12.1 Clinical immunology Flashcards
Describe the innate vs adaptive immune systems.
Innate: non-specific, general, immediate, no memory
- Humoural: pattern receptors, complement, enzymes, cytokines
- Cell mediated: phagocytes, NKcells
Adaptive: specific, lag time from exposure to response, memory
- Humoural: antibodies and cytokines
- Cellular: T cells and B cells
What are the primary and secondary organs of the immune system?
Primary:
- Bone marrow for production of all haematopoietic cells
- Thymus for T cell maturation
Secondary:
- MALT, tonsils, adenoids
- Lymph nodes and lymphatic system for tissue fluid surveillance
- Spleen for blood surveillance
What are the lymphoid organs?
Sites of generation, maturation and initiation of adaptive immune response.
- Central lymphoid organs: thymus and bone marrow
- Peripheral lymhpoid organs: lymph nodes, spleen, mucosal/gut-associated lymphoid tissue
Outline the functions of the immune system.
- Searches out and destroys pathogens
- Searches out and destroys cancerous self-cells
- Clears debris from sites of inflammation
- Promotes healing of wounds
All of this while not harming normal self-cells.
What is immunodeficiency?
Defects or deficiencies in the immune system (congenital or acquired).
What is autoimmunity?
Abnormal activation of the immune system.
Immune response directed at self-antigens due to breakdown of normal regulatory mechanisms.
Caused by failure of central tolerance: failure of deletion of self reactive T-cells and B-cells.
What is an autoimmune disease?
Damage or disturbed physiological function due to autoimmunity.
Women are more commonly affected than males.
How are autoimmune disease classified?
Organ specific:
- Thyroid disorders e.g. Grave’s
- Tybe 1 diabetes
- Autoimmune haemolytic anaemia
Non-organ specific:
- Systemic lupus erythematosus
- Connective tissue diseases (e.g. rheumatoid)
What are the risk factors and triggers of autoimmune disease?
Genetics:
- Multigeneic
- Complement classical pathway deficiency
Environment:
- Hormones: oestrogen
- Infection
- Drugs e.g. penicillamine
- Others: stress, diet, UV
How are autoimmune diseases treated?
- Endocrine: replace deficient hormone/remove oversecreting gland
- Immunosuppression: steroids, cyclosporin, methotrexate, azathioprine
- Newer treatments: monoclonal antibodies e.g. anti-B cell, anti-TNF-alpha
What autoimmune condition may present with diffuse parotid gland enlargement?
Sjogren’s syndrome
Describe the main features of Sjogren’s.
- Autoimmune disorder affecting the exocrine glands (esp salivary and lacrimal glands)
- Complaints of dry mouth and dry eyes
- Affects females more than males (9:1)
- Clinical diagnosis from history and signs
- Schirmer’s test: tear production
- Lab diagnosis: biopsy; positive ANA,
anti-Ro and anti-La antibodies
What are the oral features of Sjogren’s, how can these be managed?
Zerostomia can lead to:
- Dental caries
- Gum and tongue atrophy
- Difficulty swallowing
- Associated with other autoimmune diseases (RA, SLE)
Management:
- Mouth washes and good dental care
- Salivary stimulants
- Dental check-ups
- Artificial tears
What are autoinflammatory disorders?
Lack of control of inflammation.
Not autoimmune, as there is not an immune response targeted at self antigens in autoinflammatory disorders.
Give an example of an autoinflammatory disorder.
Periodic fever with apthous stomatitis, pharyngitis and cervical adenitis (PFAPA).
Hereditary.
What cytokines do activated macrophages secrete?
- IL-1
- TNF-alpha
- IL-6
- IL-8
- IL-12
How might a dentist recognise an immunodeficiency?
Patients with peristsent infection e.g. oral candida
How are immunodeficiencies classified?
Primary: genetic defect, can cause missing component, missing cell type, missing enzyme
Secondary: acquired, secondary to an underlying disease or drug induced.
What are the possible signs of primary immunodeficiency in children?
