molecules.
T helper-2
associated with disease progression by pro-
inflammatory responses against extracellular antigen.
There are 4 subsets (CD4+T lymphocyte)

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T regulatory (Treg)
Anti-inflammatory response against extracellular
antigen
They comprise a foxp³ dependent CD4+, CD25+,
have suppressive effect on inflammatory osteolysis.
Thought to be mediated by cytokines such as TGF-β,
IL-10

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T helper-17
IL-17 produced contribute to disease progression.
IL-17 increase TLR responsiveness in gingival
epithelial cells potentiate innate immunity.
In addition it up-regulate pro-inflammatory cytokines
& described as an inducer of RANKL production

58. • Adhesion of T cell & APC
mediated by adhesion such as
LFA-1 & ICAM-2adhesion
• Scanning of APC by T cell co receptors
CD4 or CD8, helps activate the TCR,
recognition of antigen by TCR results in
activation of CD28
scanning
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• CD28 co-stimulate T cells
by binding co-stimulatory
factor B7-1
Co-stimulation
• Scanning of antigen results in
transcription of IL-2 receptors.
T cell produce IL-2 which
differentiate the cells
Differentiation

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T helper-1
IL-2, IFN-γ, IL-12,
T helper-2
IL-4, IL-5, IL-6, IL-10
T helper-17
IL-17
Treg
TGF-β, IL-10

62.  B cells produce immunoglobulin (Ig)
Ig that binds known antigen is an antibody. B cell express
only IgM when exit from bone marrow.
B cell bind with soluble antigen by using BCR if enough
antigen is bound, they ingested, processed & presented to
CD4+ T cell by MHC class ll.
After antigen presentation T cells provide activation signal
to B cell by Gp39 &Gp34, receptors for these
CD40,OX40 respectively +nt on B cell.
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T cell Gp39 enable B cells entry into memory pathway.
-nce of Gp39 leads to terminal differentiation of B cell
toward IgM producing plasma cell.
B cell up-regulate B7-1, B7-2 while activated by Gp39
enable T cell activation.
Primary response immunoglobulin IgM capable of
complement activation but not opsonization.
IgD often co-expressed along with IgM.

64.  secondary response IgG, IgE mediated inflammatory
isotype
 IgA anti-inflammatory B/C does’t stimulate
complement
 IgA protect mucosal surface above & below
epithilium & is an important molecule in mucosal
immunity
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65.  characteristically found in inflammatory
sites around parasitic infections or as part of immune
reactions mediated by IgE, typically associated with
allergies.
Eosinophil & basophil both produce cytokines & lipid
mediators
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66.  increasing vascular permeability
 altering the chemotactic, adhesive and proteolytic
properties of the endothelial cells
prolonged changes in cytoskeleton of endothelial cells.
endothelial cell contraction & leads to intercellular
gaps in post capillary venules
 take 4-6 hours to develop
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68.  Neutrophil production
 Neutrophil trafficking
 Neutrophil clearance
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Neutrophil production
Granulopoiesis & neutrophil realese are regulated
primarily by granulocyte colony stimulating factor
(G-CSF)
Mature neutrophil retained in bone marrow by
interaction of CXCL12 (stromal derived factor-1)
with CXCR4 (chemokines receptor 4 +nt on
neutrophil surface).
G-CSF induce neutrophil exit by interfering with
CXCL12-CXCR4 intraction.

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At chronic inflammation site neutrophil can attract
IL-17 producing CD4+ T lymphocyte (Th17 cells).
Neutrophil release CCL2 & CCL20 chemokines
which are ligands for CCR2 on macrophages &
CCR6 chemokines receptors on Th17 cells.
Thus neutrophil & Th17 cells recruit each other at
the site of infection.
IL-17 promotes granulopoiesis & neutrophil release
by up-regulation of (G-CSF)
Production IL-17 occurs by neutrophil recruitment

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Neutrophil trafficking
 IL-1, TNFα, C5a & LPS stimulate endothelial cells to
express P selectins, E selectins and to facilitate release
of chemokines.
 Neutrophil gets activated by chemokines (induce
integrin conformational changes) & roll on activated
endothelial cells, which express adhesion receptors
such as E & P selectins.
 Rolling depends on selectins, transient interaction of
selectins with glycoprotein ligand on neutrophil.

