1A. Periodontal Pathology I Flashcards

1
Q

• Typically, what’s the measurement from the CEJ to the alveolar crest in health? Answer: somewhere b/w ____. Sometimes, it’s a little controversial as to if it’s closer to 2mm, bc I’m gonna give you a number in a minute that would argue that it’s closer to 1mm, but in radiology, they’ve probably said 2mm.

A

1 and 2mm

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2
Q

Structures of the Periodontium in Health

The measurement from the ____ to the most ____ is equivalent to the depth of the gingival sulcus.

This typically ranges between ____mm.

A

gingival margin
coronal aspect of JE

1 to 3

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3
Q

Structures of the Periodontium in Health

The measurement between the most coronal aspect of the JE and it’s most apical extent represents the length of the ____ of gingiva to the tooth surface (~1mm).

The measurement between the most apical aspect of the JE and the bone crest is equivalent to the length of the ____ attachment of the gingiva to the tooth surface (~1 mm).

A

epithelial attachment

connective tissue

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4
Q

Biologic width = ____

____ attachment (1mm) + ____ attachment (1mm) = biologic width

A

2mm

epithelial
connective

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5
Q

Experimental Gingivitis Model

Initial study conducted by Harold Löe and his colleagues in Aarhus, Denmark.

Purposes:

  1. 􏰑To attempt to produce ____ in patients with healthy gingiva by withdrawing all active efforts directed towards oral cleanliness, and
  2. to study the sequence of changes in the ____ and in the gingivae thus produced.􏰒
A

gingivitis

microbial flora

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6
Q

Experimental Gingivitis Model

Conclusions:
• ____ is essential for the development of gingivitis.
• The presence of certain bacteria at the onset of gingival inflammation suggests that there may be ____ organisms acting as periodontal pathogens.
• Individuals are differentially ____ to developing gingivitis; some develop the disease more quickly than others.
• Removal of ____ leads to resolution of gingivitis.

A

bacterial plaque
specific
susceptible
plaque

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7
Q

The Natural Progression of Periodontal Disease in Humans

  • 480 male laborers at two tea plantations in Sri Lanka.
  • No conventional oral ____ measures or dentistry; all subjects displayed uniformly large aggregates of ____, calculus and stain.
  • Virtually all sites exhibited ____.
A

hygiene
plaque
gingival inflammation

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8
Q

The Natural Progression of Periodontal Disease in Humans

Three subpopulations were identified based on the rate of progression of disease (determined by CAL and tooth loss.
• ____ Progression (8%)
• ____ Progression (81%)
• ____ Progression (11%)

A

rapid
moderate
no

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9
Q

The Natural Progression of Periodontal Disease in Humans

“ Perhaps the finding of a small group (10%) of Sri Lankan tea laborers, participating in these studies who showed no progress of periodontal disease beyond the ____, was the most significant result.

The mere presence of such a group among a population who generally exhibits various degrees of rampant periodontal disease, is surprising and intriguing, and will be subject to future study.”

A

gingival lesion

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10
Q

◦ First of all: the 17yo pt was not free of dental plaque. She just didn’t have lot of calculus on her teeth, but there was a lot of plaque. In my mind, I would say that keeping teeth free of plaque is probably not the ____ (see the x) for why different people have different presentations bc obviously if it were just a matter of keeping plaque off, then you would expect that the patient in the top left pic would have teeth that looked like what’s seen in the lower right radiograph, and that just isn’t the case.

A

explanation

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11
Q

Page and Schroeder Histologic Stages of Gingivitis and Periodontitis

Initial Lesion (Clinical Health)

  • Slightly elevated vascular ____ and vasodilation.
  • ____ flows out of the sulcus.
  • Migration of ____, primarily PMNs, in relatively small numbers through the gingival connective tissue, across the junctional epithelium and into the sulcus.

Early Lesion (Early Gingivitis)
- Increased vascular ____, vasodilation and GCG flow.
- Large numbers of infiltrating ____ (mainly PMNs and lymphocytes.
- Degeneration of ____.
- ____ degradation, resulting in collagen depleted
of the connective tissue.
- Proliferation of the ____ and sulcular epithelium
collagen-depleted areas.

