Hypersensitivity case studies Flashcards
A 52-year-old woman has been brought into the emergency room in an unconscious state. She was watching the test match at Lord’s, when she suddenly developed swelling on the face, complained of feeling nauseous and then collapsed. On arrival at the hospital she has angiodema of the face. Her blood pressure is low and heart rate fast.
What disease might it be?
What hypersensitivity reaction could it be?
What might the immunological mechanism be?
Bee sting- anaphylaxis
Type I
Expression of IgE antibodies against certain antigens
Allergen enters the skin and collected by immature dentritic cell and taken to the lymph node.
In node presented to Th2 cell which activate B cells. These then travel to the site of the antigen where Th2 produce IL-4, IL-5 and IL-13 which cause class switching of the B cells to produce IgE
IgE binds to basophils and mast cells to produce primed cells
Upon a second encounter the primed Mast and Basophils, causes degranulation of the cells releasing histamine, serotonin, chemotactic factors and proteases
which cytokines cause class switching of B cells
IL-4,5,13
A 62-year-old women complains of increasing anxiety and restlessness. Her doctor notices that she has an enlarged thyroid gland and fast pulse. In addition she has exophthalmos.
Graves’ disease
Type II
Thyroid is overactive, producing an excessive amount of thyroid hormones
Thyroid autoantibodies that activate the TSH-receptor, thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth
High serum thyroid autoantibodies (TSHR-Ab)
Antibodies bind directly to antigen on the surface of the cell and induce their lysis.
Mainly IgG and IgM antibodies. Activates classical complement pathway, C3b binds to the surface of the and the cascade leads to MAC formation and cell lysis. Or C3b can bind to CR1 receptors on neutrophils and cause them to be killed via ‘frustrated phagocytosis’. Or ADCC with NK cells
Anti-thyroid drugs
Thyroidectomy
A 55 year old woman with joint pains and a rash on her face and ulcers on her tongue is given a blood test. Her blood contains anti-nuclear antibodies, many of which are against DNA. Several months later she mentions her joint pain is worse and she has high protein levels in her urine.
Systemic Lupus Erythematosus
Type III
Is a systemic autoimmune disease (or autoimmune connective tissue disease) that can affect any part of the body Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE, Anti-dsDNA antibodies are highly specific for SLE
Abnormalities in apoptosis and cell clearance
Binding causes the triggering of the classical complement cascade and clearance by phagocytes and deposition of C3b interferes with the growth of the antigen-antibody structure- however inefficient removal allows the antigen-antibody complex to grow and an immune complex to form.
Immune complexes become lodged in vessels and cause inflammation and damage to endothelial cells which then allows immune cells and complement to enter underlying tissues and cause damage
A 35-year-old man complains of visual impairment in his left eye. Six months earlier he had noticed numbness and tingling in both legs for approximately 3 weeks. An MRI scan of his brain is performed and shows many lesions in the white matter.
Multiple sclerosis
Type IV reaction
Fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring
Mediated by antigen-specific effector T cells
Antigen recognised by APCs and presented to Th1 effector cells and cause activation.
Th1 initiate further inflammatory responses, recruit fluid, proteins and other leucocytes and phagocytes to the area
Th1 release chemokines for macrophage recruitment, IFN-gamma for macrophage activation, TNF for increased expression of adhesion molecules, IL-3/GM-CSF monocyte production
A 50-year-old man complains of a 6 month history of pain in his hands, wrists and feet. The pain is worse in the morning, when his joints are stiff for an hour or so. The small joints in his hands are swollen and tender. He has swelling of the metacarpophalangeal and proximal interphalangeal joints. He has high levels of CRP in his blood.
Rheumatoid Arthritis
Type IV
May affect many tissues and organs, but principally attacks flexible (synovial) joints
A year ago a 45-year old man began a new career as an agricultural worker, he complains of breathlessness, coughing, malaise and fever on several occasions after feeding the cattle. The symptoms develop several hours after exposure to hay and last for 2 days. A blood sample shows he has antibodies against mould extract. In addition his symptoms are reproduced 5 hrs after deliberate challenge with mould.
Farmers lung/ Pigeon Fanciers lung
Type III reaction
Inhalation of biologic dusts, usually moulds and fungi
Soluble antigen and antibodies bind together to form complexes
Binding causes the triggering of the classical complement cascade and clearance by phagocytes and deposition of C3b interferes with the growth of the antigen-antibody structure- however inefficient removal allows the antigen-antibody complex to grow and an immune complex to form.
Immune complexes become lodged in vessels and cause inflammation and damage to endothelial cells which then allows immune cells and complement to enter underlying tissues and cause damage
Immune complexes in the lung damage the alveoli and cause fluid build up which decreases lung function and reduces gaseous exchange
A 45 year old women has developed increasing fatigue over three weeks. She is jaundiced and her spleen is enlarged. A blood count shows features of haemolysis. A direct Coombs test shows her red blood cells are coated in IgG antibodies.
Autoimmune haemolytic anaemia
Type II
Lytic destruction of RBCs
Autoantibodies against the bodies own RBCs
Corticosteroids are the treatment
Antibodies bind directly to antigen on the surface of the cell and induce their lysis. Mainly IgG and IgM antibodies. Activates classical complement pathway, C3b binds to the surface of the and the cascade leads to MAC formation and cell lysis. Or if bound by IgM they travel to the liver where they are phagocytosed by resident Kuppfer cells. If they are bound by IgG they travel to the spleen and are phagocytosed by resident macrophages using ADCC