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Interaction of both selectin & integrins with their
corresponding ligand leads to slow rolling & firm
adhesion bringing to a full stop.

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 Neutrophil crawl on endothelium & finally
transmigrate into peripheral tissue.
 transmigration is regulated mainly by β2 integrins
 These are heterodimeric receptors formed by a unique
α(CD11) & a common β(CD18) subunit that interact
with adhesion ligand such as ICAM-1 & ICAM-2 on
endothelial cells
 Integrins LFA-1 (CD11a/CD18) is involved in firm
adhesion.
 Integrins Mac-1 (CD11b/CD18) involved in
transmigration.

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76. Endothelial Molecule Leukocyte Molecule
 P selectin (CD62P)
 Sialomucine (CD34)
 E selectins
 VCAM-1
 ICAM-1
 CD31(PECAM-1)
 Sialyl lewis x modified
glycoprotein
 L selectin
 Sialyl lewis x modified
glycoprotein
 VLA-4 integrins
 CD11/CD18 integrins
 CD31/(PECAM-1)
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77.  Ones neutrophil are in tissues , they follow gradient of
chemo-attractants in inflamed or infected sites.
 Potent chemoattractants for neutrophil are some
bacterial components such as formyl-methionyl-
leucyl-phenylalanine, & activated complement
component e.g. C5a, leukotrine B4 & IL-8.
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78.  Chemotaxis
 Phagocytes
 Antigen Processing & Presentation
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 Neutrophils in tissues undergoes apoptosis & then
cleared by resident phagocytes, such as macrophage
& dendritic cells.
 Phagocytosis of apoptotic trigger an anti-
inflammatory response by reduction in IL-23 by
macrophage which is a major cytokine for inducing
IL-1. Thus reduced IL-17 level leads to less G-CSF &
less neutrophil production. “Neurostat”

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Toll Like Receptors

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 TLR is a major class of signaling receptors,
stimulated by highly conserved bacterial component
such as LPS & important in innate immune system.
 TLR causes APCs to up-regulate co-stimulatory B7
molecule.
 Discovery of TLR proved to be critical for recognition
of microbes by innate immune system for bridging the
innate & acquired immune response

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10 TLRs identified till date
They contain
a common extracellular leucine rich domain
a conserved intracellular domain
Intracellular domain homologous to IL-1 receptor
TLR-PAMP interaction results in recruitment of specific
adaptor molecule such as MyD88 & Mal
Thereafter signals is transmitted through a chain &
activation of kinase & transcription factor(NF-κB)
activation of immunity, notably pro-inflammatory
cytokines

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 Some literature says- CD-14 +nt on the surface of
gingival & PDL fibroblast
Fibroblast expressed membrane CD-14 & responded to
P. gingivalis LPS in membrane CD-14 dependant
manner.
CD-14 is responsible for pattern recognition of bacterial
cell surface component such as LPS, PGN.
CD-14 expression is directly related to chemokine
production.(IL-8).

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 PDL & gingival fibroblast express TLR-2, TLR-4
 PDL cells express higher level of TLR-2
 Cementoblast also express TLR-2, TLR-4 as well as
CD-14
ds RNA TLR-3
ss RNA TLR-7 endosomal TLRs
ds DNA TLR-9

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Flagellin TLR-5
Gram +ve bacteria TLR-2
Gram –ve bacteria TLR-4
P. gingivalis LPS utilize TLR-2 not 4

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Complement system

88.  complement cascade can be activated through three
pathways
 Classical pathway
 Lectin pathway
 Alternative pathway
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89.  C1
C1 exist in blood serum as a molecular complex
containing
 1 molecule of C1q
 2 molecule of C1r
 2 molecule of C1s
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 Classical pathway activated by immunoglobulins -
IgM or IgG which binds first complement C1q, to a
domain of its Fc tail.
 Bound C1q binds other C1 proteins to form a
complex, C1qrs, which initiates a series of enzymatic
reaction, cleaving C4 to C4a & C4b,
and C2 to C2a & C2b
Complex of C4b.C2b become part of C1 complex,
forming C3 convertase.

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C2a is a vasoactive substance, termed kinin-like which
induce pain, increase vascular permeability & dilation.
 C3 convertase cleaves C3 to C3a & C3b.
 C3b binds factor G to form more C3 convertase.
 Factor H enables factor I to inactivate C3b forming
inactivated C3b (iC3b) which no longer can bind factor G.
iC3b is an opsonin covalently bound to foreign body
enables phagocytes to ingest them.

