2. Periodontal Pathology II Flashcards
Progression of periodontal disease
why does gingivitis progress to periodontitis in some patients and not others?
- presence of uniquely ____ strains of bacteria
- an over-exuberant ____ to the bacterial challenge
- an inadequate host response that is overwhelmed by pathogenic bacteria
- enhanced susceptibility to progression secondary to a ____ determined phenotype
- acquired and/or ____ factors enhance an individual’s relative susceptibility to progression
virulent
host response
genetically
environmental
• so now we’re using electron microscope
• here’s the gingival margin and gingival pocket.
• this would represent the biofilm that is positioned subgingivally and in a liquid
environment due to edema in the CT.
• what we start to see is another transition in the composition of the plaque –> a lot of
it is mediated by this organism (brown rod) known as ____. It’s one of the secondary colonizers of dental biofilm.
- what’s unique about it, is that it has receptors and adhesions on its cell surface that allows it to interact with another group of organisms that we consider to be the ____ colonizers
- It’s the appearance of this group of organisms (late colonizers) that appears to be critical to be on set of breakdown of the ____
F. nucleatum
late
attachment apparatus
Periodontitis
- ____ gingivalis
- prevotella intermedia
- ____ nucleatum
- tannerella forsythia
- ____
- selenomonas spp
- ____ spp
- spirochetes
associated with Health, onset of gingival inflammation found in mature supragingival plaque, and now the late colonizers that may be involved in the path. of periodontitis. Most of these are ____organisms. Majority are strictly ____ organisms, and some of them like a little bit of ____ in their environment. So very different from what we see in health and gingivitis.
porphyromonas
fusobacterium
AA
capnocytophagia
gram-negative
anaerobe
carbon dioxide
Dysbiosis of the periodontal microflora
microbial dysbiosis:
a condition of ____ microbiota that is associated w disease
the dysbiosis of the periodontal microbiota represents an alteration in the relative ____ or ____ of individual members of the polymicrobial community (relative to their abundance or influence in health) leading to dysregulated host-microbial interactions that mediate destructive inflammation and bone loss
keystone pathogen:
a microorganism that, relative to its numbers, plays a disproportionately large role in transforming a benign microbial community into one that can cause ____
imbalanced
abundnace
influence
disease
- and when we look in the periodontal microenvironment, the organism that is thought to represent the Keystone pathogen is ____
- the reason for that, is that P. gingivalis exhibits a number of ____ factors, but in particular, it is capable of modulating the host response and creating ____ that facilitates the appearance of these other organisms
- So what is concept advocates is that P. gingivalis, is not directly responsible, for inducing the inflammatory reaction that leads to the degradation of the components of the attachment apparatus. But it creates an environment that allows the outgrowth of the bugs that are responsible for inducing that inflamm. reaction. It creates that ____ that allows those bugs to flourish.
- P. gingivalis plays a very important role in the transition from gingivitis to periodontitis
- I should also point out that it’s not necessarily in everyone. Only for individuals “____” for developing periodontitis.
p gingivalis
viurlence
conditions
enviornment
susceptible
Reinterpretation of the ecologic plaque hypothesis
- So putting this all back into the context of ecological plaque hypothesis and what we discussed up until this point :
- here’s health with the symbiotic microbiota → plaque accumulation leading to a transition in the composition of the microbiota and the development of plaque that has the characteristics of mature supragingival plaque → the development of gingivitis
- The hallmark of gingivitis is that it’s an ____ condition
- we start to see accumulation of inflammatory mediators and lots of proteins in gingival crevicular fluid
- these conditions are conducive to the growth of a variety of different organisms, include Keystone pathogen like ____
- now that the Keystone pathogen is present, it starts messing around with the host ____ response and it’s been shown that PG can do all sorts of different things to the host response → but ultimately what it leads to is creating a ____ that results in this phenomenology of dysbiosis and facilitates the out growth of organisms that are capable of mediating the inflammatory reaction that leads to the breakdown of the attachment apparatus
- Via this process, there is an increase of ____ (so more proteins in gingival crevicular fluid, higher gingival crevicular fluid flow, changes in the composition of the subgingival microenvironment) and ultimately the collection of a group of organisms that are now considered to be disease provoking.
inflammatory
p gingivalis
immune
condition
inflammation
Reinterpretation of the ecologic plaque hypothesis
• The point: under the influence of this dysbiotic microflora, virtually every element of the
immune system is activated, including ____ mechanisms of immunity
• We are not responsible for memorizing all the names of the bugs
• but you can see ____, neutrophils, macrophages, T cells and B cells, dendritic cells, ____ cells are all involved.
