Exam

• Autoimmunity


  Range of disorders caused by inflammation of organs due to production of antibodies against self-structures and cytotoxic T cells
• Autoimmune thyroid disease is the most prevalent type of autoimmune disease
• Autoantibodies found in patients with AITD


  • Antibodies against thyroid peroxidase
  • Antibodies against thyroid-stimulating hormone receptor (TSHR)
  • Anti-thyroglobin
• Types of AITD


  • Graves disease
  • Hashimotos thyroiditis
• Graves disease


  • Increased heart rate
  • Anxiety, restlessness, irritability, insomnia
  • Weight loss
  • Increased stool frequency
  • Irregular menstrual cycle
  • Muscle weakness
  • Goitre
  • Bulging eyes and vision problems
• Hashimoto's disease


  • Sluggishness and fatigue
  • Constipation
  • Goitre
  • Memory lapses and acute depression
  • Brittle nails and puffy face
  • Hair loss
  • Unexplained weight gain
  • Muscle weakness
  • Prolonged and excessive menstrual bleeding (menorrhagia)
• Graves disease


  Cause of hyperthyroidism - overproduction of triiodothyronine (T3) and thyroxine (T4)
• Hashimoto's disease


  Cause of hypothyroidism - immune system makes antibodies that attack the thyroid gland, leading to large numbers of WBCs building up in the thyroid and damaging it
• Pathogenesis of AITD


  Antigen release with or without thyrocyte damage, leading to auto-antigen presentation by antigen presenting cells
• Pathogenesis of Hashimoto's


  1. Release of B cell activating complement → thyrocyte necrosis

  2. CD4 release → death cell receptor/death ligand interaction → release of caspases, CD95 up-regulation → apoptosis

  3. CD8 release perforin → apoptosis
• Pathogenesis of Graves disease


  1. CD4 release → cAMP, PKA → iodide metabolism, proliferation

  2. B cell activating apoptosis

  3. High T3/T4 levels → hyperthyroidism
• Autoantibodies involved in AITD


  • Anti-TSHR
  • Anti-TPO
  • Anti-Tg
• Lab tests involved in testing for AITD


  • Autoantibody detection via immunoassay
  • Thyroid hormone level measurement
  • FBC to check Hb levels
  • Thyroid biopsy
• Diagnosis of AITD


  1. Measurement of TSH, FT3 and FT4

  2. Measurement of thyroid antibodies

  3. Immunoassay performed: labelled antibody, chemiluminescence used biotin labelled antibody
• Treatment for Graves disease


  1. Thionamides (carbimazole or propylthiouracil) - TSH receptor inhibitors

  2. Surgical thyroidectomy - complete or partial removal of thyroid, requires lifelong levothyroxine treatment

  3. Radioactive iodine treatment - destroys thyroid cells, leading to reduced T3/T4 production and decreased thyroid size
• Allergy


  Abnormal immune-mediated response to an antigen, usually responds to antihistamines and avoidance of the trigger
• Types of allergic mechanisms


  • Type 1 - IgE (urticaria, bronchospasm, anaphylaxis, angioedema, rhinoconjunctivitis)
  • Type 4 - cell mediated, delayed
• Thyroid biopsy


  Fine needle biopsy sent to histopathology
• How is AITD diagnosed?

  1. Measurement of TSH, Ft3 and Ft4

  2. Measurement of thyroid antibodies

  3. Immunoassay is performed: labelled antibody, chemiluminescence used biotin labelled antibody
• What is the treatment for Graves' disease?


  1. Thionamides- carbimazole or propylthiouracil→ TSH receptor inhibitors

  2. Surgical thyroidectomy→ once confirmed from histopathology, complete or partial removal of thyroid resulting in little or no t3/t4 production; requires lifelong treatment with levothyroxine

  3. Radioactive iodine treatment→ destroys cells in the thyroid, leading to reduction in production of thyroxine and decreased size of thyroid gland
• Allergy


  Abnormal immune-mediated response to an antigen
• Allergies


  Usually respond to antihistamines and avoidance of the trigger
• Types of allergic mechanisms


  • Type 1- IgE- urticaria, bronchospasm, anaphylaxis, angioedema, rhinoconjunctivitis
  • Type 4- cell mediated, delayed- dermatitis, eczema
• What tests are done on type 1 allergies?


  1. Serum specific IgE (RAST)

  2. Skin prick test
• What test is done on type 4 allergies?

  Patch test
• Key questions to ask when obtaining a clinical history

  • Are the symptoms consistent with IgE-mediated allergy?
  • Is there a history of atopy?
  • Is there a credible trigger? (Rapid reaction within minutes, consistent reaction on exposure, multiple unrelated triggers usually means its not)
  • Could this be spontaneous (idiopathic)?
• Spontaneous urticaria (red patches)/angio-oedema is common in adults. Can be caused by infection, stress, pre-menstrual. Allergy tests are not useful unless strong candidate suggested by history
• Angio-oedema without urticaria: check for ACE inhibitors, which can cause facial and oral swelling. It is not a drug allergy.
• A negative test does not exclude allergy
• A positive test does not prove allergy
• A high grade or level of specific IgE does not mean severe allergy
• The higher the level of IgE the more likely it is to cause allergic symptoms
• Severity of a reaction is multifactorial and generally not predictable
• HIV


  Human immunodeficiency virus- member of the lentivirus family- retrovirus
• Symptoms of HIV


  • Fever, headache, sore throat, malaise, rash, weight loss, appetite affected
  • Leads to recurrent infections
• Pathophysiology of HIV


  • Infects mature CD4+ T cells
  • Binds to CD4 and CCR5 receptors
  • Destroys CD4+ T cells → AIDS
  • Immune system compromised
• Prognosis of HIV


  • Most are asymptomatic for 2-15 years
  • Some rapidly progress to Acquired Immunodeficiency Syndrome without treatment
  • Other are long-term non-progressors and remain asymptomatic with normal CD4+ cell levels, undetectable HIV-1 viral load, and no opportunistic infections
• Transmission of HIV


  • Sexual transmission
  • IV drug use
• AIDS


  • Most advanced stage of HIV, resulting from immune system destruction
  • Characterised by opportunistic infections that would not occur in healthy people e.g. tuberculosis, toxoplasmosis, meningitis, syphilis
  • AIDS defined by clinical criteria rather than lab tests
• Methods in diagnosing and monitoring HIV


  • antigen/antibody measurement - ELISA
  • HIV-1 viral load
  • CD4 count
  • Reverse transcription-PCR