Immune Disorders

GDC Learning Outcomes

• Medical and psychological conditions impact a patient.
• A general overview of immune disorders will affect the population.
• There will be contextualisation to oral manifestations.

Intended learning outcomes

• Immunopathology includes hypersensitivity reactions, autoimmunity and immunodeficiency.
• Hypersensitivity and its types will be defined.
• Immunodeficiency and its causes will be defined.
• Autoimmune disease and its impact will be defined.
• How autoimmune disease manifests in the oral cavity will be related

Assessment

• Formative questions relate to the subject in the Biomedical Sciences online quiz.
• Summative questions are incorporated in the Biomedical Sciences Eassessment.

Immunopathology

• Faulty innate or adaptive immune responses may incur illness or disease.
• Hypersensitivity is an overactive immune response.
• Immunodeficiency is an ineffective immune response.
• Autoimmunity is an inappropriate reaction to self.

Hypersensitivity

• Hypersensitivity occurs when the body meets an antigen for the second or succeeding times.
• This results in the production of an excessive immune response causing gross tissue damage.

Type I hypersensitivity reaction

• The most common type includes rapid onset and it occurs within 1 hour.
• It is provoked by re-exposure to a specific type of antigen, allergen.
• High levels of IgE are secreted by plasma cells.
• IgE antibodies bind to receptors on the surface of mast cells and basophils, causing them to be sensitized.
• At subsequent exposure to the same allergen, the antigen binds to parts of IgE molecules, initiating degranulation of mast cells and the release of active mediators, like histamine.

Type I continued

• Reactions may be localized or generalized.
• Systemic reactions are life-threatening, like penicillin or bee sting.
• Localized reactions include hay fever, extrinsic asthma and urticaria (skin swellings).
• Triggers can include pollen, animal fur – cat/dog/horse, dust mites, mould, and some foods.
• Treatment includes avoidance of triggers, pharmacological intervention, or immunotherapy for severe cases.

Type II hypersensitivity reaction - cytotoxic

• This reaction is rare and develops between 2-24 hours.
• IgG and IgM antibodies bind to cell surfaces.
• Mediated by complement system or by killer cells.
• Results include opsonization, red blood cell agglutination, and cell lysis
• For example, haemolytic reactions during transfusion of incompatible blood, some drug reactions, and autoimmune anaemias.

Type III hypersensitivity reaction- immune complex mediated

• Develops over hours, days, to weeks.
• IgG and IgM antibodies bind to free, soluble antigen forming immune complexes.
• Immune complexes lodge in and pass through blood vessel walls.
• Leads to complement activation, initiates inflammatory and tissue damaging reactions.
• Neutrophil influx and mast cell degranulation.
• Examples of the reaction: systemic lupus erythematosus, serum sickness, and rheumatoid arthritis

Type IV hypersensitivity reaction- cell mediated

• The second most common hypersensitivity type which develops in 2 or more days.
• It is cell mediated and antibody independent.
• Caused by overstimulation of T cells and monocytes/macrophages.
• Leads to a release of cytokines, causing inflammation, cell death and results in tissue damage which causes prolonged inflammation, damaging normal tissues.
• Mitigated by trigger avoidance and use of corticosteroids.

Dental Implications

• Check medical histories of atopic individuals.
• Be aware of latex allergies for staff and patients.
• Chlorhexidine can cause allergies.
• Allergies can be caused by benzocaine topical anaesthetic or sodium metabisulphite and dentine bonding agents.
• Contact dermatitis can affect staff and patients.
• More information is shared when subjects are covered & in medical emergencies session.

Immunodeficiency

• This is a compromised or absent immune system response to infectious diseases.
• It includes primary and secondary immunodeficiencies, which lead to immunodeficiency diseases.

Primary immunodeficiency

• Includes B cell and T cell immunodeficiencies, both adaptive.
• Severe combined immune deficiencies (SCID) are also adaptive.
• Phagocyte and complement defects are innate components.

Primary immunodeficiencies

• It is genetically determined and rare.
• Classified according to immune defect.
• B cell defects e.g. IgA deficiency.
• T and B cell defects e.g. Severe combined immunodeficiency.
• Complemented by complement deficiencies and granulocyte defects e.g. Papillon-Lefevre syndrome.
• Getting serious life-threatening infections, and increased incidences of malignancy or autoimmune disease.
• There is a Down's Syndrome correlation to tendencies towards advanced periodontal disease.

