Immune Disorders DTH SEPT24 PDF

Immune Disorders Tutor: Ms P Lazarou Module: Biomedical Sciences GDC Learning Outcomes 1.7.2 Explain the impact of medical and psychological conditions in the patient Aim: To gain an overview of general immune disorders affecting the population and contextualise to oral manifestations Intended...

Immune Disorders Tutor: Ms P Lazarou Module: Biomedical Sciences GDC Learning Outcomes 1.7.2 Explain the impact of medical and psychological conditions in the patient Aim: To gain an overview of general immune disorders affecting the population and contextualise to oral manifestations Intended learning outcomes Discuss immunopathology (diseases of the immune system) including hypersensitivity reactions, autoimmunity and immunodeficiency Define hypersensitivity and outline the various types of hypersensitivity Define immunodeficiency and outline the causes Define autoimmune disease and discuss it’s impact Relate how autoimmune disease manifests in the oral cavity Assessment Formative Summative Questions relating to the Questions incorporated in subject in Biomedical Biomedical Sciences Sciences online quiz Eassessment 6 Immunopathology Hypersensitivity reactions, immunodeficiency and autoimmunity If the innate or adaptive immune response become faulty in some way this may incur illness or disease to develop. Hypersensitivity: overactive immune response Immunodeficiency: ineffective immune response Autoimmunity: inappropriate reaction to self Hypersensitivity 8 Hypersensitivity: the production of an excessive immune response causing gross tissue damage when the body meets an antigen for the second or succeeding times. mediators onset examples 9 Type I hypersensitivity reaction Commonest type of hypersensitivity reaction-rapid onset- within 1 hour Provoked by re-exposure to specific type of antigen: allergen High levels of IgE are secreted by plasma cells IgE antibodies bind to receptors on the surface of mast cells and basophils causing them to be sensitized. At subsequent exposure to same allergen, the antigen binds to parts of IgE molecules which initiates degranulation of mast cell and Video: release of active mediators (e.g. (43) Type I Hypersensitivity - Mechanism (Described Concisely) - Y histamine) ouTube 1 0 Type I cont… Reaction may be localized or generalized Systemic- can be life threatening. E.g. Penicillin, bee sting Local- e.g. hay fever, extrinsic asthma, urticaria (skin swellings) Triggers: pollen, animal fur- cat/dog/horse, dust mites, mould, some foods Treatment: Avoidance of triggers Pharmacological intervention Immunotherapy (for severe cases) 1 1 Type II hypersensitivity reaction - cytotoxic Rare Develops between 2-24 hours IgG and IgM antibodies bind to cell surface Mediated by complement system or by killer cells Result: opsonization, red blood cell agglutination, cell lysis E.g. haemolytic reactions during transfusion of incompatible blood; some drug reactions; autoimmune anaemias Video: (43) Type II Hypersensitivity - Mechanisms (Described Concisely) - Y ouTube 1 2 Type III hypersensitivity reaction- immune complex mediated Develops over hours, days, weeks IgG and IgM antibodies bind to free, soluble antigen forming immune complexes Lodge in and pass through blood vessel walls Lead to complement activation = initiates inflammatory, tissue damaging reactions Neutrophil influx and mast cell degranulation Examples: systemic lupus erythematosus; serum sickness; rheumatoid arthritis Video: (43) Type III Hypersensitivity – YouTube https://www.youtube.com/watch?v=-_yUsZO6Vio 1 3 Type IV hypersensitivity reaction- cell mediated Second commonest hypersensitivity type Develops in 2 or more days Cell mediated Antibody independent Caused by overstimulation of T cells and monocytes/macrophages Leads to release of cytokines- causing inflammation, cell death and tissue damage- prolonged inflammation damages normal tissues Mitigated by trigger avoidance; use of corticosteroids Video: (43) Type IV Hypersensitivity (Described Concisely) – YouTube https://www.youtube.com/watch?v=kQFmrQfBW5k Dental Implications  Atopic individuals – check MH  Latex allergy – you or the patient  Chlorhexidine allergy  Allergy to benzocaine topical anaesthetic  Allergy to sodium metabisulphite in LA  Allergy to dentine bonding agent  Contact dermatitis – you or other staff  More information when subjects covered & in medical emergencies session Immunodeficiency 1 6 Immunodeficiency Compromised or absent immune system response to infectious disease Primary Secondary Immunodeficiency immunodeficiency