Immune Disorders GN 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 Intende...

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 hypersensi7vity reac7ons, autoimmunity and immunode:ciency De:ne hypersensi7vity and outline the various types of hypersensi7vity De:ne immunode:ciency and outline the causes De:ne autoimmune disease and discuss it’s impact Relate how autoimmune disease manifests in the oral cavity Assessment Forma7ve Summa7ve Ques7ons rela7ng to the subject in Ques7ons incorporated in Biomedical Sciences online quiz Biomedical Sciences 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. Humoral or cell mediated 4 types Occurs when there is an inappropriate response to an allergy Immune response causes damage to body Immediate Cytotoxic or Immune complex Delayed First time exposure to allergen causes sensitisation antibody Second or further generates disproportionate allergic response dependent that can lead to tissue damage mediators onset examples — affects skin and mucous membranes 9 Anaphylactic reaction Type I hypersensitivity reaction Commonest type of hypersensi7vity reac7on- rapid onset- within 1 hour Provoked by re-exposure to speci:c type of an7gen: allergen High levels of IgE are secreted by plasma cells IgE an7bodies bind to receptors on the surface of mast cells and basophils causing them to be sensiFzed. At subsequent exposure to same allergen, the anFgen binds to parts of IgE molecules which ini7ates degranulaFon of mast cell and release of acFve mediators (e.g. histamine) Causes vasodilation and smooth muscle contraction of surrounding tissue and changes in vascular tone and permeability Video: (43) Type I Hypersensi7vity - Mechanism (Described Concisely) - YouTube https://www.youtube.com/watch?v=CjRAkawBRaI 1 0 Anaphylaxis = Dentistry type I reactions: Latex allergy Contraction of smooth muscle - including airways Vasodilation - drop in blood pressure Vascular permeability - movement of fluid and proteins into tissue from bloodstream SHOCK - not enough blood Type I cont… Signs of allergic reaction: Skin of face read and flushed Reaction may be localized or generalized Hives Itchy Systemic- can be life threatening. E.g. Abdominal pain Nausea Penicillin, bee sting Diarrhoea Wheezing Local- e.g. hay fever, extrinsic asthma, Difficulty breathing urticaria (skin swellings) Swelling Laryngeal edema Rapid or weak pulse Hypotension Triggers: pollen, animal fur- cat/dog/horse, Paler Dizziness dust mites, mould, some foods Restlessness Thirsty Treatment: Avoidance of triggers Unconscious can follow. Pharmacological intervention Inhalers, antihistamines, anti inflammatory, adrenaline (vasoconstrictor) DO NOT DELAY ADRENALINE Immunotherapy (for severe cases) Identify cause and reduce future reactions if first experience 1 1 Type II hypersensiFvity reacFon - cytotoxic Rare Develops between 2-24 hours IgG and IgM antibodies bind to cell surface Mediated by complement system or by killer cells Molecule that enhances phagocytosis by marking antigen or dead cells Result: opsonization, red blood cell agglutination, Red cells clump together cell lysisCellular destruction E.g. haemolytic reactions during transfusion of incompatible blood; some drug reactions; autoimmune anaemias Video: (43) Type II Hypersensi7vity - Mechanisms (Described Concisely) - YouTube hUps://www.youtube.com/watch?v=dSM-TwWTtV0 1 2 Type III hypersensiFvity reacFon- 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 Painful long term conditions Video: (43) Type III Hypersensi7vity – YouTube hUps://www.youtube.com/watch?v=-_yUsZO6Vio 1 3 Important to check with patient any allergies or hypersensitivity Make note on notes Vital to ask at every appointment Type IV hypersensiFvity reacFon- 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 Hypersensi7vity (Described Concisely) – YouTube hUps://www.youtube.com/watch?v=kQFmrQfBW5k Dental Implications Those that have history of allergies - may be susceptible  Atopic individuals – check MH  Latex allergy – you or the patient Use latex free gloves, polishing cups  Chlorhexidine allergy Cause red swollen lips  Allergy to benzocaine topical anaesthetic  Allergy to sodium metabisulphite in LA Red swollen face  Allergy to dentine bonding agent  Contact dermatitis – you or other staff To many products - even hand soap - keep hands moisturised  More informa7on when subjects covered & in medical emergencies session Immunodeficiency 1 6 When a persons immune response is not able to remove or resolve infection Impairment of innate or adaptive immune response - higher risk of recurrent infection Much more prone to conditions Immunodeficiency Compromised or absent immune system response to infectious disease 300 types Secondary or environmental factors that weaken immune system - viral or bacterial infection - HIV/AID/malnutrition/chemotherapy Primary ImmunodeMciency Secondary immunodeMciency PID Rare but life threatening SID More common - result of primary infection ImmunodeMciency diseases May need bone marrow transplant Life long complex treatment and care May need routine use of antibiotics/antivirals More prone to infections 1 7 Live vaccines must be avoided for some types of primary immunodeficiency 5 types Important for heard immunity in community for protection Genetic defects - mutations or deficiency in genes Rare Primary immunodeMciency T cells = Active B cells and relate details of pathogens. Pathogen destruction Mutation in genes controlling T cells less or ineffective Inability to destroy pathogens is effected B cell T cell Severe combined immunodeMciencies immunodeMciencies immune deMciencies (adapFve) (adapFve) (SCID) (adapFve) Loss of antibody production Rare - due to serious lack of T cells and variable numbers of B cells Risk of severe bacterial infections Little or no immune protection Managed with antibody or immunoglobulin replacement therapy Minor infection can be fatal. Usually diagnosed in 1st year of life. Phagocyte disorders Complement (innate) defects (innate) Remove pathogens Rarest Gene mutations effect phagocytes ability to phagocytose effectively Allows autoimmune conditions to develop (example rheumatoid arthritis) Bacterial and fungal infections can cause serious harm or death  Immune response not working well so other