Pathogenesis of Periodontal Disease 1 Workbook PDF

This workbook is to be used in conjunction with your session on the subject of **Pathogenesis of Periodontal Disease.** - The premise of this session is for you to complete the tasks in a self-directed way - There are links to documents/resources which will enable you to gain knowledge...

This workbook is to be used in conjunction with your session on the subject of **Pathogenesis of Periodontal Disease.** - The premise of this session is for you to complete the tasks in a self-directed way - There are links to documents/resources which will enable you to gain knowledge of this subject and to complete the tasks as you proceed - It is important that you complete and have your notes in preparation for the next session **Pathogenesis of Periodontal Disease 2** in order that you have underpinning knowledge of the subject. - Please complete prior to self-checking your responses and self-assessing your knowledge of this subject. **Review lectures of: Development of oral mucosa, junctional epithelium, immunology, dental plaque biofilm, virulence factor, Periodontal Disease-Microbiology** **'Host Defences' pdf** You will need to complete the workbook to meet the intended learning outcomes: - Define periodontitis - Recall the development and role of plaque biofilm in periodontal disease - Review the tissues of the periodontium - List at least 3 types bacteria thought to be associated in the pathogenesis of periodontal disease and review the virulence factors deployed in the process - Outline the host defence in the oral cavity, with reference to the innate and acquired immune responses - Describe the functions of cytokines, prostaglandins and matrix metalloproteinases (MMPs) in the host response - Describe the basic factors which may contribute to the initiation of periodontitis **Periodontitis** 1. Define the term periodontitis: **Caused by a microbial infection that causes an inflammatory response leading to irreversible destruction of the periodontal tissues and supporting structures.** **Development and role of plaque biofilm in periodontal disease** 2. Define the term **plaque biofilm** **One or more communities of micro-organisms embedded within an extra cellular matrix.** 3. Composition of dental plaque biofilm: Intra-cellular Matrix Organic **Proteins\ Glycoproteins\ Polysaccharides\ Lipids\ Intra-cellular matrix\ ** Inorganic (sources between supra & sub) **Calcium\ Sodium\ Phosphorous\ Potassium\ ** 4. Complete the four stages of dental plaque biofilm formation: 1. Initial attachment of bacteria to pellicle 2. Initial colonisation of the tooth surface -- new bacteria join 3. Secondary colonisation -- production of extracellular slime layer 4. Mature biofilm formation - mushroom shaped colonies **Tissues of the periodontium** 5\. Name the three distinct parts of the gingival epithelium with a description of where they are found. a\) Oral epithelium -- keratinised stratified squamous -- what you can see in the mouth covering free and attached gingiva -- keratinised for protection against mechanical stress. b\) Sulcular epithelium -- non keratinised stratified squamous -- faces tooth but not in contact -- semi-permeable allows for gingival crevicular fluid to flow -- lines sulcus. c\) Junctional epithelium -- non keratinised stratified squamous -- joins gingiva to tooth -- tightly packed epithelial cells and desmosomes -- base of sulcus. 6\. Label the tissues of the periodontium: (a, b, c, d from top to bottom) a\) Gingivae b\) Periodontal ligament c\) Cementum d\) Alveolar bone  **Bacteria associated in the pathogenesis of periodontal disease and their virulence factors** 7. The subgingival environment supports mainly anaerobic bacteria. True False 8. Name at least 3 bacteria species found to be associated with periodontal disease P.gingivallis T.denticola T.forsythia A.actinomycemcomitans 9\. Note some of the virulence factors of named bacteria which enable them to colonise, invade and damage the periodontium P.gingivallis --\ Produce gingipains to allow use of gingival crevicular fluid for nutrients. Carbohydrate capsule to resist host defences. T.denticola -- Adherence mechanisms to bind to fibroblasts. Degrade cytokines -- disruption of host defences. T.forsythia -- Produces proteases and apoptopic factors -- causes cell death to immune cells. A.actinomycemcomitans -- Leukotoxin -- can destroy white blood cells, inhibits immune response. Produces proteases and toxins -- destroy and invade host epithelial cells. **Host defences in the oral cavity, innate and acquired immune responses** 10\. Which type of immune response will be initiated by plaque in the first instance? Innate/primary immune response a. What are the key components of this immune response? Inflammatory response, epithelium and saliva. b. Complete the table: +-----------------------------------+-----------------------------------+ | Host defence | Role in defence | +===================================+===================================+ | Inflammatory response | a. What is the **fluid | | | component**, when does it | | | form and what is it's | | | function at this stage? | | | | | | Gingival crevicular fluid.\ | | | Forms from the inflammatory | | | response to inflammation. | | | | | | Rinse out microorganisms from the | | | sulcus, the higher the | | | inflammation, the increase in | | | gingival crevicular fluid. | | | Contains inflammatory mediators | | | and antibacterial agents. | | | | | | b. Which cells are mainly | | | involved in the **cellular | | | response** at this stage and | | | what is their role? | | | | | | PMNs (neutrophils, mast cells, | | | basophils) and macrophages -- | | | both attack and removed invading | | | microorganisms/pathogens. | +-----------------------------------+-----------------------------------+ | Epithelium | a. How does the epithelium | | | defend against plaque | | | microorganisms? | | | | | | Physical barrier against plaque | | | microorganisms, cells tightly | | | packed and attached to each other | | | through desmosomes. | | | | | | Some parts semipermeable to allow | | | for flow of gingival crevicular | | | fluid. | | | | | | b. How and when is the | | | protective function of | | | epithelium compromised? | | | | | | Tissue destruction at the | | | junctional epithelium leading to | | | a periodontal pocket. Creates | | | inflammatory response and | | | compromises