Measures of Central Tendency: Mean, Median and Mode
Molecular biology of the host-microbe interaction in periodontal disease
1.
2.
3. AMNA HASSAN
ROLL NO : 12
Chapter : 25
Molecular biology of the host microbe interaction in
periodontal disease
4. Topics outline
1 . I N N AT E I M M U N I T Y
ADAPTIVE IMMUNITY
PAT H O B I O LO G Y O F P E R I O D O N TA L
DISEASE
HOST CELL SIGNALING
5. INTRODUCTION
Provides an overview of molecular biology of the host-parasite
relationship
Deals with the microbiota associated LPS and other MAMPs
,innate responses,tLRs signaling and periodontal pathogenesis
Includes pathobiology of periodontal disease
Induction of disease by pro inflammatory cytokines
6. PATHOGENESIS OUTLINE
Direct recognition of microbes by the host is mediated by the
recognition of MAMPs by PPR
It requires expression of number of bioactive agents i.e. pro
inflammatory and anti inflammatory cytokines , growth factors and
enzymes
Activated Biologic mediators are involved in the induction of
adaptive immunity
7.
8. INNATE IMMUNITY
Innate immunity is rapidly activated with in minutes
Responsible for the defiance during initial hours and days of
infection
Challenge is to discriminate among a large number of
periodontal pathogen from the host with a limited number of
cell surface receptor
9. H OW I N N AT E I M M U N E SYST E M
FUNCTIONS?
The discovery of TLRs proved to b critical for recognition of
microbes.
With in the periodontal tissues , the expression of various TLRs
appears to b increased in severe diseased states
TLR are a type of PRR ( pattern recognition receptor) Egg
TLR1,TLR2,TLR3.TLR4. etch
10. CONTD..
PPR can b secreted into plasma as humoral protein
others are localized in the cytoplasm as intracellular sensors
Soluble PRR include collectins,ficolins and acute phase
pentraxins (e.g. C reactive protein)
The soluble mannose binding receptors can interact with
structures and activate complement system
11. Other receptors are :
1. NOD proteins
Nod1 recognizes meso-DAP
peptidoglycan in most gram –
ve and +ve
Nod2
recognizes
MDP ,found
in both gram
–ve and +ve
13. Receptors not only recognize various MAMPs to activate
INNATE RESPONSE but they also have a role in inflammation and
adaptive responses.
Other cells also play important role and respond by expressing
biologically active molecules such as cytokines n MMPs which will
effect homeostasis of host tissue in periodontal environment
14. CELLS INVOLVED
Macrophages & PMNs as phagocytes
Dendritic cells as antigen presenting cells
Natural killer cells that recognizes n kill host
cells
15. Fibroblast and • Produce IL -6
osteoblasts ,prostaglandin E2,MMPs.
And RANKL
Work as a physical barrier, equipped
EPITHELIAL CELLS with PRR and respond to MAMPs by
secreting cytokines and chemokine's
16. Commensals bacteria such as Streptococcus gordonii or
streptococcus sanguinis induce expression of antimicrobial
peptides without expression of IL 8
Periodontopathogenic bacteria from the ORANGE BACTERIA
such as Fusobacterium nucleatum and Prevotella intermedia
induce strong expression of both anti microbial and IL -*8
17. RED COMPLEX ORGANISM such as Ttreponema denticola,
Tannerella forsythia, Porphyromonas gingivalis suppress the
immune response by inhibiting anti microbial peptides and IL -8 or
both.
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19.
20. C E L L U L A R S I G N A L I N G I N I N N AT E I M M U N I T Y
RESPONSE
MAMPs get recognize by PRR as a result signal is initiated -
>signal is transduced through cytoplasm and nucleus -> post
transitional modifications take place --- determine the cell
response to MMAPs
Recognition of a ligand by TLR-- signals generated use
pathways similar to IL 1 receptors .
21.
22. ADAPTIVE IMMUNITY
Innate immunity plays a role in initiating and modulating
adaptive immune responses
Innate immune mechanisms are not turned off once the
adaptive responses is activated
Cells from adaptive immune response also express PRRs and
respond to MAMPs
23. The adaptive immune response is characterized by the activities of
pathogen-specific B and T lymphocytes
the cell type primarily responsible for translating innate signals into
adaptive immunity is the dendritic cell (DC).
adaptive immunity initiates with DCs recognizing MAMPs in the sites
of infection then subs migrating into the regional draining lymph
nodes
It then present the processed antigen peptides in the context of
major histocompatibility complex (MHC) molecules to naive T
lymphocytes
24.
