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 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 Immunopathology deals with immune responses associated with disease, Immunodeficiency: ineffective immune response therefore we can say that it’s an Autoimmunity: inappropriate reaction to self inappropriate immune response to an infection which can cause harm to the host in various ways If the innate or adaptive immune response become faulty in some way this may incur illness or disease to develop. 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. 4 types of hypersensitivity reactions Humoral or cell mediated Immune response causes damage to the body This occurs when there is an inappropriate response to an allergen The immune response causes the damage to the body The first exposure to an allergen causes the sensitisation The second and subsequent exposures to the allergen generates a disproportionate allergic response which could mediators lead to tissue damage onset examples 9 Type 1 hypersensitivity: IgE (antibody) molecules have an affinity and stick to the surface of mast cells. This Initiates a sequence of cell surface and intracellular reactions which cause mast cells to degranulate and release chemical mediators Type I hypersensitivity reaction (signals): histamine, heparin, leukotrienes, prostaglandin which cause vasodilation and smooth muscle contraction of surrounding tissue. This causes changes in vascular tone, permeability- especially in bronchi of the lungs–which leads to Commonest type of hypersensi7vity reac7on- bronchospasm This is ANAPHYLAXIS rapid onset- within 1 hour Contraction of smooth muscle includes the airway, leading to airway restriction and bowel emptying. Provoked by re-exposure to speci:c type of Vasodilation leads to a drop in blood pressure. an7gen: allergen Vascular permeability leads to movement of fluid and proteins into the tissues from the blood stream. High levels of IgE are secreted by plasma cells Your body experiences shock when you don’t have IgE an7bodies bind to receptors on the surface of enough blood (and therefore oxygen) circulating through your system to keep organs and tissues mast cells and basophils causing them to be functioning properly. sensiFzed. A good example is the immediate rash with penicillin. But note – you can get other forms of At subsequent exposure to same allergen, the hypersensitivity with penicillin too. anFgen binds to parts of IgE molecules which In dentistry, can get allergic reactions to many things, latex allergy is particularly important- both ini7ates degranulaFon of mast cell and release of patients and clinicians were experiencing acFve mediators (e.g. histamine) hypersensitivity reactions to latex which led to latex gloves being withdrawn in dentistry - we now use nitrile gloves. Video: (43) Type I Hypersensi7vity - Mechanism (Described Concisely) - YouTube https://www.youtube.com/watch?v=CjRAkawBRaI 1 0 Local anaphylaxis (atopy): About 10% of people Systemic anaphylaxis: In some individuals, a have "atopy" and are easily sensitized to severe reaction occurs within minutes, leading allergens that cause a localized reaction when to symptomatology such as acute asthma, inhaled or ingested. This can produce hay fever, laryngeal oedema, diarrhoea, urticaria, and Type I cont… shock. Classic examples are penicillin allergy and bee sting allergy. hives, asthma, etc. Classic examples are food allergies and hay fever to ragweed pollen. Allergen gains access locally to an surface on the body, especially prevalent in the mucous Reaction may be localized or generalized membranes (hayfever/asthma) Systemic- can be life threatening. E.g. Penicillin, bee sting Treatment Needs to be immediate for systemic anaphylaxis: pharmacological intervention- Local- e.g. hay fever, extrinsic asthma, bronchodilators (inhalers), antihistamines, anti- urticaria (skin swellings) inflammatory agents e.g steroids. Adrenaline (vasoconstrictor and bronchodilator) Prompt administration of adrenaline is vital. Triggers: pollen, animal fur- cat/dog/horse, Other treatments such as anti-histamines, intravenous dust mites, mould, some foods fluids and steroids are also commonly used, but should not lead to a delay in the administration of adrenaline. Treatment: Adrenaline autoinjectors are commonly prescribed to Avoidance of triggers patients at high risk of anaphylaxis, so that they are able to self-administer adrenaline in an emergency. Pharmacological intervention After surviving an episode of anaphylaxis, it is Immunotherapy (for severe cases) important that the patient is referred to an Immunology or allergy clinic to identify the cause, and thereby reduce the risk of future reactions and prepare the patient to manage future episodes. What are the signs of an allergic reaction? ØSkin of face & upper chest appear red, blotchy, flushed, urticaria (hives), pruritis (itchy) ØAbdominal pain, nausea, vomiting, diarrhoea ØChest pain, tight chest, coughing, wheezing, difficulty breathing (pulmonary oedema), bronchospasm, rhinitis/sneezing ØSwelling- eyes/tongue/lips/pharynx/laryngeal oedema ØRapid or weak pulse ØPalpitations ØTachycardia ØHypotension ØPallor, light-headedness, giddiness, faint, anxious, distressed, restless, sweating, thirsty ØCyanosis of mucous membranes, nail beds ØUnconscious ØCardiac arrest Anaphylactic shock: this is when blood pressure falls and unconsciousness follows. 