Untitled Quiz

Immune Disorders

• Module: Biomedical Sciences
• Tutor: Ms P Lazarou
• Topic: Immune Disorders

GDC Learning Outcomes

• Explain the impact of medical and psychological conditions in the patient
• Aim: 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 its impact.
• Relate how autoimmune disease manifests in the oral cavity.

Assessment

• Formative assessment: Questions related to the subject in Biomedical Sciences online quiz.
• Summative assessment: Questions incorporated in Biomedical Sciences eassessment.

Immunopathology

• If the innate or adaptive immune response becomes faulty, illness or disease can develop.
• Hypersensitivity: Overactive immune response.
• Immunodeficiency: Ineffective immune response.
• Autoimmunity: Inappropriate reaction to self.

Hypersensitivity

• Hypersensitivity: An excessive immune response causing tissue damage when the body encounters an antigen for the second or subsequent times.
  • Type I: Allergen-mediated, rapid onset (within an hour). IgE-mediated.
    • Mediators: IgE-mediated.
    • Onset: Within 1 hour.
    • Examples: Anaphylaxis, Hemolytic Anemia
  • Type II: Cytotoxic, develops between 2-24 hours. IgG or IgM-mediated.
    • Mediators: IgG or IgM cytotoxic.
    • Onset: Hours to days.
    • Examples: Hemolytic reactions during transfusion of incompatible blood, some drug reactions, autoimmune anemias.
  • Type III: Immune complex-mediated, develops over hours, days, or weeks. IgG and IgM-mediated.
    • Mediators: Immune complex-mediated.
    • Onset: 1-3 weeks.
    • Examples: Systemic lupus erythematosus, serum sickness, rheumatoid arthritis.
  • Type IV: Cell-mediated, develops in 2 or more days. Antibody-independent.
    • Mediators: Cytokines released by T cells and macrophages.
    • Onset: Days to weeks.
    • Examples: Prolonged inflammation, cell death, tissue damage.

Type I Hypersensitivity Reaction

• Most common type of hypersensitivity reaction.
• Rapid onset (within one hour).
• Provoked by re-exposure to specific antigens (allergens).
• High IgE levels secreted by plasma cells bind to receptors on mast cells and basophils, sensitizing them.
• Subsequent allergen exposure triggers IgE molecule binding and mast cell degranulation, releasing mediators (e.g., histamine).

Type I cont...

• Reactions can be localized or generalized.
• Systemic reactions can be life-threatening (e.g., penicillin, bee stings)
• Local reactions: hay fever, extrinsic asthma, urticaria.
• Triggers: pollen, animal fur, dust mites, mold, some foods.
• Treatment: Avoidance of triggers, pharmacological intervention, immunotherapy (severe cases).

Type II Hypersensitivity Reaction (Cytotoxic)

• Rare.
• Develops within 2-24 hours.
• IgG and IgM antibodies bind to cell surfaces.
• Mediated by complement system or killer cells.
• Results: Opsonization, red blood cell agglutination, cell lysis.
• Examples: Hemolytic reactions, some drug reactions, autoimmune anemias.

Type III Hypersensitivity Reaction (Immune Complex Mediated)

• Develops over hours, days, or weeks.
• IgG and IgM antibodies bind to free, soluble antigens forming immune complexes.
• Lodged and pass through blood vessel walls.
• Lead to complement activation (inflammatory, tissue-damaging reactions).
• Neutrophil influx, mast cell degranulation.
• Examples: SLE, serum sickness, rheumatoid arthritis.

Type IV Hypersensitivity Reaction (Cell-mediated)

• Second most common type.
• Develops in 2 or more days.
• Cell-mediated; antibody-independent.
• Caused by overstimulation of T cells and monocytes/macrophages.
• Leads to cytokine release causing inflammation, cell death, and tissue damage.
• Prolonged inflammation damage normal tissues.
• Mitigated by trigger avoidance and corticosteroids.

Dental Implications

• Atopic individuals: Check for latex and chlorhexidine allergies.
• Benzocaine, Sodium metabisulphite (in LA), Dentine bonding agent allergies.
• Contact dermatitis.
• Additional information during medical emergencies session.

Immunodeficiency

• Compromised or absent immune system response to infectious diseases.
  • Primary immunodeficiency
  • Secondary immunodeficiency

Primary immunodeficiency

• Genetic origin.
  • B-cell immunodeficiencies
  • T-cell immunodeficiencies
  • Phagocyte disorders
  • Complement defects
• Severe combined immunodeficiencies (SCID)

Primary Immunodeficiencies

• Genetically determined.
• Rare.
• Classified according to immune defect (e.g., IgA deficiency, Severe combined immunodeficiency, complement deficiencies, granulocyte defects).
• Increased incidence of malignancy and autoimmune disease.
• Associated with Down syndrome and advanced periodontal disease.

