1B. Periodontal Pathology I

Question 1

Microbial sucession associated w periodontal disease

PIONEER SPEICES:
\_\_\_\_ oralis
streptococcus mitis
streptococcus gordonii
streptococcus sanguis
\_\_\_\_ naeslundii
actinomyces viscosus
\_\_\_\_ spp.
\_\_\_\_ parainfluenzae

Answer 1

streptococcus
actinomyces
veillonella
haemophilus

Question 2

Microbial succession associated w/ periondontal disease

Gingivitis

• ____ israelli
• ____ intermedia
• ____ spp
• ____ nucleatum

The characteristics of these organisms, are that they tend to be predominantly ____ organisms and they are leaning towards becoming anaerobic. Many of them were still facultative anaerobes, but organisms like Prevotella intermedia and Fusobacterium nucleatum prefer to grow in relatively ____-poor environment 


Answer 2

actinomyces
prevotella
capnocytophagia
fusobacterium

gram-negative
oxygen

Question 3

Recruitment/activation of neutrophils

Neutrophils migrate through the junctional epithelium into the gingival crevice forming a ____ to bacterial invasion of underlying tissues

Neutrophils are a key component of the host response to bacterial infection:

• ____
• intracellular killing of bacteria
• recruit other cells to site of infection including ____
• interaction w other components of the ____

Answer 3

barrier
phagocytosis
macrophages
immune system

Question 4

Recruitment and activation of neutrophils

Chemoattractant

• ____
• platelet-activating factor
• ____
• interleukin-8 (IL-8)
• ____

Source

• ____ activation
• platelets, leukocytes
• ____, macrophages, eosinohpils
• junctional epithelial cells, mononuclear cells
• ____ (bacterial proteins are blocked at N-terminus by formylated methionine)

Answer 4

C3a and C5a
leukotriene B4
FMLP

complement
PMNs
bacteria

Question 5

◦ Collectively are involved in bringing large numbers of neutrophils into this site where mature supragingival plaque is developing 

◦ So in cartoon version, we start to see the accumulation of more neutrophils and an increase in ____ fluid flow, so we start to see the accumulation of serum proteins in the gingival crevice, including antibody molecules 

◦ What can antibodies do with complement? Remember there’s three Pathways of complement activation: there’s the ____ pathway, which requires the presence ____. Then the other 2 pathways.

◦ In presence of bugs and antibody, there are number of mechanisms that can attribute to the activation of complement and it’s become very well established that the activation of complement also plays a role in the progression from gingivitis to periodontitis 


Answer 5

gingival crevicular
classical
IgG and IgM

Question 6

Activation of PMNs and macrophages results in localized inflammation

pro-inflammatory molecules induce an elevation in the expression of adhesion molecules on endothelial cells and an increase in vascular permeability. this leads to:

• efflux of serum components including ____ and antibodies
• emigration/accumulation of ____

this response (____) may be sufficient to control the altered microflora

Answer 6

complement
lymphocytes
gingivitis

Question 7

Disruption of periodontal homeostasis

◦ This explains the microbiologic changes relative to the clinical changes- if we look at health, relatively little plaque. But plaque is present- has the characteristics of early supragingival plaque, gram positive facultative anaerobes

minimal ____
lower ____
These conditions support what we consider to be the growth of commensal organisms that make up our ____ microbiota
◦ Again, all of us have this on our teeth right now, even right after you brush and floss in
the morning or the evening before you go to bed. Even then is it going to be remnants of plaque left on your teeth. You’re not going to get it off 100%
◦ In the absence of oral hygiene, we start to see the accumulation of plaque


Answer 7

inflammation
gingival crevicular gluid
symbiotic

Question 8

Disruption of periodontal homeostasis

◦ We start to see the appearance of ____ organisms
◦ The gram-negative organisms interact with the elements of immune system. Initially at the junctional epithelium.
◦ There is the induction of a ____ response. The neutrophils are recruited into the junctional epithelium, and ultimately this inflammatory response starts to manifest itself to the point that we can visually see. But it also changes the events in the environment in which the plaque is forming and it drives transition from something that is considered to be symbiotic to something that is altere, and represents the microbiota that is associated with gingivitis.
◦ Initially, this is associated with what we will refer to as ____ 


Answer 8

gram-negative
neutrophil
early gingivitis

Question 9

“Early” gingivitis: clinical and histologic correaltes

due to mild edema, the gingival margin “moves” in a ____ direction possibly resulting in a slight increase in the ____

Analogous to the “____”

Answer 9

coronal
depth of the sulcus
early sulcus

Question 10

“early gingivitis”

in ____, this condition usually does not progress whereas in adults it quickly develops into what is described as ____

Answer 10

children

established gingivitis

Question 11

Transition from early to established gingivitis

if plaque is not removed there is a continuing shift in the composition of the microflora. this leads to accumulation of ____ organisms resulting in exacerbation of the ____ reaction

Answer 11

gram-negative

inflammatory

Question 12

◦ As a result, this is sensed by the ____ immune cells. 

