The document discusses innate immunity in periodontics, covering its definition, importance, classification, and various components such as physical and chemical barriers, phagocytosis, and the complement system. It emphasizes the roles of immune responses in defending against infections, the process of inflammation, and the function of various immune cells like phagocytic leukocytes and dendritic cells. Additionally, it highlights the interaction of cytokines and defensins in the immune response, particularly in the context of gum health and disease.

1. INNATE IMMUNITY IN
PERIODONTICS
-SHEETHALAN M S R

2. THIS TOPIC INCLUDES
 WHAT IS IMMUNITY
 IMPORTANCE OF IMMUNITY
 CLASSIFICATION OF IMMUNE SYSTEM
 COMPARISON BETWEEN INNATE AND ADAPTIVE IMMUNITY
 INNATE IMMUNITY
 COMPONENTS OF INNATE IMMUNITY
 PHYSICAL AND CHEMICAL BARRIERS
 PHAGOCYTIC LEUCOCYTES
 INFLAMMATION
 PHAGOCYTOSIS
 DENDRITIC CELLS
 NK CELLS AND ITS DESTRUCTION
 RECOGNITION OF MICROBES IN INNATE IMMUNITY
 COMPLEMENT SYSTEM

3. The term IMMUNITY means,
“free of burdens”
now in medical terms, it
denotes
“freedom from disease”

4.  IMMUNITY: Resistance to infectious disease
 IMMUNE SYSTEM: is a network designed for the homeostasis of large
molecules(oligomers) and cells based on specific recognition proteins.
 IMMUNE RESPONSE: Coordinated reactions of these cells and molecules to
infectious microbes
 IMMUNOLOGY: Study of immune system and its response to invading
pathogens

5. IMPORTANCE OF IMMUNITY
Role of the IMMUNE SYSTEM Implications
Defense against infections Deficient immunity results in
increased susceptibility to infections
Vaccination boosts immune
defenses and protects against
infections
Immune system recognizes and
responds to tissue grafts and newly
introduced proteins
Immune responses are barriers to
transplantation and gene therapy
Defense against tumours Potential for immunotherapy of
cancer

6. ACTIVE AND PASSIVE IMMUNITY
ACTIVE IMMUNITY
PASSIVE
IMMUNITY
RESISTENCE DEVELOPED BY AN
INDIVIDUAL AS A RESULT OF CONTACT
WITH THE ANTIGEN
RESISTENCE DEVELOPED BY AN
INDIVIDUAL BY INDUCING
PREFORMED ANTIBODIES
NATURAL ARTIFICIAL
NATURAL ARTIFICIAL
BY
VACCINATION
BY CLINICAL AN
SUB CLINICAL
INFECTION
BY
TRANSPLACENTAL
MATERNAL
ANTIBODIES
BY ANTISERUM
INJECTION

7. CLASSIFICATION OF IMMUNE SYSTEM

8. COMPARISION BETWEEN INNATE AND
ADAPTIVE IMMUNITY
COMPONENTS
ACTIVITY
RESPONSE AND
POTENCY
SPECIFICITY
COURSE
MEMORY

9. COMPARISION OF CELL MEDIATED AND
HUMORAL IMMUNITY
HUMORAL IMMUNITY CELL MEDIATED IMMUNITY
Antibodies produced by B
lymphocytes , recognize
extracellular microbial antigens
.
T lymphocytes recognize antigens
produced by intracellular microbes.
Antibodies are able to recognize
many different types of
molecules such as proteins,
carbohydrates , lipids .
T cells recognize only protein antigens.

10. CELLS OF IMMUNITY

11. INNATE IMMUNITY
 Also called Natural or Native immunity.
 Components present before the onset of infection.
 Disease resistant mechanisms that are not specific to a particular pathogen
 Pathogens must first breach barriers that protect host
 Provides the first line defence right after exposure.
 Most micro-organisms are readily cleared within a few days by innate immune
system before adaptive immune system is activated

12. COMPONENTS OF INNATE IMMUNITY
 Physical and chemical barrier
 Complement system
 Phagocytic leucocytes
 Dendritic cell
 Natural killer cell

13. EPITHELIAL BARRIERS
 The epithelium is impermeable to water-soluble substances, and attached firmly
to a base of dense gingival connective tissue.
 Four clearly defined cell layers are present:
 the basal cell layer,
 the spinous cell layer,
 the granular cell layer,
 the cornified cell layer.
 There is a high degree of interdigitation (rete peg formation) between the OGE
and the underlying connective tissue.
 The upper most layer of stratum spinosum contains numerous dense granules
called keratinosomes which are modified lysosomes.
 Langerhans cell present in the suprabasillar layer belong to mononuclear
phagocyte system.
 Function as antigen presenting cells for lymphocytes.