- 4 or more new ear infections within a year
- 2 or more serious sinus infections within a year
- 2 or more months on abx with little effect
- 2 or more pneumonias within a year
- Failure to gain weight or grow normally
- Reccurent, deep skin or organ abscesses
- Persistent thrush or fungal infection
- Need for IV abx to clear infection
- 2 or more deep seated infections including septicemia
- Family history of PI
What underlying disease or drugs can cause secondary immunodeficiencies?
- Malignancy
- Infection (e.g. HIV)
- Malnutrition
- Immunosuppressive drugs e.g. chemo, biologic drugs such as Rituximab, long term prednisolone
Describe antibody deficiencies.
- Can be hereditary, acquired, iatrogenic, idiopathic
- Recurrent sinus/respiratory infections
- Diagnosis: family history, Ig levels measures, functional test respinses to vaccination
- Management: prophylactic abx, replace immunoglobulin, promptly treat infections
How do antibody deficiencies affect dental treatmemt?
- If patient is diagnosed, they’re likely to be established on immunoglobulin replacement therapy
- Other than usual high standards of hygiene no further special measures may be necessary
- Low threshold for treating (suspected) infection
- If in doubt, discuss case in advance with immunologist looking after the patient
Describe neutrophil deficiencies.
- Reduced numbers either due to decreased production (e.g. cytotoxic drugs, leukaemia) or increased destruction (e.g. hypersplenism)
- Causes impaired intracellular killing and impaired leukocyte adhesion
Describe T cell deficiencies.
- T-cell deficiency is often very severe
- SCID: severe combined immunodeficiency
- Presents early (weeks/months after birth)
- Chronic diarrhoea and failure to thrive are common
- Lymphopenia
- Bone marrow transplant is usually the only possible treatment
Describe complement deficiencies.
- C3 deficiency = recurrent bacterial infections
- Terminal pathway deficiencies = recurrent Neisserial infections (meningitis)
What is hereditary angiodema?
- Autosomal dominant condition
- Mutation in SERPIGN1 gene
- Uncontrolled classical pathway complement activation, deficiency of C1 esterase inhibitor
- Oedema of skin and mucous membranes
- Dental procedures are potential triggers of angiodema attacks
- NOT an allergy
How should hereditary angiodema be managed in dental practice?
- Liaise with physicians
- Cover procedure with an increase in medications (e.g. tranexamic acid) and/or with C1 inhibitor concentrate
- Emergency: protect airway and give C1 inhibitor
Describe HIV and AIDS.
- HIV: retrovirus, single stranded RNA
- Main target cells are CD4+ T helper cells and macrophages
Stages of disease: - Infection and seroconversion
- Asymptomatic phase
- Symptomatic phase (generalised lymphadenopathy)
- AIDS
What are the possible dental complications of HIV and AIDS?
- Oral candidiasis
- Oral hairy leukoplakia: triggered by EBV
- Kaposi’s sarcoma: virally driven cancer, associated with HSV-8
- Aphthous ulceration
- NUG
How are pts with HIV and AIDS managed?
- Antiretroviral therapy
- Monitor CD4 T cell count and viral load
What is infective endocarditis?
Inflammation of the endocardium, particularly affecting the heart valves, caused mainly by bacteria but occasionally by other infectious
agents.
Life threatening disease with significant mortality (approx. 20%) and morbidity.
What are the important causative organisms in IE?
- Streptococci
- Staphylococcus aureus
- Enterococci
What are the signs and symptoms of IE?
- Fever
- Murmur
- Roth spot (eyes)
- Janeway lesions (palms of hands and feet)
- Splinter haemorrhages (nails)
- Anaemia
- Osler nodes (hands)
- Emboli
What medication do hereditary angiodema patients require prior to dental treatment?
Prophylactic C1-esterase inhibitor
What medication do patients with antibody deficiencies require prior to treatment?
- Preoperative prophylactic abx +/- immunoglobulin replacement according to lecture
- No official guidelines
