Immunology Flashcards
(117 cards)
1
Q
Gingivitis
(4)
A
– Plaque-induced
– Inflammation (edema/bleeding upon probing)
– No destruction of PDL and bone
– No apical migration of epithelial attachment
2
Q
Epithelial attachment =
A
Junctional epithelium
3
Q
Periodontitis
(4)
A
–Plaque-induced
–Inflammation (edema/bleeding upon
probing)
–Destruction of bone
–Apical migration of epithelial
attachment
4
Q
–Not all cases of gingivitis
progress to —
A
periodontitis
5
Q
In other words, periodontitis is:
1. —induced similar to gingivitis.
2. —-related (susceptible host).
3. Each site is
4. A % of affected population experiences
5. The progression of the disease is
probably (?)———–
A
Plaque
Host
individualized or a specific
environment.
severe destruction.
6
Q
Continuous model (1900-1950’s)
A
– Continuous throughout life at same rate of
loss (i.e. Everyone gets perio disease.)
* Progressive model (1940-1960’s)
7
Q
Progressive model (1940-1960’s)
(4)
A
– Progressive loss over time of some sites
– No destruction in others
– Time of onset and extent vary among sites
– (i.e. Periodontal disease affects mainly
posterior teeth.)
8
Q
Random burst model (1980-2000’s)
(5)
A
– Activity occurs at random at any site
– Some sites show no activity
– Some sites have one or more bursts of activity
– Cumulative extent of destruction varies
among sites
– (i.e. Periodontitis is different in various
sites in the same individual and it is
difficult to predict attachment loss.)
9
Q
Asynchronous multiple burst model
(1980-2000’s)
–
– Prolonged period of —; remission
– Cumulative extent of — varies
among sites
– Some sites don’t develop —
– (—=not occurring at same time)
– Bursts due to —
A
Several sites have one or more bursts of
activity during one period of life
inactivity
destruction
attachment loss
asynchronous
Risk Factors
10
Q
Signs of Inflammation
(5)
A
- Rubor (redness)
- Calor (heat)
- Dolor (pain)
- Tumor (swelling)
- Functio Laesa (loss of function)
11
Q
Inflammation is a — phenomenon
A
vascular
12
Q
Inflammation:
(2)
A
– Leukocyte migration
– Vasculitis
13
Q
Vasculitis
(3)
A
Vasculitis
* Dilation
* Venous stasis (congestion)
* Increased Permeability
– Transudate
– Exudate
14
Q
Adaptive and Innate Immunity
1st defense
A
a. Innate (non-adaptive, genetic) (kills by
phagocytosis)
– PMNs
– Monocytes/Macrophages
15
Q
Adaptive and Innate Immunity
2nd defense
A
b. Adaptive (production of immunoglobulins by
antibodies)
– highly specific
– B and T cells involved
– Plasma cells produce specific antibodies to
individual antigens
16
Q
B lymphocytes
(2)
A
– Activated B-cells become Plasma cells
– Plasma cells produce immunoglobulins
17
Q
T lymphocytes
(3)
A
– developed in the thymus
– several functions (antigen presentation)
– help B-cells divide; can destroy virally infected cells;
can down-regulate immune response
18
Q
T cells can differentiate into 2 major
forms:
(2)
A
CD4
CD8
19
Q
CD 4 - MHC class II molecules
– T helper cells (TH0/TH1/TH2)
(3)
A
- help B cells to divide
- control leukocyte development
- activate innate cell lining
20
Q
CD 8 - MHC class I molecules
– T cytotoxic
(1)
A
- destroy virally infected target cells
21
Q
PMNs:
A
phagocytosis; produce lysosomal enzymes
22
Q
Macrophages:
A
phagocytosis; process antigens;
cytokine secretion
23
Q
B-Lymphocytes
* Plasma cells:
A
produce antibodies
24
Q
T-Lymphocytes
* T-helper (CD4):
* T-suppressor (CD8 & CD25):
* NK cell (natural killer-T cell) (CD56):
* T-cytotoxic cell (CD8):
* K (killer-T cell) (CD28):
A
helps B-cells divide
down-regulates T and B cells
kills virally-infected cells
destroys infected cells
kills infected cells
25
Humoral immunity
a. Antibodies
* IgM :
* IgG :
* IgA:
* IgD :
* IgE :
first responder; largest in size
second responder; most abundant; crosses
placenta
salivary IgA; a dimer
co-expressed with IgM (role?)
