Pathogenesis of Periodontal Disease Flashcards
What is the first bacteria to colonise the tooth surface?
Streptococci- gram positive bacteria
How long does it take for gram negative bacteria to be present in the plaque biofilm subgingivally?
2 days if plaque is not removed withi 2 days
What are endotoxins?
membrane bound compounds on gram negative bacteria than elicit an immune response e.g. LPS
What are the histological stages of the immune response?
- initial lesion
- early lesion
- established lesion
- advanced lesion
When does the initial lesion develop?
2-4 days after plaquea accumulation
What is the main occurrence in the initial lesion?
vasculitis of blood cells below the JE occurs; inflammation
increased leucocyte migration to the JE
The initial lesion is clinically visible. True or false
false
The initial lesion is a ________ condition
stable
The early lesion is also known as ___________.
early gingivitis
When does the early lesion develop?
7-10 days after plaque accumulation
What bacteria dominate in the early lesion stage?
anaerobic filamentous bacteria
What bacteria dominate in the early lesion stage?
anaerobic filamentous bacteria
What are the hallmarks of the early lesion stage?
- increased fluid exudate
- increase in PMNL
- oedema and erythema visible (reddening of the skin and mucosa)
- proliferation of the basal cells at the junctional epithelium)
What is the junctional epithelium made up of?
internal basal lamina
external basal lamina
The internal basal lamina of the JE is attached to …
tooth surface
The external basal lamina of the JE is attached to …
connective tissue
What is a PMNL? What types of cells does it include?
Polymorphonuclear cells
granuloycytes- neutrophils, basophils, eosinophils
What is an erythema ?
increase blood flow which causes reddening of th skin or mucosa
The established lesion is also referred to as …
established gingivitis
When does the established lesion develop?
21-28 days
What types of cells dominate the established lesion?
T cells >B cells
increased neutrophils
What are the hallmarks of the established lesion?
- further proliferation at the junctional epithelium
- gingival crevice deepens
- continuing loss of collagen
- breakdown of connective tissue but no bone loss
What are the hallmarks of the advanced lesion?
*junctional epithelium migrates apically to form a periodontal pocket
* plaque and endotoxins are able to permeate the surface layer of the cementum
* loss of collagen and bone
What types of cells dominate the advanced lesion ?
B cells > T cells in the advanced lesion
plasma cells
Most patients will develop the advanced lesion and it is often present in all sites. True or false
false
only 10-15% of patients will develop an advanced lesion and it is not present at all sites
The development of periodontitis is dependent on what factors?
risk factors
host factors (response of the immune system)
What is a histological hallmark of the early lesion?
rete pegs formation
What are rete pegs ?
rete pegs form due to proliferation of SE and JE into collagen depleted areas
What is the common hallmarks of established and advanced lesions
- apical proliferation; conversion into pocket epithelium (pocket formation)
What are the 2 types of responses in the immune system ?
Innate response
adaptive/acquired response
What are the mechanisms of the innate immune response?
- epithelial barriers
- fluid with antibacterial factors e.g. saliva, GCF
- complement cascade
- vasoactive peptides e.g. histamine
- adhesion molecules
- neutrophils (PMNL) and macrophages
What occurs to the epithelial barriers (JE) in periodontitis/gingivitis ?
junctional epithelium becomes more permeable in disease
it becomes permeable to bacterial products, GCF and neutrophils
What is the first line defence against periodontal bacterial infection?
junctional epithelium
How is the saliva able to provide an immune response?
- washes and dilutes
- provides a medium for swallowing bacteria
- contains antibacteria factors, lysozyme- IgA, IgG
How is the GCF able to provide an immune response?
composed of serum and locally generated materials
carries components of serum such as complement proteins and immunoglobulins (IgG)
What causes oedema observed in gingivitis/periodontitis ?
increased GCF flow
What is the function of cytokine molecules?
molecule that stimulate cells to perform other functions
they can cause cells to release other molecules
cytokines and lymphokines cause cells to perform other functions
What is the function of chemokine molecules?
attract other cells to the site of infection
What cytokine is heavily implicated in bone resorption? What kind of cytokine is it?
IL-1- proinflammatory molecule
What are the effects of IL-1?
- activation of osteoclasts
- increases PMNL margination
- increases PGE2 production
- increase TNFa production
- causes bone resorption
What are the effects of IL-6?
increases bone resorption
What are the effects of IL-8?
PMNL chemotaxis
What are the effects of IL-10?
cytokine suppression
potent anti-inflammatory properties
(produced by T and B lymphocytes)
What is the effect of TGF-B?
stimulates collagen synthesis
implicated in the pathogenesis of fibrosis
What is the effect of TNF-a ?
- increased IL-1 production
- increased PGE2 production
What is the effect of PGE2 molecules?
stimulates bone resorption
What is the main vasoactive peptide of interest in periodontal disease? What cells release this vasoactive peptide ?
Histamine
mast cells and basophils
What complement proteins are responsible for the release of histamine?
C3a and C5a
What complement protein induces the release of histamine from mast cells?