A

permeability
GCF
leukocytes

permeability
leukocytes
fibroblasts
collagen
junctional
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12
Q

Page and Schroeder Histologic Stages of Gingivitis and Periodontitis

Established Lesion (Established Gingivitis)

  • Dense ____ cell infiltrate (PMNs, plasma cells, lymphocytes).
  • Accumulation of inflammatory cells in ____ tissue.
  • Elevated release of ____ and the lysosomal contents from PMNs.
  • Significant ____ depletion and epithelial proliferation.
  • Formation of ____ epithelium containing large numbers of PMNs.

Advanced Lesion (Periodontitis)

  • Predominance of PMNs in the ____ epithelium and pocket.
  • Dense inflammatory infiltrate in connective tissues that is made of predominantly ____ cells.
  • ____ migration of the junctional epithelium to preserve an intact epithelial barrier.
  • Continued collagen breakdown resulting in large areas of collagen depleted connective tissue.
  • ____ resorption of bone.
A
inflammatory
connective
MMPs
collagen
pocket

pocket
plasma
apical
osteoclastic

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13
Q

Bacterial Biofilms

Matrix that are adherent
to each other and/or to surfaces or substrates.

  1. May contain a single or multiple ____ species.
  2. Composed of multiple ecological “____” communities
  3. Numerous distinct ____ exist within a biofilm each with radically different pHs, [oxygen], temperatures and electrical potentials.
  4. Biofilms exhibit ____ circulatory systems
  5. Biofilm bacteria exhibit metabolic ____.
  6. Bacteria living within a biofilm are relatively ____ to host defense mechanisms.
  7. Bacteria living within a biofilm are relatively resistant to systemically and locally
    delivered ____.
A
bacterial
micro
microenvironments
primitive
cooperativity
resistant
antimicrobials
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14
Q

• Now we look at someone who has gingivitis and look at their histologic situation - we can see that the junctional epi (the coronal aspect of it) has moved slightly ____, the apical aspect of JE has NOT ____ and is still at the CEJ, and the bone crest has not ____ either. So, e.g. of how someone could get this situation - they start off in perio health and then do the experimental gingivitis model for enough time to collect some plaque on their teeth and then they have this histo situation.
◦ Does anyone remember what else happens here that I didn’t put into the picture? (answer: ____)
‣ Edema where? Why does edema happen? He heard like 5 answers and didn’t understand any of them
(I can relate to this on a spiritual level, since this sentence is me throughout all of dental school, tbh). (see below)

A

changed
changed
changed
edema

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15
Q

Determinants of the microbial

• Where are the fluids in edema coming from?
◦ If we’re talking about edema, we’re not going to say the fluids come from the gingival sulcus. The fluid might
contribute to what’s in the gingival sulcus, aka GCF, but in order to get edema, there are certain structures that you have to have present. Think about Dr. Ali’s lectures when he talked about inflammation. (tbt to one hell of an exam @FS2) There’s increased vascular permeability and vasodilation, so we’re talking about blood vessels. Where are the blood vessels? They’re in the gingival connective tissue. There are no blood vessels in the epi itself. So, there’s a collection of edematous fluid in the gingival connective tissue, and there was an anatomic change that I told you about that occurs as a result of edema in the underlying connective tissue: the gingival margin can migrate in an incisal or ____ direction.
‣ Why is this important?
• As a result of incisal/coronal movement of the gingival margin, some of the plaque that’s
accumulated supra-gingivally is now gonna be positioned ____. That matters because it’s going to develop into a different ____ than the plaque that existed supra-
gingivally. Now we have to think of sub-G conditions and how that impacts the composition of the plaque matrix. Change in the position of the JE = pretty minor; just about a fraction of a millimeter.

A

coronal
sub-G
microenvironment

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16
Q

• Now looking at periodontitis picture.
◦ Number of significant changes:
‣ The apical extent of JE is NO LONGER AT THE ____. The remnants of the epi attachment have moved ____, and that’s indicated by this yellow arrow. This is a very significant change.
‣ In periodontitis, there is overt resorption of ____ bone. We can measure the amount of bone loss based on comparing where the crestal bone is to where it was in health - can range from 1-15mm depending on how long the root of the tooth is.