on Mast cells, allergic reactions
26
Complement:
part of both innate and adaptive
immunity systems. (A biochemical cascade that
helps clear pathogens by lysis, opsonization,
binding, and clearance of immune complexes).
27
Fab=
Fc =
spec. antigen
binding
Constant
portion
28
* T suppressor cells –
now T-regulatory cells,
down-regulate T and B cells (CD8 ,CD25expression); prevent autoimmune disease
29
* K (Killer) cells -
mononuclear cells that kill cells
sensitized with antibody (via Fc receptors) (CD28cells which were signaled by CD8 cells)
30
* NK (Natural Killer) cells -
kill virally infected
and transformed target cells that have not been
previously sensitized (CD56 cells)
31
* Monocytes (5%)
- activation in connective tissue
►will become macrophages*
32
* Neutrophils (> 70%)*
- 48 hours lifespan in
blood with migration to sites for phagocytosis
33
* Eosinophils (2-5%)
- cause damage by
exocytosis (eg: histamine release)
34
* Mast cells -
contain mediators of inflammation
(histamine, prostaglandins, leukotrienes and
cytokines)-involved in allergic reactions
35
* Basophils (< 0.5%)
- are in some ways
functionally similar to mast cells
36
Cytokines
* Definition:
produced by
soluble, locally active polypeptides;
regulate cell growth, differentiation, function;
cells of the immune system
37
Specific cytokines may have different
biologic properties dependent on:
(4)
– Their concentration
– The cells that produce them
– The cells being attracted and acted upon
– Presence and extent of extracellular matrix
38
IL-1
Pro-inflammatory: stimulates osteoclasts,
fibroblasts, macrophages
39
IL-6
Pro-inflammatory: stimulates T and B cells
40
IL-8
Pro-inflammatory: attracts and activates
PMNs
41
PGE2
(4)
Vasodilation
Pyrogenic
Releases mediator from mast cells
Cell-mediated cytotoxicity
42
TNF
Pro-inflammatory: activates osteoclasts
43
TGF
Stimulates epithelial cells and fibroblasts
44
PDGF
Stimulates fibroblasts
45
FGF
Stimulates fibroblasts
46
EGF
Stimulates epithelial cells
47
Can we then accurately predict
which patients with gingivitis are
going to develop periodontitis?
48
One can only identify risk
factors such as:
(3)
The answer is in the host’s
- Habits: Smoking
- Systemic disorders: HIV and Diabetes
- Patients with risk factors are more
likely to have attachment loss!!!
