IM4: Immunity and Oral Diseases Flashcards
1. Importance of oral cavity in health and disease 2. Significance of oral cavity as portal of entry to pathogens 3. Immune mechanisms operating in the mouth in association with: - caries and periodontitis - oral cancer - Bechet's disease - Sjogrens syndrome - oral lichen planus - pemphigus vulgaris
List internal and external factors associated with oral disease
- Infectious agents
- Genetics
- Hormones
- Metabolism
- Age
- Stress
- Smoking
Outline how P. gingivalis promotes unrestrained Interferon responses
- P. gingivalis breaks through gingival epithelium
- Causes MYD88 degradation (regulator of pro-inflammatory pathways) - also manifests in lymphoid tissue
- Causes down-regulation of AXL protein - this induces activation of plasmacytoid dendritic cells
- Plasmacytoid dendritic cells cause up-regulation of INF-a which affects interaction between dendritic cells and CD4+ T-cells
- This causes up-regulation of INF-Y which is a contributor to constitutive T-cell priming
- INF-Y causes
- B-cells to produce pathogenic antibodies targeting bone tissue causing bone destruction
- Pathogenic response as Tregs cannot down-regulate INF-Y
What are the three types of mucosal tissue in the oral cavity
- Lining mucosa (no keratin layer)
- Masticatory mucosa (keratin layer)
- Tongue mucosa (keratin layer)
Most common oral cancer
Tongue cancer
How can chemical compounds in cigarette smoke contribute to oral cancer
Compounds affect genes controlling proliferation and growth of epithelial cells leading to uncontrolled proliferation
How does cigarette smoke effect epithelial cells
- Produces molecules activating signalling pathways associated with inflammation
- Damages DNA causing mutations in genes controlling cell growth = cell transformation occurs leading to tumour growth
- Causes autophagy = cells try to eliminate damaged components
- Produces cellular senescence = when cells are recognised as targets for destruction
What is Sjogren’s syndrome
- Autoimmune condition affecting glands age 40-60
- F > M and increases risk of lymphoma
- Combination of genetics, viral/bacterial infections which trigger auto-immune mechanisms
Describe the autoimmune mechanism in Sjogren’s syndrome
- Triggers epithelial cell death and release of auto antigens Ro/SSA and La/SSB
- Viral infection activated DCs which increase antigen presentation and cause production of INF-a and B cell growth factor BAFF
- Proliferation of B cells and production of autoabtibodies within secondary lymph organs and lymphatic network
What is the relevance of ectopic lymphoid structures in Sjogren’s syndrome
ELS/ Tertiary lymphoid structures are when
Cells aggregate to resemble lymph nodes within salivary glands - this can determine disease activity in Sjogrens syndrome
What does the presence of the following cells indicate
- CD3 ( T-cell detection )
- CD20 ( B-cell detection )
- CD21 ( follicular DCs )
- CD138 ( plasma cell detection )
If these are present in biopsy it indicates ectopic lymphoid structures which can help predict and diagnose lymphoma development in patents with Sjogren’s Syndrome
This suggests there is uncontrolled proliferation of B cells
What is Behcet’s disease
- Rare autoimmune disorder causing blood vessel inflammation throughout body
- Genetic links to HLA-B51
Signs and symptoms of Behcet’s disease
- mouth sores
- eye inflammation
- skin rashes
- genital sores
Describe the autoimmune mechanism in Behcet’s disease
- Antibodies to heat shock proteins target HSPs produced by S. sanguinins and M. tuberculosis
- Antibodies target human HSPs by cross-reaction
- There is presentation of HSP60 and HSP65 derived antigens leading to inflammation and activation of TH1, TH17, cytotoxic T cells and neutrophils
- Combined activation causes systemic inflammation targeting organs: eyes, joints, vascular tissue
What is oral lichen planus
- Chronic inflammatory condition affecting mucosal membranes in the mouth
- Lesions appear white, lacy patches; Red, swollen tissues; Open sores - Lesions can cause burning pain and discomfort
- It is characterised by immune damage to basal keratinocytes in oral mucosa that are recognised as being antigenically foreign or altered
Outline the autoimmune mechanism in Oral Lichen Planus
- Following viral/bacterial infections, epithelial cells secrete IL-23 inducing TH17 activation
- Secretion og IL-17 induces keratinocytes to secrete defensins 2 and 3
- Defensins = small peptides with potent chemotactic activity causing CD8+ cytotoxic T cell recruitment
- Causing cell death and inflammation through TNF-a, granzyme B (causes apoptosis) and Fas-FasL interactions
