Periodontal Immunology Flashcards
2 stages of periodontal diseases
gingivitis
periodontitis
gingivitis
Inflammation localised to gingival tissues
Acute inflammation
Normal physiological response to infection or injury
- Active normal physiological responses
- Repair tissue to return to homeostasis
periodontitis
Inflammation of the gingival tissues and supporting periodontal structures
- extended
Chronic inflammation
- If acute inflammation unsuccessful descend into this
Pathological inflammatory response associated with tissue destruction
gum appearance in health
pink
scalloped shaped knife edge margin
stippling
gingivitis appearance of gums
gingival swelling
redness
inflammation
periodontal diseases are triggered by
plaque
amount of plaque correlates to amount of inflammation in gums
composition of the oral biofilm
All microbes on teeth and oral surfaces
- 150-200 different species
- Types and proportions differ between individuals
Late colonisers typically Gram negative anaerobes
Bacterial interactions
Modify the environment
Early colonisers typically commensal species
most virulent complex in sub-gingival plaque
red (periodontal pathogens)
3 bacterial in red complex
porphyromonas gingivalis
tannerella forsythia
treponema denticola
what is the orange complex of pathogens virulence in comparison to red pathogens
lesser extent than red but still associated
proportion of periodontal pathogens in healthy sites
present in low numbers
proportion of periodontal pathogens in diseased sites
usually increased numbers
but in some complex situations can be absent
colonisation
microbial presence on a body surface without clinical signs of inflammation or disease
commensal
- doesn’t involve disease
can become pathogenic if conditions favour the expression of virulence
- oppurtunistic
1st stage of infection
infection
Microbial invasion of host tissues
Pathogens
Can behave like commensals if conditions do not favour expression of virulence
how is pathogenicity portrayed by different bacteria
Pathogenicity is not an Inherent microbial trait
Host immune system actively suppresses overt expression of virulence factors
Wait for opportunity to strike
Some microbes are more virulent so easier to overcome host defences
describe technique used by P.gingivalis as its virulence factor
immune invasion and subversion
4 virulence factors of P.gingivalis
Asaccharolytic
Gingipains
Atypical LPS - TLR4 antagonist
Inflammophilic
Asaccharolytic
virulence factor of P.gingivalis
nutrients from breakdown of proteins and peptides
- Cannot use carbohydrates for energy
gingipains
virulence factor of P.gingivalis
proteases with broad-specificity
Degrade host proteins
- Make available for nutrient use
Activate MMPs
- Help in tissue repair by removing damaged tissue
- Cleave host proteins – hi jacked
atypical LPS - TLR4 antagonist
virulence factor of P.gingivalis
Doesn’t signal through TLR4
- Different way to survey immune system
inflammophilic
virulence factor of P.gingivalis
Inflammatory environment favours expression of virulence
- Like inflammation
In this environment they are able to express their virulence factors
In healthy environment present but not actively doing anything
what modifies pathogens virulence factors ability
internal and external factors
what is a more systemic factor which can cause a bacteria to have increased virulence
medical conditions
- Weaken immune system
- Lesser pathogens more able to cause disease in this situation
Meaning periodontal pathogens can be absent from disease as lesser pathogens are involved
3 factors which trigger gingival inflammation
changes in oral biofilm
- accumulation
- composition
- expression of virulence
what determines periodontal pathogenesis
host bacterial interactions
what is the consequence of excessive biofilm accumulation
not accessible to cell mediated immune responses
what protect function and integrity of teeth
vast array of enzymes, MMPs, protect function and integrity of teeth
physcial barrier to prevent microbes invading underlying tissue
role of TLR in immune defence in oral cavity
TLR will bind to and recognise pathogens
- respond by release of cytokines and chemokines
neutrophils role in immune defence in oral cavity
neutrophils traverse through gingival tissue
- degranulate and release histamine
why is the immune system active in health in the oral cavity
to maintain the biofilm
symbiotic means
benefit us and benefits itself by pleasant environment
- Exists with host tissue in health
is the oral biofilm easily disrupted
yes
sensitive
what is the basic description of periodontal pathogenesis
accumulation and acquisition of virulent pathogens
causes change in immune response
immune response in gingivitis
Increased TLR stimulation
- Greater level in gingivitis
Increased production of pro-inflammatory mediators
- More inflammation
Triggers acute inflammatory response
- Redness, swelling, bleeding
- Increased vasodilation, cell migration
Neutrophils remain the predominant cell type in the initial lesion
Monocytes are recruited, activated and differentiate into macrophages
- Activated by cytokines and chemokines present
Lymphocytes are recruited
- To fine-tune the immune response
what causes there to be a resolution in inflammation
elimination of the pathogen
tissue returns to health
what happens if unable to control infection
progression of disease process
inflammation persists
give bacterial species a competitive advantage over commensal organisms as incompatible with inflammation
dysbiotic biofilm
competitive advantage of periodontal pathogens
give bacterial species a competitive advantage over commensal organisms as incompatible with inflammation
9 environmental and genetic risk factors that alter ecological pressure exerted on oral biofilm
diseases e.g. diabetes
genetic differences
activity of salivary proteins
salivary flow rates
innate/adaptive immune factors
oral hygiene
diet
smoking
antibiotics/antimicrobial agents
what are the levels of symbiotic to pathogenic species of MO in health
pathogenic species are present in health but not clinically relevant
how can ecological pressures alter the levels of bacteria in the biofilm
can upregulate virulence factor
predominate and drive inflammation further
what is the effect of inflammatory response on symbiotic (avirulent) species?