14. KERATINOCYTE
 Contact between the two tissues is further amplified by the presence of
numerous serrated keratinocytes and the formation of prominent cell
processes (pedicles) that protrude into the connective tissue.
 Most of proliferation done by transient amplifying cells (TA cells)
 Transition from stem cell to TA cell is the first step in keratinocyte
differentiation
 TA cells migrate laterally along the basement membrane
 TA cells only divide 2-3 times before they withdraw from the cell cycle.

15.  When a keratinocyte releases from the basement membrane, it undergoes
changes in morphology and gene expression.
 There is a gradual change in cell strength and water impermeability
 Terminally differentiated keratinocytes synthesize a cornified cell envelope
and undergo programmed cell death
 Major defects in keratin molecules are incompatible with life
 Minor defects in keratin molecules lead to major debilitating skin disease

16. ORAL SULCULAR EPITHELIUM
 Although the OSE is stratified, it does not contain a clearly defined stratum granulosum, nor
does it normally undergo cornification .
 The differentiating compartment of OSE contains inner and outer zones
 The inner zone resembles a spinous layer, the outer zone contains viable cells with intact
nuclei and abundant cytoplasmic organelles.
 Keratin filaments are bundled into small tonofibrils that are loosely distributed throughout
the cytoplasm
 In inflamed gingiva the OSE is infiltrated by numerous (PMNs) .
 Changes brought about by the infiltrating inflammatory cells include a loss of desmosomes
and a widening of the intercellular spaces.
 Sulcular epithelium is extremely important because it act as semi permeable membrane
through which injurious bacterial products pass into the gingival fluid from the gingiva seeps
into the sulcus.

17. JUNCTIONAL EPITHELIUM
 Formed by the confluence of oral and reduced enamel epithelium.
 Junctional epithelium is firmly attached to the tooth structure forming a
epithelial barrier against the plaque bacteria.
 It allows excess of gingival fluid , inflammatory cells and components of
immunologic host defense to gingival margin.
 Expression of cell surface attachment molecules by the cells of the JE, and
the underlying endothelium, have been shown to promote PMN transmigration
across the JE.
 Junctional epithelium exhibit rapid turnover , which contributes to the host
parasite equilibrium.

18. EXPRESSION OF CELL SURFACE
ADHESION MOLECULES IN GINGIVA
 Basal cells and suprabasal cells of the JE, OSE, and OGE express the integrins
α2β1, α 3 β 1, and α 6 β1.
 α6β1 integrin is a component of desmosomes.Hemidesmosomes contain the
α6β4 integrin (laminin receptor) localized on both the internal and external
basal laminae of the JE
 During gingival inflammation the expression of integrins, especially those
that function as fibronectin receptors, increases in cells of both the epithelial
and connective tissues.

19.  Another class of cell surface adhesion molecules that is of significance to the
biology of gingival tissues is the immunoglobulin class , of which intercellular
adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1
(ELAM-1), and vascular cell adhesion molecule 1 are known to increase in
gingiva during inflammation.
 Intercellular adhesion molecule 1 is present on the cell membrane of JE cells
and adjacent fibroblasts and endothelial cells but absent from healthy OSE
and OGE and adjacent blood vessels.
 Adhesion factor important for leukocyte transmigration in inflammatory
lesions is ELAM-1 Endothelial leukocyte adhesion molecule 1 has been
localized on blood vessels of gingivitis lesions.

20. THE ROLE OF PROINFLAMMATORY CYTOKINES
SECRETED BY THE COMPONENTS OF THE
GINGIVAL EPITHELIUM .
 Soluble proteins
 Secreted in small amounts in response to an external stimulus and bind to
high affinity receptors on target cells.
 Presently 200 cytokines have been identified which are grouped under 6
categories.
 Many of this cytokines have further subtypes as alpha, beta or identified by
numbers . cytokines involved in leucocyte-endothelial interaction are called
chemokines while growth factors and other cytokines are named crinopectins.