**Why I say all of this is to get you to start thinking about the fact that the env in a periodontal pocket is different than the env in a gingival pocket, which is very different from the conditions that affect plaque that grows supra-gingivally. Supra-G plaque is exposed to saliva and a high O2 conc. of oral cavity.
◦ Middle pic (gingivitis):
‣ ____ from something where the plaque is bathed in saliva to a situation where some of it is bathed in gingival crevicular fluid
‣ O2 tension may be a little bit lower
◦ Right pic (periodontitis):
‣ All of the nutrients are derived from GCF
‣ O2 tension is very very very low, if theres even any O2 there at all
‣ Temp is different
So, the types of bacteria found in each of these scenarios are dramatically different from one another - again, the composition of bacteria is driven largely by the characteristics of the local microenvironment that the bacteria are exposed to.

A

CEJ
crestal
transitiioning

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17
Q

• When we talked about this last year in the context of perio microbiology, we talked a lil bit about the ecologic plaque hypothesis said by Dr. Marsh. He already accepted that supra-G and sub-G plaque are different types of plaque, but he really appreciated that it was the ecology or the ____ of a given niche that dictated the types of organisms that were present.

• So, in a state of health:
◦ Minimal inflammation, low ____ flow, and a higher ____ conc
◦ Microflora = consistent with periodontal health
‣ Mainly ____, many of which are ____ anaerobic organisms
‣ His argument is that the reason for the presence of these organisms is the environment they were
exposed to - high O2 conc, carbs as nutrient source, and this whole idea that this was relatively consistent in the supra-G environment.

A
microenvironment
GCF
higher O2
gram-positive cocci and rods
facultative
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18
Q

The ecologic plaque hypothesis

• Change in pt’s oral hygiene and plaque accumulates –> plaque induces an inflammatory reaction. The inflammatory reaction alters the flow of GCF, it alters the conc. of O2, and as a result, it drives the transition in the composition of the microflora from something that’s gram-positive and facultatively anaerobic to something that’s predominantly ____ composed of mainly ____ anaerobic organisms.
◦ If you remember, these were the types of organisms that are typically found in the pockets of patients who have periodontitis. His info was really trying to associate these changes in the composition of the microflora with the changes that occur from perio health to the environment that we find in the periodontal pocket.

A

gram negative

obligate

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19
Q
  • Just reminding you - the organisms that are characteristic of early supra-gingival plaque, consistent with perio health, tend to be ____. (reads the names of the organisms associated with onset of gingival inflammation and also the names of the organisms that are associated with the induction of attachment loss)
  • We will talk about individual organisms and the individual organisms are the ones he will ask us to remember.
  • ***Bottom line: as we transition from health to periodontitis, there’s a transition from Gram-positive to ____ microflora and transition from something that’s predominantly ____ anaerobic to one that contains large numbers of strict ____ and ____ (organisms that prefers a little bit of CO2 in their environment).
A
gram-positive cocci and rods
gram-negative
facultatively
anaerobes
capnophiles
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20
Q

NEED TO MEMORIZE THESE TWO LISTS
• This info is from work done by Forsythe research facility in Boston under direction of dr. Socransky
• Left box: consensus perio pathogens
◦ The ones that most people agree upon as being important.
◦ These first three (____, ____, ____) are the members of the red complex that was fined by Dr. S and his coworkers.
• Last year, I told you that these complexes (top pic with colored circles) are based upon the fact that you tend to find these organisms associated with each other. E.g. if you find Prevotella intermedia, there’s a high likelihood that you’ll find these other orange organisms with it, or organisms in the green circle with other organisms in the green circle.
• Similarly, for RED complex: if you find P. gingivalis, you’re also likely to find Tannerella forsythia and Treponema denticola. Some people think these three (red complex) are the really bad guys, but the American Academy of Periodontology argues that AA is also an important perio pathogen. Therefore, we NEED TO KNOW THESE FOUR ON THE LEFT (P. gingivalis, T. forsythia, T. denticola, ____).

A

p gingivalis
tannerella forsythia
treponema denticola
AA

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21
Q

• Right box: he’ll tell us the ones we need to know as we go through the info.
◦ Many of these are gram-negative. A couple are ____ (reads Peptostreptococcus micros and Eubacterium species). The other thing I should point out is that there’s some evidence that herpesviruses are involved here. Around 80-85% of herpesvirus papers regarding perio dz have this one dude as a coauthor. He was here in the late 80s and early 90s. Pro tip from Dr. Korostoff: When the same guy’s name is on these papers over and over again and no one else is publishing similar data, you have to start questioning how meaningful the data is. He’d like to believe that viruses can cause perio disease but the consensus among Dr. Korostoff and people he knows is that ____ do not cause perio disease, but the viruses may modulate the efficacy of the immune system and may serve as potentially a ____ for development of perio disease, but he would not say that they cause it. He still doesn’t think we know which organisms cause periodontal diseases (reassuring <3).