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 C3b binds to bacterial surface & with several accessory
proteins, forms a new enzyme to cleave C5 to C5a &C5b.
C3a & C5a termed as anaphylatoxins, produce anaphylaxis
by inducing mast cell secretion.
C5a acts as a chemotaxin, attract leukocytes
 C5b interacts with terminal proteins,C6 to C9 to form a
membrane attack complex
That inserts C8 & C9 into bacterial membrane, forming
pores to disrupt the membrane

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Chemotaxins
C3a for monocyte
C4a for lymphocyte
C5a for neutrophils
C3a & C5a anaphylatoxins which activate specific G
protein-copouled receptors(C3aR & C5aR respectively)
mediate mobilization & activation of leukocyte.

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Alternative pathway
Activated by bacterial polysaccharide, such as
zymosen, liposacchride or aggregated IgA, through
factor P (properdin) to cleave C3
C3b and factor B & D convert C5 to C5a &C5b, and
cascade contiues to completion.

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Lectin pathway
This pathway employs a mannose-binding lectin to bind
carbohydrate on bacterial cell surface to form
mannose associated serine protease2.
This molecule has capacity to interact with complement
proteins C4 & C2 to convert C3 to C3a &C3b as in
classical pathway.

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 both gingivitis & periodontitis characterized
primarily as activators of alternative pathway
 this is of some interest because pathogen specific
antibodies are formed in chronic periodontitis
It is also known that other than these very well studied
pathways, there are proteins that can interact directly
with C3 & C5
Plasmin can cleave C3 into C3a & C3b
Thrombin can cleave C5 into C5a & C5b

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Tissue destruction in
periodontitis

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 A protease (also termed peptidase or proteinase) is any enzyme
that performs proteolysis, that is, begins protein catabolism by
hydrolysis of the peptide bonds that link amino acids together
in the polypeptide chain forming the protein.
Catalytic residue
 – Serine proteases
 – Threonine proteases
 – Cysteine proteases
 – Aspartate proteases
 – Glutamic acid proteases
 – Metalloproteases - using a metal usually zinc

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 Matrix metalloproteinases (MMPs) are a large family
of calcium-dependent zinc-containing endopeptidases.
 which are responsible for the tissue remodeling and
degradation of the extracellular matrix (ECM),
including collagens, elastins, gelatin, matrix
glycoproteins, and proteoglycan.
 Matrix metalloproteinases are excreted by a variety
of connective tissue and proinflammatory cells
including fibroblasts, osteoblasts, endothelial cells,
macrophages, neutrophils, lymphocytes & pathogens.

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 MMPs are synthesized as proenzyme, inactive formes
resulting from interaction b/w cysteine residue of
prodomain & zinc ion of catalytic site
Disruption of this
Intraction by chemical
modification or by
proteolytic removal of
enzyme’s prodomain
results in activation of
enzyme.
Machanism known as “cysteine switch”

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Protease capable of activating MMPs
chymotrypsin-like protease produced by
Treponema denticola as well as neutrophil cathepsin G.
MMPs grouped as-
Collagenase MMP-1, MMP-8, MMP-13, MMP-18
Gelatinase MMP-2, MMP-9
Stromlysin MMP-3, MMP-10, MMP-11
Matrilysin MMP-7, MMP-26
Membrane type MMP-14,15,16,17, 24
Enamelysin MMP-20

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106.  MMPs activation may vary depending on specific
tissue & disease microenvironment.
 During periodontitis progression MMPs can be
activated by independent or co-operative cascade
involving pathogen & host proteases.
 Membrane bound MMP-14 activates proMMP-13,
proMMP-8 & proMMP-2
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 MMP-13 activates proMMP-9 & MMP-13 auto
activation by self proteolysis.
 MMP-9 in turn activate proMMP-2 & proMMP-13
 Reactive oxygen species (ROS) are able to induce
activation of key MMPs in periodontal tissue.
through direct enzyme oxidation.
Neutrophil degranulation is stimulated by micro-
organisms, their virulence factor, cytokines &
prostaglandins & results in release of
myloperoxidase(MPO) from their primary granules.