21. THE ROLE OF INTERLEUKIN 1 & 8
 Interleukin 1 inhibits the expression of procollagen mRNA and stimulates gingival
fibroblasts to secrete collagenase and prostaglandins.
 It also increases the amount of ICAM-1 on gingival fibroblasts which may be
important in retaining various inflammatory cells within the local connective
tissues.
 Osteoclastic bone resorption is increased by IL-1 Interleukin 1 has a direct
stimulatory effect on osteoclasts as well as an indirect effect through its ability to
increase the expression of IL-6 by osteoblasts.
 Interleukin 1 increases the expression of ELAM-1 and ICAM-1, key molecules for
neutrophil margination and transmigration.
 Key gene transcription products induced by IL-1 include two chemoattractant
cytokines (chemokines), interleukin 8 (IL-8) and monocyte chemoattractant
protein 1 (MCP-1)

22.  Chemokines have the following characteristics:
1. They are secretory, low-molecular weight proteins.
2. They are secondary proinflammatory mediators.
3. They have a chemoattractant effect on polymorphonuclear neutrophils.
 There are two subfamilies of chemokines, based on the position of cysteine
residues in the polypeptide chain.
 The CXC (α) chemokines, including 1L-8, have an intervening amino acid
located between the first two cysteine residues, Interleukin 8 and other CXC
chemokines attract and stimulate neutrophils.
 In the CC (β ) chemokines, the first two cysteines are positioned adjacent to
each other.

23.  Monocyte chemoattractant protein and other members of the CC subfamily
attract and stimulate monocytes and lymphocytes.
 Monocyte chemoattractant protein 1 is believed to be partly responsible for
the large monocyte macrophage infiltration of gingival connective tissue in
early gingival inflammation.
 Oral keratinocytes produce IL-8when stimulated by TNF-alpha or interferon
gamma .Endothelial cells and fibroblasts express IL-8 and MCP-1 when
exposed to LPs.

24.  Interleukin 8 is capable of effecting a wide spectrum of biologic responses ,
including the migration and phagocytic activity of neutrophils.
 Fibroblasts lose focal adhesions and assume a migratory phenotype when
exposed to IL-8 in vitro.The administration of IL-8 to host tissues leads to
numerous inflammatory changes, such as plasma leakage and edema,
characteristics of gingival inflammation.

25. DEFENSINS
• Defensins are small cationic proteins found in both vertebrates and invertebrates.
• They are active against bacteria, fungi and many enveloped and
nonenveloped viruses.
• Cells of the immune system contain these peptides to assist in killing phagocytized
bacteria, for example in neutrophil granulocytes and almost all epithelial cells.
• Most defensins function by binding to the microbial cell membrane and, once
embedded, forming pore-like membrane defects that allow efflux of essential ions
and nutrients.

26.  Defensin can be alpha or beta .
 α defensins are slightly smaller peptides that are arranged in a β sheet arrangement of
29 to 35 residues.
 Β defensin are basic and have 38 to 42 amino acids .
 α defensins in humans are found in six different forms.β defensins are found in humans
are in 4 different forms.

27. ALPHA DEFENSINS
• It is present in the auzrophilic granules of the neutrophils.
• It is amphiphilic in nature .
• It has a basket like structure .
• The structure is open at the top , it has terminal N and C regions.
• The hydrophobic part is in the bottom of the basket .
• The disulfide bonds present are in between C1-6,C2-4,C3-5.

28. BETA DEFENSIN
• β defensin are primarily found in association with epithelial surfaces of the human skin,
gut ,trachea and oral epithelia including the gingiva.
• The various disufide bonds present are
 1. C1-5
 2. C2-4
 3. C3-6

29. ROLE OF DEFENSINS IN IMMUNITY
 Defensins are directly involved in antimicrobial killing .
 They can upregulate the IL 8 production and enhance the neutrophil recruitment to the
site of infection.
 α defensin are capable of activating naïve T cells and immature dendritic cells
.(chertov et al 2000, zasloff et al 2002).
 In vitro they enhance the release of tnf α and IL 1 , from monocytes that have been
activated by bacteria .