1 1 Type II hypersensi,vity reac,on - cytotoxic Type II hypersensitivity reaction refers to an antibody- mediated immune reaction in which antibodies (IgG or Rare IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, Develops between 2-24 hours functional loss, or damage to tissues. Inflammation mediated by complement: Antibodies can IgG and IgM antibodies bind to cell surface activate the complement pathway by binding to self- antigens resulting in the formation of complement Mediated by complement system or by killer components, which act as chemotactic factors for cells neutrophils, causing the recruitment of neutrophils to the site and resulting in the activation of neutrophils. These Result: opsonization, red blood cell agglutination, neutrophils then release enzymes and reactive oxygen species, which damage the tissues. cell lysis The binding of these antibodies leads to strong activation of the complement system which recruits leukocytes E.g. haemolytic reactions during transfusion of resulting in inflammation incompatible blood; some drug reactions; autoimmune anaemias Opsonization: An opsonin is any molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling Cell agglutination: clumping together Cell lysis: cellular disruption is a method in which the Video: (43) Type II Hypersensi0vity - Mechanisms (Described Concisely) - YouTube outer boundary or cell membrane is broken down or hAps://www.youtube.com/watch?v=dSM-TwWTtV0 destroyed 1 2 Type III hypersensi,vity reac,on- immune complex mediated Tissue damaging reactions. Polymorphonuclear leukocytes (esp neutrophils) are attracted by chemotaxis Develops over hours, days, weeks (movement of an organism in response to a chemical stimulus). These release enzymes IgG and IgM antibodies bind to free, soluble antigen forming e.g. elastase and neutral collagenase. Platelets aggregate and thrombus formation immune complexes occurs. This can cause: Systemic immune complex disease which is Lodge in and pass through blood vessel walls a potentially fatal syndrome If the immune complexes stick in the small, terminal blood Lead to complement activation = initiates inflammatory, tissue vessels of joints, kidneys, heart, skin – serum sickness. Symptoms of this include: damaging reactions arthritis; glomerulonephritis, oedema, cutaneous vasculitis and carditis. Neutrophil influx and mast cell degranulation Type lll hypersensitivity can also cause: Local immune complex disease: e.g. if Examples: systemic lupus erythematosus; serum sickness; antigen remains at area of injection (due to infection/autoimmune response) immune rheumatoid arthritis complex deposition can be recurrent with long term consequence of remaining disease. E.g. rheumatoid arthritis & polyarteritis (this mechanism is active in these diseases); Farmer’s lung Video: (43) Type III Hypersensi0vity – YouTube hAps://www.youtube.com/watch?v=-_yUsZO6Vio 1 3 Type IV hypersensi,vity reac,on- cell mediated Second commonest hypersensitivity type Develops in 2 or more days Also known as delayed type hypersensitivity (DTH): Activation- Cell mediated recruitment-response- no antibodies involved Antibody independent Tuberculosis (TB) Skin test (Mantoux reaction) Caused by overstimulation of T cells and Metal allergies- nickel monocytes/macrophages Latex- contact dermatitis Graft rejection- targeted by cytotoxic Leads to release of cytokines- causing inflammation, cell T cells- they recognise the cells as foreign- endocytosis enables apoptosis death and tissue damage- prolonged inflammation (programmed cell death) damages normal tissues Mitigated by trigger avoidance; use of corticosteroids Video: (43) Type IV Hypersensi0vity (Described Concisely) – YouTube hAps://www.youtube.com/watch?v=kQFmrQfBW5k Dental Implications Atopic individual means that those that have a history of allergies, often several. They can be allergic to foods and are more likely to have an allergy response  Atopic individuals – check MH Latex allergy – can create type I anaphylaxis  Latex allergy – you or the patient Deaths have occurred in dental practice after rinsing with chlorhexidine (rare)  Chlorhexidine allergy This is an example of a patient who experienced a swollen red face after LA lidocaine  Allergy to benzocaine topical anaesthetic Some patients may have allergy to topical benzocaine  Allergy to sodium