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H2O2 HOCl + H2O
HOCl activate proMMP-8 & proMMP-9
H2O2 activate proMMP-2 & proMMP-9
MPO is antimicrobial & plays an important role
in regulation of C.T. catabolism, through
protease & anti-protease balance.
MPO
Cl, Br, I

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111.  MMP-13 degrade type 1 collagen which constitute
bulk component of radicular cement, periodontal
ligament, & alveolar bone extracellular matrix.
 MMP-1 keratinocyte migration & re-epithilialization
 MMP-13, MMP-7 osteoclast activation
 MMP-1, MMP-3, MMP-9 pro-inflammatory
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113.  Several signaling molecules such as cytokines,
chemokines & growth factors can be processed by
active MMPs.
 Cytokines are key modulators of cellular responses
during periodontal inflammation.
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114. 2/22/2018 11
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 persistent secretion of pro-inflammatory cytokines
Th-1 cytokines –TNFα, IL-1β, IL-6, IL-12 & INF-γ
Th-17 cytokines – IL-17
Treg – IL -10, TGF-β1
associated with continued inflammation & destruction of
supporting structure of teeth.
Chemokines favoring infiltration of neutrophils CXCL8
favoring infiltration of macrophages CCL2
infiltration of Th-1/Th-17 lymphocyte CCL20
associated with inflammatory destruction of
periodontal tissue

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 MMP-2 is present in the synovial fluid junction
and cartilage, and degrades protein and collagen fibers.
 Chronic periodontitis symptoms include
– inflammation caused by MMP-2, MMP-8 & MMP-9
– tooth mobility caused by MMP-8 and MMP-9
 Due to the gelatinase function of MMP-2, we
hypothesize that MMP-2 may also be associated with
tooth mobility caused by periodontitis

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6
Activation of osteoclast-secreted pro-MMP-9 digest
denatured collagen derived from MMP-13 activity &
cleaving of galectin-3.
Galectin-3 inhibit osteoclastogenesis, present on the
osteoclast surface.
Abrogation of its inhibitory effect by receptor activator
of nuclear factor-κB ligand (RANKL)

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 MMPs can cleave chemokines to inactivate
e.g. CCL7 cleaved by MMP-1, 2,3, 13
Chemokines recruit monocyte from circulation to
infection site.
Inactivated chemokines represent regulatory feedback
mechanism to prevent uncontrolled monocyte
infiltration.
Tetracycline or doxycycline inhibit MMPs to decrease
inflammation of periodontal tissue, functioning as
tissue inhibitors of metalloproteinases (TIMP).

118.  RANKL is a member of TNF ligand family.

 T cells & B cells express a RANKL
 it attached to RANK a receptor on the surface of
osteoclast & osteoclast precursor to stimulate
proliferation & differentiation.
 A soluble decoy osteoprotegerin (OPG) produced by
osteoblast modify effect of RANKL by inhibiting
RANKL/RANK interaction.
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119. 2/22/2018 11
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120. Three pro-inflammatory cytokines IL-1, IL-6, TNF-α
appear to have a central role in periodontal tissue
destruction.
IL-1 & TNF-α both are potent pro-inflammatory,
activate osteoclast & induce tissue degrading
proteinases (MMPs)
IL-6 another inflammatory leads to bone remodelling.
IL-1 is produced primarily by activated macrophages or
lymphocyte.
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121. 2/22/2018 12
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Pro-inflammatory effect of IL-1 & TNF-α include
stimulation of endothelial cell to express selectins
& facilitate recruitment of leukocyte.
Activation of macrophage IL-1 production.
Induction of prostaglandin E2 by macrophage &
gingival fibroblast.

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2

123. 2/22/2018 12
3

124.  Metabolite generated by COX-1 & COX-2
 PGE2 in GCF as a diagnostic marker for future bone
loss
 COX-2 is up-regulated by IL-1β, TNF-α & LPS of
bacteria & responsible for generating PGE-2
i.e. associated with inflammation.
Primary cell responsible for PGE-2 production in
periodontium are macrophage & fibroblast.
Induction of MMPs & osteoclastic bone resorption is
induced by PGE-2.
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125. 2/22/2018 12
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126. Net effect of inflammatory response is determined by
balance between pro-inflammatory cytokines & anti-
inflammatory cytokines.
Such as
IL-1β, TNF-α, IFN-α, GM-CSF
IL-4, IL10, TGF-β, IL-1ra, IL-6,
IL-8, IL-16
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127. 2/22/2018 12
7
Thank you