Immunology Flashcards
1
Q
Name some examples of autoimmune diseases affecting the MSK system
A
- rheumatoid arthritis
- myasthenia gravis
- scleroderma
- polymyositis
- dermatomyositis
- lupus
- sjogrens syndromes
- relapsing polychondritis
- eosinophilic fasciitis
- vasculitis
2
Q
What is myasthenia gravis?
A
- an autoimmune neuromuscular disorder characterised by severe muscular weakness and progressive fatigue
- autoimmune disease in which auto-reactive antibodies (auto-IgG) binds with ACh receptors on muscle cells
- also associated with other autoimmune disorders such as SLE, rheumatoid arthritis and thyrotoxicosis
3
Q
Describe the epidemiology of myasthenia gravis
A
- can occur at any age
- 90% of cases - no known cause
- thymic tumour; 10% of cases
- genetic predisposing factor - HLA associations
4
Q
Describe the clinical manifestations of MG
A
- onset typically insidious, initial symptoms involve ocular muscles in 60% of cases
- may first appear during pregnancy, postpartum or with the administration of certain anaesthetic agents
- complaints are fatigue and progressive muscle weakness
5
Q
Describe the pathophysiology of MG
A
- autoimmune response mediated by specific IgG antibodies that recognise postsynaptic ACh receptors
- involvement of CD4+Th cells and ACHr self-antigens in activating auto-reactive B cells
- CD4+ T cells are activated by unfolded ACHr subunits expressed by thymic epithelial cells
- Cde4+ Th cells stimulate auto-reactive B cells, resulting in the production of anti-AChR IgG auto-antibodies
- thymic myoid cells that express intact AChRs are then attacked by these antibodies, and release AChR immune complexes
- AChR immune complexes in turn activate antigen presenting cells and diversify the autoantibody response to recognise intact AChRs
6
Q
Thymic myoid cells correspond to what?
A
A muscle like cell population present in the thymus, express ACh receptors
7
Q
Describe action potentials in MG
A
- the antibodies bind to ACh receptors in post synaptic membrane and block them to diminish muscular response
- more profound effect on muscles by altering the architecture of cells so clefts etc are lost
- this down regulates muscle responsiveness
8
Q
Describe the diagnosis of MG
A
- laboratory tests; presence of anti-AChR IgG in serum
- repetitive nerve stimulation; gradually reducing responses (smaller and smaller muscle response with each repetitive stimulus) indicated NMJ dysfunction
9
Q
Describe the treatment of MG
A
- increase neurotransmission (first line treatment > improve symptoms); anti cholinesterase agents (eg pyridostigmine), increase half life of ACh in synaptic cleft
- surgery (first line treatment, if indicated); thymectomy
- reduce autoimmune reactions (second line treatments); immunosuppressive drugs, corticosteroids
10
Q
What is rheumatoid arthritis?
A
- an autoimmune disease characterised by inflammatory polyarthritis caused by chronic inflammation of the synovium > destruction of cartilage and bone > pain and disability
- systemic inflammation > extra-articular comorbidities, including cardiovascular disease
- the initiating auto-antigen is unknown
11
Q
Describe the pathophysiology of rheumatoid arthritis
A
- autoimmune response mediated by auto-reactive CD4+ T cells that recognise an unknown peptide antigen
- involvement of pro-inflammatory CD4+ Th1 and Th17 effector cells and macrophages
12
Q
Rheumatoid arthritis is drive by what type of reaction?
A
Type 4 hypersensitivity but secondary type 3 hypersensitivity responses also occur
13
Q
Describe the diagnosis of rheumatoid arthritis
A
- laboratory tests; presence of rheumatoid factor or anti-CCP antibodies
- x rays of the hands and feet; help with diagnosis and determination of disease severity
14
Q
Describe treatment of rheumatoid arthritis
A
- immunosuppression (first line > improve symptoms), conventional disease modifying anti-rheumatic drugs (cDMARDs), oral methotrexate, leflunomide or sulfasalazine
- anti-inflammatory drugs; glucocorticoids
- biological disease modifying anti-rheumatic drugs (second line treatment); monoclonal antibodies eg anti-TNF alpha (infliximab)