metabisulphite in LA  Allergy to dentine bonding agent  Contact dermatitis – you or other staff  More informa0on when subjects covered & in medical emergencies session Immunodeficiency 1 6 Immunodeficiency is when a person’s immune system is not able to remove/ resolve infection; there may be an impairment of one/more parts of innate/ adaptive immune response; there is therefore a high risk of recurrent infection & more prone to conditions which are not normally an issue to healthier people. Immunodeficiency Compromised or absent immune system response to infectious disease Secondary immunodefiency (SID): this is acquired from secondary/ Primary immunodeficiency environmental factors weakening the (PID): Primary congenital Primary Immunode9ciency Secondary immunode9ciency immune system, e.g. viral/bacterial defect. Approx. 300 types- rare; infection (HIV/AIDS); malnutrition; can be life threatening treatment can be with medicaments which suppress the immune system (chemotherapy). More common than Primary immunodeficiencies, usually as a result of primary infection e.g. HIV. Various diseases may directly or indirectly impair the immune system Immunode9ciency diseases such as leukemia; multiple myeloma 1 7 Primary immunode9ciency B cell T cell Severe combined immunode9ciencies immunode9ciencies immune de9ciencies (adap,ve) (adap,ve) (SCID) (adap,ve) Vaccination: ‘Key vaccines are recommended for patients with innate deficiencies, but Phagocyte disorders Complement live vaccines (such as MMR) must be avoided for patients (innate) defects (innate) with some of these types of PID.  patient with Papillon-Lefevre syndrome. Get precocious aggressive periodontitis, leading to premature loss Primary immunodeficiencies of deciduous and permanent dentition at a very young age. 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 In many secondary immunodeficiency diseases- treatment of primary condition enables resolution of the immunodeficiency. Not so much with chronic conditions- these need to be managed long term to minimise effects. Comorbidities (e,g, secondary infections) in SID patients are concerning as cause increased death rate. Secondary immunode9ciency Malnutri,on Chronic infec,ons Drug regimens Drug regimens: e.g. side effect of chemotherapy = immunosuppression- reduce the immune response. Malnutrition: in developing Chronic infections: e.g. Acquired immune Recovery of immune system on completion of countries up to half of the deficiency syndrome (AIDS) resulting treatment; immunosuppressive medication for population in some communities from HIV (human immunodeficiency transplant rejection- required to dampen hosts can be affected with protein- virus). Virus attacks CD4+ T cells immune system to prevent rejection of donor tissue/ calorie malnutrition. Can result depleting their numbers. Once T cell count organ. Patient more vulnerable to opportunistic in number and impairment of T 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… EHect on lives: Joint pain and swelling, fa0gue, rashes/skin problems, recurring temperatures/low grade fever, swollen glands, abdominal pain/diges0ve issues Di\culty in many areas e.g. mobility, mental health Lost opportuni0es in work and life Speci^cally…. How can this impact on Patient may be too tired to carry out routine oral care our pa0ents? Mobility issues may impede optimum oral hygiene e.g. rheumatoid arthritis Mental health issues may mean patient is not able to care for themselves effectively/ low motivation, doesn’t see the point Financially- may not have the means to buy necessary oral hygiene aids on a regular basis 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 arthri0s Mul0ple 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 Sjogren Syndrome: Autoimmune disease affecting salivary and lacrimal glands= reduction of secretions saliva and tears= xerostomia and xerophthalmia Pathogenesis: genetic and environmental factors 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 adap0ve immune response become faulty in some way this may lead to illness or disease due to:  Hypersensi0vity: overac0ve immune response  Immunode^ciency: inedec0ve immune response  Autoimmunity: inappropriate reac0on to self As a dental care professional, it is vital to: Ensure that you take a comprehensive medical history from the pa0ent at each visit. Have up to date knowledge in any condi0ons/diseases/medica0ons which are likely to have an impact on the pa0ent’s oral and systemic health Engage the pa0ent to help them understand how to help themselves- reassure, educate, mo,vate Further Reading hAps://www.nhs.uk/condi0ons/sjogrens-syndrome/ hAps://www.lupusuk.org.uk/what-is-lupus/ hAps://www.diabe0c.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 introduc,on 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: hAps://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]