5 - Periodontal Pathogenesis Flashcards
1
Q
what is the origination and development of a disease
A
pathogenesis
2
Q
what is the host respose to a CHALLENGE (insult or injury)
A
inflammation
3
Q
inflammation is linked to most chronic diseases of aging and premature births such as what
A
RVD, RA, alzheimer’s, pancreatic cancer, obesity, pre-term low-bith weight infants, periodontitis
4
Q
inflammation leads to what remodeling
A
soft and hard tissue
5
Q
inflammation is part of what repair process
A
wound healing repair process
6
Q
what plays a key role in pathogenesis of periodontal disease
A
inflammation
7
Q
what happened in Sri Lankan study
A
8%: Rapid progression of periodontal disease
81%: Moderate disease progression
11%: No disease progression beyond gingivitis
ALL patients had abundant plaque and calculus.
8
Q
what causes the different expressions of periodontal disease in all patients in the Sri Lankan study?
A
the host inflammatory response is different in all patients
9
Q
what is the etiologic role of bacterial plaque
A
initiate and perpetuate inflammatory responses in gingival tissues
10
Q
___ responses determines susceptibility to disease
A
immune-inflammatory
11
Q
what is the primary etiology to perio disease
A
biofilm
12
Q
what is the paradox to the role of inflamamtion
A
Host defense processes to prevent
ingress of bacteria result in most of
the tissue damage leading to clinical
manifestations of disease.
13
Q
unique features of perio disease
A
- Not caused by a single organism
- Bacteria that colonize the subgingival sulcus are effectively OUTSIDE the body
- Yet, the inflammatory response develops INSIDE the body.
14
Q
what are present in clinically healthy gingiva
A
- PMN leukocytes
- lymphocytes
- macrophages
- outflow of GCF
- steady state equilibrium between low-grade inflammation and subgingival microflora
15
Q
what migrates thru CT thru JE into sulcus
A
PMN leukocytes
16
Q
what is attracted by chemotactic stimuli created by bacterial products
A
macrophages
17
Q
what disease occurs prior to periodontitis
A
gingivitis
18
Q
T/F: all gingivitis progresses to periodontits
A
FALSE! not all gingivitis progresses to perio
19
Q
gingivitis is dependent on what
A
host inflammatory response and susceptibility to disease
20
Q
what are the different stages of lesions in the histopathology of of gingivitis and periodontitis
A
- intial lesion
- early lesion
- established lesion
- advanced lesion
21
Q
what lesion:
Develops within 2-4 days of plaque accumulation
Slightly elevated vascular permeability
GCF flow
PMN
A
initial lesion
22
Q
what lesions corresponds to “clinical gingival health”
A
initial lesion
23
Q
what lesion:
Increased vascular permeability, vasodilation, GCF flow
PMN
Lymphocytes
Collagen destruction: apical and lateral to JE and sulcular epithelium
60% of collagen destruction occurs
proliferation of JE
A
early lesion
24
Q
what lesion corresponds to EARLY GINGIVITIS
A
early lesion
25
what lesion
Plasma cells
Lymphocytes
PMN
Elevated release of MMPs and lysosomal contents
from PMN
Significant collagen destruction
established lesionw
26
what lesion corresponds to ESTABLISHED GINGIVITIS
established lesion
27
what lesion
Plasma cells in CT
PMN in pocket epithelium
Apical migration of JE
Collagen destruction extends into PDL and bone
Osteoclastic bone resorption
advanced lesion
28
what lesion correspons to PERIODONTITIS
advanced lesion
29
what are the inflammatory responses in periodontium
1. molecules signal tissue damage
2. majority of tissue destruction results from host inflammatory process
3. bacteria drive and perpetuate the inflammation
30
how do molecules signal tissue damage?
1. microbial virulence factors
2. host immune-inflammatory response
31
how does tissue destruction occurs from host inflammatory processes
excessive, dysregulated production of inflammatory mediators, enzymes
32
T/F: bacteria drive and perpetuation to inflammation contributes to a LARGE proportion of tissue damage
FALSE! contributes to SMALL proportion of tissue damage
33
lipopolysaccharide (LPS) is recognized by what TLR
TLR-4
34
what is a cell surface receptor that recognizes microbe associated molceular patterns and is found on innate immune cells
TLR-4
35
what is:
Lipid A component
Polysaccharide component
Found in outer membrane of gram-negative
bacteria
Endotoxin
Elicits strong immune response
Recognized by host Toll-like receptor (TLR)
LPS
36
porphyromonas gingivalis has an atypical LPS that is recognized by what
TLR-2 and TLR-4
37
the host response to LPS results in what
1. increased production of cytokines
2. differentiation of immune cells
38
what stimulates immune response less potently than LPS and is made of gram+ cell walls
lipoteichoic acid (LTA)
39
what recognizes LTA
TLR-2
40
what are bacterial enzymes and noxious products
1. ammonia
2. hydrogen sulfide
3. butyric acid
4. bacterial proteases
41
butyric acid leads to apoptosis of what cells
T-cells, B-cells, and fibroblasts
42
what digest proteins and provide nutrition for bacteria
bacterial proteases
43
T/F: bacterial proteases increase tissue breakdown
TRUE
44
what are gingipains?
