Immune Disorders medium

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: Overview of general immune disorders affecting the population, contextualized to oral manifestations.

Intended Learning Outcomes

• Discuss immunopathology (diseases of the immune system), including hypersensitivity reactions, autoimmunity, and immunodeficiency.
• Define hypersensitivity and outline various types.
• Define immunodeficiency and outline causes.
• Define autoimmune disease and discuss its impact.
• Relate how autoimmune disease manifests in the oral cavity.

Assessment

• Formative: Questions in Biomedical Sciences online quiz.
• Summative: Questions in Biomedical Sciences e-assessment.

Immunopathology

• If the innate or adaptive immune responses become faulty, illnesses or diseases may develop.
• Hypersensitivity: overactive immune response.
• Immunodeficiency: ineffective immune response.
• Autoimmunity: inappropriate reaction to self.

Hypersensitivity

• Excessive immune response causing tissue damage when the body meets an antigen for the second or subsequent times.
• Types: I, II, III, IV
  • Type I (Immediate): Allergic reaction (e.g., anaphylaxis).
  • Type II (Cytotoxic): Antibodies attack cells (e.g., blood transfusion reactions).
  • Type III (Immune Complex): Immune complexes deposit in tissues (e.g., serum sickness).
  • Type IV (Delayed): T cell-mediated response (e.g., contact dermatitis).

Type I Hypersensitivity Reaction

• Commonest hypersensitivity reaction, rapid onset (within 1 hour).
• Triggered by re-exposure to an allergen.
• High IgE levels secreted by plasma cells bind to receptors on mast cells and basophils.
• Subsequent exposure to the same allergen initiates mast cell degranulation and release of active mediators (histamine).

Type I cont...

• Reaction can be localized or systemic (life-threatening).
• Triggers: pollen, animal fur, dust mites, mold, some foods.
• Treatment: Avoidance of triggers, pharmacological intervention (inhalers, antihistamines, anti-inflammatory, adrenaline), immunotherapy (severe cases).
• Dental implications: Latex allergy, chlorhexidine allergy, allergy to benzocaine, sodium metabisulphite, dentine bonding agent, contact dermatitis.

Type II Hypersensitivity Reaction - Cytotoxic

• Rare, develops between 2-24 hours.
• Mediated by IgG and IgM antibodies binding to cell surfaces, triggering complement activation or killer cells.
• Results: Opsonization, red blood cell agglutination, cellular lysis.
• Examples: incompatible blood transfusions, drug reactions, autoimmune anemias.

Type III Hypersensitivity Reaction - Immune Complex Mediated

• Develops over hours, days, or weeks.
• IgG and IgM antibodies bind to soluble antigens forming immune complexes.
• Complexes lodge in and pass through blood vessel walls, initiating complement activation.
• Results: Inflammatory and tissue-damaging reactions.
• Examples: Systemic lupus erythematosus, serum sickness, rheumatoid arthritis.

Type IV Hypersensitivity Reaction - Cell Mediated

• Second commonest hypersensitivity type, develops in 2 or more days.
• Cell-mediated, caused by overstimulation of T cells and monocytes/macrophages -> cytokine release.
• Prolonged inflammation, cell death, and tissue damage.
• Mitigated by trigger avoidance and corticosteroids.

Immunodeficiency

• Compromised/absent immune system response to infections.
• Primary immunodeficiency (PID): Genetic defects resulting in impaired immune function.
  • Examples: B-cell deficiencies, T-cell deficiencies, phagocyte disorders, complement defects, Severe combined immunodeficiencies (SCID).
• Secondary immunodeficiency (SID): Resulting from secondary factors (e.g. malnutrition, chronic infections, drug regimens).

Primary Immunodeficiencies

• Genetically determined immune defects.
• Classified based on the specific immune cell defect (B-cells, T-cells, complement, granulocytes).
• Increased risk of infections, malignancies, and autoimmune diseases (e.g., Down's Syndrome and periodontal disease).

Secondary Immunodeficiency

• Caused by secondary/environmental factors that weaken the immune system.
• Examples: Malnutrition, chronic infections (e.g., HIV/AIDS), drug regimens (e.g. chemotherapy).

Oral Implications of Immunosuppressant Drugs

• Increased risk of oral candidiasis, bacterial infections, viral infections, periodontal disease, gingival swelling, oral ulceration, poor healing, and malignancy.

Conditions that Affect Patients' Immunocompetence

• Poorly controlled diabetes, HIV infection, some malignancies (e.g., Hodgkin's disease, leukaemias, lymphomas, multiple myeloma), malnutrition, anaemia, splenectomy, vitamin D deficiency, kidney failure, sickle cell disease.

Periodontal Destruction

• Host defense vs bacterial challenge.
• Impaired immune system affects the balance, leading to increased risk of periodontal disease.

Dental Care Professional Role

• Risk assessment (full histories).
• Liaison with physician.
• Antibiotic premedication before dental surgery.
• Prevention and aggressive treatment of infections
• Good infection control.
• Check post-operative bleeding risk.
• Close monitoring.

Autoimmune Disease

• Chronic, progressive disorder where the immune system mistakenly attacks the body's own tissues.
• Normally body can differentiate self and foreign cells.
• Can be organ-specific (e.g., Type 1 diabetes) or generalized (e.g., systemic lupus erythematosus).

Autoimmunity

• Breakdown of tolerance to self-antigens.
• Factors that trigger include: Emerging hidden antigens, infections, drugs (e.g., penicillin-induced hemolytic anemia, hydralazine-induced lupus), genetics, endocrinological changes.

Autoimmune Disease Testing

• Antinuclear antibody tests (ANA) - look for antibodies attacking cells nuclei.
• Autoantibody tests - search for antibodies to the body's own tissue
• Complete blood count (CBC) to evaluate immune system cells
• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to measure inflammation
• Urine tests (urinalysis) for related changes

Autoimmunity Prevalence

• More than 80 known autoimmune conditions.
• Affects 5-7% of the population in the UK.
• 4 million people in the UK live with at least one autoimmune condition.
• Women are disproportionately affected (85% or more patients of multi-autoimmune diseases are female).

Autoimmunity - Effects

• Joint pain and swelling, fatigue, rashes, skin problems, digestive issues, mobility difficulties, mental health problems, lost work and life opportunities.

Autoimmunity Treatment

• No cure, specific drugs and therapy dampen down the immune response, reducing inflammation. (e.g., non-steroidal anti-inflammatory drugs, immunosuppressants).
• Other treatments for specific symptoms (pain, swelling, fatigue, etc.).
• Balanced diet, regular exercise.

Autoimmunity Costs

• Direct and indirect costs in the UK total £13 billion annually for common autoimmune conditions like Type 1 diabetes, Rheumatoid Arthritis, and Multiple sclerosis.

Autoimmune Diseases, 2 Broad Groups

1. Organ-specific disease: Auto-antibodies targeting specific body organs (e.g., thyroid, gut, adrenal glands).
2. Generalized disease: Immune complexes deposit in various tissues/organs; affecting various systems (e.g., Rheumatoid arthritis, lupus).

Autoimmune Diseases and Oral Manifestations

• Oral signs may be the initial manifestation of various autoimmune diseases.
• Examples include, Systemic lupus erythematosus, Sjögren's syndrome, pemphigus vulgaris, and mucous membrane pemphigoid.

Covid-19 and the Immune System

• Emerging field of research, potential role of rogue antibodies driving severe COVID-19 cases.
• Destructive immune response in acute COVID-19 and Long COVID.

Further Reading

• Provided links for further research on Sjögren syndrome, lupus, and type 1 diabetes.