A

gram-pos
herpesviruses
risk factor

22
Q

“Suspected” Periodontal pathogens: culture-dependent evaluation of the oral microbiome

Common characteristics

  • detected in higher proportions in ____ plaque from diseased versus healthy sites
  • tend to be ____
  • are typically “____ colonizers” of dental plaque
  • tend not to grow well under ____ conditions (obligate anaerobes, anaerobes, capnophiles)
  • exhibit potential ____ factors
  • evidence of induction of acquired ____ in diseased subjects relative to healthy controls
A
subgingival
gram-negative
late
aerobic
virulence
immune responses
23
Q
  • Most of the stuff above is based on work done before the early 2000s, when most research was based on our ability to culture bacteria from oral cavity. If you remember, I told you last year that that there’d been around ____ different bacterial species identified from the oral cavity, but a lot of this has been done thru ____ methods, aka the organisms have not been grown thru culturing in laboratories. So, it’s tough to appreciate if they’re important or not. We need to take a more global approach to seeing what’s present, and that’s what’s shown on this slide.
  • Prior to genetic and immunofluorescent techniques, what we depended on was culture-dependent approaches to identifying organisms. Although that was very effective and it allowed you to do experiments with the organisms themselves in an in vitro system, it def wasn’t giving us the whole story, bc we know there’s a bunch of ____ bacteria that live in the oral cavity, and these (points to ____ approaches) are the techniques to ID the non-cultivable organisms.
A

600-1000
molecular

non-cultivable
culture-independent approaches

24
Q

“Suspected” periodontal pathogens: culture-independent evaluation of the oral microbiome

  • with the advent of culture independent, ____ based methods of bacterial ID and enumeration, our understanding of the bacterial composition of the periodontal region has changed
  • at least ____ bacterial species are capable of colonizing the oral cavity and approximately ____ can simultaneously colonize an individual host
  • the oral microbiome also includes numerous ____ and viral (bacteriophages) organisms that can influence the composition of its bacterial component
  • in addition to the consensus red-complex ‘pathogens’ in chronic and severe periodontitis, newly recgonized non- or poorly-cultivable organisms that increase in number in diseased sites include the gram-positive ____ & ____, and species in the genera ____, megasphaera, ____, desulfobulbus, ____ and synergistes
A
molecular
700
150
fungal
filifactor alocis
peptostreptococcus stomatis
prevotella
selenomonas
dialister
25
Q

• First half was a review of microbiology. Just a couple more comments from microbiological perspective. (reads question on the slide) aka “how do bacteria cause disease in general?”
◦ Answer: it’s really a characteristic associated with ____, aka the properties of an organism that allow it to cause some form of pathology.
◦ Can be broken down into 1 of 4 categories:
Factors that facilitate ____ (colonization is the very first step that has to occur in the context of an infectious disease).
In some situations, the bugs should be able to ____ a tissue.
They certainly should be able to evade ____ by the host immune system.
In many situations, if not all, there’s some extent of ____
***He thinks the two most important ones are 1 and 3 (aka ability to colonize a site and ability to evade host immune system detecting it).

A
virulence factors
colonization
invade
detection
tissue damage
26
Q

How do these organisms avoid the host’s immune system?

  1. inhibition of ____
  2. secretion of toxins
  3. disruption of ____ integrity
  4. adaptation of antimicrobial peptides
  5. inhibitino of ____ and chemokine secretion
  6. cell invasion and entry into the cytosol
  7. escape from ____
  8. persistence in modified endosomes
A

opsonization
mucosal
intracellular signaling
phagosomes

27
Q

Avoidance of Phagocytes

Induction of \_\_\_\_
Inhibition of uptake by presence of capsules Disruption of \_\_\_\_ integrity
Adaptation to antimicrobial peptides
Inhibition of \_\_\_\_ and chemokine secretion
Cell invasion and entry into the \_\_\_\_ 
Escape from phagosomes
Persistence in modified \_\_\_\_
inhibition of intracellular recognition
A
apoptosis
mucosal
intracellular signaling
cytosol
endosomes
28
Q

How do these organisms avoid the host’s immune system?

