Week 3 Immunology Lecture Flashcards
describe gingivitis
- plaque induced
- inflammation (edema/BOP)
- no destruction of PDL and bone
- no apical migration of epithelial attachment
what epithelium is involved with epithelial attachment
junctional epithelium
describe periodontitis
- plaque induced
- inflammation (edema/BOP)
- destruction of bone
- apical migration of epithelial attachment
- not all cases of gingivitis progress to periodontitis
periodontitis is:
-plaque induced
- host related - susceptible host
- each site is individualized or a specific environment
- a % of affected population experiences severe destruction
what are the models of disease progression
- continuous model (1900s-1950s)
- progressive model (1940s-1960s)
- random burst model (1980s-2000s)
- asynchronous multiple burst model (1980s-2000s)
describe the continuous model
continuous throughout life at same rate of loss
- everyone gets perio disease
describe the progressive model
- progressive loss over time of some sites
- no destruction in others
- time of onset and extent vary among sites
- periodontal disease affects mainly posterior teeth
describe the random burst model (1980s-2000s)
- 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
- periodontitis is different in various sites in the same individual and it is difficult to predict attachment loss
desribe the asynchronous multiple burst model
- several sites have one or more bursts of activity during one period of life
- prolonged period of inactivity; remission
- cumulative extent of destruction varies among sites
- some sites dont develop attachment loss
- bursts due to risk factors
what are the signs of inflammation
- rubor (redness)
- calor (heat)
-dolor (pain) - tumor (swelling)
- functio laesa (loss of function)
inflammation is a ______ phenomenon
vascular
what happens in inflammation:
-vasculitis
- leukocyte migration
what happens in vasculitis
- dilation
- venous stasis (congestion)
- increased permeability
- transudate
- exudate
what is the 1st defense in immunity
- innate
- non-adaptive, genetic
- kills by phagocytosis
- PMNs
- monocytes/macrophages
what is the 2nd defense in immunity
- adaptive
- production of immunoglobulins by antibodies
- highly specific
- B and T cells involved
- plasma cells produce specific antibodies to individual antigens
describe B lymphocytes
- activated B cells become plasma cells
- plasma cells produce immunoglobulins
describe T lymphocytes
- developed in the thymus
- several functions - antigen presentation
- help B cells divide; can destroy virally infected cells; can down regulate immune response
what are the 2 major forms of T cells
CD4 and CD8
describe the CD4 cell and what is recognizes
- recognizes MHC Class II molecules
- T helper cells - TH0, TH1, TH2
- help B cells divide
- control leukocyte development
- activate innate cell lining
describe the CD8 cell and what it recognizes
- recognizes MHC Class I molecules
- T cytotoxic
- destroy virally infected target cells
what do PMNs do
- phagocytosis
- produce lysosomal enzymes
what do macrophages do
- phagocytosis
- process antigens
- cytokine secretion
what is another name for B lymphocytes and what do they do
- plasma cells
- produce antibodies
what are the types of T lymphocytes and what do each do
- T-helper (CD4): helps B cells divide
- T-suppressor (CD8 and CD25): down regulates T and B cells
- NK cell (natural killer cell and CD56): kills virally infected cells
- T-cytotoxic cell (CD8): destroys infected cells
- K (killer T cell and CD28): kills infected cells
what are the components of humoral immunity
- antibodies
- complement
describe IgM
- first responder
- largest in size
describe IgG
- second responder
- most abundant
- crosses placenta
describe IgA
-salivary IgA
- a dimer
describe IgD
- co-expressed with IgM
describe IgE
- on mast cells
- allergic reactions
what immune system is the complement system a part of
innate and adaptive
what is the complement system and what does it do
a biochemical cascade that helps clear pathogens by lysis, opsonization, binding, clearance of immune complexes
what does the Fab region of immunoglobulins do
specific antigen binding
what is the Fc portion of the immunoglobulin
constant portion
what are t-suppressor cells
- now t-regulatory cells
- down- regulate T and B cells
- CD8 and CD25
- prevent autoimmune disease
what are K (killer) cells
- mononuclear cells that kill cells sensitized with antibody via Fc receptors
- CD28 cells which were signaled by CD8 cells
what are NK (natural killer cells)
- kill virally infected and transformed target cells that have not been previously sensitized
- CD56 cells
what percentage do monocytes make up and what do they do
- 5%
- activation in CT
- will become macrophages
what percentage do neutrophils make up and what do they do
- greater than 70%
- 48 hours lifespan in blood with migration to sites for phagocytosis
what percentage do eosinophils make up and what do they do
- 2-5%
- cause damage by exocytosis
- histamine release
what do mast cells do
contain mediators of inflammation such as histamine, prostaglandins, leukotrienes and cytokines