◦ There is the induction of ____ within the gingival connective tissue 

◦ There is a coronal migration of the gingival margin, such that ultimately what happens is that some of the plaque that was previously situated Supragingival is now positioned ____.


Answer 12

innate and adaptive
edema
subgingivially

Question 13

◦ The other event that takes place is that there is increased ____ flow, such that this now developing gingival pocket is filled with fluid.
◦ It contains many of the proteins that are found in serum, as a result of the increase in vascular permeability in the vessels in the gingival connective tissue.

◦ We start to see not only an increase in the numbers of neutrophils and the amounts of antibodies, but all of the other types of proteins that are found in serum.


We already mentioned that it can activate ____, so that’s one really important thing. Also, ____- in the presence of antibodies, it’s going to bring bacteria together and neutrophils together. Then it would become easier for phagocytosis in the presence antibody. Why? the antibody marks the bacterial cells for phagocytosis. The neutrophils recognize that flag by the FC receptor. FC receptors are molecules found on distinct types of cells that can interact with the heavy chain constant regions of different classes of antibody. Neutrophils have FCgamma receptors on their cell surfaces. So if there are ____ molecules here, that bind to the surface of bacterial cells. That now makes it easier for neutrophils to phagocytose those bacterial cells. 


Answer 13

gingival crevicular fluid
opsonization
IgG

Question 14

What is critical here, is that in this subgingival environment (which is a developing pocket) the environmental conditions are going to be very different from the environmental conditions that the supragingival plaque is exposed to.

◦ First of all, these bugs are now going to be living in a ____ environment 

◦ There is going to be a change in ____ availability -it’s going to drop
dramatically.

◦ The source of nutrients is very different. The major source of nutrients up here (supraging.) is dietary carbohydrates. Whereas subging, it’s going to be serum ____. 

◦ Also, the changes in ____, as well as, temperature 

◦ Collectively, all of these factors interacting with one another are going to drive another transition in the composition of bacterial plaque.


Answer 14

liquid
oxygen
protein
pH

Question 15

Disruption of periodontal homeostasis

◦ So we went from something that symbiotic, consistent with periodontal health. Then accumulation of plaque, and accumulation initially of gram-negative organisms. This leads to the exacerbation of an ____ reaction.

◦ so now we’re going to take a step further beyond early gingivitis, and as we see the accumulation of more and more gram-negative organisms- the extent of inflammation increases dramatically.

◦ We start to see changes in gingival crevicular fluid flow - it becomes more active 

◦ We see an increase in a mass of inflammation provoking bugs, basically gram- negative organisms. 

◦ Ultimately as this reaches a critical number, we see an exacerbation of the inflammatory condition within the gingiva - that is clinically, we see more severe gingival inflammation.


Answer 15

inflammatory

Question 16

Accumulation of gram-negative bacteria exacerbates the inflammatory reaction

• increasing numbers of ____ and other inflammatory cells
• increased production of ____ mediators in variety and quantity
• induction of “immunologic” response as evidence by the presence of large number of activated T cells, B cells and ____ cells

◦ The predominant cell type in this lesion are ____ cells. But no one really understands exactly the significance of that (K..) 


Answer 16

PMNs
inflammatory
plasma
plasma

Question 17

Histopathology of established gingivitis

◦ this is a histological section superimposed on a cartoon of the tooth, points to the oral epithelium and the sulcular epithelium, and remnants of the junctional epithelium down here. It’s most apical extent is still at the level of the CEJ. So it has not moved in an ____ direction…
◦ but it is also associated with all this purple stuff, which are ____ cells.
◦ So this is a very significant inflammatory infiltrate of the connective tissue underlying the junctional epithelium. So this is really the histologic view of the events that we just mentioned.

◦ One of the other events that occurs is the degradation of ____ molecules in the extracellular matrix of gingival connective tissue. This is eventually going to have very significant sequela in the progression from established gingivitis to ____.
◦ It also has some clinical ramifications because now if you stick a periodontal probe into here, the junctional epithelium is no longer ____ as it was in health. The connective tissue underlying the JE is starting to break down. So when you put a periodontal probe in here, bleeding will occur, and the periodontal probe probably is not going to stop until it hits intact connective tissue.
◦ So even though the most coronal aspect of the JE might be up here, even with very light pressure of periodontal probe is going to ____ the JE, degrading gingival connective tissue, and it probably won’t stop until it gets here.


Answer 17

apical
inflammatory
collagen
periodontitis
intact
perforate

Question 18

Collagen degradation

Extracellular degradation of collagen by enzymes has a minor role in ____ turnover but a major role in the breakdown of the ____ of gingival connective tissue adjacent to the junctional epithleium

Where do the enzymes come from?

• they might be produced by plaque ____
• they might be produced by ____ cells
• both ____

◦ The major mechanism of collagen turnover in homeostasis is intracellular breakdown of collagen. ____ are very very very important in homeostatic turnover of collagen.