Bacterial strategies for avoiding the adaptive immune system

Induced expression of “immunosuppressive ____
Inhibition of pro
production and surface expression of co stimulatory molecules
3. Inhibition of ____ uptake
4. Inhibition of phagosome maturation
5. Inhibition of ____
6. Inhibition of antigen presentation
7. Inhibition of ____ of T and
B cell antigen receptors
8. Activation of inhibitory CEACAM1 receptor on
T cells
9. Induction of the differentiation of ____ that dampen immune responses
10. Induction of apoptosis

A
cytokines
bacterial
antigen processing
tyrosine phosphorylation
regulatory T cells
29
Q

Bacterially-mediated tissue damage: direct and indirect mechanisms

Direct effects of bacterially molecules on: host cell \_\_\_\_ proliferation/differentiation /activationof “\_\_\_\_” host cells tissue \_\_\_\_

Indirectly via interaction w the host immune system:

  • immune ____/subversion
  • induction of ____
A

viability
catabolic
integrity

evasion
inflammatory responses

30
Q
  • A number of other molecules, one of which we’ve heard about - ____… (he doesn’t say anything about it. Just lists the name as one of the other organisms. Ok. Seems like maybe he was just saying that these are other molecules involved in the direct effects of bacteria.)
  • All of these molecules are capable of interacting with various elements of the host immune system and either killing certain types of immune cells, e.g. leukotoxin can kill neutrophils, monocytes, and lymphocytes; CDT can affect epi cells and lymphocytes by inducing them to undergo cell cycle arrest and possibly apoptosis. I’m not going to go through all of this, but we’re going to talk about the role of LPS in mediating the induction of inflammation and the activation of osteoclasts.
  • ***It’s very clear that the bacteria themselves DO have the potential to directly affect host tissues, and to some extent, they do play a role in the breakdown of the components of gingiva and the attachment apparatus, but probably nowhere near to the extent that their ____ effects are important.
A

LPS/endotoxin

indirect

31
Q

• First question: how do host innate immune cells recognize the presence of bacterial cells?
◦ Much of this results from the existence of ____, a series of molecules found on the surfaces of immune cells; to some extent, they represent the eyes of the ____ immune system - they allow the cells of the innate immune system to see the presence of bacterial cells.
‣ These receptors are ____
‣ They detect and respond to very conserved microbial structures, e.g. LPS & lipoteichoic acid, etc.
‣ Molecules that PRRs interact with = ____
‣ There’s another series of molecules that the PRRs can interact with - does anyone remember those?
•____ - damage-associated molecular patterns: molecules that are released upon damage to host cells/upon cell deaths - also capable of triggering responses upon interacting with PRRs (but I think his point of this slide is to know that MAMPs are released and that helps the innate immune system figure out that stuff is going wrong re: bacterial cells being there)

A
PPRs
innate
germ-line encoded
MAMPS
DAMPS
32
Q
  • Here’s a list (tbh, I think we’re at list #23908290 by now, but who’s counting. Anyway - carrying on.) of some of the PRRs that have been identified until now. I hope that you remember the term ____ receptors. There’s a series of them - some of them are on the cell surface membrane and some are cytoplasmic proteins. They can interact with a variety of microbe-associated molecules.
  • **I’m not going to ask you to memorize what’s on these tables. When we get to specifics, I’ll tell you which ones I want you to know. But I just put this slide up here bc it illustrates the distribution on a number of different cell types, not all immune - many of them are ____ cells, including epi cells and fibroblasts. A number of these receptors are also expressed on the surfaces of both innate and ____ immune cells.
  • Many of them can interact w/molecules found on the surfaces of a number of perio pathogens and we’ll talk about a manifestation of what happens when some of the TLRs interact with molecules on the surfaces of distinct perio pathogens.
  • This is just to get your minds thinking about the existence of these mlc, not so much about memorizing the names.
A