bacterial enzymes produced by P, gingivalis
45
what are examples of microbial invasion
1. A.a. and P. gingivalis invade gingival epi and CT
2. fusobacterium nucleatum invades oral epi cells
46
what is the clinical significance of microbial virulence factors
- bacteria in tissue is not removed by scaling and root planing
- sheltered from host defense
47
what are host derived inflammatoyr mediators
1. cytokines
2. prostaglandins
3. matrix metalloproteinases (MMPs)
48
what are:
Soluble proteins
Messengers- transmit cell-cell signaling
Produced in tissues, act locally in tissues
cytokinesw
49
what are cytokines produced by
PMN
Macrophage
Lymphocytes
Fibroblasts
Epithelial cells
50
what cell
Elevated in gingivitis and periodontitis
Correlates with disease severity
Exacerbates inflammation, bone resorption
Stimulates production of PGE2, NO, MMPs
Mainly produced by monocyte, macrophage, PMN
IL-1beta (cytokine)
51
what cell
Stimulated by IL-1B and TNF-a
Produced by T-cell, B-cell, macrophage, dendritic
cells, fibroblasts, osteoblast
Stimulates development of osteoclasts
Stimulates bone resorption
IL-6 (cytokine)
52
what is this:
Secreted by macrophages in response to LPS
Increased levels in periodontitis
Stimulates development of osteoclasts
Apoptosis of fibroblasts (limits tissue repair)
Upregulation of MMPs
TNF-alpha (cytokine)
53
prostaglandins are derived from what
arachidonic acid
54
arachidonic acid is metabolized by ___ and ___
COX-1 and COX-2
55
what is PGE-2 responsible for
Vasodilation
Induces cytokine production
Produced by macrophages, fibroblasts
Induces MMPs production
Induces osteoclastic bone resorption
Inhibited by NSAIDs
56
what is a family of proteolytic enzymes and degrades collagen, gelatin, and elastin
MMP
57
what are PMN MMP produced by
PMN, macrophages, fibroblasts, epithelial cells, osteoblasts, osteoclasts
58
what MMP degrade Type I collagen found in PDL
MMP-8 and MMP-8 (PMNs)
59
what MMP affect collagenase-1
MMP-1 (fibroblast)
60
what is MMP inhibited by
TIMP (specifically TIMP-1) and tetracycline
61
what does TIMP stand for
tissue inhibitor of metalloproteinases
62
TIMP-1 is produced by what
fibroblast, macrophage, and endothelial cells
63
osteoclastic boen resorption occurs at ___ approaches the bone
tissue inflamamtion
64
what is a protective mech to prevent bacterial invasion of bone and leads to tooth mobility, tooth loss
osteoclastic bone reorption
65
inflammatory mediators must be ___ mm from bone to stimulate bone reosorption. this is the critical distance
<2.5 mm
66
what prevents binding of RANKL to RANK
osteoprotegerin (decoy to prevent resorption)
67
sites with periodontitis have [increased or diecreased] RANKL and [increased or decreased] OPG
increase RANKL, decrease OPG
68
what can be used as a therapeutic role to "switch off" inflammation
lipoxin, resolvins, and protextins, and antiinflammatory cytokines
69
what are anti-inflammatory cytokines
IL-10 and TGF-beta
70
in innate immune response, is the response improved as a result of previous exposure to pathogen
innate immune response
71
T/F: cells of innate immune response kill many different pathogens rather than one specific pathogen
TRUE
72
what are the cells of innate immune response
Monocytes
Macrophages
Neutrophils
Peripheral dendritic cell
Eosinophil
Basophil
Mast cell
NK cells
73
what cell of innate immune response:
Resides in epithelium
Ingests antigen and transports it to lymph nodes
peripheral dendritic cell
74
what cell of innate immune response:
Phagocytic leukocyte
Layer of PMNs in junctional epithelium: host defense
barrier
neutrophil (PMN)
75
monocyte vs. macrophage
Phagocytic leukocyte
Monocyte: circulating in blood
Macrophage: differentiate and live in the tissue
Macrophages present antigen to T cells
76
what cells orchestrate the CHRONIC immune response
macrophages and lymphocytes
77
what are large granular cytotoxic lymphocytes
NK cells
78
what recognizes and kills tumor cells and virally infected cells in innate immunity
NK cells
79
what Recognizes changes in Major Histocompatibility
Complex (MHC) Class I molecule (found on all
cells)
NK cells
80
are normal cells killed by NK cells
no
81
alterations in antigen presented in MHC class I molecule of tumor-infected cells result in what
NK killing of infected cell
82
what increases after exposure to pathogen and maintains higher levels of immunity for years