more susceptible
numbers and proportions become diminished
what is the effect of inflammatory response on pathogenic species?
they are capable of evading immune response
periodontal pathogens
how can it be that periodontal pathogens are present in health but not causing disease
because conditions don’t favour expression of virulence
clinical appearance of healthy gums
small periodontal pocket
clinical appearance of gingivitis
pocket increases slightly due to increase swelling of tissues
periodontal disease
attachement loss
biofilm to new sites
descend deeper into pocket
alveolar bone loss and deeper pocket depth is caused by host immune response to bacterial biofilm
what are host-bacterial interactions like in periodontal disease?
they are disrupted so become destructive
what is the effect of host-bacterial interactions on perio disease pathogenesis
Immune response continues and inflammation continues
Acute protective response in gingivitis
To destructive and associated with tissue destruction
neutrophil function
crucial for maintaining healthy periodontium
what is a deficiency associated with aggressive periodontitis
leukocyte-adhesion deficiency – IMMUNE UNDER-REACTION
- Neutrophils are trapped in blood
Cannot traverse through BV wall to tissue
- Present with aggressive perio from young age
- Absence of neutrophils in gum tissue causes them to run riot
Need neutrophils to maintain healthy periodontium
what is the outcome if neutrophils are increased and able to contain infection
return to health
what is the outcome if neutrophils are increased but unable to contain infection
predispose to disease progression
ineffective neutrophil action at controlling biofilm
excessive neutrophil infiltration associated with…
Degradative enzymes (Major source of matrix metallo-proteinases [MMPs])
Inflammatory cytokines and oxygen radicals contribute to hypoxic environment
- unhealthy
Connective tissue destruction manifests clinically as loss of attachment
- Too many degradative enzymes, sources of MMPs, contribute to attachment loss
role of adaptive immunity in periodontal destruction
T and B lymphocytes present in early lesion
- Present in gingivitis
- Eliminate the pathogen and return to health
Aggregates rich in CD4 T cells, B cells and dendritic cells evident as lesion progresses
- Infiltrate tissue
Unable to regulate dysbiotic biofilm
B cell/plasma cells predominate advanced lesions
- From innate to adaptive immune response
- Still unable to regulate dysbiosis biofilm
- Descends deeper into pocket
IgG fails to regulate dysbiotic biofilm
- Plasma cells release high affinity IgG
Protective – prevents systemic infection
Destructive – inflammation induced alveolar bone loss
osteoblast
synthesis and secretion of bone tissue (osteoid)
bone formation
osteoclast
resorbs bone (recyclers)
derived from monocyte/macrophage lineage
in health, bone formation and bone resorption are coupled
- bone volume maintained
healthy relationship of bone formation/resorption
bone formation and bone resorption are coupled
- bone volume maintained
what triad regulated bone formation/resorption
RANK/RANKL/OPG
microbial composition of periodontal lesion
Activated T and B cells in periodontal lesion Release and secrete RANKL into environment
- RANKL Binds to RANK on pre osteoclasts
- —Induce osteoclast differentiation
- Monocytes recruited into tissue
- OPG Bind to RANK and inhibits pathway
- —-Prevent RANKL binding to RANK
- —Inhibits osteoclasts differentiation
how does inflammation lead to bone loss
High levels of RANKL
Low levels of OPG
- Not balanced
Inflammation induced bone resorption
Pathological bone destruction
7 stages of cellular and molecular events linking bacterial induced inflammation with pathologic tissues destruction
- Bacterial products bind TLRs on epithelium, stimulating secretion of cytokines, chemokines and AMPs
- Vasodilation and selective recruitment of leukocytes (predominantly neutrophils, also monocytes and lymphocytes)
- Bacterial products activate neutrophils, further release of pro-inflammatory mediators. Amplification loop of neutrophil infiltration.
- Activated lymphocytes express RANKL. RANKL/OPG balance disrupted
- RANKL binds RANK on osteoclast precursors (monocytes). Activates osteoclastogenesis leading to alveolar bone resorption
- Pro-inflammatory cytokines (IL-1, IL-6, IL-17, TNFa) contribute to bone resorption by inhibiting bone formation (osteoblast)
- Elevated and dysregulated MMP activation contributes to connective tissue destruction
- Excessive neutrophils present
- Degrade ECM leads to loss of attachment
what determines the severity and progression of periodontal disease
interaction between bacteria challenge and host immune response
what governs patient susceptibility to periodontal disease
immune-inflammatory mechanisms governs pt susceptibility and is modified by environmental factors