toll-like
stromal
adaptive

33
Q
  • This is another slide that’s about the same thing but more in the context of different types of cells in the periodontium - epi cells, dendritic cells, endothelial cells, gingival fibroblasts, PDL fibroblasts, and cementoblasts (aka reads left column of table where it lists all the cell types).
  • With the exception of ____ cells, very few, if any, of these cells are considered immune cells. The component cells of the periodontal microenvironment do have the capacity to sense the presence of bacteria on your teeth. This is really very dramatic departure from what he learned when he was in dental school, esp re: epi cells. Epi cells used to just be thought of as a primitive barrier from outside world and didn’t do much else, but what’s getting more and more obvious is that because epi cells have a number of ____ on their cell surfaces, they really are ____ to detect the presence of microbial agents, not only in the mouth but also throughout the rest of the ____. Therefore, they’re very important in the initiation of host defense responses against not only bacteria but against all sorts of microbial entities.
A

dendritic
PRRs
sentinels
body

34
Q

Current concepts on the bacterial etiology of periodontal disease

  • today, it is increasingly recognized that periodontal diseases are not bacterial infections in the ____ sense, i.e., caused by a single or a limited number of pathogens
  • rather, periodontal disease is the result of a ____ community-induced perturbation of the host homeostasis leading to inflammation in susceptible individuals
  • bacterial constituents of these communities often exhibit ____ interactions that will enhance colonization, persistence or virulence, and some bacteria may be involved in the breakdown of ____ whereas others may trigger ____ inflammation once homeostasis
A
classical
polymicrobial
synergistic
homeostasis
destructive
35
Q

Reinterpretation of the ecologic plaque hypothesis

review of terminology

____ - an organism w a disproportionately large impact on the environment relative to its abundance in the overall community

____ - microbes that can colonize hosts without causing disease or tissue destruction

____ - commensal bacteria living in a particular niche that are not pathogenic by themselves but can enhance the virulence of other organisms

____ - commensals that exhibit the potential to induce pathology under conditions of disrupted homeostasis

A

keystone pathogens
commensals
accessory pathogens
pathobionts

36
Q

Reinterpretation of the ecologic plaque hypothesis

review of terminology

homeostasis - a condition of equilibrium or stability in a system, which is maintained by adjusting physiological processes to counteract external changes, i.e., a ____ relationship between a host tissue and the resident microbiota in ways that prevent destructive inflammation or disease

____ - close association of two different species (i.e. a microbe and a mammalian host) that live together without necessarily implying that either partner benefits

____ - a situation resulting in an imbalanced microbiota that is associated w disease, i.e., periodontitis or IBD

A

balanced
symbiosis
dysbiosis

37
Q

Reinterpretation of the ecologic plaque hypothesis

  • This is just a pictorial representation of what I just said. Homeostatic state is associated with a ____ microflora of organisms that can be tolerated by the host. Under situations where external conditions change (e.g. stopping brushing/flossing), we see the accumulation of larger numbers of organisms, not necessarily different ones, just ____ of them (with maybe the addition of one/two more types) that can trigger the induction of an inflammatory reaction. As a result, patients get gingivitis - super ____. Just brush your teeth and gingivitis resolves itself within a couple of days.
  • But in some people, in the absence of plaque control (or possibly even in the presence of plaque control), this situation creates an environment that alters the composition of the microbiota - aka ____ happens. And ultimately, what starts is an increase in numbers of pathobionts, keystone pathogens, and other organisms that are capable of initiating a more significant inflammatory reaction, which is capable of resulting in breakdown of components of the ____.
A

more
reversible

dysbiosis
attachment apparatus

38
Q

Reinterpretation of the ecologic plaque hypothesis

• Most people, in the presence of plaque, will dev gingivitis. (gives the following example) - If all of you stopped brushing for a few days and got gingivitis and I told you to keep not brushing for another six months, would all of you get periodontitis? ____. There’s definitely a small population of you that won’t (remember the Sri Lankan tea worker population). There’s going to be a population that get ____ breakdown of attached apparatus and then there’s another population that will have more ____ breakdown of attachment apparatus.
◦ Can you do this experiment ethically? No.
◦ He guesses that maybe 20-50% are resistant to getting attachment loss, but he says that is definitely a
guess and don’t quote him. Point is that there is some population of individuals that will be resistant to ____ breakdown. He wants to figure out what’s unique to those people and figure out how we can use that to help other people become resistant. This hasn’t been achieved yet.