30. COMPLEMENT SYSTEM
 Interacting network of 30 membrane-associated cell receptors and soluble
serum glycoproteins.
 Account 5% of the total serum proteins.
 Mostly synthesized in the liver and also by macrophages(c1,c2,c3,c4,c5,factor
B ,D and H.
 They are the central component of inflammation that enables endothelium
and leucocytes to recognise and bind to foreign substances which lack
receptors.

31.  Promotes inflammation by producing following :
-vasoactive substances termed KININ-LIKE,C2a,which induces pain and
increases vascular permeability and dilation.
-molecules termed as ANAPHYLOTOXINS,C3a and C5a, which produce
anaphylaxis by inducing mast cell secretion.
-chemotaxin,C5a, which attracts leucocytes and stimulates antigen
secretion.
- an opsonin named iC3b, which covalently binds to molecular
aggregates, particles or cells which enables phagocytes to ingest them.

32. ACTIVATION OF COMPLEMENT
 C3 is the most important and also predominant component accounting around one
third of the total complement.
 C3 splits into C3a and C3b.
 Two main pathways of splitting :
-alternative pathway
-classical pathway
 The alternative pathway is triggered when some complement proteins are
activated on microbial surfaces and cannot be controlled, because complement
regulatory proteins are not present on microbes (but are present on host cells).
This pathway is a component of innate immunity.
 The classical pathway is triggered after antibodies bind to microbes or other
antigens and is thus a component of the humoral arm of adaptive immunity.

33. • Two main process can occur with the formation of
bound C3 convertase in the presence of bacterial cells.
-AMPLIFICATION
-FORMATION OF MEMBRANE ATTACK
COMPLEX.
• AMPLIFICATION is exponential increase in the formation
of C3b.
• MEMBRANE ATTACK COMPLEX is formed by the
association of C5b component with C6,C7,C8,C9.
results in lysis of the bacteria by forming large
pore on target membrane.

34. REGULATORS OF COMPLEMENT
ACTIVATION
 6 regulators:
1. Factor H
2. Membrane cofactor protein(MCP)
3. Complement receptor 1(cr1)
4. Complement receptor 2(cr2)
5. Decay accelerating factor
6. C4-binding protein
 4 of these regulators are working with proteolytic soluble enzyme FACTOR I
:factor H,MCP,CR1,C4BP.

35.  Factor H and C4BP are most important for the inactivation of fluid phase of
C3b and C4b.
 Factor H enables factor I to inactivate C3b by clipping out a small piece,
forming inactive C3b(iC3b).
 MCP and DAF are widely distributed on host cell and are mainly designed to
protect the host cell against C3b and C5 convertase.(protects the host cell)
 CR1 is the trans membrane molecule expressed by the phagocytes, B cells and
RBCs.CR1 binds to C3b, attracts factor I , leading to inactivation of
amplification by formation of iC3b phagocytes possess receptors for iC3b
and will ingest the iC3b bound cell by a process known as opsonic
phagocytosis.

36. PHAGOCYTIC LEUCOCYTES
 This include
1.NEUTROPHILS
2.MONOCYTES-MACROPHAGE

37. NEUTROPHIL
 Predominant leucocyte in the blood
 4000-8000 cell/cubic mm
 They differentiate completely in the bone marrow(14 days)
 multilobulated nucleus.
 Golgi apparatus is small, sparse mitochondria and ribosomes.
 Because neutrophil do not need to differentiate substantially to function ,they are
suited for rapid response.
 Possess receptors for metabolites of complement molecule c3, designated
complement receptors 1,3,4 and c5, igG antibodies.
 These receptors enable neutrophils to
-recruited from the blood.
-locate the affending agents
-phagocytose and kill the affending agents.

38. Granules of neutrophil
 azurophilic granules (or "primary granules)-
myeloperoxidase, bactericidal/permeability-increasing
protein (BPI), defensins, and the serine proteases neutrophil
elastase and cathepsin –g.
 Specific or secondary granules-alkaline phosphatase, lysozyme, NADPH
oxidase, collagenase, lactoferrin and cathelicidin
 Tertiary granules-cathepsin and gelatinase.