Immunodeficiency diseases 1 7 Primary immunodeficiency B cell T cell Severe immunodeficie immunodeficie combined ncies ncies immune (adaptive) (adaptive) deficiencies (SCID) Phagocyte Complement (adaptive) disorders defects (innate) (innate) Primary immunodeficiencies Genetically determined Rare Classified according to immune defect B cell defect e.g. IgA deficiency T and B cell defects e.g. Severe combined immunodeficiency Complement deficiencies Granulocyte defects e.g. Papillon-Lefevre syndrome Get serious life-threatening infections Increased incidence of malignancy Increased incidence of autoimmune disease Down’s Syndrome - tendency towards advanced periodontal disease 1 9 Secondary immunodeficiency Malnutrition Chronic Drug infections regimens Oral implications of patients taking immunosuppressant drugs Oral candidiasis - common Higher incidence of bacterial infections Viral infections e.g. herpes simplex or zoster Periodontal disease Gingival swelling with ciclosporin Oral ulceration Poor healing Increased risk of malignancy Can you think of any diseases that make a patient immunocompromised? Poorly controlled diabetes Anaemia HIV infection Spleen removal Some malignancies e.g. Vit D deficiency Hodgkin disease, Kidney failure leukaemias, lymphomas, multiple myeloma Sickle cell disease (leads to hypofunction of spleen) Malnutrition (iron and vitamin deficiencies)  Periodontal destruction Host Health defence Bacterial challenge Disease  Dental Care professional role Risk assessment- full histories Liaison with physician Antibiotic cover may be required by physician before dental surgery Prevention, prevention, prevention! Oral infections may need aggressive treatment Good infection control e.g. management of dental unit water lines Check risk of post-op bleeding if immunosuppressive drugs taken Close monitoring and follow up Autoimmune Disease  Autoimmune disease Chronic and progressive disorder that occurs when healthy tissue is targeted and destroyed by the body’s own immune system Normally, the immune system can tell the difference between foreign cells and the body’s cells (tolerance) In autoimmune disease, the immune system mistakenly attacks part of the body e.g. joints or skin, recognising these cells as foreign. It releases autoantibodies that attack healthy cells Some autoimmune diseases target only one organ. Type 1 diabetes damages the pancreas. Other diseases, like systemic lupus erythematosus, affect the whole body 2 6 Autoimmunity However: with age, natural T cell suppression reduces. Therefore, self antigens may be viewed as foreign = breakdown of tolerance to self-antigens which gives rise to….autoimmunity. Other factors that lead to autoimmunity include: Emergence of normally hidden antigens Infections, especially viral Drugs, e.g. penicillin may cause: Penicillin-induced hemolytic anaemia Hydralazine (hypertensive drug) may cause: Drug-induced lupus (DIL) Genetics Endocrinological changes (hormones) 2 7 2 8 Autoimmune reactions – how may they occur? Several different ways in which an autoimmune reaction may be created:  When a foreign substance or microbe resembles the body e.g. rheumatic fever - proteins found in group A streptococcal bacteria resemble proteins in the heart muscle → antibodies attack the heart  When normal body cells are altered e.g. a virus altering a body cell so that it is recognized as "non-self" by the immune system  If the immune cells that make antibodies malfunction and make abnormal antibodies that attack normal cells in the body.  If a substance in the body that is normally hidden from the immune system (such as the fluid within the eye) enters the bloodstream e.g. after trauma 2 9 Testing for autoimmune disease Antinuclear antibody tests – tests that looks for antibodies that attack the cell nuclei Autoantibody tests – tests that search for specific antibodies to body’s own tissues Complete blood count C-reactive protein – measurement used to indicate inflammation throughout the body Erythrocyte sedimentation rate - test that indirectly measures the level of inflammation in the body Urine test or urinalysis 3 0 Autoimmunity cont… Prevalence: More than 80 known autoimmune conditions Seen in 5-7% of the population > 4 million people in UK living with at least one autoimmune condition Affects women more than men. 85% or more patients of multiple autoimmune diseases are female. Autoimmunity cont… Effect on lives: Joint pain and swelling, fatigue, rashes/skin problems, recurring temperatures/low grade fever, swollen glands, abdominal pain/digestive issues Difficulty in many areas e.g. mobility, mental health Lost opportunities in work and life Specifically…. How can this impact on our patients? Treatment of autoimmune diseases No cure for autoimmune conditions Specific drugs/medicaments can dampen down the immune response, therefore reducing the inflammation. E.g.  