25. in periodontal diseases, both MAMPs and inflammatory
cytokines are usually present to fully activate the DCs, which
suggests that there is no impairment to a competent activation of
adaptive immunity.
26.
27. H O ST M I C RO B E I N T E R AC T I O N S
DCs activated by MAMPs and inflammatory cytokines (also induced by MAMPs in
innate immune/resident cells) will initiate an adaptive immune response by driving
naive T lymphocytes into a CD8+ (for cytotoxic response) or CD4+ with Th1 or
Th2 phenotypes.
more pieces have been added to the puzzle, including the regulatory T
lymphocytes (Tregs), which appear to have their inhibitory functions suppressed by
activated DCs.
Activated T cells and their “specific” cytokine profiles will modulate the
inflammatory response and also the activation of B lymphocytes.
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31.
32. PAT H O B I O L O G Y O F P E R I O D O N TA L
DISEASE
Host response to periodontal expression of various pro
inflammatory and anti inflammatory cytokines, growth factors and
enzymes that are the result of activation of multiple signaling
pathways
PPR signaling is the most important interface between the host
and the microbes
33.
34. C Y T O K I N E S A N D M E D I AT O R S O F
I N F L A M M AT I O N
Local inflammatory reaction is characterized by an initial
increase in blood flow , enhanced vascular permeability , and
influx of cell from blood to crevice
For acute and rapid defense the mediators involved are
1. Histamine
2. Bradykinin
3. PGE2 and nitrous oxide
35.
36. Once activated by cytokines, bioactive molecules , and MAMPs
,infiltrating cells produce other inflammatory cells that modulate
the activity of other cells
Pro inflammatory : LIF
Cytokines include are : IL- ,IFN-,CNTF ,TGFb ,GM-
Ccytkines include
1@,IL-1b,IL -6 ant TNF@ CSF,IL-11,IL-12,IL-17,IL-
18,IL-8
38. A characteristic type of cytokine profile is associated with each type of
periodontal disease ( gingivitis or periodontitis)
Once immune and inflammatory processes are initiated and
complex cytokines network is established ,inflammatory
molecules play a direct role in degradation of both mineralized
and non mineralized tissues of periodontium
39. R O L E O F R A N K L I N P E R I O D O N TA L
DISEASE
Rankl plays a pivotal role in bone response since it is involved in
osteoclast differentiation , activation and survival
As periodontal disease progresses - collagen fibres &
connective tissue attachment to tht tooth is destroyed ---
junctional epithelial cells proliferate apically along the root surface
---- CLINICALLY seen as ATTACHMENT LOSS
40.
41. E.g. : MMPs released from different cell lesions --- capable of
degrading all components of ECM
MMPs increases with inflammation and disease activity
Detection in saliva is a host response bio marker of periodontal
disease
42. CONTD…
RANKL is secreted by fibroblasts ,osteoblast, chondrocytes
,mesenchymal cells and T and B lymphocytes.
• OPG is the endogenous inhibitor of RANKL
• It functions as its decoy receptor
• Secreted by osteoblastic cells ,bone marrow stromal
cells and fibroblast
43. The ratio between RANKL and OPG is the current
paradigm for modulation of coupled bone turnover and
specifically in periodontal disease
Patients with advanced periodontitis presents with high
level of RANKL.
44. Based on susceptibility analysis ,individual
difference in the host response to MAMPs and to
host derived cytokines that are the result of
genetic variations may also play important role in
modulating the pathogenesis of periodontal
disease
45. CELL SIGNALING EVENTS
1. Production of cytokines and inflammatory mediators is usually
a tightly controlled that is initiated by external stimuli>
2. Signals are rapidly transduced through the cytoplasm into the
nucleus ----gene expression === DNA transcription
3. Final assembly of biologically active protein there a great
number of regulatory mechanism
46. T H E R A P E U T I C ST R AT EG I ES
Strategies have develop to target the host response to LPS
mediated tissue destruction
Doxycycline
Scaling root planning
Surgical therapy
MMP inhibitors
TNF & IL -1 antagonist