Histopathology of the lesions in periodontitis

• What is the host bacterial interaction theory?

  MOs cause periodontitis but clinical expression disease aka. the extent and severity depends on how the host responds to the the extent and virulence of the microbial burden
• Host response involves both innate and adaptive immunity
• Innate immune responses are rapid 0-4 hrs and non-specific
• Adaptive immune response is delayed (72 hrs) and specific
• Innate immune response dose?

  Complement activation

  white cell degranulation:

  • mast cells
  • Eosionphils
  • Basophils

  white cell phagocytosis:

  • macrophages
  • Neutrophils
  • dendritic cells

  Activation of adaptive immune response via antigen presentation :

  • dendritic cells
  • Macrophages
• What triggers the adaptive immune response ?

  antigens which can be endogenous or exogenous

  Exogenous = bacteria, toxins, parasite IN the tissues

  Endogenous = produced by bacteria or virus within a host cells
• complement activation?

  1. inactive precursor proteins circulating in blood
  2. Bacteria cell surface endotoxin / polysacc trigger enzyme cascade of sequential reactions
  3. form an active membrane attack complex on bacterial surface = lysis
  4. Attraction of macrophages, neutrophils and activation of mast cells
• Adaptive immune response requires what to be activated?

  antigen presentation to lymphocytes
• Lymphocytes numbers in the body?

  • 2 trillions in the body
  • 2% circulate in peripheral blood
  • 98% in tissues and lymph system
• What are T lymphocytes maintained and matured?

  secondary lymphoid tissue:

  • lymph nodes
  • spleen
• Where are lymphocytes generated?

  primary lymphoid tissue:

  • Thymus
  • Bone marrow
• Examples of lymphocytes?

  T and B cells
• T cells in the adaptive immune response?

  Either T helper or T cytotoxic
• T helper cell in adaptive immunity ?

  • CD4+
  • Type 1 and Type 2

  Produce: cytokines - interleukins and interferons
• T cytotoxic cell in adaptive response?

  • CD8+

  Produce: cytotoxins which includes:

  • cytolytic proteins
  • serine proteases
  • Cytolitic proinflammatory molecules
• What are the two types of T helper cells?

  CD4 + type 1 = TH1

  • CMI
  • tiggers effector cells (macrophages and CD8+)
  • Kills endogenous antigen in infected host cell

  CD4+ Type 2 = TH2

  • cytokine production
  • Triggers effector cells ( B cells, basophils, mast cells, eosionophils)
  • B cells create plasma cells and then antibodies against exogenous antigen
• Cytokines and prostaglandins both do what?

  amplify and perpetuate their own production
• what are Cytokines?

  1. cell signalling and regulation molecules used for intercellular communication
  2. Not stored but quickly synthesised and secreted by immune response
• What are the proinflmmatory cytokines and what do they promote?

  systemic inflammation

  IL1

  IL6

  IL8

  TNF alpha
• Cytokines can up regulate and down regulate what dose this mean?

  up regulate = increase cell activity

  Down regulate = decrease cell activity
• IL1?

  stimulates bone resporption and inhibits formation
• IL6??

  • induces bone resorption
  • stimulates T helper cells
  • Protects T helper cells from death
  • Stimulates b lymphocyte differentiation and therefore IG secretion
• IL8

  • initiates and develops inflammatory process
  • Attracts + activates neutrophils
• TNF alpha?

  • Stimulates innate immunity (acute phase reaction)adhesion molecules, bone resorption factors
  • Up-regulates production of collagenases, PGE2, cytokines, cell
  • Regulates immune cells/Mediates cell destruction
• what is a Prostaglandin ?

  physiologically active lipid compound derived from fatty acids
• What does prostaglandins PGE2 do?

  • Act on platelets, endothelium, uterine and mast cells
  • Key mediator of immunopathology in chronic infection and cancer
  • Bone resorbing inflammatory lipid
• How do prostaglandins resorb bone ?

  • enhances MMP production
  • Suppress lymphocytes products
  • Decrease collagen synthesis by fibroblasts
  • Influence osteoclast bone resorption
• MMP stands for ?

  Matrix metalloproteinases
• What is an MMP

  proteolytic zinc dependent endopeptidases
• What are MMPS produced by?


  Activated inflammatory cells

  • neutrophils
  • macrophages

  Wound cells

  • epithelial
  • fibroblast
  • vascular endothelial cells
• What do MMPS do?

  • degrade extracellular matrix proteins
  • Regulate cell proliferation, differentiation and migration
  • Modulate inflammatory and immune response
• Initial lesion - 2-4 days of plaque accumulation?

  1. Vasculitis of the vessels subjacent to the JE 2. Exudation of fluid into the gingival crevice3. Chemotaxis of polymorphonuclear leucocytes4. Increased migration of leucocytes through theJE into the crevice5. Presence of fibrin and serum proteins extravascularly6. Loss of perivascular collagen
• Clinical features of the initial lesion?

  appears healthy and normal
• The early lesion - 7-14 days:

  1. Accentuation of features at initial lesion (dilated capillaries, intercellular oedema)
  2. Seeding of T lymphocytes
  3. Accumulation of lymphocytes at the site of acute inflammation
  4. Cytopathic changes in fibroblasts
  5. Further loss of collagen fibre network
  6. 6. Early proliferation of basal cells of JE
• Clinical features of the early lesion ?

  • erythema
  • oedema
  • Pitting on pressure
• Established lesion 14- 28 days:

  Gingivitis

  1. persistent acute inflam
  2. Continued loss of connective tissue
  3. B cells greater in number than T cells
  4. +++ plasma cells with extravascular IG in CT and JE
  5. PMN and macrophages = less than 5% of cells
  6. Microulcerations of JE
  7. Proliferation, apical migration and lateral extension of JE
  8. Early pocket formation may commence but no significant bone loss
• Clinical features of the established lesion ?

  • erythema
  • Oedema
  • BOP
• The advanced lesion - Periodontitis ?

  prev features of established lesion as well as:

  • extension of lesion into PDL and alveolar bone
  • Continued loss of collagen subjacent to the pocket, fibrosis at more distant sites
  • Formation of pockets with loss of alveolar bone
  • Periods of quiescence and exacerbation
  • Hypersensitivity reactions type 3 and 4 and maybe 2 and 1
  • Widespread manifestations of inflammatory and immunopathologic tissue reactions
• Hypersensitivity reactions in advanced lesions (periodontitis)

  3 = Ag/Ab complexes

  4 = T lymphocytes and cytokines

  Maybe:

  1= Ag/membrane bound IgE

  2 = Ab/ cell bound Ag lysis
• Clinical features of the advanced lesion?

  • pocket formation
  • loss of attachment
  • abscess formation
  • pus exudate
  • bone loss