Pathogenesis Flashcards
Describe 4 host defence mechanisms
- Saliva (general feature)
- Epithelial barrier (general feature)
- Inflammatory response
- Immune response
Describe 2 purposes of inflammation
- Isolate, neutralise and remove cause
2. Initiate healing and repair
Describe the role of inflammatory response in periodontal disease
Periodontal pathogens release LPS and virulence factors leading to inflammatory response
Describe what occurs when the bacterial challenge outweighs the immune response
- Bacterial insult overwhelms inflammatory response
- Dysbioitic biofilm forms from periodontal pathogens
- State of chronic inflammation occurs
- Tissue destruction due to chronic inflammation
Describe the inflammatory response of the body
- Rapid
- Non-specific
- Soluble effectors and cellular component
- Cytokines important in the regulation
- Degree of bystander damage is likely
Name the stages of the initial inflammatory response
- Fluid exudate
- Soluble effectors from plasma
- Complement system
- Cellular exudate
Describe how fluid exudate occurs
- Dilatation of blood vessels
- Increased vascular permeability
- Fluid exudate dilutes causative agent and carries plasma protein
Describ 2 soluble effectors from plasma
Complement System - Group of 20 proteins which have key roles in mediating inflammation
Kinin System - Peptides of 9-11 amino acids e.g bradykinin
Name 2 components exudate
- Neutrophils (PMNs)
2. Macrophages
What does PMNs stand for?
Polymorphonuclear Leucocytes
Describe the production, lifespan and function of PMNs
- Produced in bone marrow
- Lifespan of 2-3 days
- Phagocytose foreign agents
- Cytokine release
Describe how neutrophils move from the blood stream to have an effect on inflammation
- Vasodilatation facilitates this
- LFA-1 receptor on neutrophil and ICAM-1 on endothelium bind
- This stops the neutrophil from moving through lumen
- Allows neutrophil to squeeze between endothelial cells
What does LAD-1 stand for?
Leucocyte adhesion deficiency
Describe LAD-1
- Rare genetic disorder
- Lack of CD-18 expression on PMNs, required for adhering to endothelial cell wall
- Recurrent RTIs, mucosal infections and aggressive periodontitis
What is cyclic neutropenia?
Neutrophil numbers drop cyclically which can lead to serious furcation in deciduous teeth
Describe the production, lifespan and function of macrophages
- Derived from blood monocytes
- Lifespan of 2-3 months
- Phagocytosis
- Antigen processing and presentation
- Cytokine and prostaglandin release
Name 3 examples of cytokines
- interleukins
- Tumour necrosis factor alpha
- Prostaglandins
What is the function of cytokines?
Cell-cell communication in a paracrine / autocrine fashion
What is the difference between autocrine and paracrine function?
Autocrine affects the same cells where paracrine is communication with other cells in the same area
What is the general function of interleukins?
Family of cytokines which regulate the inflammatory and immune responses
Name 4 sources for IL-1
- Macrophages
- Epithelial cells
- Fibroblasts
- PMNs
Name 3 effects of IL-1
- Activates neutrophils and macrophages
- Activates B and T lymphocytes
- Induces cytokine release
Name 2 ways IL-1 can cause bystander damage
- Induce matrix metalloproteinase (MMP) release
2. Induces osteoclast activation and bone resorption
Describe MMPs
- Family of proteases with zinc ion in active centre
- Capable of degrading ECM molecules
- Secreted as inactive pro-MMP
- Inhibited by TIMP (tissue inhibitor of Metalloproteinases)
Describe the production and function of IL-6
- Produced by lymphocytes, monocytes and fibroblasts
- Stimulates plasma cell proliferation
- Stimulation osteoclast activation
- Higher levels in GCF from periodontitis site
What is the function of IL-8?
- Chemoattractant for neutrophils
- Higher levels in GCF from periodontitis sites
- Stimulates MMP expression
What is the function of prostaglandins?
- Proinflammatory mediators
- Induce bone resorption via the RANK ligand signalling pathway
What does RANK ligand stand for?
Receptor Activator of Nuclear factor Kappa B ligand
Describe the relationship of RANK ligand and osteoprotegerin (OPG) and bone resorption
- RANKL is a member of TNF superfamily
- Expressed on surface of osteoblasts and binds to RANK receptor on osteoclast precursor cells, stimulating osteoclast activation
- RANKL inhibited by OPG
- Osteoclastogenic molecules stimulate expression of RANKL while inhibiting OPG
Describe active immunity
- Memory cells produced and highly specific
- Soluble effectors and cellular components
- Cytokines important in regulation
- Bystander damage less likely
What is the soluble effector of the adaptive immune response?
Antibody
Name 4 cellular components of the adaptive immune response
- T lymphocytes
- B lymphocytes
- Plasma cells
- Macrophages
Describe humoral immunity
- Protection against extracellular infectious agents
- Production of antibodies by B-cells under influence of activated T-helper cells
Describe cell-mediated immunity
- Protection against intracellular infectious agents
- Mainly through release of toxic agents by cytotoxic T-cells, stimulated by IFN gamma, produced by activated T-helper cells
Describe the initiation of the humoral immune response in periodontal tissues
- Bacterial antigen
- Macrophage
- Local lymph node
- Presented to B-lymphocyte
- Plasma cell created
- Secretes antibody
- Antibody reaches gingival tissues via circulation
- Interacts with specific antigen
Name 4 biological activities of IgM (pentamer)
- Toxic neutralisation
- Agglutination
- Opsonisation
- Activates complement IgM and IgG
Name 3 biological activities of IgA
- Major Ig in secretions
- Surfaces protection
- Toxin neutralisation
Name a biological activity of IgE
Histamine release from mast cells
Name a biological activity of IgD
Receptor on B-cells
What is the function of T-helper cells?
Required for maturation of B cells and activation of phagocytes
What is the function of T-suppressor cells?
Inhibit immune response
What is the function of T-killer cells?
Cytotoxic
Describe the antibacterial effects of saliva
- Inhibition of attachment of bacteria (sIgA)
- Killing bacteria by peroxidase system
- Killing bacteria by lysozyme and histatins
Name 3 causes of xerostomia
- Drug induced (antihypertensives and antidepressants)
- Head and neck radiation
- Salivary disease
Describe the epithelial barrier
- Barrier against invading microbes
- Release of pro-inflammatory cytokines
- Produces antimicrobial peptides
- Bacterial proteases from P.gingivalis break down barrier function
Describe the early lesion at the junctional epithelium
- Increased PMN migration
- Macrophage and lymphocytic infiltrate
- Localised collagen degradation
- Localised fibroblast degeneration
- Clinically normal
Describe the established lesion (gingivitis) at the junctional epithelium
- PMNs walling off plaque
- Increased lymphocytic infiltrate
- 60-70% collagen destruction
- Lateral proliferation of JE with micro-ulceration
- Gingival redness and swelling
Describe periodontitis at the junctional epithelium
- Apical migration of JE
- Loss of periodontal ligament attachment
- Loss of alveolar bone
- Micro-ulceration of JE
- True pocket formation
What is the most commonly accepted theory of the progression of periodontal disease?
Burst hypothesis
- Relatively short period of time patient will lose some attachment
- Attachment loss is slow following this before another burst
- Loss does not occur at same rate constantly for years