C5a
What is the effect of histamine on the pathogenesis of periodontal disease?
they are vasoactive- have an effect on blood vessells
they cause vasodilation- this slows the blood flow allowing margination of PMNL
also increase permeabiluty of blood vessels
List important adhesion molecules involved in the innate immune system
- ICAM- I
- ICAM- II
- ELAM-I
- LFA-I
The expression of adhesion molecules on vasculature is controlled by …
cytokines
Leukocyte extravasation is mediated by …
signalling molecules and adhesion molecules
What are the steps of leukocyte extravasation in inflammation?
- rolling- make or break contacts
- margination-stronger receptor binding
- diapedesis - squeezing through blood cells
- chemotaxis
What are the components of the PMNL?
- receptor - pathogen recognition, opsonisation
- cytoskeleton- permits movement
- lysosomes- contain lysozymes to destroy bacterial structures
- oxygen radicals- superoxides to destroy bacterial structures
What is opsonisation?
use of opsonins to tag foreign pathogens for elimination by phagocytes (PMNL, macrophages)
Give examples of opsonins
IgG, C3b
Briefly describe the intracellular killing of bacteria in PMNL cells
- PMNL phagocytes bacteria
- internal degranulation of PMNL
- digestion of microbe
- expels remnants of microbe
- PMNLthe undergoes apoptosis
- host cell damage may occur
What method of killing bacteria increases the risk of collateral damage?
extracellular killing of bacteria
Macrophages developed from …
circulating monocytes in the blood
What is the role of macrophages in inflammation?
- phagocytosis
- secrete tissue degrading enzymes
- secrete compement components
- secrete mediators - IL-1, TNFa, prostaglandins
What is the role of macrophages in immunity?
- process and present antigens (B and T cells)
- secrete IL-1
Macrophages have a dual- role, what is their other function?
Aside from phagocytosis
they are antigen presenting cells
What do macrophages contain that allows recognition between host and foreign tissue? Where else are they present?
MHC-II
also found on other APCs, dendritic cells and B cells
When is the complement cascade activated?
inflammatory response
What form do complement proteins circulate in?
inactive form
What is the main role of complement activation?
- recruit phagocytes
- aid phagocytosis- opsonisation
- kill bacteria by forming a membrane attack complex (MAC)
What are the 2 complement pathways?
Classical and alternative
What do both complement pathways lead to?
activation of C3 (C3a, C3b)
What is the larger cleaved molecule of activated C3 protein? What is the function of this protein?
C3b
opsonisation
What is the function of the C3a molecule?
activation of C5
What is the effect of the C3a molecule?
chemotaxis of phagocytes
What is the effect of the C3b molecule?
cytokine production
secreted from macrophages
opsonisation
What is the effect of the C5a molecule?
- leucocytes stick to vessel walls
- neutrophils release enzyme amd O2 radicals
What is the effect of the C3a and C5a molecule?
increased vascular permeability due to histamine release from mast cells
What is the effect of the C3b and C5a molecule?
production of oxygen radicals
What is the effect of the C5a and C567 complex?
leucocyte chemotaxis
What is the effect of C5b, C6, C7, C8 and C9?
bacterial cell lysis
MAC
What cells are involved in the acquired immune response?
T and B lymphocytes
What are the classes of immunoglobulin?
IgM
IgG
IgA
IgE
IgD
What are the most important immunoglobulins periodontal disease and where are they found?
IgG- GCF; originates from blood plasma
IgA- exists as a dimer; from the saliva
What lymphocytes cells are present in the initial and early lesions?
T lymphocytes
Briefly outline the role of T lymphocytes in the pathogenesis of periodontal disease (activation of T lymphocytes)
- antigen presented to T cells by APC
- undifferentiated T cells express IL-2 receptor and bind to the IL-2 produced by the T-helper cells
- undifferentiated T cells differentiate into effector T cells as a result of IL-2 binding
- cytotoxic T cells reach tissue and lyse bacteria
- memory T cells remain in lymph tissue
How are B lymphocyes are activated?
- Th2 cells necessary for anti-body production in B cells
- endotoxin causes activation of independent T cells
- native/independent T cells release IL-2 and causes proliferation of B cells which head to the tissue
- this causes tissue enlargement and production of immunoglobulins
- foreign antigens bind to B cells via Ig receptors
Where does the antibody-antigen complex bind on PMNL cells?
the Fc receptors on PMNL
What are the features of the innate immune response?
- constantly in function
- rapid response
- usually involved in gingival inflammation
- T cells> B cells
What are the features of the adaptive immune response?
- specific cell-cell interactions
- slower response
- ususally in advanced gingivitis and periodontitis
- B cells >T cells
What stage of periodontal disease is the adaptive immune response involved in?
advanced gingivitis
periodontits
What stage of periodontal disease is the innate immune response involved in?
early gingival inflammation
What are the bacterial factors of periodontitis?
- increased numbers
- specific pathogens
- direct tissue
- invasion
What are the host factors of periodontitis?
- reduced effectiveness of host defences
- increased damage in response to microbial changes
What is the most important aspect of treatment of periodontitis?
mechanical removal of causative bacteria
