Tolerance & Autoimmunity Flashcards
Define immunological tolerance and autoimmunity
Tolerance = unresponsiveness of the immune system to an antigen (inc self-antigens)
Autoimmunity = an immune response to self antigens, usually from a failure of immunological tolerance leading to immune mediated damage of specific tissues (environmental and genetic factors)
Define antigen
Substance capable of generating an immune response
How can the immune system respond to an infinite number of antigens?
Immune system pre-programmed to recognise any threat by T & B cell genetic recombination = infinite variety of specific receptors for any possible antigen on each cell (one type of receptor on each cell)
If a specific T or B cell is activated by a specific antigen, it will undergo clonal selection to replicate and produce a specific response
What type of immunity is involved in autoimmunity?
Adaptive immunity as requires T and B cell response
T cell cytotoxicity
B cell antibody production
Outline central tolerance
Main role is to prevent immune responses to self antigens - most active in foetus and declines after birth (develops in thymus and bone marrow)
Immature lymphocytes that recognise self antigens undergo clonal deletion by apoptosis
Outline peripheral tolerance
Active throughout life - develops in peripheral lymphoid tissue to develop tolerance to things foetus not exposed to
Mature lymphocytes that recognise self-antigens undergo clonal suppression by regulatory T-cells
Why is it important for us to understand immunological tolerance?
Improves understanding of: Autoimmune diseases Recurrent miscarriages Hypersensitivity disorders Chronic infections Malignancies that induce tolerance Rejection of organ transplants
Why are autoantibodies measured for tolerance?
Almost all loss of tolerance seems to be B-cell mediated
What are the different HLA genes associated with?
HLA-B27: ankylosing spondylitis, reactive arthritis
HLA-DR2: systemic lupus erythematous
HLA-DR3: autoimmune hepatitis, Sjogrens syndrome, T1DM
HLA-DR4: rheumatoid arthritis, T1DM
What are some environmental causes of autoimmune diseases?
Infection (eg gastroenteritis -> reactive arthritis)
Chemicals (anticonvulsants/antibiotics -> drug induced lupus)
Neoplasms (eg teratoma -> autoimmune encephalitis)
Trauma (exposure of self antigens at protected sites eg eyes)
What are the most common autoimmune diseases? Which gender?
Graves disease and Rheumatoid arthritis
75% of cases are female
Outline Grave’s disease, include clinical features
Autoantibodies against TSH receptor -> persistent thyroid gland stimulation to release T3/T4 and increase basal metabolic rate
Cause of hyperthyroidism
Exopthalmous (autoantibodies against ophthalmic muscles)
Pretibila myxoedema
Goitre
Hyperthyroidism (sweating, anxiety, tiredness, weight loss, increased appetite)
How are autoimmune conditions diagnosed? (the autoantibodies involved in the common ones)
Presentations depend on organs affected
Maybe by HLA typing
Confirmed by identifying specific autoantibodies
Grave’s disease - against TSH receptor
RA = Rheumatoid Factor
Sjorgens syndrome - ANA (antinuclear antibody)
SLE = ANA or dsDNA
What’s Systemic Lupus Erythematous?
Systemic autoimmune disease affecting many tissues: Skin: rash, photosensitivity CNS: cerebral lupus Heart: pericarditis Lungs: pleural effusion, pulmonary fibrosis Kidneys: glomerulonephritis Blood: anaemia Systemic: malaise, fever, weight loss
Anti-phospholipid syndrome = thrombophilia and recurrent miscarriages (secondary form is seen with SLE)
How are autoimmune conditions treated?
Steroids: anti-inflammatory and immunosuppressive to reduce cytokines (IL-2) and humoral immunity
DMARDs: anti-inflammatory and immunosuppressive
Monoclonal antibodies: more specific actions than DMARDs (infliximab, anti-TNF or rituximab, anti-CD20)