39. MACROPHAGES
 The word macrophage means the big eater
 It was proposed by metchinkoff in the year 1892.
 Macrophages originate from monocytes and the proliferating precursors in
the bone marrow
 The monocytes remain in the bone marrow for 1.5 to 3 days .
 They remain in the circulation for 6 days and then on entering the tissue get
converted to macrophages .

40.  Macrophages are larger cells, up to 60 um in diameter, usually somewhat
elongated and often exhibiting polarity.
 The cell surface contains microvilli and coated pits.
 Coated vesicles and elongated smooth vesicles are abundant in the cortical
cytoplasm.
 The hallmark of the macrophage is its large number of lysosomal granules.
 Older macrophages contain numerous phagosomes and residual bodies, the
remnants of past phagocytic activity.

41. INFLAMMATION
 The natural history of inflammation actually starts before an irritant exists ,
with the trans endothelial migration of leucocytes especially mast cells.
 Mast cell interaction with the vascular system leads to erythema and
edema.,also signal endothelial cells to recruit inflammatory leucocytes which
are active in phagocytosis,killing, antigen presentation and
processing,specific immune responses , tissue remodelling.

42. TRANS ENDOTHELIAL MIGRATION OF
LEUCOCYTES
 Invovles 8 steps before chemotaxis
1. Rolling of leucocyte
2. Insult to the local tissue
3. Signalling the endothelium
4. Increased rolling
5. Signal for rolling arrest
6. Strong adhesion(arrested rolling)
7. Zipper phase
8. Basement membrane degradation

44. CHEMOTAXIS
 The leucocyte must be able to identify the site of insult – by CHEMOTAXIS.
 The phagocytes sense chemical termed as chemotaxins, for which it has
receptors.
 They belong to a family G-PROTEIN COUPLED RECEPTOR.
 To migrate towards the target, the leucocyte assume a polarized shape rather
than rounded morphology , forming a anterior lamellipod and posterior
uropod . cytoplasm appears to squirt through a contractile ring.

46. PHAGOCYTOSIS
 Defined as process of engulfment of solid particulate matter by phagocytic cells.
 Involves 1.recognition and attachment
2.engulfment
3.killing and degradation
 RECOGNITION AND ATTACHMENT involves expression of surface receptors on the
phagocytes-MANNOSE AND SCAVENGER RECEPTORS
 Further enhanced by OPSONINS , proteins from the serum coats the micro-organism.(
IgG,C3b and lectins).
 Opsonins are molecules that act as binding enhancers for the process of
phagocytosis, especially antibodies, which coat the negatively charged molecules
on the membrane.
 ENGULFMENT is facilitated by formation of cytoplasmic pseudopods around the
particle due to activation of actin filaments beneath the cell wall.

47. Killing and degradation
OXIDATIVE KILLING NON- OXIDATIVE KILLING
• BY FORMING REDUCED OXYGEN
METABOLITES SUCH AS
SUPEROXIDE ANION USING NADPH
OXIDASE SYSTEM.
• SUPER OXIDE ANION HELPS IN
THE FORMATION OF H2O2,WHICH
IS FURTHER REDUCED INSIDE THE
TARGET CELL TO HYDROXYL
RADICAL CAUSING DNA DAMAGE.
• H2O2 IS CONVERTED TO HOCL BY
MYELOPEROXIDASE-MORE
POTENT IN ANTIMICROBIAL
KILLING
• INVOVLES FUSION OF
PHAGOSOME AND LYSOSOME
–PHAGOLYSOSOMES
RESULTS IN THE SECRETING
OF LYSOSOMAL
COMPONENTS.

48. NON OXIDATIVE KILLING
 Neutrophils possess two main types of lysosomes
- SPECIFIC GRANULES: for both extracellular and intra
lysosomal secretion. Secreted immediately after phagocytosis.
-AZUROPHILIC GRANULES : for intra phagolysosomal
secretion. secreted minutes after secretion of sp granules.
 Specific granules contain several components including lysosome and lactoferrin .
 Lysosome is an enzyme that possess enzyme dependent and independent
bactericidal and fungicidal activity.
 Lactoferrin is bacteriostatic.
 Among the microbicidal compounds are small antimicrobial peptide known as
serprocidins, alpha defensins.
 IMPORTANCE IN PERIODONTICS : because highly anaerobic condition in subgingival
environment.