adaptive immune response
83
what are the different lyphocytes
T cells (helper CD4, cytotoxic CD8) and B cells
84
what cells are in stable perio
t cells
85
what cells are in active perio
B-cells, plasma cells, progression of disease
86
do lymphocytes generate progeny that recognize same antigen
yes
87
what enables the immune system to respond more rapidly when re-exposed to same pathogen
lymphocytes
88
what are the T cells of adaptive immune response
lyphocytes, TCR, CD4+, Th1, Th2, CD8
89
what recognizes antigens on surface of antigen presenting cells
T-cell antigen receptor
90
what helps immune response by providing proliferation and differenation signals thru cytokine secretion
CD4+
91
what secretes IFN-gamma, activates cell-mediated immunity
Th1
92
what secretes IL-4, IL-5, IL-13 and regulates humoral (antibody) mediated immunity
Th2
93
what controls intra-cellular antigens (bacteria, fungi, viruses)
CD8+ cytotoxic T cells
94
in absence of T cell, what do B cells do
differentiate to form PLASMA CELLS that secrete IgM antibody (primary response immunoglobulins)
95
in presence of T cell, what do B cells do
differentiate to MEMORY B cells
96
what cells give rise to plasma cells that secrete IgG, IgA, IgE antibody
memory B cells
97
due to memory, secondary response is what?
rapid onset, longer duration, greater in strength, greater specificity against antigen
98
what are antigen presenting cells
1. peripheral dentritic cells
2. langerhans cells
3. macrophages
4. B cells
99
what are the function of antigen presenting cells
1. express MHC Class II molecules
2. present antigen to CD4+ T cells, which control proliferation of other T and B cells
100
what is a network of membrane associated cell receptors and soluble serum glycoproteins
complements
101
where are complements produced
liver and macrophages
102
what enables leukocytes to recognize and bind foreign substances for which they lack receptors
complement
103
does complement promotes inflammation
YES
104
do complements exert negative regulation on T-cell immunity
yes
105
does complement promote immune homeostasis
yes
106
are complements activated within the cell (in addition to circulation and cell surface)
yes
107
do complements participate in basic cellular processes
yes
108
what is an intracellular effector system and plays a critical role in induction and control of T cell responses
complement
109
what complement:
increases vascular permeability and dilation
C2a
110
what complement:
Anaphylotoxins
Induce mast cell secretion
Chemotaxin
Attracts leukocytes
C3a, C5a
111
what complement:
Opsonin
Coats molecules to enable phagocytes to ingest
them
C3b
112
what complement:
C5b, C6, C7, C8, C9
Lyses bacteria and fungi by forming a large pore
in the target cell membrane
membrane attack complex
113
what is directed movement of leukocytes from blood into local tissues
transendothelial migration
114
defects in transendothelial migration are associated with what
periodontits as a manifestation of systemic disease
115
steps of transendothelial migration
1. rolling
2. insult
3. signaling endo
4. increased rolling
5. rolling arrest
6. strong adhesion
7. zipper phase
8. basement membrane degradation
9. chemotaxis
116
what are the leukocyte functions
1. chemotaxis
2. phagocytosis
3. killing
4. antigen presentation
117
mast cells in tissue chemotaxis release what
neutrophil chemotactic factor
118
in chemotaxis C5a attracts what
nutrophils
119
localized aggressive periodontitis (1999) has been renamed to what in 2018
Stage III-IV, Grade C
120
what causes localized aggressive perio/stage III-IV, Grade C
decrease in chemotactic response to C5a due to dysfunctional neutrophils
121
what is a defect in neutrophil transendothelial migration
leukocyte adhesion deficiency
122
what has a lack of extravascular neutrophils in perio tissues and affects primary and perm dentitions
leukocyte adhesion deficiency
123
what deficiency causes bacteria destroy host tissue unimpeded by normal host immune response
leukocyte adhesion deficiency
124
what is a cyclic reduction in circulating neutrophils
cyclic neutropenia
125
what is a tetracycline used in SUB-antimicrobial doe as an adjuct to treat periodontitis
doxycycline
126
what is doxycycline and example of
tetracycline
127
what enzymes is doxycyline inhibitins
MMPs (know it as collagenase that breaks down bone)