immune system/genetics
49
Clinically Healthy Gingiva**
* Some (2) are present in
connective tissue
* A few neutrophils are migrating
through the ---
* No --- destruction
* Intact ---
* --- is present
* Appears clinically healthy
(Color, Contour, Consistency)
neutrophils and macrophages
JE
collagen
epithelial barrier
Gingival crevicular fluid
50
Mechanical (plaque retention factors)
(5)
a. Calculus
b. Caries
c. Restorations: defective margins, subgingival
margins, overcontoured margins
d. Prosthesis
e. Tooth Anatomical Factors
* i.e. Palatogingival Grooves, Furcations
51
Inflammatory Response Modifiers
* Systemic
(8)
– Uncontrolled/controlled diabetes**
– PMN defects
– Hematological
– Hormonal: Puberty, Pregnancy***
– Immune disturbances
– HIV/AIDS**
– Medications*
– Nutrition deficiencies
52
Inflammatory Response Modifiers
* Genetic
(9)
– Agranulocytosis
– Neutropenias
– Lazy Leukocyte
– Leukocyte adhesion deficiency (LAD)**
– Down’s syndrome
– Papillon-Lefevre
– Hypophosphatasia**
– Chediak-Higashi
– Ehlers-Danlos syndrome
53
Initial Lesion
* Develops in --- days
* Cells of --- inflammation present
* Increased --- flow
* Start of --- formation
2 to 4
acute
GCF
pseudopocket
54
Remember:
Acute =
Chronic =
Increase in chronicity ►►►
PMNs
Lymphocytes
Plasma cells
55
The Initial Lesion
Plaque is deposited on the tooth
Bacterial byproducts are released into
the periodontal tissues (virulence
factors)
56
Virulence factors
* 2 types
– Stimulation of the host defense systems
– Degradation of the host tissues
57
Stimulation of the host defense systems
(2)
* Stimulates cells to release cytokines (ie: IL-1, TNF
and PGE) and chemoattractant factors (IL-8)
* Attracts inflammatory cells (example of LPS
causing chemotaxis of PMNs)
58
Degradation of the host tissues
* Enzymes
(4)
– Collagenase
– Trypsin-like enzymes
– Keratinase
– Phospholipase A
59
Bacterial-Host Interaction*
(Aa, Fn, Pg)
Increased release of Interleukin-1
PMNs and Macrophages
60
(Aa, Cr, Ec)
Increased release of Interleukin-6
Macrophages, epithelial cells and fibroblasts
61
(Aa, Ec, Fn, Cr)
Increased release of Interleukin-8
PMNs, epithelial cells and fibroblasts
62
(Aa, Fn)
Increased release of TNF
PMNs and Macrophages
63
(Cr, Aa, Pi, Pg)
Increased release of PGE
Monocytes
64
Poor plaque control
Bacterial byproducts are released into the
periodontal tissues (virulence factors)
Stimulation of epithelial cells and
fibroblasts to release IL-8 into the CT
which attracts and activates PMNs
PMNs are present in the
connective tissue
PMN’s are attracted to and
near JE and sulcular epithelium
65
Plaque accumulation
(3)
Bacterial byproducts are released into the
periodontal tissues (virulence factors)
Stimulation of inflammatory cells to
release cytokines into the CT
PMN’s attracted near and to the
JE and sulcular epithelium
66
Clinical Features of Initial
Lesion
(3)
* Increased GCF flow
* Sulcus increases from 0→3 mm by
formation of a pseudopocket
* Alveolar bone is normal on the
radiograph
67
Selectins
“slow” the
PMNs and
cause
them to
“roll”.
68
Cytokines
activate
ICAM
receptors
on
endothelial
cells for
PMN
attachment
69
Early Lesion
(4)
* 4-7 days
* Acute inflammation persists (initial
lesion►►), increased GCF,
pseudopocket formation
* Cells of chronic inflammation appear and
then dominate
* (chronic→shift to T lymph. from PMNs)
Collagen loss continues**
MMPs Activation begins**
70
How is collagen lost
(3)
Microbial Factors(LPS and Antigens)
Stimulate not only
release of Cytokines
But also activation
and release of
MMPs
But also activation
and release of
MMPs
71
The MMP family includes
28 metal-dependent endopeptidases (proteases) with activity
against most, if not all, extracellular matrix macromolecules. (used for normal tissue remodeling)
72
Sub-Classes (MMPs)
(6)
- Interstitial Collagenases**
- Gelatinases
- Stromelysins
- Secreted RXKR (Arg-X-Lys-Arg)
- Membrane type
- Metalloelastase
73
Early Lesion Histopathology
1. Collagen loss up to
70%*
74
What causes collagen destruction?
PMN’s products, Cytokines, MMPs are
included, so a combination of bacterial
products and host’s defense system cause
the destruction.