Secondary Immunodeficiency

• Acquired conditions.
  • Malnutrition
  • Chronic infections
  • Drug regimens

Oral Implications of Immunosuppressant Drugs

• Oral candidiasis.
• Higher incidence of bacterial infections.
• Viral infections (e.g., herpes simplex, zoster).
• Periodontal disease.
• Gingival swelling (with ciclosporin).
• Oral ulceration.
• Poor healing.
• Increased risk of malignancy

Immunocompromised Patients

Examples from the presented list :

• Poorly controlled diabetes.
• HIV infection.
• Malignancies (e.g., Hodgkin disease, leukemia, lymphoma, multiple myeloma).
• Malnutrition (iron and vitamin deficiencies).
• Anemia.
• Spleen removal.
• Vitamin D deficiency.
• Kidney failure.
• Sickle cell disease (leads to spleen dysfunction).

Periodontal Destruction

• The balance between host defense and bacterial challenge impacts periodontal health.

Dental Care Professional Role

• Risk assessment, including full medical histories
• Physician liaison
• Antibiotic cover (as needed).
• Prevention (of infection).
• Aggressive treatment for oral infections.
• Good infection control (e.g., dental unit water lines).
• Risk assessment for post-operative bleeding if patient takes immunosuppressants.
• Close monitoring and follow-up.

Autoimmune Disease

• Chronic, progressive disorder.
• Healthy tissues are targeted and destroyed by the body's immune system.
• Normally, the immune system can distinguish between foreign cells and body cells (tolerance).
• In autoimmune disease, the immune system mistakenly attacks body tissues, releasing autoantibodies that attack healthy cells.
• Some diseases target specific organs (e.g., Type 1 diabetes damages the pancreas), while others affect the whole body (e.g., systemic lupus erythematosus).

Autoimmunity

• With age, natural T-cell suppression decreases and self-antigens may be mistaken as foreign.
• Other factors leading to autoimmunity:
  • Emergence of hidden antigens.
  • Infections (especially viral infections).
  • Drugs (e.g., penicillin-induced hemolytic anemia, hydralazine-induced lupus).
  • Genetics.
  • Endocrinological changes.

Autoimmune Disorder

• Immune system reacts against self-molecules, causing damage to tissues and cells.

Autoimmune Reactions

• Foreign substances or microbes resembling body components can trigger an autoimmune reaction.
• Altering normal body cells via viruses also triggers the immune system.
• Malfunctioning immune cells can produce abnormal antibodies.
• Substances normally hidden from the immune system, entering the bloodstream, can cause an autoimmune reaction (e.g., trauma).

Testing for Autoimmune Disease

• Antinuclear antibody (ANA) tests.
• Autoantibody tests.
• Complete blood count (CBC).
• C-reactive protein (CRP).
• Erythrocyte sedimentation rate (ESR).
• Urine test/urinalysis.

Autoimmunity cont...

• Prevalence: More than 80 known autoimmune conditions affect 5-7% of the population in the UK, with a significant percentage affecting women, particularly those with multiple autoimmune conditions.

Autoimmunity cont...Effect on Lives

• Difficulty in many areas.
• Joint pain, swelling, fatigue, rashes, skin and digestive problems, fever, mobility issues, mental health health and opportunities lost.

Treatment of Autoimmune Diseases

• No cure; aims to dampen down the immune response.
• Specific drugs or medications can reduce inflammation (e.g., non-steroidal anti-inflammatory drugs, immunosuppressants).
• Other treatments may include therapies to relieve symptoms (e.g. pain, swelling, fatigue, rashes).
• Diet and regular exercise may be beneficial.

Autoimmunity cont...Cost

• Direct and indirect costs of autoimmune diseases in the UK are around £13 billion annually.
• Examples of relevant conditions include Type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.

Autoimmunity cont...Groups

• Organ-specific: Autoantibodies target components of specific organs (e.g., thyroid, gut tissue).
  • Thyroiditis, Grave's disease, Hashimoto's disease, autoimmune gastritis, pernicious anaemia, autoimmune adrenalitis.
• Generalized systemic/organ-nonspecific: Immune complexes are deposited in tissues, activating complements and damaging joints and tissues.
  • Rheumatoid arthritis, and systemic lupus erythematosus.

Autoimmune Diseases

• List of various autoimmune conditions.

Autoimmune Diseases and Oral Manifestations

• Oral signs might be the first indicators.
• Dental professionals should be aware of the potential oral complications resulting from autoimmune pathologies, examples include: Systemic lupus erythematosus, Sjögren syndrome, pemphigus vulgaris, and mucous membrane pemphigoid.
• Visuals provided for these types.

Summary

• The immune system is complex, with innate and adaptive responses. Faulty responses can lead to illness (hypersensitivity, immunodeficiency, autoimmunity).
• Dental professionals should take a thorough medical history, stay updated on conditions and medications potentially affecting oral health, and engage patients to support their overall health.

Further Reading

• Include links to websites for further research.