50. PERIPHERAL DENTRITIC CELLS
 They are leucocytes with cytoplasmic projections or dentrites.
 Dendritic cells reside in the suprabasilar portion of squamous epithelium
termed as Langerhans cells.
 Ingest antigen locally and transport to the lymph nodes,
 They are a family of antigen presenting cells.
 They circulate in the blood stream and are present in nearly all tissues of the
body .
 They serve as a bridge to the adaptive immune response.
 Their basic action is to capture the microbes in their immature state and
stimulate T cell mediated immune response in their mature state .

51. Types of dendritic cells

52. ROLE OF LANGERHANS CELL IN ORAL
HEALTH AND DISEASE
• CD 1 a + langerhans cells are principal leucocytes involved in the response of
the oral mucosal epithelium to infectious diseases.
• Langerhans cells increase in number in epithelium in experimental gingivitis
and periodontitis.It reaches a peak in 7 days and attains a plateau and starts
falling in 21 days.(seguier &godeau et al 2000)

53. NATURAL KILLER CELLS
 Recognise and kill virus and tumour infected cells.
 Possess KILLER INHIBITORY RECEPTOR(KIR) AND KILLER ACTIVATING
RECEPTOR(KAR).
 Normal cells possess MHC class1 molecules that present antigen recognised as
‘self’ interacts with KIRs and protect the cell from NK mediated killing.
 In tumour and virally infected cells KAR activation can override the KIR
inhibition and cause NK cells to kill the target cell.

54. Destruction by natural killer cells
 NK cells are activated through Killer Activating Receptors (KARs). The most
important KARs are
 NKp46
 NKp30
 NKp44
 Each of these receptors contain a (+) charge in their transmembrane domain.
 This (+) charge corresponds to a (-) charge in the transmembrane domain of
adaptor molecules, allowing them to interact.

55.  They contain immunoreceptor tyrosine-based activation motifs or ITAMs.
 ITAMs consist of short homo- or heterodimer tails which extend into the
cytoplasm.
 When an NK cell comes in contact with a target cell, activating receptors on
the cell surface bind to the KARs. Activating receptors could be antibodies,
stress inducible MHC class I-like molecules, or an as yet unknown ligand.

56. upon binding, a signal is sent through the KAR to the ITAM region.
The ITAM is phosphorylated.It is then capable of inducing a signaling cascade .
These molecules subsequently stimulate granule release and cytokine
production.
The granules are released into the target cells .These are lytic enzymes
called granzymes , and special molecules like perforins , they form channels
through plasma membrane of the specific cell .(GRANULAR PERFORIN
PATHWAY )

57. RECOGNITION OF MICROBES IN INNATE
IMMUNITY
• Pathogen-associated molecular patterns, or PAMPs, are molecules associated
with groups of pathogens, that are recognized by cells of the innate immune
system.
• These molecules can be referred to as small molecular motifs conserved
within a class of microbes.
• They are recognized by Toll-like receptors (TLRs) and other pattern
recognition receptors (PRRs)

58. PATHOGEN ASSOCIATED MOLECULAR
PATTERNS-(PAMPS)
• PAMPS are pathogen associated molecular patterns .
• These PAMPS are recognised by certain germline encoded receptors.
• They are called pathogen recognition receptors .
• The toll like receptors are the best known PRRs that recognize the PAMPS .
• Examples of PAMPS include , lipopolysaccharide ,peptidoglycan, lipoproteins,
bacterial DNA ,double stranded RNA .

59. TOLL LIKE RECEPTORS
 Toll gene products were first discovered in 1985 and were described as being
critical for the embryonic development of dorsal–ventral polarity in the
fruitfly, Drosophila melanogaster(Anderson et al , bokhla et al , volhard et al
, nuslein et al ).
 proteins
 play a key role in the innate immune system.
 They are single, membrane-spanning, non-catalytic receptors.
 expressed in such as macrophages and dendritic cells, that recognize
structurally conserved molecules derived from microbes.
 10 toll like receptors are found in human and 12are found in mice.

60. TLR1
• Tlr 1- It is the first member of the tlr family , it was identified by the
presence of a domain homology found both in dorosphila toll &human Il-1
receptors.
• It acts as a co receptor with tlr 2 in response to triacylated lipopepdies.