75
Early Lesion Histopatholgy
2. PMNs accumulation in ---
3. PMNs accumulation in ---
4. Cells of chronic inflammation accumulate
and predominate
– T-cell lesion
5. --- show cell damage
6.--- proliferation of JE into CT
gingiva
sulcus
Fibroblasts
Rete pegs
76
Early lesion
(4)
More inflammatory infiltrate
Proliferation of JE rete pegs
T-cell lesion
Loss of collagen in the connective
tissue, but no bone loss
77
Clinical Features of Early Lesion
1. --- of gingiva
2. Increased ---
3. Loss of gingival ---
4. --- of gingival margin
5. No migration of ---
6. Alveolar bone is
7. Reversible?
Edema
GCF flow
stippling
Erythema
JE attachment
normal-no bone loss
Yes
78
Host Defenses
1. Inhibit Dramatic Plaque Growth thus it
2. Prevents infection becoming dramatically
worse, but a
3. Stand-off exists, since plaque unable to
be eliminated and there is a
4. Shift to a B-Cell/Plasma Cell lesion
79
The Established Lesion
(4)
1. Acute inflammation persists
2. PMN “wall”: host tries to contain the infection
3. Bystander Damage
4. Two-edged “sword” of immune system
80
The Established Lesion
1. Acute inflammation persists
(2)
-After 2-3 weeks early lesion shifts to
established lesion (a stable lesion)
-Chronic inflammation dominates
* Activated B-lymphocytes → Plasma cells**
81
The Established Lesion
2. PMN “wall”: host tries to contain the infection
(3)
-Micro-ulcerations of pocket epithelium
-More proliferation of JE
-More elongation of epithelial rete pegs into
connective tissue
82
The Established Lesion-Disease
Activity
1. Two processes
2. Shift to activated B-cell►
3. Highly ---
4. Immature ---
– Damage
* Bacterial
* Immunological
– Repair
plasma cell
lesion
vascular
connective tissue
83
Effect on the Ground Substance
1. Bacterial Enzymes produce:
(2)
a. Proteases
b. Hyaluronidase
84
2. Fibroblasts, Macrophages, PMN’s
produce:
(2)
a. Gelatinase
b. Stromelysin
85
Loss of Collagen
1. Decreased rate of ---
2. Increased rate of ---
synthesis
breakdown
86
Connective Tissue Repair
1. Attempts to minimize ---
2. Fibroblasts are ---
3. Recruitment of ---
4. --- ”The shut-off mechanism”
tissue damage
cytokine-regulated
new cells
Tissue Inhibitors of Metalloproteinases (TIMP)
87
2. Fibroblasts are cytokine-regulated
(1)
* Synthesis of extracellular matrix
88
3. Recruitment of new cells
(2)
* Cytokine regulated (TGF-beta, PDGF)
* Chemotactic collagen and elastin fragments
89
Histopathology of the established lesion
(9)
1. Cellular damage of fibroblasts, epithelium
2. Collagen loss increases
3. Micro-ulcerations of pocket epithelium
4. Persistence of acute inflammation
5. Marked numbers of PMN’s in pocket
6. Degradation of extracellular matrix
7. Dense T-cell, B-cell, Plasma cell infiltrate
8. JE proliferation and extension into CT
9. Elongation of rete peg ridges
90
The Established Lesion
* Clinical Features
(5)
1. Edema
2. Erythema
3. Bleeding on probing (BOP)
4. Gingival changes:
* color, contour, consistency
5. No bone loss
91
The established lesion is the final stage of
“pure” gingivitis
92
This lesion can remain stable for weeks,
months, or even years until/if it
progresses to
periodontitis
93
The mechanisms that cause the change from
gingivitis to periodontitis are not well
understood:
Host factors?
* Difficult to predict which patients will develop
periodontitis –but one can identify the risks
groups (smokers, diabetics, etc.)