protection function | | | due to micro ulcerations. | | | | | | c. Which cells of the junctional | | | epithelium secrete cytokines | | | and Tumour Necrosis Factor | | | during the initiation of the | | | inflammatory response in the | | | gingival tissues? | | | | | | KERATINOCYTES | | | | | | d. What is the name of the | | | tissue macrophages which are | | | responsible for releasing | | | host defences? | | | | | | Langerhans' cells | +-----------------------------------+-----------------------------------+ | Saliva | What is the role of saliva? | | | | | | Stops drying of oral tissues. | | | | | | Antimicrobial effect -- Secretory | | | and serum IgA -- influence | | | bacteria attachment so more | | | likely to be swallowed. | +-----------------------------------+-----------------------------------+ The adaptive immune response is also known as the [specific] or [acquired] immune response and it is activated when innate immunity is ineffective in eliminating [pathogens] and infection becomes established. It is highly specific to a particular pathogen by recognising it's [antigen] due to immunological [memory]. Adaptive immunity uses two main mechanisms, known as [humoral] immunity ([antigen] response) and [cell-mediated] immunity. **~~antigen~~ ~~humoral~~ ~~antibody~~ ~~acquired~~ ~~cell-mediated~~ ~~memory~~** **~~specific~~ ~~pathogens~~** a. Humoral Immune response is when antibodies are produced against agents existing in the humours (extra-cellularly). Complete the table which relates to the humoral immune response: +-----------------------------------+-----------------------------------+ | **Mode** | **Function** | +===================================+===================================+ | Epithelial Langerhans' cells | Present antigenic parts from | | | pathogens and present to | | | circulating lymphocytes which | | | stimulates clonal expansion after | | | recognising the specific antigen. | +-----------------------------------+-----------------------------------+ | B-cell lymphocytes | Differentiate into plasma cells | | | which then release antibody | | | against the specific antigen | +-----------------------------------+-----------------------------------+ | Antibody IgG and IgA | Protective function. | +-----------------------------------+-----------------------------------+ | Locally or systemically produced | Prevent adherence of | | antibody | microorganisms | | | | | | Recognise and neutralise | | | pathogens to mark for | | | phagocytosis. | | | | | | Work with complement system to | | | lyse bacteria. | +-----------------------------------+-----------------------------------+ b. Cell-mediated response does not require the use of antibodies- uses it's own T-Cell receptor. +-----------------------------------+-----------------------------------+ | Antigen presentation via | TH cells: | | Langerhans'/dendritic cells to | | | T-Cell | - produce cytokines | | | | | | - assist B cell differentiation | | | into plasma cells. | | | | | | - activate macrophages and | | | neutrophils. | +===================================+===================================+ | Progression from gingivitis to | T-cells have immunoregulatory | | periodontitis elicits a shift | role | | from T-cell to B-cell lesions | | +-----------------------------------+-----------------------------------+ **Cytokines, prostaglandins and matrix metalloproteinases (MMPs) in the host response** 12\. There are several types of chemical mediators involved in periodontal disease. They are chemical messengers which link and regulate the inflammatory response, the immune response and tissue damage. Research where they are released from and complete the following table: +-----------------------------------+-----------------------------------+ | **Mediator type** | **Action/function in | | | periodontitis** | +===================================+===================================+ | Cytokines e.g. Pro-inflammatory | What are cytokines? Small | | IL-1, IL-6 and TNF-α | proteins important for | | | controlling immune cell growth | | Anti-inflammatory IL-4 and IL-10 | and activity. | | | | | | Action of cytokines in | | | periodontitis: Pathogens release | | | pro-inflammatory cytokine that | | | promote further tissue | | | destruction. | +-----------------------------------+-----------------------------------+ | Prostaglandins e.g. PGE\_2 | Bone resorption, chemotaxis, | | | vascular permeability, dilation. | +-----------------------------------+-----------------------------------+ | Matrix metalloproteinases (MMPs) | Pro-inflammatory- degrade | | | connective tissue. | +-----------------------------------+-----------------------------------+ **Factors contributing to the initiation of periodontitis** 13\. In health and in stable gingivitis, there is a dynamic equilibrium between dental plaque and the host defences. This equilibrium is disturbed in periodontitis which tips in favour of tissue damage. Describe what these factors are (refer to Periodontal disease- Microbiology session): \> Microbial -- increased presence of plaque \> Increased pathogenicity of microorganisms within the biofilm -- virulence factors \> Compromised host defence 14\. For each of the following theories on the role of bacteria in periodontal disease, give an **outline** of the hypothesis, identify any **issues and/or support** for them. **a) Non-specific Plaque Hypothesis** Stagnation of plaque biofilm within gingival sulcus leads to gingival inflammation, periodontal disease and tissue destruction. Too simplistic Some cases of gingivitis don't lead to periodontitis Some patients can have light plaque biofilm and have periodontitis**\ ** **b) Specific Plaque Hypothesis** As periodontal disease develops, oral microbiota shifts from gram positive beneficial microbes to gram negative pathogens. Since been found that gram negative microbes are also found in healthy and stable periodontal sites. Gram positive bacteria also have been found in larger amounts within periodontal pocket sites. **c) Keystone Pathogen- Host Response Hypothesis** Keystone species in biofilm can have large effects on communities regardless of number. Triggers shift to dysbiotic biofilm community and uncontrolled host response is initiated -- causes damage to periodontal tissues. Current evidence demonstrates that immune response and uncontrolled host inflammatory response cause tissue destruction found in periodontal disease.