diseases will follow in these patients 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 Treatment of primary condition enables resolution of immunodeficiency Not so much in chronic conditions - they need to be managed long term to minimise effects Acquired from secondary or environmental factors that weaken immune system Secondary immunodeMciency MalnutriFon Chronic infecFons Drug regimens AIDS resulting from HIV Side effect from chemotherapy - causes immunosuppression Protein calorie malnutrition - result in number and impairment of T cells Virus attacks T cells - T cell count is depleted - AIDS symptoms can appear Recovery of immune system after chemotherapy Vulnerable to respiratory tract infections - high risk of infection or death If malnutrition addressed - condition can improve Retro viral medications = enable T cells to increase and function Mediation to prevent rejection of transplant - effect immune response normally - extends life expectancy - have to be taken for life More vulnerable to opportunistic infections Oral implications of patients taking immunosuppressant drugs Thrush Oral candidiasis - common Higher incidence of bacterial infections Viral infections e.g. herpes simplex or zoster Periodontal disease Gingival swelling with ciclosporin Immunosuppressant 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)  INCREASED RISK Periodontal destruction Host defence is poor if immunocompromised If bacterial challenge is present - plaque bacteria If normal host defect not present - balance will tip and lead to breakdown in tissues surrounding teeth Host Health defence Bacterial challenge Disease  Dental Care professional role Risk assessment- full histories Liaison with physician Specialist, GP, dentist - with patients persmission - DO NOT go ahead with invasive treatment if unsure Antibiotic cover may be required by physician before dental surgery Prevention, prevention, prevention! Tailor treatment to individual patients Oral infections may need aggressive treatment May need referral to specialist for treatment - possibly surgery 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 No interaction in normal healthy state T cell release antibodies which bind to self molecules and cause destructions of joint cells Hasn’t recognised its own parts Now the white blood cell will attack its body’s own cells 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 Can be difficult as symptoms can be vague and come and go Not a single blood test that can check combination of causes 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… EPect on lives: Joint pain and swelling, fa7gue, rashes/skin problems, recurring temperatures/low grade fever, swollen glands, abdominal pain/diges7ve issues Dieculty in many areas e.g. mobility, mental health Lost opportuni7es in work and life Speci:cally…. How can this impact on our pa7ents? Unable to maintain optimal oral hygiene - increased risk of periodontal disease Financially - might not be able to afford interdental brushes/toothbrushes etc. Jaw pain - dental treatment may be difficult 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 arthri7s Mul7ple 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 Treatment may need to be adapted for patients with these diseases 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 Early diagnosis will aid with early treatment and aid with quality of life 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 Severe chronic and progressive autoimmune disease Generalised systemic Skin lesions Impaired of organ function Redness skin on cheeks, nose Butterfly rash across cheeks Systemic lupus Sjögren Syndrome Redness/soreness across fingertips Involvement with CNS, muscles, joints, eyes erythematosus Affects salivary and lacrimal glands — reduction in secretion (saliva and tears) Xerostomia and dryness of eyes Pathogenesis - genetic and environment factors Orally — Desquamative gingivitis, oedematous, very red, ulcerative lesions (may appear as burn), layers of gingiva separating (allows bacteria to thrive) Low blood platelet count — blood doesn’t clot so easily — no invasive treatment unless blood tests prior Orally — Cracking of tongue - appears fissured, no/minimal saliva evident  Autoimmune diseases and oral manifestations Found on gingivae Also found on mucous membranes; genetic, conjunctival, skin mucous membranes Remain in oral cavity for 48 hours Very sore and painful for patient Inhibits oral hygiene Very tender and sore — blisters that break — leave painful erosion — also evident in gingival tissues Probing and oral hygiene sore Due to cell structure (desmosomes) Pemphigus Vulgaris Mucous Membrane Genetic aetiology Triggers — stress, drugs, viruses, hormones Pemphigoid Most time its first diagnosed in mouth 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 adap7ve immune response become faulty in some way this may lead to illness or disease due to:  Hypersensi7vity: overac7ve immune response  Immunode:ciency: inejec7ve immune response  Autoimmunity: inappropriate reac7on to self As a dental care professional, it is vital to: Ensure that you take a comprehensive medical history from the pa7ent at each visit. Have up to date knowledge in any condi7ons/diseases/medica7ons which are likely to have an impact on the pa7ent’s oral and systemic health Engage the pa7ent to help them understand how to help themselves- reassure, educate, moFvate Further Reading hUps://www.nhs.uk/condi7ons/sjogrens-syndrome/ hUps://www.lupusuk.org.uk/what-is-lupus/ hUps://www.diabe7c.org/is-diabetes-an-autoimmune-disease/ 4 2 References: Marshall J, Warrington R, Watson W, Kim H (2018) An introduc1on to immunology and immunopathology. Allergy, Asthma & Clinical Immunology Journal, Vol 14 (suppl 2). Available at: An introducFon to immunology and immunopathology | Allergy, Asthma & Clinical Immunology | Full Text (biomedcentral.com)[Accessed 20/08/22] McMahon R., Sloan P. (2000) Essen1als of Pathology for Den1stry. London: Harcourt Publishers Immunology.org (2021) Allergy. Available at: h;ps://www.immunology.org/public-informa1on/bitesized-immunology/immune-dysfunc1on/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: hUps://www.immunology.org/sites/default/:les/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]