Non-steroidal anti-inflammatory drugs e.g. Ibuprofen  Immunosuppressants e.g. Prednisolone, Ciclosporin, Mycophenolate Other treatments are available which relieve symptoms like pain, swelling, fatigue and rashes Advisable to eat a well balanced diet and take regular exercise as this could also help 3 3 Autoimmunity cont… Cost: Direct & indirect costs (UK) for 3 autoimmune diseases: £13 billion annually Type 1 diabetes Rheumatoid arthritis Multiple sclerosis Autoimmunity cont…2 groups: 1. Organ specific disease: disorders caused by autoantibodies directed at specific components of the organ. E.g. thyroiditis (Grave’s and Hashimoto’s diseases); autoimmune gastritis (pernicious anaemia); autoimmune adrenalitis (Addison’s disease). 2. Generalized systemic disease/organ non-specific disease: disorders caused by tissue deposition of immune complexes, consisting of antigens and antibodies. Deposited on epidermal basement membranes, vascular basement membranes, inside joints where complement is activated and tissue is damaged. E.g. rheumatoid arthritis, systemic lupus erythematosus 34 3 5 3 6 What do we know now about Covid-19? Emerging field Possible role of destructive immune response in severe acute illness and Long Covid British Society for Immunology (2020) Long term immunological consequences of Covid-19. Available at: https://www.immunology.org/sites/default/files/BSI_Briefing_Note_August _2020_FINAL.pdf [Accessed 30.3.21] 3 7 Autoimmune diseases and oral manifestations Oral signs of autoimmune diseases are often the initial manifestation Dental clinicians should be aware of evident autoimmune pathologies Examples of oral manifestations of autoimmune disease include: Systemic lupus erythematosus Sjögren syndrome Pemphigus vulgaris Mucous membrane pemphigoid Autoimmune diseases and oral manifestations Systemic lupus Sjögren Syndrome erythematosus Autoimmune diseases and oral manifestations Pemphigus Vulgaris Mucous Membrane Pemphigoid Summary The immune system is highly complex and there are many ways that it protects and defends our body externally and internally with the innate and acquired responses However, if the innate or adaptive immune response become faulty in some way this may lead to illness or disease due to:  Hypersensitivity: overactive immune response  Immunodeficiency: ineffective immune response  Autoimmunity: inappropriate reaction to self As a dental care professional, it is vital to: Ensure that you take a comprehensive medical history from the patient at each visit. Have up to date knowledge in any conditions/diseases/medications which are likely to have an impact on the patient’s oral and systemic health Engage the patient to help them understand how to help themselves- reassure, educate, motivate Further Reading https://www.nhs.uk/conditions/sjogrens-syndrome/ https://www.lupusuk.org.uk/what-is-lupus/ https://www.diabetic.org/is-diabetes-an-autoimmune-d isease/ 4 2 References: Marshall J, Warrington R, Watson W, Kim H (2018) An introduction to immunology and immunopathology. Allergy, Asthma & Clinical Immunology Journal, Vol 14 (suppl 2). Available at: An introduction to immunology and immunopathology | Allergy, Asthma & Clinical Immunology | Full Text ( biomedcentral.com) [Accessed 20/08/22] McMahon R., Sloan P. (2000) Essentials of Pathology for Dentistry. London: Harcourt Publishers Immunology.org (2021) Allergy. Available at: https://www.immunology.org/public-information/bitesized-immunology/immune-dysfunction/allergy [Accessed 12/01/21] Juvenile Diabetes Research Foundation (JDRF). Garcia, P. (2018), Report on autoimmune awareness: connect-immune- research-are-you-autoimmune-report.pdf (immunology.org).Available at: https://www.immunology.org/sites/default/files/connect-immune-research-are-you-autoimmune-report.pdf [Accessed 12/01/21] British Society for immunology: (2021), Immunodeficiency. Available at: https://www.immunology.org/policy-and-public-affairs/briefings- and-position-statements/immunodeficiency [Accessed 12/01/21] Saccucci, M. Carlo, G.Bossù,M. Giovarruscio, F. Salucci, A and Polimeni, A (2018). Autoimmune Diseases and Their Manifestations on Oral Cavity: Diagnosis and Clinical Management. Available at: https://doi.org/10.1155/2018/6061825 [Accessed 12/01/21]