A

no
rapid
chronic/gradual

attachment apparatus

39
Q

Reinterpretation of the ecologic plaque hypothesis

Pathogenic synergism
A situation in which individual microorganisms within a polymicrobial community that do not fulfill the requirements necessary to cause a disease, interact w other members of the community to collectively induce ____

Polymicrobial synergy and dysbiosis model
“biofilm accumulation can invoke and deregulate a host inflammatory response, which will change the ____ microenvironment, which in turn can drive a reorganization of the composition and activity of the microbiota, resulting in a more aggressive host response, leading to further changes in the ____, and subsequently the selection of communities of microorganisms that are even more suited to the prevailing conditions

A

pathology

subgingival
environment

40
Q

Reinterpretation of the ecologic plaque hypothesis

• Here’s the original pic of the ecologic plaque hypothesis as proposed by Dr. Marsh. He wants to add all of the new info that’s come about over the last 10 years.
◦ New Ideas
‣ ____ phase that hopefully all of us are capable of maintaining
• During this phase, there’s minimal plaque; minimal gingival inflammation; minimal GCF flow; ample ____
• This all facilitates the growth of ____, facultative anaerobic organisms

‣ Dysbiosis
• When homeostasis is thrown out of whack
• The environmental conditions change to the point that they no longer support the growth of
the homeostatic organisms, but the conditions mediated by the microflora will support the outgrowth of a collection of organisms that interact w/one another to induce the type of response that causes the breakdown of components of the ____

A

homeostatic
O2
gram-positive

attachment apparatus

41
Q

Periodontal homeostasis

  • even within clinical healthy gingiva there is ample ____ evidence of a host response to various components of the symbiotic microflora
  • this physiological inflammatory state or ‘____’ is the result of host interactions w commensal bacteria which are in close contact with (but do not invade) the periodontal tissues
A

histologic

armed peace

42
Q

Gingival health: clinical and histologic correlates

• Here’s the same clinical picture followed by a corresponding histo and then a diagram showing that histo pic.
• What you can see is that there are some bv that are ____ and there are some inflammatory cells in the
underlying tissue adjacent to the ____ (JE and part of sulcular epi are in a green
box).
• It’s not as if these tissues are absolutely free of inflammation; there are inflammatory cells present, and how does this all develop? See next slides for the series of cartoons he’s gonna use to show this. (going to be a wild cartoon ride, kids. buckle your seatbelts.)

A

dilated

sulcular epi and junctional epi

43
Q

• All of this is supra-gingival and is occurring in the conditions of the oral cavity. Bottom line - the ____ conc. are relatively high. There’s ____ circling within saliva, and the first thing that happens in the context of formation of dental plaque is the formation/conditioning of the tooth surface to give rise to what we call the ____.

A

O2
carbs
acquired pellicle

44
Q

◦ Acquired pellicle - a ____-free, amorphous structure that has deposited within it, a large number of salivary ____, as well as some other molecules derived from the host.
‣ Why these are important is that there are certain bacteria that have ____ specifically cable of engaging the distinct molecules within the acquired pellicle.
(see below for more on these bacteria - he later makes it seem like the pellicle is what has the receptors while the bacteria have ____, aka molecules that will bind to the pellicles’s receptors. The diagram corresponds to this second explanation.)

• PIONEER species (aka the early/initial colonizers) of the acquired pellicle:
◦ Mainly ____ orgs, which are ____ facultative anaerobes, and then a couple organisms in the genus of ____
◦ All of this is due to interactions b/w ____ on this unique group of organisms and the receptors found in the acquired pellicle. This is what we all have right now. When you brush your teeth and floss, you might disrupt it a bit, but probably a couple hours after you brush/ floss, the pioneer organisms start to re-colonize the acquired pellicle.

A

cell
glycoproteins
receptors
adhesins

streptococcal
gram-positive
actinomyces
adhesins

45
Q

Induction of host innate immune responses by plaque bacteria

• This is what this (colonization of the acquired pellicle by initial colonizers) looks like ____. These are his teeth, and he’s shown us this when he stopped brushing and inflammation developed as plaque started to form. One of the first things that starts to happen is that epi cells recognize the presence of the bacteria that accumulate on the surfaces of our teeth. Initially, it’s the normal microflora, or early supra-gingival plaque, that’s present. Via interactions w/ ____ on the surfaces of epi cells, there are signals that are derived from epi cells and are transmitted to the underlying CT, which is responsible for eliciting this super low-level ____ response, which is consistent with periodontal health. That’s what this cartoon shows.

