Pathogenesis of Periodontal Disease 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: **A severe gum infection that can damage soft tissues and destroys supporting bone supporting the teeth. This can lead to mobility of teeth, and tooth loss and is associated with an increased risk of systemic diseases.\ \ Host mediated inflammatory response\ Within periodontium\ Irreversible destruction** **Development and role of plaque biofilm in periodontal disease** 2. Define the term **plaque biofilm** **A structured community of bacterial cells enclosed in a self-produced polymeric matrix and attached to a surface, such as teeth. It is involved in the development of dental caries and periodontal disease.** **Extracellular glycocalyx smile layer** 3. Composition of dental plaque biofilm: Intra-cellular Matrix Organic **Polysaccharides, proteins and lipids glycoproteins** Inorganic (sources between supra & sub) **Calcium, phosphorous sodium 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: extracellular slime layer formation 4. Maturation of bacterial 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: faces the oral cavity b\) Sulcular Epithelium: Lines the gingival sulcus, between the tooth and gum c\) Junctional epithelium: Attaches the gingiva to the tooth surface 6\. Label the tissues of the periodontium: (a, b, c, d from top to bottom) a\) Gingiva 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 8. Name at least 3 bacteria species found to be associated with periodontal disease 1. Porphyromonas gingivalis 2. Tanneralla forsythia 3. Treponema denticola\ \ Aggregatibacter actinomycetemcomitans\ Fusobacterium nucleatum\ Prevotella intermedia 9\. Note some of the virulence factors of named bacteria which enable them to colonise, invade and damage the periodontium 1. Porphyromonas gingivalis - Produces proteases that degrade host tissue 2. Tanneralla forsythia -- Produced toxins that destroy host cells\ proteases and apoptotic-inducing factor 3. Treponema denticola -- Has enzymes that degrade host proteins\ Adherence factors can bind to fibroblasts **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 Immune response a. What are the key components of this immune response?\ Saliva, Epithelium Inflammatory response Neutrophils, macrophages and production of cytokines and chemokines 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? | | | | | | Exudate- forms during | | | inflammation to deliver immune | | | cells to the site and dilute | | | bacterial toxins | | | | | | b. Which cells are mainly | | | involved in the **cellular | | | response** at this stage and | | | what is their role? | | | | | | Neutrophils -- phaocytose | | | bacteria and release | | | antimicrobial agents | +-----------------------------------+-----------------------------------+ | Epithelium | a. How does the epithelium | | | defend against plaque | | | microorganisms? | | | | | | Acts as a physical barrier and | | | produces antimicrobial peptides | | | | | | b. How and when is the | | | protective function of | | | epithelium compromised? | | | | | | When the epithelium is damages by | | | toxins | | | | | | 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, release host | | | defences | +-----------------------------------+-----------------------------------+ | Saliva | What is the role of saliva? | | | | | | Produces lubrication, | | | antibacterial action and aids in | | | clearing bacteria from the oral | | | cavity | +-----------------------------------+-----------------------------------+ The adaptive immune response is also known as the [\_acquired\_\_]or [\_\_\_\_specific\_\_\_\_] 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 [\_\_\_antigens\_\_\_\_\_] due to immunological [\_memory\_\_\_\_\_\_\_]. Adaptive immunity uses two main mechanisms, known as [\_\_\_\_humoral\_\_\_\_]immunity ([\_\_\_antibody\_\_\_\_\_]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 antigens | +-----------------------------------+-----------------------------------+ | B-cell lymphocytes | Differentiate into plasma cells | | | which then release antibody | | | against the specific antigen | +-----------------------------------+-----------------------------------+ | Antibody IgG and IgA | Production is thought to be | | | protective- Neutralises pathogens | | | and block their adhesion | +-----------------------------------+-----------------------------------+ | Locally or systemically produced | Provide specific immune response | | antibody | to pathogens | | | | | | To clump and prevent adherence of | | | microorganisms to epithelium; | | | work with complement to lyse | | | bacteria; work with neutrophils | | | for opsonisation (marking) and | | | phagocytosis | +-----------------------------------+-----------------------------------+ 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 neutrophils and | | | macrophages | +===================================+===================================+ | 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? Mediate | | IL-1, IL-6 and TNF-α | inflammation and recruit immune | | | cells to the infection site Small | | Anti-inflammatory IL-4 and IL-10 | proteins which are crucial in | | | controlling the growth and | | | activity of other immune system | | | cells and blood cells. They | | | signal the immune system to and | | | aid in the inflammatory responses | | | in various ways. | | | | | | Action of cytokines in | | | periodontitis: During | | | periodontitis, pro-inflammatory | | | cytokines are released in | | | response to the pathogens which | | | contributes to further | | | destruction of the periodontal | | | tissues | +-----------------------------------+-----------------------------------+ | Prostaglandins e.g. PGE\_2 | Induce vasodilation and bone | | | resorption Bone resorption, | | | neutrophil chemotaxis, vascular | | | permeability and dilation | +-----------------------------------+-----------------------------------+ | Matrix metalloproteinases (MMPs) | Pro-inflammatory- degrade | | | extracellular matrix components, | | | leading to tissue breakdown | +-----------------------------------+-----------------------------------+ **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): 1- Bacterial virulence factors that causes tissue damage 2- Host immune response that becomes overly aggressive, leading to tissue destruction\ 3- Environmental factors such as smoking and poor oral hygiene, which reduce host defences - An increased amount of plaque - Increase in pathogenicity of the micro-organisms in the biofilm - 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\ **Hypothesis- suggests that periodontal disease results from the accumulation of plaque regardless of specific bacterial species.\ Issue: Does not account for the different pathogenic potentials of bacterial species\ Support- Supported by older research but lacks specificity **b) Specific Plaque Hypothesis\ **Hypothesis- Proposes that only specific pathogenic bacteria causes periodontal disease\ Issue- Limited to identifying specific pathogens without explaining why these bacteria become pathogenic\ Support- Supported by studies identifying pathogens like Pg in diseases sites **\ ** **c) Keystone Pathogen- Host Response Hypothesis\ **Hypothesis- Suggests that certain bacteria (keystone pathogens) disrupt the hosty immune system, leading to dysbiosis and disease\ Support- Current evidence supports this therapy, as it explains the role of the immune dysregulation a. Non-specific Plaque Hypothesis -Theory proposed that stagnation of plaque biofilm and numbers of bacteria within would lead to inflammation in the adjacent gingival sulcus leading to periodontium tissue destruction Issues: Simplistic theory; most gingivitis cases do not progress to PD; patients with light traces of biofilm may suffer from PD; some sites affected, others not. b. Specific Plaque Hypothesis- Proposes that as periodontal disease develops that there is a shift in **microbial composition** rather than amount which determines the development of the disease Issues: Red complex (thought to be most pathogenic) can be seen in stable periodontal sites; questions arise as to whether pathogens are single causative factor; recent research recognises further species not found in red complex zone may be more causative, therefore concept of specific types as previously thought is less certain; Gram positive bacteria found in large amounts in periodontal pockets c. Keystone Pathogen-Host Response Hypothesis- theorises that specific bacterial species is key in shift from symbiotic microbes -- dysbiotic microbes in biofilm colonies. This community triggers the uncontrolled host response= periodontal destruction. Previous research could not provide solid evidence to show that specific bacteria are the direct cause of periodontal destruction. Current evidence demonstrates that the immune response and uncontrolled host inflammatory response cause the tissue destruction found in periodontal disease.