Lecture 16 - autoimmune diseases Flashcards
what is autoimmunity caused by ?
autoimmunity is caused by lymphocytes that recognise self antigens
what are organ specific autoimmune disease? x11
type 1 diabetes, goodpastrures syndrome, multiple sclerosis, crohns disease, psoriasis, graves disease, hashimotos thyroiditis, autoimmune haemolytic anaemia, autoimmune Addisons disease, vitiligo, myasthenia gravis
what are systemic autoimmune disease? x5
rheumatoid arthirits, scleroderma, systemic lupus erythematosus, priamry sjorgens syndrome, polymysoitits
what is the mechnism of tissue damage in rheumatoid arthritis?
antibodies to IgG Fc (“rheumatoid factor”) and citrullinated peptides activate macrophages and promote inflammatory response in the joint
Cytokines such as TNF-a, IL-1, IL-6, IL-15 and IL-17 play a role
is there also an unknown synovial joint antigen?
what is the conventional drug treatment for rheumatoid arthritis?
Disease modifying antirheumatic drugs (DMARDs): methotrexate; hydroxychloroquine; sulfasalazine – primary treatments, found to improve symptoms and decrease joint damage
Methotrexate is most important and useful and is usually the first treatment
Anti-inflammatory agents; NSAIDs - reduce pain and stiffness but do not affect long-term disease course
what is biological treatments for rheumatoid arthritis?
Anti-TNF-a inhibitors: e.g., infliximab; etanercept
Other cytokines: e.g., anakinra (IL-1R antagonist)
Reagents against cell surface molecules: e.g., rituximab (mab against CD20 on B cells); abatacept (CTLA4-Ig fusion protein – binds to CD80/CD86 on antigen presenting cells)
Targeting signal transduction: e.g. Janus kinases (tofacitnib)
what does parasitic worm protect?
the parasitic worm product ES-63 protects against the development of collagen-induced arthritis in mice when administered at 1microgram/ subcutaneous injection
what is the mechanism of tissue damage for the systemic lupus erythematous ?
This occurs because the immune system produces antibodies that target self-antigens, which are molecules normally present in the body’s own tissues and generates immune complex mediated inflammation in the kidneys, skin, joints and cardiovascular system
mortality is majority contributed by glomerulonephritis and accelerated atheroscelerosis
what is the conventional treatment for systemic lupus arthematosus?
Disease modifying antirheumatic drugs (DMARDs), e.g., methotrexate and hydroxychloroquine: reduce incidence of flairs
Corticosteroids: treatment of flares
Cytotoxic drugs, e.g., cyclophosphamide: treatment of glomerulonephritis
Intravenous immunoglobulin: for vasculitis
what are biological treatments for sle?
Reagents against B cell molecules:
Rituximab: one of several mabs against CD20
Epratuzumab: mab against CD22
Belimumab: mab against BAFF (first FDA-approved SLE treatment for 50 years)
what is the mechanism of action of multiple sclerosis?
disease due to nerve cell demyelination. promoted by myelin-specific T cells which are able to cross the blood brain barrier. results in inflammation triggered magnified response involving macrophages, cytokines etc
what are conventional treatments of MS?
during symptomatic attacks: uv cortocostreoids, eg methyprednisolone
Disease modifying treatments for relapsing remitting MS: IFNb - considered to reduce disease progression if started early and also reduce rate of relapses
Glatiramer acetate: FDA-approved random polymer of 4 amino acids from myelin basic protein – reduces rate of relapses
what are biological treatments of MS?
Natalizumab: humanised mab against the cell adhesion molecule a4-integrin
Prevents immune system cells from exiting the bloodstream to cross the blood-brain barrier thereby preventing relapse and cognitive decline
what can biologic agents do?
biologic agents can block cell migration to sites of inflammation and reduce immune responses. Treatment with anti-alpha4 integrin humanised monoclonal antibody reduces relapses in multiple sclerosis
what is the mechanism of tissue damage in T1D?
in type 1 diabetes, an effector T cell recognises peptides from a beta cell specific protein and kills the beta cell. glucagon and somatostatin are still produced by the alpha and beta cells, but no insulin can be made.
