Immunopathology and Immune Disorders Overview

Immune Disorders

• GDC Learning Outcomes: Explain the impact of medical and psychological conditions in patients.
• Aim: Gain an overview of general immune disorders affecting the population and contextualize 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 involves questions related to the subject in Biomedical Sciences online quiz. Summative assessment involves questions incorporated in Biomedical Sciences e-assessment.

Immunopathology

• Immunopathology is when the innate or adaptive immune response is faulty, leading to illness or disease.
• Hypersensitivity: Overactive immune response.
• Immunodeficiency: Ineffective immune response.
• Autoimmunity: Inappropriate reaction to self.

Hypersensitivity

• Hypersensitivity is an excessive immune response causing tissue damage when the body encounters an antigen for the second or subsequent times.
• Type I: Allergic reactions, rapid onset (within 1 hour). Mediated by IgE antibodies binding to mast cells and basophils.
• Type II: Cytotoxic hypersensitivity, develops between 2-24 hours. Mediated by IgG and IgM antibodies binding to cell surface, leading to cell lysis (e.g., hemolytic reactions during transfusion).
• Type III: Immune complex-mediated hypersensitivity, develops over hours, days, or weeks. Mediated by immune complex deposition, causing inflammation. Examples: systemic lupus erythematosus (SLE), serum sickness, and rheumatoid arthritis.
• Type IV: Cell-mediated hypersensitivity, develops in 2 or more days. Antibody-independent reaction, caused by T cells and monocytes/macrophages. Prolonged inflammation and cell death.

Type I Hypersensitivity

• Commonest type of hypersensitivity reaction, rapid onset within 1 hour.
• Provoked by re-exposure to a specific antigen, called an allergen.
• Plasma cells secrete high levels of IgE antibodies; IgE binds to receptors on mast cells and basophils, causing sensitization.
• Subsequent exposure to the allergen causes antigen binding to IgE molecules, which then initiates mast cell degranulation and triggers release of active mediators, such as histamine.

Type II, III and IV Hypersensitivity (Summary)

• These types differ in time of onset, mechanism (antibodies versus cells), and the implicated immune components.
• They lead to diverse clinical manifestations and complications.

Dental Implications

• Atopic individuals: Check for allergies to latex, chlorhexidine, benzocaine, sodium metabisulfite, and dentine bonding agents.
• Contact dermatitis: Consider allergies in dental staff and patients.
• General implications: More information covered in medical emergencies sessions.

Immunodeficiency

• Immunodeficiency involves a compromised or absent immune system, making individuals susceptible to infectious diseases.
• Primary immunodeficiency: Genetically determined, rare. Classified according to the specific immune defect (B cell, T cell, phagocyte, complement). Examples include IgA deficiency, severe combined immunodeficiency (SCID), and Papillon-Lefevre syndrome.
• Secondary immunodeficiency: Acquired from factors such as malnutrition, chronic infections, or drug regimens.

Secondary Immunodeficiency

• Examples: malnutrition, chronic infections, and drug regimens (immunosuppressants).

Oral Implications of Immunosuppressant Drug Use

• Oral manifestations: oral candidiasis, higher incidence of bacterial infections, viral infections (e.g., herpes simplex or zoster), periodontal disease, gingival swelling, oral ulceration, poor healing, increased risk of malignancy.

Diseases that Weaken the Immune System

• Poorly controlled diabetes, HIV infection, some malignancies (e.g., Hodgkin disease, leukemia, lymphoma, multiple myeloma), malnutrition (iron and vitamin deficiencies), anaemia, spleen removal, vitamin D deficiency, and kidney failure.

Periodontal Destruction

• A balance between host defense and bacterial challenge determines periodontal health or disease. A compromised host defense leads to periodontal destruction.

Dental Care Professional Role

• Risk assessment, full medical histories, physician liaison, antibiotic cover (when necessary), prevention, aggressive treatment of oral infections, good infection control, risk assessment for post-operative bleeding.
• Close monitoring and follow-up.

Autoimmune Disease

• A chronic, progressive disorder due to the immune system mistakenly attacking healthy body tissues.
• The body fails to recognize its own cells (tolerance). Antibodies are released to attack healthy cells.
• This can affect one organ (like in Type 1 diabetes), or the entire body (like SLE).

Autoimmunity

• With age, natural T-cell suppression may decrease; therefore, some self-antigens might be viewed as foreign.
• Other factors include emergence of normally hidden antigens, viral infections, certain medications (e.g., penicillin-induced hemolytic anemia, hydralazine causing drug-induced lupus), genetics, and endocrinological changes.

Testing for Autoimmune Disease

• Includes antinuclear antibody (ANA) tests, autoantibody tests, complete blood count (CBC), C-reactive protein (CRP) measurements, erythrocyte sedimentation rate (ESR), and urinalysis.

Autoimmunity Prevalence

• More than 80 known autoimmune conditions.
• Affects 5–7% of the population.
• 4 million people in UK living with at least one autoimmune condition.
• Women are affected significantly more often than men (85% or more) with multiple autoimmune conditions.

Autoimmune Effect on Patients

• Joint pain, swelling, fatigue, rashes, recurring temperatures, swollen glands, and gastrointestinal issues.
• Can impact mobility and mental health; and can result in lost opportunities in work and life.

Autoimmune Treatment

• There is no cure, but treatments aim to dampen the immune response. Example therapies include specific, immune-dampening drugs (non-steroidal anti-inflammatory drugs, immunosuppressants like prednisolone or ciclosporin, or mycophenolate). Other treatments exist to reduce individual symptoms (like pain, swelling, fatigue, and skin rashes).
• A well-balanced diet and regular exercise may also aid alleviation of symptoms.

Autoimmune Cost

• Direct and indirect costs in the UK for three common autoimmune diseases (Type 1 diabetes, Rheumatoid arthritis, and Multiple sclerosis) total £13 billion annually.

Autoimmunity Classification (2 groups)

• Organ-Specific: Autoantibodies target specific components of an organ, such as thyroid, stomach, and adrenal glands (e.g., Graves', Hashimoto's, Addison's).
• Generalized/Non-Specific: Immune complexes deposit on tissues, causing damage to basement membranes and organs (e.g., rheumatoid arthritis, SLE).

Examples of Autoimmune Diseases

• The presentation contains a list of autoimmune diseases and corresponding images with brief descriptive details regarding each condition

Autoimmune Diseases and Oral Manifestations

• Oral signs of autoimmune diseases can be initial manifestations, so clinicians need awareness to recognize these conditions.
• Specific oral signs include those associated with SLE, Sjögren syndrome, pemphigus vulgaris, and mucous membrane pemphigoid. Visual examples are shown in slides 37 and 38.

Summary (Dental Care Professional's Role)

• Importance of detailed medical history, current knowledge regarding autoimmune, systemic, and infectious conditions.
• Discussing medication, and the impact these conditions can have on oral and systemic health.
• Patient engagement for self-management advice.

Further Reading

• Included are links to relevant information sources.