- involved in allergic reactions
what percentage do basophils make up and what do they do
- less than 0.5%
- functionally similar to mast cells
what are cytokines
- soluble, locally active polypeptides
- regulate cell growth, differentiation, function
- produced by cells of the immune system
specific cytokines may have differnet biologic properties dependent on:
- their concentration
- the cells that produce them
- the cells being attracted and acted upon
- presence and extent of ECM
what does IL-1 do
-pro-inflammatory
- stimulates osteoclasts, fibroblasts, and macrophages
what does IL-6 do
pro-inflammatory
- stimulates T and B cells
what does IL-8 do
pro-inflammatory
- attracts and activates PMNs
what does TNF do
- pro-inflammatory
- activates osteoclasts
what does PGE2 do
- vasodilation
- pyrogenic
- releases mediator from mast cells
- cell-mediated cytotoxicity
what does TGF do
stimulates epithelial cells and fibroblasts
what does PDGF do
stimulates fibroblasts
what does EGF do
stimulates epithelial cells
what does FGF do
stimulates fibroblasts
what are risk factors for perio
- smoking
- HIV and DM
patients with risk factors are more likely to have:
attachment loss
what are the criteria for clinically healthy gingiva
- some neutrophils and macrophages are present in CT
- a few neutrophils are migrating through the JE
- no collagen destruction
- intact epithelial barrier
- gingival crevicular fluid is present
- appears clinically healthy in color, contour and consistency
what are the mechanical inflamatory response modifiers that are plaque retention factors
-calculus
- caries
- restorations: defective margins, subgignival margins, overcontoured margins
- prosthesis
- tooth anatomical factors such as palatogingival grooves and furcations
what are the systemic inflammatory response modifiers
- uncontrolled/controlled diabetes
- PMN defects
- hematological
- hormonal: pubery and pregnancy
- immune disturbances
- HIV/AIDS
- medications
- nutrition deficiencies
what are the genetic inflammatory response modifiers
- Leukocyte adhesion deficiency
- hypophosphatasia
- agranulocytosis
- neutropenia
- lazy leukocyte
- downs syndrome
- paipillon- lefevre
- chediak-higashi
- ehlers danlos
describe the inital lesion
- develops in 2-4 days
- cells of acute inflammation present
- increased GCF flow
- start of pseudopocket formation
what are the cells of acute infalmmation
PMNs
what are the cells of chronic inflammation
lymphocytes
what are the cells that appear when chronicity increases
plasma cells
what are the 2 types of virulence factors
- stimulation of the host defense systems
- degradation of the host tissues
describe the types of virulence factors that stimulate the host defense system
- stimulates cells to release cytokines and chemoattractant factors such as IL-8
- attracts inflammatory cells
what are the enzymes that are virulence factors that degrade the host tissues
- collagenase
- trypsin like enzymes
- keratinase
- phospholipase A
what is released in the bacterial to host interaction
- increased release of IL-1
- increased release of IL-6
- increased release of IL-8
- increased release of TNF
- increased release of PGE
what is the mechanism of action in poor plaque control
- bacterial byproducts are released into perio tissues called 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 CT
- PMNs are attracted to and near JE and sulcular epithelium
what is the mechanism of action in plaque accumulation
- virulence factors are relased into perio tissues
- stimulation of inflammatory celsl to release cytokines into the CT
- PMNs are attracted near and to the JE and sulcular epithelium
what are the clinical features of the initial lesion
- increased GCF flow
- sulcus increases from 0->3 mm by formation of a pseudopocket
- alveolar bone is normal on the radiograph
what slows the PMNs in diapedesis and cause them to roll
selectins
what do cytokines activate on endothelial cells for PMN attachment in diapedesis
ICAM receptors
describe the early lesion
- 4-7 days
- acute inflammation persists -> 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
how is collagen lost
- microbial factors: LPS and antigens
- stimulate release of cytokines
- activation and release of MMPs
- a combination of bacterial products and host’s defense system
what are MMPs
a family that includes 28 metal dependent endopeptidases (proteases) with activity against most if not all ECM macromolecules used for normal tissue remodeling
what are the subclasses of MMPs
- interstitial collagenases
- stromelysins
- membrane type
- gelatinases
- secreted RXKR
- metalloelastase
in the early lesion collagen lost is up to:
70%
what is the early lesion histopathology
- collagen loss
- PMNs accumulation in gingiva and sulcus
- cells of chronic inflammation accumulate and predominate : t-cell lesion
- fibroblasts show cell damage
- rete pegs proliferation of JE into CT
- no bone loss
what are the clinical features of the early lesion
- edema of gingiva
- increased GCF flow
- loss of gingival stippling
- erythema of gingival margin
- no migration of JE attachment
- alveolar bone is normal- no bone loss
- reversible