Secondary immunodeficiency

• Causes include malnutrition, chronic infections, and drug regimens

Oral implications of patients taking immunosuppressant drugs

• Oral candidiasis is common.
• There is a higher incidence of bacterial and viral infections e.g. herpes simplex or zoster.
• Periodontal disease may emerge.
• Gingival swelling with ciclosporin may emerge.
• Oral ulceration and poor healing.
• There is increased risk of malignancy

Diseases that make a patient immunocompromised

• These include poorly controlled diabetes and HIV infection.
• Some malignancies can cause it, e.g. Hodgkin disease, leukaemias, lymphomas, and multiple myeloma.
• It can be caused by malnutrition (iron and vitamin deficiencies)
• Further causes include: Anaemia, Spleen removal, Vit D deficiency, Kidney failure, Sickle cell disease leads to hypofunction of spleen

Dental Care professional role

• Perform risk assessments and take full histories.
• Liaise with the patient’s physician.
• Antibiotic cover may be required by physician before dental surgery.
• Focus on prevention!
• Oral infections may need aggressive treatment.
• Implement good infection control e.g. management of dental unit water lines.
• Check risk of post-op bleeding if immunosuppressive drugs are taken and close monitoring and follow up is needed.

Autoimmune disease

• An autoimmune disease is a chronic and progressive disorder.
• Healthy tissue is targeted and destroyed by the body’s own immune system.
• Normally, the immune system can distinguish foreign cells from the body’s cells (tolerance).
• In autoimmune disease, the immune system mistakenly attacks part of the body, e.g. joints or skin, recognizing these cells as foreign, releasing autoantibodies attack healthy cells.
• Some autoimmune diseases target only one organ, like Type 1 diabetes damages the pancreas.
• Other diseases, like systemic lupus erythematosus, affect the whole body.

Autoimmunity

• With age, natural T cell suppression reduces, impacting autoimmunity.
• Self-antigens may be viewed as foreign = breakdown of tolerance to self-antigens, giving rise to autoimmunity.
• Other factors that lead to autoimmunity include normally hidden antigens, Infections (especially viral) and drugs, genetics, and endocrinological changes (hormones).
• Penicillin can cause Penicillin-induced hemolytic anaemia.
• Hydralazine can cause Drug-induced lupus (DIL).

Autoimmune reactions – how may they occur?

• 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 leading to antibodies attack the heart.
• 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
• The immune cells that make antibodies malfunction and make abnormal antibodies that attack normal cells in the body.
• A substance in the body that is normally hidden from the immune system enters the bloodstream e.g. after trauma.

Testing for autoimmune disease

• Antinuclear antibody tests check for antibodies that attack the cell nuclei.
• Autoantibody tests search for specific antibodies to body’s own tissues.
• Complete blood counts.
• C-reactive protein measures inflammation throughout the body.
• Erythrocyte sedimentation rate indirectly measures the level of inflammation in the body.
• Urine test or urinalysis.

Autoimmunity continued

• There are more than 80 known autoimmune conditions.
• Seen in 5-7% of the population.
• Greater than 4 million people in UK living with one condition.
• It affects women more than men, as 85% or more patients of multiple autoimmune diseases are female.

Autoimmunity continued, Effect on lives

• Joint pain and swelling, fatigue, rashes/skin problems, recurring temperatures/low grade fever, swollen glands, abdominal pain/digestive issues
• It results in difficulties in many areas, e.g. mobility, mental health, and lost opportunities in work and life.

Treatment of autoimmune diseases

• No cure is available.
• Specific drugs can dampen down the immune response, reducing inflammation.
• Non-steroidal anti-inflammatory drugs, like Ibuprofen, and immunosuppressants e.g. Prednisolone, Ciclosporin, Mycophenolate can alleviate the condition.
• Other treatments relieve symptoms such as pain, swelling, fatigue, and rashes.
• Eating a well balanced diet and regular exercise can help

Autoimmunity continued, financial cost

• Direct & indirect costs (UK) for 3 autoimmune diseases are high.
• £13 billion annually is directly and indirectly spent.
• The conditions are Type 1 diabetes, Rheumatoid arthritis and Multiple sclerosis.

Autoimmunity continued, two groups

• Organ specific disease: disorders caused by autoantibodies directed at specific components of the organ such as thyroiditis (Grave's and Hashimoto's diseases); autoimmune gastritis (pernicious anaemia); autoimmune adrenalitis (Addison's disease).
• 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, like rheumatoid arthritis, systemic lupus erythematosus

What do we know now about Covid-19?

• It is an emerging field.
• There is a possible role of destructive immune response in severe acute illness and Long Covid.

Autoimmune diseases and oral manifestations

• Oral signs of autoimmune diseases are often the initial manifestation.
• Examples include Systemic lupus erythematosus, Sjögren syndrome, Pemphigus vulgaris, Mucous membrane pemphigoid

Summary

• The immune system defends our body externally and internally with the innate and acquired responses.
• Faulty innate or adaptive immune responses may lead to illness or disease.
• Hypersensitivity is an overactive immune response.
• Immunodeficiency is an ineffective immune response.
• Autoimmunity is an inappropriate reaction to self.
• As a dental care professional, it is vital to take a comprehensive medical history from the patient at each visit, have up to date knowledge of conditions/diseases/medications likely impacting the patient’s oral and systemic health, and engage the patient to help them understand how to help themselves- reassure, educate and motivate.