wk 16- clinical immunology

• Clinical Immunology


  The study of diseases caused by disorders of the immune system
• Clinical Immunology


  • Crosses all Biomedical Science disciplines – Haematology, Histopathology, Microbiology and Biochemistry
  • Specialising in Immunology allows for a multidisciplinary career and all Biomedical Scientists need to understand the principles of clinical immunology
• What happens in a routine clinical immunology laboratory

  • Allergy
  • Autoimmune diseases
  • Immunodeficiency
• Allergy


  An unnecessary immune response to a normally harmless substance
• Common substances people are allergic to

  • Pollens
  • Dust mites
  • Insect venom
  • Food such as nuts or shellfish
• Allergies can range in severity with the most extreme symptoms seen in anaphylaxis
• Every year in the UK, the number of allergy cases increases, mainly in children
• In the UK 40% of children have been diagnosed with some form of allergy
• Allergy


  • Hypersensitivity reaction caused by immune system
  • Two phases: First exposure – IgE Abs are made, Second exposure – Release mediators
• Type I hypersensitivity (IgE-mediated hypersensitivity)


  Causes, symptoms, pathology
• Symptoms of anaphylaxis


  • Airway swelling (laryngeal oedema)
  • Hypotension and resultant shock
  • Diarrhoea and other organ dysfunction
• Adrenaline


  The emergency medicine used to treat a severe allergic reaction, it works quickly to reverse the symptoms of anaphylaxis by helping to reduce swelling, opening up the airway, and improving the blood pressure
• Suspected allergy diagnosis methods

  • Clinical history
  • Skin Prick Tests
  • Patch Tests
  • Challenge Tests
  • Avoidance Tests
  • In vitro Diagnosis: Total IgE, Allergen Specific IgG, Allergen Specific IgE, Basophil activation
• Allergy skin prick test

  Performed in clinic, not laboratory, by placing drops of allergen extract onto the skin and pricking through with a lancet, a positive test results in a small raised wheal
• IgE and allergen testing in the lab

  1. Antigen immobilised to solid phase

  2. Add sample

  3. Wash to remove unbound sample

  4. Add conjugate-enzyme linked antibody

  5. Wash to remove unbound conjugate

  6. Add substrate – reacts with enzyme to develop fluorescence

  7. Add stop to stop reaction

  8. Read fluorescence
• Component testing in allergy

  Tests for certain specific proteins in an allergen that you may be reacting to, rather than just whole allergen testing
• Allergies that can get component testing

  • Peanut allergy
  • Tree nut allergy
  • Milk allergy
  • Egg allergy
  • Pet dander allergy (dog, cat, and horse)
  • Alpha-Gal allergy (delayed red meat allergy)
  • Insect venoms (wasp and bee)
• Tryptase


  The most abundant mediator stored in mast cells, a marker of mast cell activation that is increased in anaphylaxis and anaphylactoid reactions
• Tryptase has an important role in inflammation but its biological function has not been fully clarified
• Allergy testing in the clinical immunology lab may be used alongside skin prick testing, can be used as a reason to refer patients to the allergy team, and requires a good history to be taken from the patient
• Autoimmunity


  An inappropriate immune response directed at "self" rather than pathogen, can target an organ or be systemic
• There are over 100 recognised autoimmune conditions, they affect 10% of the adult population in the UK, and affect women in a ratio of 3:1
• In the USA autoimmune disease is one of the top 10 causes of death in women under the age of 65
• The government is recognising that there needs to be faster and better diagnosis of autoimmune disease, especially the rarer types
• Methods used to diagnose autoimmune diseases

  • ELISA
  • IIF (indirect immunofluorescence)
  • Immunoblotting
  • Chemiluminescence
• Vasculitis


  Inflammation of the blood vessels that can cause the walls to thicken, reducing blood flow and resulting in organ and tissue damage
• Types of vasculitis


  • Microscopic polyangiitis (MPA)
  • Granulomatosis with polyangiitis (GPA)
  • Eosinophilic granulomatosis with polyangiitis (EGPA)
• ANCA


  Autoantibodies that target neutrophils, specifically binding to proteinase 3 (PR3) or myeloperoxidase (MPO) in ANCA-associated vasculitis
• The outcomes of ANCA-associated vasculitis are frequently poor, with 25% mortality at 5 years and 20% of survivors developing end-stage renal disease
• Older patients with ANCA-associated vasculitis are more likely to be MPO-ANCA positive, present with more advanced renal disease, and are less tolerant of current therapies
• Plasma exchange (PLEX)


  Plasma is separated from other blood constituents and removed from the patient, replaced with fresh frozen plasma or albumin solutions, to remove a circulating pathogenic factor
• Rituximab (MabThera)


  A chimeric therapeutic monoclonal antibody that depletes B-cells by binding to the CD20 antigen, licensed for treatment of ANCA-associated vasculitis
• Coeliac disease


  A common autoimmune condition where the body has an inappropriate immune response to gluten
• Symptoms of coeliac disease

  • Diarrhoea
  • Malabsorption leading to steatorrhoea
  • Abdominal pain
  • Bloating and flatulence
  • Indigestion
  • Constipation
  • Vomiting
  • Fatigue
  • Unexpected weight loss
  • Itchy rash
  • Difficulty getting pregnant
  • Tingling and numbness
  • Disorders affecting coordination, balance and speech
  • Swelling of hands, feet, arms and legs
• Coeliac disease screening


  IgA-based test with high sensitivity and specificity, positive results followed up with endomysial antibody testing by IIF
• Routine testing for coeliac disease is not recommended unless you have symptoms or an increased risk of developing them
• While being tested for coeliac disease, you need to eat foods containing gluten to ensure the tests are accurate, and should not start a gluten-free diet until the diagnosis is confirmed
• Peripheral neuropathy


  Tingling and numbness in your hands and feet
• Ataxia


  Disorders that affect co-ordination, balance and speech
• Oedema


  Swelling of the hands, feet, arms and legs caused by a build-up of fluid