what are the host defenses in the established lesion
- inhibit dramatic plaque growth thus it
- prevents infection becoming dramatically worse
- stand off exists, since plaque unable to be eliminated and there is a
- shift to a B-cell/plasma cell lesion
describe the established lesion
- acute inflammation persists
- PMN wall: host tries to contain the infection
- bystander damage
- two- edged sword of immune system
how long does acute inflammation persist in the established lesion
2-3 weeks early lesion shifts to established lesion - a stable lesion
describe the PMN wall in the established lesion
- micro ulcerations of pocket epithelium
- more proliferation of JE
- more elongation of epithelial rete pegs into CT
describe the established lesion disease activity
- two processes: damage and repair
- shift to activated B cell-plasma cell lesion
- highly vascular
- immature CT
what are the types of damage done in the established lesion disease activity
bacterial and immunological
what are the effects on ground substance in established lesion
- bacterial enzymes produce proteases and hyaluronidase
- fibroblasts, macrophages, PMNs produce gelatinase, stromelysin
what are the mechanisms that cause the loss of collagen in the established lesion
- decreased rate of synthesis
- increased rate of breakdown
describe connective tissue repair in the established lesion
- attempt to minimize tissue damage
- fibroblasts are cytokine-regulated and synthesize ECM
- recruitment of new cells- cytokine regulated, chemotactic collagen and elastin fragments
- tissue inhibitors of metalloproteases- the shut off mechanissm
is there bone loss in the established lesion
no
what is the histopathology of the established lesion
- cellular damage of fibroblasts, epithelium
- collagen loss increases
- micro ulcerations of pocket epithelium
- persistance of acute inflammation
- marked numbers of PMNs in pocket
- degradation of ECM
- dense T-cell, B-cell and plasma cell infiltrate
- JE proliferation and extension into CT
- elongation of rete peg ridges
what are the clinical features of the established lesion
- edema
- erythema
- BOP
- gingival changes: color, contour, consistency
- no bone loss
the _____ is the final stage of “pure” gingivitis
established lesion
the established lesion can remain stable for:
weeks, months or even years before it progresses to periodontitis
what are the features of periodontal breakdown in the advanced lesion
- pocket formation
- asynchronour multiple burst model
- bystander damage
- host balance of damage/repair is upset
what is happening in pocket formation in the advanced lesion
- PDL destruction
- apical migration of JE
- bone resorption
what is the periodontitis definition
- pocket formation results from apical migration of JE
- loss of fiber attachment - cementum and PDL
- loss of bone
what is happening in alveolar bone resorption in the advanced lesion
- activation of osteoclasts
- ruffled border produced- active site
- hydrolytic enzymes released
- cytokines released
- prostaglandins produced
- leukotrienes produced
what are leukotrienes
inflammatory mediators and involved in allergic reactions
what is the mechanism of bone loss in advanced lesion
- microbial factors:LPS
- activates inflammatory cells to release IL-1 and PGE2
- activates PMNs to release collagenase (MMP-8)
- collagen loss
- activates osteoclasts to release collagenase for bone (MMP-13)
what is the histopathology of the advanced lesion
- PMNs
- B cells, plasma cells dominate
- inflammatory infiltrate
- extension of lesion into PDL and bone
- loss of collagen continues
- cytopathologically altered plasma cells
- progressive pocket formation- attachment loss
- quiescence and exacerbation
what are the clinical features of advanced lesion
- periodontal pocket formation
- pocket epithelium ulceration
- radiographic bone loss
- BOP
- changes in gingival color, contour, and consistency
- attachment loss
- mobility
what percentage of volume/density of bone needs to be lost before detection on radiograph
50%
what are the immune cells in the initial lesion
PMNs and macrophages
what are the immune cells in the early lesion
- PMNs
- macrophages
- T-lymphocytes
what are the immune cells in the established lesion
- PMNs
- macrophages
- T-lymphocytes
- B-lymphocytes
- plasma cells
what are the immune cells in the advanced lesion
- PMNs
- macrophages
- T-lymphocytes
- B-lymphocytes
- plasma cells
what is the tx for gingivitis
reversible
- suppression of microflora for plaque-induced gingivitis through scaling, polishing and patients daily removal of plaque
what is the tx for periodontitis
- irreversible
- suppression of microflora through SRP, surgery and maintenance
- modulation of host with low dose doxycyline- collagenase inhibitor
what is necessary and sufficient to intitiate gingivitis
plaque
is plaque necessary and sufficient to initiate peridontitis
necessary but not sufficient
primary etiology of periodontal disease is:
bacterial plaque in a susceptible host
immune system provides a defensive process but also may account for most of _______ observed in gingivitis and periodontitis
tissue injury