94
Features of periodontal breakdown
(4)
1. Pocket formation
2. Asynchronous Multiple Burst Model (?)
3. Bystander damage
4. Host balance of damage/repair is upset
95
1. Pocket formation
(3)
a. PDL destruction
b. Apical migration of JE
c. Bone resorption
96
2. Asynchronous Multiple Burst Model (?)
(2)
a. Short bursts of disease activity
b. Long periods of quiescence
97
Pocket formation results from
apical migration of JE
Loss of fiber attachment
- cementum
- PDL
Loss of bone
98
5. Alveolar bone resorption
a. Activation of ---
b.--- produced (active site)
c. --- enzymes released
d. --- released
e. --- produced
f. --- produced (inflammatory
mediators and involved in allergic reactions)
osteoclasts
Ruffled border
Hydrolytic
Cytokines )* IL-1, IL-11, TNF
Prostaglandins * PGE 2
Leukotrienes
99
Advanced lesion:
Mechanisms of bone
loss
Microbial factors:
Activates inflammatory cells
to release (2)
Activates PMNs to release ---
Activates Osteoclasts to
release --- for
bone (MMP-13)
--- loss
LPS
IL-1 and PGE2
Collagenase (MMP-8)
Collagenase
Collagen
100
Histopathology of the Advanced
Lesion
1. PMNs
2. --- cells dominate
3. Inflammatory infiltrate
4. Extension of lesion into PDL and bone
5. Loss of collagen continues
6. Cytopathologically altered plasma cells
7. Progressive---
8. Quiescence & exacerbation
B-cells, plasma
pocket formation
– Attachment loss
101
Clinical Features of Advanced
Lesion
1. --- formation
2. Pocket epithelium ---
3. Radiographic ...
4. Bleeding on ---
5. Changes in gingival (3)
6. Attachment Loss
7. Mobility
Periodontal pocket
ulceration
bone loss
– 50% of volume/density needs to be lost before
detection on radiograph
probing
color, contour, consistency
102
Immune cells Overview
* Initial lesion
(2)
– PMNs, macrophages
103
* Early lesion
(3)
– PMNs, macrophages, T-lymphocytes
104
* Established lesion
(5)
– PMNs, macrophages, T-lymphocytes, B-lymphocytes,
plasma cells
105
* Advanced lesion
(5)
– PMNs, macrophages, T-lymphocytes, B-lymphocytes,
plasma cells
106
Treatment
* Gingivitis
– Reversible
* Method
– Suppression of microflora for plaque-induced
gingivitis
* Scaling
* Polishing
* Patient’s daily removal of plaque
107
Treatment
* Periodontitis
– Irreversible
– There is no cure for periodontitis, only control
* Method
– Suppression of microflora
* Scaling and root planing
– (SRP + Antibiotics (?))
– Reeval
* Surgery
* Maintenance
– Modulation of host
* Low Dose Doxycycline- collagenase inhibitor
108
Is plaque necessary to initiate
gingivitis and/or periodontitis?
yes
109
Does everybody that has poor
plaque control eventually develop
gingivitis?
yes
110
Does everybody that has
gingivitis because of poor long-
term plaque control eventually
develop periodontitis?
no
111
--- is the primary etiology
for both gingivitis and periodontitis
Plaque
No plaque (bacteria) =No disease!
112
Plaque is necessary and sufficient
to initiate ---
gingivitis
113
Plaque is necessary but not
sufficient to initiate ---
periodontitis
114
Old concept = everybody develops gingivitis
and eventually will progress to periodontitis
New concept =
everybody develops
gingivitis but only
susceptible patients will develop
periodontitis
115
Definition of primary etiology
Primary etiology of periodontal
disease is bacterial plaque
in a susceptible host
Plaque Dysbiosis
116
Therefore, patient’s --- is
extremely important in the pathogenesis
of periodontal disease
immunology
117
Immune system = provides a --- process but
also may account for most of the tissue injury observed
in
defensive
gingivitis and periodontitis
