Immunology - Autoimmunity Flashcards
List the common sites and organs affected by autoimmune conditions
- autoimmune uveitis: eyes
- autoimmune oophritis: ovaries
- Sjogrens Syndrome: mouth
- pemphigus: skin and mucosa
- Goodpasture’s syndrome: lung
Describe self-tolerance
Self-tolerance is the body’s ability to recognise and therefore not respond to self-produced antigens. There are 2 mechanisms - recessive (during development) and dominant (regulated by T cells).
Recessive (deletional) tolerance: self-reactive T cells are deleted in the thymus, some are able to escape this mechanism and cause damage to tissues in the periphery
Dominant (regulatory) tolerance: T cells specific to self-antigens become regulatory T cells responsible for keeping in check the activation and expansion of abnormal lymphocytes/T cells by producing cytokines which inhibit other self-reactive T cells
List the processes thought to be involved in the breakdown of self-tolerance
- failure to delete autoreactive lymphocytes
- central/peripheral self-tolerance failure
- molecular mimicry
- abnormal presentation of self-antigen
- overproduction of self-antigen
- aberrant expression of HLA-Class II molecule
- release of sequestered self-antigens
- cryptic T cell epitopes
- spread of epitopes
Describe a condition that breaks down self-tolerance through molecular mimicry
Rheumatic fever (group A strep - mainly throat)
- antibodies are generated against the strep carbohydrate which mimics normal cardiac myosin
- a cross reaction occurs and T cells are also generated
- causes heart valve damage and can cause brain/neuronal damage
Describe the signs and treatment of systemic lupus erythematosus (SLE)
Signs:
- butterfly rash with raised red patches
- photosensitivity
- mouth ulcers
- heart and lung lining inflammation
- seizures/nerve problems
- proteinuria
- ANA in serum
Treatment: systemic corticosteroids, steroid creams, antimalarials (hydroxychloroquine) and monoclonal antibodies (rituximab)
What are the cautions and treatment for Sjogren’s Syndrome (dry eyes, dry mouth)?
Cautions: 5x increased risk of developing non-Hodgkin’s lymphoma, night sweats, swollen glands, and unexplained weight loss
Treatment: eye drops, antifungals, NSAIDs, hydroxychloroquine, methotrexate
What is the pathogenesis and treatment of Grave’s Disease?
Pathogenesis: antibodies are generated against the TSH receptor mimicking TSH resulting in the overstimualtion of the thyroid
Treatment: methimazole, thyroidectomy, radioactive iodine
What is the pathogenesis, signs and treatment of Hashimoto’s Disease?
Pathogenesis: anti-thyroid antibodies are generated which attack the thyroid tissue causing inflammation and fibrosis
Signs: feeling cold, fatigue, weight gain and enlarged thyroid (goiter)
Treatment: replacement with levothyroxine
What is the pathogenesis, signs and treatment of Myasthenia Gravis?
Pathogenesis: antibodies are generated which attack the components of the post-synaptic membrane of the NMJ (ACh receptors) resulting in impaired NMJ transmission and function
Signs: diplopia, ptosis, drooping of facial muscles, skeletal muscle weakness esp. after exercise
Treatment: thymectomy, immunosuppressant drugs, plasmapharesis to remove circulating antibodies
Describe the pathogenesis and treatment of autoimmune pernicious anaemia
Pathogenesis: antibodies are formed which attack intrinsic factor and parietal cells resulting in a vitamin B12 deficiency
Treatment: vitamin B injections
Describe the pathogenesis, signs and treatment of autoimmune haemolytic anaemia
Pathogenesis: antibodies generated (drug induced/agent that changes RBC surface) and bind to RBCs causing lysis and clumping of RBCs which is cleared by the spleen
Signs: chills, tachycardia, pale, fatigue, jaundice, dark urine
Treatment: avoid causative drug, plasmaphresis, splenectomy
Describe the genes associated with RA
- HLA-DR genes (closely linked to other genes in MHC)
- believed to bind to arthritogenic peptides
- act as a target for autoreactive T cells
Describe the drugs used to treat RA
- symptomatic relievers: corticosteroids, NSAIDs, analgesics
- disease modifiers: methotrexate, sulfasalazine, cyclosporine, azathioprine, hydroxychloroquine, minocyline
- biological modifiers: infliximab (anti-TNF), rituximab (anti CD-20)
- combo DMARD therapy