61. TLR2
• TLR 2 is involved in the recognition of various components of the pathogens.
• It includes various pathogens peptidoglycans,lipoarabinomannan
glycosylphosphatidyl inositol anchors, zymoson.
• Mycoplasma activating lipopeptide -2 was shown to utilize TLR 2 as it’s a
signal tranducer .
• Tlr 2 cooperates with tlr 6 to peptidigycan and associates with TLR 1 to
triacylated lipopeptides .

62. TLR3
• TLR 3 recognises the double stranded rna associated with viral infection .
• Viral replication within infected cells, results in the generation of double
stranded rna defence hence the are PAMPS .

63. TLR4
• TLR 4 is the principal lps receptor .
• LPS can provoke a variety of immunostimulatory responses .
• Studies using the TLR 4 knock out mice confirmed that TLR 4 is critical for LPS
signalling.

64. TLR5
• TLR 5 recognises flagellin from both gram positive and gram negative
bacteria.
• Flagellin is the monomeric sub unit of bacterial flagella.
• It it not activated by non flagellated bacteria.

65. TLR6
• TLR 6 is expressed in spleen and peripheral blood leukocytes .
• It also acts as a co receptor .
• It cooperates with tlr 2 to recognize Peptidoglycan and yeast cell wall
particle , zymosan.

66. TLR7
• TLR 7 is abundantly expressed in the lung , placenta , spleen and peripheral
blood leucocytes.
• Its close to TLR 8 &TLR 9 .
• recognize single stranded rna.

67. TLR9
• TLR 9 is located intracellularly , it is involved in the recognition of specific
unmethylated Cpg - ODN sequences that distuinguishes bacterial DNA from
mammalian DNA .
• Bacterial DNA can stimulate immune cells .
• This activity is because of unmethylated CpG motifs which are rarely
detected in vertebral DNA , which is highly methylated.

68. TLR10
• TLR 10 is the last human member of the human TLR family.
• Human TLR 10 is present on immune cells present on the lymphoid tissues
like spleen , lymph node , thymus and tonsil .
• It might act as a coreceptor like TLR 1 & TLR 6 .

70. ACTIVATION OF TLRS
• The activation of TLR signalling pathways originates from the cytoplasmic TIR domains .
• The proline residue in TIR domains is conserved among all TLRS .
• TLR 3 has histidine instead of proline.
• In the signalling pathway downstream of the TIR domain containing adaptor , MYD 88 is
characterised to play an important role .
• Activation can be
1.MYD88 dependent(myeloid differentiation primary response protein88)
2.MYD88 independent(TIRDOMAIN CONTAINING ADAPTOR INDUCING INFBETA)
 Activation of TLRS leads to recruitment of adaptor protein activation of
transcription factors (NF-kB ,IRF -3) EXPRESSION OF INFLAMMATORY CYTOKINES(IL-
1,IL-12,TNF),CHEMOKINES(IL-8),ENDOTHELIAL ADHESION MOLECULE(E-SELECTIN),
COSTIMULATORY MOLECULE,ANTIVIRAL CYTOKINES(INF-ALPHA).

72. IMPORTANCE OF INNATE IMMUNITY IN
PERIODONTITIS
 Although periodontal disease is caused by infection, the resulting tissue
damage is due to the immune response .
 The first response triggered by bacterial infection is the innate immune
response.
 Bacteria are taken up by macrophages, causing the macrophage to release
cytokines.
 The cytokines cause the inflammation associated with periodontal disease.
 Cytokines cause the blood vessels to dilate and become permeable, leading to
increased local blood flow, thus causing inflammation.

73.  Studies have shown that polymorphonuclear neutrophils (PMN) are the most
abundant immune cells found in areas of periodontal disease.
 Interleukin-8 (IL-8) is a chemoattractant for neutrophils, therefore increased
levels of IL-8 are found in gingival cells.
 The increase PMN and IL-8 are likely contributors to the inflammatory
response
 Research has been conducted that associates periodontal disease with
cardiovascular disease, premature births, and other problems.
 The mouth may serve as a "bacterial reservoir" for the lungs, possibly
resulting in bacterial pneumonia .
 But , Research is currently being done to further substantiate the above
mentioned associations.

74. REFERENCES
 CLINICAL PERIODONTOLOGY –CARANZZA
 Text book of immunology (roiit , kuby, abbass litchman)

75. THANK YOU