• What happens next? (he goes back to the cartoon slide above this one for a second)
◦ Epi cells start to sense the presence of these bacteria. Bacteria also secrete metabolites and other stuff that are capable of triggering the host ____ response, and that’s what’s shown in the next slide.

A

clinically
PRRs
inflammatory

immune

46
Q

Junctional epithelial cells in health: initiators of the inflam process

Interleukin-8
• Chemokine also known as ____
• Acts as a ____ for PMNs, T cells and basophils
• Triggers alterations in the conformation of leukocyte ____ and subsequently enhances extravasation of WBCs
• Induces ____ of PMNs

Increased expression of ____

Antibacterial Factors:
• ____
• Soluble and membrane bound CD14
• ____ Protein

A

CXCL8
chemoattractant
integrins
activation

ICAMS

defensins
LPS-binding

47
Q

• Collectively, what happens is that in the presence of this normal flora, we see an increase in the migration of ____ as well as the contents of ____ into the gingival sulcus. As a result, there’s a ____-level number of PMNs as well as possibly bacterial-specific ____ molecules as well as complement.

Collectively, if any of these bacteria find their way down in this direction (aka into the gingival sulcus), there’s a very high likelihood that this low-level inflammatory reaction is enough to eliminate those bacterial cells.

• Ultimately, even though these bacteria are present, a sufficient enough inflammatory reaction has developed such that homeostasis can be ____. The bugs are still present, so they’re happy, and the host is still happy, bc the inflammatory reaction is low enough that it doesn’t affect the integrity of the structures of the periodontium. This is what we think is happening to all of us as we sit here right now. (We’re all in this together, kids. High School Musical was talking about normal periodontal health this whole time.)

A

neutrophils
serum
low
antibody

maintained

48
Q

Periodontal homestasis

“Initial lesion”

  • even within clinical healthy gingiva there is ample ____ evidence of a host response to various components of the symbiotic microflora
  • this physiological inflammatory state or ‘____’ is the result of host interactions w commensal bacteria which are in close contact with (but do not invade) the periodontal tissues

• When we talk about periodontal homeostasis, which he’s already told us the definition for, this really represents the “initial lesion” described by Schroeder and Page. So, the initial lesion = clinical ____ health.

A

evidence
armed peace
periodontal

49
Q

Cellular and molecular biology of gingival inflammation: the onset of clinically detectable inflammation

• Right side: this is what happens as plaque starts to accumulate.
• One of the things we want to understand is what are the underlying mechanisms responsible for the ____
from what looks like periodontally healthy gingiva and periodontium to something that exhibits gingival inflammation?

A

transition

50
Q
  • Here are his teeth again. Can see that there’s some plaque there; some of it might be calcified and have some calculus there. If you look closely, you might be able to see that there are individual engorged ____ at the gingival margin. This is no longer health. We’re now heading into the transition where there’s overt ____, and this is the point where he said he was done with the experiment and he started brushing and flossing again and everything went back to normal.
  • What’s responsible for this happening?Why do we see a more significant inflammatory reaction as there’s more and more plaque present? Is it the composition of the plaque or is it purely a characteristic of the host response? He says they’re not mutually exclusive from one another.
A

blood vessels

inflammation

51
Q

• As these bugs increase in number, they start to consume the ____ and carbs present and now we see a transition in the ecologic environment that the plaque is living in. There’s a decrease in ____ conc. and a decrease in the availability of dietary ____. What does that result in?

A transition in the composition of dental plaque. We start to see the appearance of a second group of organisms, called the ____ colonizers. If we want to know the names of them, we can see the key to figure it out. Again, he will tell us the ones that are most important when they come up in discussion. He will ask us to remember ____ - this is important because this organism serves as a ____ connecting the secondary colonizers to the initial colonizers, and it also allows the colonization of the area by the late colonizing organisms.

• (Ps- sorry that some of the writing is covered by the orange bar in the diagram, but it’s just saying that there’s a shift from a relatively high O2 concentration and high CHO availability to having decreased O2 concentration and decreased CHO availability.)

A

O2
O2
carbohydrates

secondary
fusobacterium nucleatum
bridge