Histopathology of the periodontal lesion

• What is the host bacterial interaction theory?

  • Micro-organisms cause periodontitis
  • Clinical expression of disease (extent/severity) depends on how host responds to the extent and virulence of the microbial burden
• How is the host/bacterial interaction shown as a diagram?

  
• The immune response is divided into which two sections?

  • Innate immediate 0-4 hrs non - specific
  • Adaptive delayed more than 72 hrs specific

  
• The innate immune response is the immediate defence against microorganisms, it is non specific

  True of False?

  • True!
  • Non Specific
  • Complement activation
  • Inactive precursor proteins circulating in blood
  • Bacterial cell surface endotoxin/polysaccharides trigger enzyme cascade of sequential reactions in these proteins
  • Form an active 'membrane attack complex' on the bacterial surface causing lysis
  • Attract macrophages and neutrophils, activates mast cells
• What cells are involved in the innate immune response (non specific)?

  White cell degranulation(release molecules)- Mast cells, Eosinophils, Basophils

  White cell phagocytosis- Macrophages, Neutrophils, Dendritic cells

  Activation of adaptive immune response(antigen presentation)- Dendritic cells- Macrophage

  
• What does the adaptive immune response require?

  Requires Antigen presentation to Lymphocytes
• What are Lymphocytes?

  • (T & B Cells)
  • generated in primary lymphoid tissue (thymus & bone marrow)
  • Maintained/matured in secondary lymphoid tissue (lymph nodes/spleen)
  • 2 Trillion lymphocytes in body- 2% circulating in peripheral blood- 98% in tissues & lymphatic system

  
• What are the two types of antigen?

  Antigens trigger an immune response!

  Exogenous antigens

  - Bacteria, toxins, parasites in the tissues

  Endogenous antigens

  -Produced by bacteria or virus within a host cell
• What are the types of T cells which contribute to the adaptive immune response?

  • t helper cells
  • CD4+
  • Type 1 and type 2

  these form cytokines, interferon and interleukins

  • t cytotoxic cells
  • CD8+

  form cytotoxins, cytolytic proteins, serine proteases, cytolytic proinflammatory molecules

  
• What are the 2 types of T Helper (CD4+) Cells?

  • type 1: CELL MEDIATED - macrophages, CD8+ cells, to kill endogenous antigens in infected host cell
  • type 2: HUMORAL - B cells, mast cells, basophils, eosinphils to become plasma cells producing antibodies against exogenous antigens

  
• What is cell mediated immunity?

  • immune response
  • does not involve antibodies
  • involves activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and release of various cytokines in response to antigen.

  
• What is humoral immunity?

  antibody-mediated immunity

  
• Cytokines and Prostaglandins can amplify and perpetuate their own production...

  
  

  True or False?

  True!

  
• What are Cytokines?

  • Chemical messengers produce response to stimulus
  • Cell signaling/regulating molecules used for intercellular communication
  • not stored
  • rapidly synthesised/secreted by the immune response

  
• What are the pro- inflammatory cytokines which promote systematic inflammation?

  Interleukin (IL-1, IL-6, IL-8), TNFα

  
• What are Prostaglandins?

  • local hormones
  • active lipid compounds from fatty acids
  • Act on platelets, endothelium, uterine and mast cells
  • Key mediator in chronic infections and cancer
  • Bone resorbing inflammatory lipid:- Enhances MMP production
  • Suppresses lymphocyte production
  • Decreases collagen synthesis by fibroblasts
  • Influences osteoclast bone resorption
• What are MMPs? (Matrix Metalloproteinases)

  • proteolytic enzymes
  • perform roles in the normal immune response to infection.
  • Leucocyte recruitment
  • cytokine and chemokine processing
  • defensin activation
  • matrix remodelling

  
• What do MMPs comprise of?

  • Collagenase
  • Gelatinase
  • Stromelysin
  • MT (membrane type) MMP
• What are MMPs produced by?

  • Activated inflammatory cells (neutrophils and macrophages)
  • Wound cells (epithelial, fibroblast and vascular endothelial cells)
• MMP are enzymes which break down....

  ...peptide bonds in polypeptide or protein
• What happens in Initial Lesion (2-4 days plaque accumulation)

  1. Vasculitis of vessels subjacent to the JE

  2. Exudation of fluid into gingival crevice

  3. Chemotaxis of polymorphonuclear leucocytes

  4. Increased migration of leucocytes through JE into crevice

  5. Presence of fibrin and serum proteins extravascularly

  6. Loss of perivascular collagen
• What is the clinical appearanceof the initial lesion?

  no clinical signs - appears health

  
• What are the

  clinical featuresof theEarly Lesion?- Erythema

  - Oedema

  - Pitting on pressure

  
• What happens in an Established Lesion(14 -28 days - gingivitis)?

  1. Persistence acute inflammation

  2. Continued loss of connective tissue

  3. B cells > T cells. Plasma cells with extravascular immunoglobulins present in connective tissue and JE

  4. PMNs and macrophages comprise less than 5% of the cells.

  5. Ulceration of JE

  6. Proliferation, apical migration and lateral extension of the JE

  7. Early pocket formation but no significant bone loss
• What are clinical features of an established lesion?

  - Erythema

  - Oedema

  - Bleeding on probing

  
• What happens in an Advanced Lesion? (Periodontitis)

  1. Persistence of established lesion features

  2. Extension into alveolar bone and PDL

  3. Continued loss of collagen subjacent to the pocket with fibrosis

  4. Formation of periodontal pockets with loss of alveolar bone

  5. Periods of quiescence and exacerbation

  6. Hypersensitivity reactions Types III (Ag/Ab complexes) and IV (T lymphocytes and cytokines) [possibly types I (Ag/membrane bound IGE) and II (Ab/ cell bound Ag lysis)]

  7. Widespread manifestations of inflammatory/immunopathologic tissue reactions
• What are the clinical features of an

  Advanced Lesion?

  - Pocket formation

  - Loss of attachment

  - Abscess formation

  - Pus exudate

  - Bone Loss

  
• what do MMPs do?

  • Degrade extracellular matrix proteins
  • regulation of cell proliferation, differentiation and migration
  • Modulate inflammatory/immune response