Answer 18

physiologic tissue
extracellular matrix
bacteria
host
sources

fibroblast

Question 19

Degradation of the ECM

bacterial enzymes capable of degrading various host cell-surface molecules and/or components of the ECM:

• ____
• trypsin-like enzymes
• ____ enzyme
• elastase-like enzyme
• ____

Answer 19

collagenases
fibronectin-degrading
phospholipases

Question 20

MMPs and Periodontal DIsease

in studies assessing enzymatic activity in patients w periodontal disease, ____ have been detected in saliva, GCF and/or gingival tissues

◦ This demonstrating the presence of a series of enzymes known as Matrix metalloproteinases (MMP) and saliva gingival crevicular fluid from patients who had gingivitis and periodontitis. This told us that even though the bacteria themselves can release enzymes capable of degrading the extracellular matrix, it is the ____ derived enzymes that are really responsible for an overwhelming majority of the damage.

Answer 20

MMPs

host

Question 21

MMPs

1. family of host-derived enzymes (>28 in number) that each degrade various components of the extracellular matrix including collagen

◦ Remember the names relevant to periodontal disease

◦ The ____ are the most important series of MMPs when we talk about gingivitis and periodontitis


Answer 21

collagenases

Question 22

Matrix Metalloproteinases (MMPs)

2. produced by a vast array of ____, parenchymal and immune cells including ____, epithelial cells and ____
3. biosynthesis and enzymatic activity is tightly ____ at multiple levels
4. Involved in both ____ processes

Answer 22

stromal
fibroblasts
neutrophils
regulated

physiologic and pathologic

Question 23

Matrix metalloproteinases in periodontal disease

MMP-2 = \_\_\_\_
MMP-8 = \_\_\_\_
MMP-9 = \_\_\_\_
MMP-13 = \_\_\_\_
MMP-14 = \_\_\_\_

◦ ____ are believed to play a critical role in the breakdown of the extracellular matrix in individuals who are suffering from severe gingivitis and ultimately periodontitis 


◦ Turns out that MMP13 is involved also in degradation of ____. Bone is made up of an organic and inorganic component- the inorganic component is mostly calcium phosphate. The organic component has a very significant amount of collagen in it, so when we look at bone resorption, not only do we have to have a mechanism to result in ____. There are also have to be mechanisms that explain the breakdown of the organic matrix and MMP13 is thought to play a very important role in that.


Answer 23

gelatinase A
neutrophil-derived collagenase 2
gelatinase B
epithelial/bone cell-derived collagenase 3
membrane-type 1 MMP

MMP8 and MMP13
bone

Question 24

Role of MMPs in periodontal pathogenesis

degradation of ____
degradation of ____
• Degradation of
“protective” proteinases such as ____.
• Release of ____ from the extracellular matrix.
• Regulation of ____ activity and inflammatory reactions.
• Regulation of ____ differentiation.
• Removal of ____ matrix during bone resorption.

Answer 24

basement membrane
extracellular matrices
serine proteinase inhibitors (serpins)
cytokines
cytokine
osteoclast
organic

Question 25

Transition from gingival health to established gingivitis

◦ Under the induction of an inflammatory reaction, what we start to see is an increase in ____ activity (explained in the 2nd hour)

◦ Then we see is a transition from situation where these two events were equivalent to one another —> to now there is an increased tissue degradation and then as the balance changes, now we go from the state of health (left picture) to something that looks like this (right picture). 

◦ Most of this is associated with the induction/activation of ____. This is very characteristic of established gingivitis.


Answer 25

MMP

MMPs

Question 26

Established gingivits: clinical and histologic correlates

increasing ____ within the gingiva and breakdown of the JE leads to deepening of the sulcus and formation of a ____

analogous to the “established lesion”

Answer 26

edema

gingival pocket

Question 27

Established gingivits: clinical and histologic correlates

◦ Left pic- someone who has established gingivitis. There’s edema, erythema, ____ bleeding and increase in the variety of inflammatory cells that are present. An increase in the quantity and types of inflammatory mediators that are present. Induction very significant inflammatory infiltrate, as well as, the degradation of collagen and gingival connective tissue.

◦ Not only is there a coronal migration of the gingival margin, but now there’s a very significant detachment of the junctional epithelium, such that the probing depth goes from 2-3 mm in the state of health to ____ mm in someone who has established gingivitis

◦ collectively these two events lead to the formation of the structure that we describe as a ____
◦ so if I were to put a periodontal probe in here very gently, and it stops where the junctional epithelium is still intact, the structure that that probe is occupying is what we refer to as a gingival pocket. This is analogous to be established lesion that was described by Schroeder and Page.


Answer 27

spontaneous
3-4
gingival pocket

Question 28

Transition from gingival health to gingivitis

summary:

1. possible increase in ____ as a result of edema and/or detachment of the JE from the tooth (true gingival pocket)
2. loss of epithelial attachment but no loss of ____ attachment or bone
3. totally ____ if plaque is removed
4. may occur concurrent w ____

“really important- no loss of CT attachment or bone.” We’re talking about someone like one of you guys who stopped brushing their teeth for 3-4 weeks. We’re not talking about someone who also has periodontitis. This is a person who has an intact attachment apparatus.

▪ Gingivitis does NOT result in breakdown of the components of the ____. “very very important point to keep in mind”

Answer 28

probing depth
connective tissue
reversible
periodontitis