immunology autoimmune disease Flashcards
what are features of the innate immune response
- rapid first response to infection (0-96 hours)
- no immunological memory
- non specific
what are features of acquired immunity
- lag time from exposure to response (>96 hours)
- immunological memory thus subsequent responses are faster and more powerful
- specific for each antigen encountered
- self regulating through regulatory T cells
- can distinguish self from non self and should only react against non self
what is myasthenia gravis
an autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest
what is the epidemiology of myasthenia gravis
- females <40 years on average and males >60 years old on average
- strong links between thymomas and myasthenia gravis
what is the pathophysiology of myasthenia gravis
- initiating event
- self reactive B cells activated by nAchR subunits in secondary lymphoid tissues
- plasma cell differentiation
- secretion of IgG antibodies that bind to nAchRs
- decreased stimulation of nAchRs by endogenous Ach
- decreased muscle contraction
why does muscle contraction return to normal in myasthenia gravis patients after a period of rest
- antibody bound receptors are transiently internalised into muscle cells by endocytosis
- the bound antibody is released into acidic environment of the endo-lysosomal compartment
- early on in the disease, nAchRs are returned to the cell membrane, ready and able to bind to endogenous Ach
- longer term: internalised nAchRs are degraded, leading to permeant muscle weakness
what is the clinical presentation of myasthenia gravis
- extaocular muscle weakness –> double vision
- eyelid weakness –> drooping of the eylids
- weakness in facial movements - difficulty with swallowing
- fatigue in the jaw when chewing
- slurred speech
- progressive weakness with repetative movements
hoe do you diagnose MG
- lab tests - look for the presence of autoreactive antibodies in serum ie anti-AChR, anti-MuSK, anti-LRP4
- scan the thymus gland and look for a thymoma
- repetative nerve stimulation - gradually reducing responses (smaller and smaller muscle response with each repetitive stimulus) indicates NMJ dysfunction
- edrophonium (or neostigmine) test
what is the treatment of MG
- increase neurotransmission (to improve symptoms) first line drugs for mild/moderate MG - reversible anti-cholinesterase agents
- surgery (if indicated) - thymectomy
- immunosuppressants (to reduce autoimmune reactions) - second line treatments for moderate/severe MG eg corticosteroids, azathioprine, rituximab
- MG crisis: O2 and/or ventilator, plasmapheresis, IVIG
what is rheumatoid arthritis
an autoimmune condition that causes chronic inflammation of the synovial lining of the joints, tendon sheaths and bursa. It is an inflammatory arthritis
what is the epidemiology of rheumatoid arthritis
- women>men
- middle age
- genetics
- smoking increases risk
what is the clinical presentation of rheumatoid arthritis
- symmetrical distal polyarthropathy
- pain, swelling, stiffness
- fatigue, weight loss, flu like illness, muscle aches and weakness
what type of hypersensitivity reaction is rheumatoid arthritis
driven by type IV hypersensitivity mechanism but secondary type III hypersensitivity responses can also occur as the disease progresses
how do you diagnose rheumatoid arthritis
lab tests
- screen for the presence of rheumatoid factor or anti CCP antibodies in patient serum
- inflammatory markers such as CRP
Xray of the hands and feet
- help with diagnosis and determination of severity
- joint destruction and deformity
- soft tissue swelling
- periarticular osteopenia
- bony erosions
what is the treatment of rheumatoid arthritis
- immunosupression = first line treatment to prevent T cell activation, proliferation and differentiation
- Biological therapies = to reduce tissue damage and improve symptoms - monoclonial antibodies that block the cation of proinflammatory cytokines of destroy B cells