• This all leads to the induction of ____ degenesis and the resorption of bone
• We need to understand how all of these events, under the Influence of dysbiotic
microbiota, lead to break down of gingival connective tissue and alveolar bone
• We’ve already talked about how gingival connective tissue breaks down. What’s the mechanism? ____. That’s the the major mechanism for the degradation of collagen within gingival CT.
innate and adaptive complement plasma osteoclast MMP
LPS (____)
• Lipopolysaccharide (endotoxin) is found on ____ bacteria.
endotoxin
gram-negative
Properties of Lipolysaccharide
- Cell wall component of ____ bacteria
Normally released when bacterial cells ____. - Thermostable when heated at ____ for 1 hour.
- Exhibits numerous biologic properties:
- Activation of ____ pathway of complement cascade.
- ____ cell activation.
- Increased vascular ____ due to effect on endothelial cells.
- Induction of ____ and vascular collapse (hypotension).
- Activation of ____.
- Activation of mast cells.
- Activation of ____ and macrophages.
- Promotes ____.
gram-negative die 100 alternative polyclonal B permeability fever clotting neutrophils osteoclastogenesis
LPS-medaited activation of macrophages
- so I just want you to be a little bit familiar with how LPS mediates these events
- ____ receptor is found on the surfaces of the number of human cell types, the one that’s most relevant for our discussion right now is the macrophage.
- TRL4 is important in order for the activation of the cell by ____
- another molecule that important is ____, which can be found on the surface of the cell but also comes in a soluble form
- 3rd molecule that’s very important is ____ protein. It interacts with free LPS and then allows LPS to interact with CD14. LPS cannot ____ interact with CD14
• So, the cells are killed by a compliment or whatever→ the LPS is released into the extracellular environment → it interacts with a LPS-binding-protein and forms of complex → then this complex interacts with ____ on the surface of a macrophage or what can happen is this complex can interact with soluble ____, forming a complex made up of three molecules: ____ protein, LPS, ____ → and this complex can then associate with the cell membrane of macrophage
- so once this complex is formed on the surface of a macrophage, the LPS interacts with ____ and this ultimately leads to the induction of signaling into the nucleus of the macrophage, causing it to become activated.
- Upon activation by LPS, macrophages will secrete a number of ____ and pro- inflammatory mediators, including IL-1B, TNFa, and prostaglandin E2–> which are extremely potent at inducing ____
- so macrophages are going to have a very key role in the breakdown of the ____
TRL4 LPS CD14 LPS-binding directly
CD4 CD14 LPS-binding LPS CD14
TLR4
cytokines
inflammation
attachment appartus
Bacteria within subgingival plaque further exacerbate the inflammatory reaction
- Elevated numbers and activity of ____ within infiltrated connective tissue.
- Further increase in production of inflammatory ____ in variety and quantity.
- ____ cells predominate within the connective tissue infiltrate.
- Destruction of ____ tissue and alveolar bone.
macrophages
mediators
plasma
connective
Osteoclast differentiation and activation
• In order for osteoclast to differentiate, osteoclast precursors, which have ____ on their cell surface, have to react with cells that have ____ on their cell surface and this interaction leads to the differentiation and activation of osteoclast→ which were primarily responsible for the resorption of bone
RANK
RANKL
Periodontal pathogenesis: the central role of macrophages
• macrophages play a very very very critical role in the overall phenomenology the breakdown of the attachment apparatus
• This relates to the types of cytokines that they release when they’re activated
• so let’s make the assumption that LPS has activated this macrophage and it secretes ____, IL-1B,and TNFa → and collectively with these molecules are capable of doing is inducing the differentiation of ____→ that results in alveolar bone resorption
• they also release ____ and that results in extracellular matrix degradation
• So collectively, the cytokines and enzymes released by activated macrophages can induce break down of bone, breakdown of gingival connective tissue, breakdown of the periodontal ligament and these are the things that we seen patients who develop periodontitis.
• The other thing that can happen is that under the influence of ____ and ____,
fibroblasts can be induced to secrete ____, which induces alveolar bone resorption
PGE2
osteoclast
cytokines
IL1B
TNFa
PGE2
Periodontal pathogenesis: the central role of macrophages
- Fibroblasts can also release ____ which can contribute to the breakdown of the extracellular matrix
- Macrophages can be very nasty cell types once activated
- So if we ask why some ppl progress to periodontitis and why others don’t→ it may be due to factors that regulate ____ activity, or ____ factors where some ppl might have “hyperactive macrophages” when stimulated by LPS. There can be certain ____ of cytokines that are produced by macrophages that are activated in different matters that may attribute to the breakdown of the attachment apparatus. There can also be bacterial factors that modulate the activity of macrophages that can also explain this.
MMPs
macrophage
genetic
patterns
Cytokines and Pro-inflammatory mediators induce bone resorption
Cytokines and Pro-inflammatory mediators induce bone resorption
Negative effects on osteoblasts:
TNFa
- inhibits ____ differentiation
- inhibits ____ and TGFB synthesis
ILB
- inhibits ____ synthesis by osteoblasts
Positive effects on osteoclasts
PGE2
- enhances ____ differentiation
IL1B
- enhanced ____ activity
osteoblast
BMPs
matrix
osteoclast
osteoclast
