Autoimmunity Flashcards
How are autoreactive t and b cells selected against?
In the bone marrow autoreactive B cells will be rearranged in the germinal centres
T cells will be negatively selected in the thymus
These are both central tolerance
What role does CTLA-4 play in tolerance?
This has a role in peripheral tolerance and it negatively regulates expansion of cells. Defects in this pathway are associated with aggressive lymphoproliferative disease
What role do CD4 cells play in tolerance?
They are T regulatory cells and suppress auto-reactive cells through the release of cytokines
What is the cause of autoimmune disease?
It is multifactorial and caused by both gene defects and environmental factors
How can infectious agents cause autoimmune disease?
It may activate the immune system or alter a self peptide causing an autoimmune reaction
What is the pathogenesis behind RA?
CD4 t cells recognise citrullinated peptides and cause immune attack. Citrullination is promoted by smoking.
When is it normal for the body to produce autoantibodes?
During an infection but this is usually self limiting and T regs usually censor this
Why can epstein barr virus cause autoantibodies to be produced?
This is because when infected cells are killed both self and viral proteins are taken up by dendritic cells and presented to CD4 cells
What are the four criteria to prove that an autoantibody is associated with the pathogenesis of a disease?
Reproduction of the disease after transfer of the antibodies
Induction of a lesion similar to the disease after immunisation with the antigen
Isolation of the autoantibody from a typical lesion
Correlation of the antibody levels with disease activity
What are the four main mechanisms that autoantibodies produce disease through?
- Complement dependent lysis e.g. paroxysmal nocturnal haemoglobinuria mediated by IgM antibodies
- Opsonisation and destruction by phagocytes, mechanism of most forms of haemolytic anaemia
- Immune complexes forming in the intravascular or extravascular spaces e.g. glomerulonephritis in SLE
- Receptor blockade stopping normal ligands from forming e.g. myasthenia gravis
What is the pathogenesis of RA?
Citrullinated self-peptides are the autoantigens and cause immune reaction. This causes release of Il-1 and TNF alpha, this is the basis for infliximab therapy which is a TNF alpha blocker
What are the main lab tests for RA?
Rheumatoid factor (against fc of IgG) anti CCP antibodies (Anti-citrullinated protein antibody)
What are the lab investigations of lupus?
Antinuclear antibodies
double stranded DNA antibodies (important for predicting disease severity)
What are the two main classifications of scleroderma?
Limited (crest syndrome)
Diffuse
Both have lots of GIT involvement
What does CREST in crest syndrome stand for?
Calcinosis (of skin) Raynauds phenomenon Esophageal dysmotility Sclerodactyly Telangectasias
What is Sjogren’s syndrome?
It is a relatively common autoimmune disease that causes exocrinopathy. This manifests as dry eyes and dry mouth
What is anti-phospholipid syndrome?
Occurs in patients with lupus by also people who do not fit the criteria for lupus.
Causes lots of thrombi from the antibodies
What are the three main types of vaculitis and how does the lab test for it?
The main types are:
- large vessel affecting e.g. giant cell arteritis
- medium sized vessels - classic polyarteritis nodosa
- small vessels - ANCA associated
The lab tests involve ANCA (antineutrophil cytoplasmic antibody) which can ditinguish between different kinds however positive ANCA is also seen in other conditions such as infection
What is cryptoglobinaemia?
Presence of immunoglobulins that precipitate on cooling. Obstruction of small blood vessels that can lead to ischaemia and infarction of the tissues they supply
What is polymyositis?
Inflammatory muscle disease that majority of which have at least one autoantibody
How can autoantibodies affect the thyroid?
Can either stimulate causing hyperthyroidism (Graves) or block the TSH receptor causing hypothyroidism (hashimotos)
What is the cause of type 1 diabetes mellitus?
Autoimmune attack of the beta cells in the pancreatic islets of langerhans
What is the main cause of addisons in the western world?
Autoantibodies against 21-hydroxylase
What are pemphigus and pemphigoid?
Pemphigus - IgG Autoantibodies directed against intercellular desmosomes in the epidermis causing blisters
Pemphigoid - IgG directed against the epidermal basement membrane causing tense blisters
What is myesthenia gravis?
Autoantibodies against the nicotinic acetylcholine receptors
This is easily fatiguable
Majority of patients have hyperplastic thymus and benefit from thyroidectomy
What is Lambert-eaton syndrome?
Autoantibodies against pre synaptic voltage gated sodium channels
Usually paraneoplastic
What is guillian barre?
Guillain-Barré syndrome (GBS) is an acute or sub-acute ascending motor polyneuropathy and radiculopathy, with patchy sensory loss. This occurs as peripheral nerve myelin sheaths become inflamed, typically following infection with Campylobacter jejuni.
This causes autoantibodies to form
