Autoimmunity Flashcards
autoimmune diseases
“self” antigen is recognized as foreign by immune system and there is a failure of regulatory mechanisms. effector mechanisms include types II,III,IV hypersensitivity reactions.
factors contributing to the development of autoimmune diseases
all autoimmune diseases involve the breakdown of T and B cell tolerance and the production of autoantibody an/or inflammatory autoreactive T cells. genetic factors and environmental factors play a part too
two-hit hypothesis
genetic susceptibility leads to failure of self-tolerance. then, when a trigger occurs, the autoimmune disease begins.
central B cell tolerance
clonal deletion of self-reactive b cells in the bone marrow
peripheral b cell tolerance
without cognate T cell help, antigen activated B cells in the T cell zone of a lymph node die by apoptosis. B cells may also become anergic after encounter with soluble antigen, and then will be eliminated by antigen-specific T cell through Fas signalling.
central t cell tolerance
normally t cells that bind to self peptides presented by MHC on the thymic cells are deleted. defects in AIRE leads to production of a variety of autoimmune B and T cell responses, and autoimmune polyglandular disease
insufficient control of T-cell costimulant
activation of T cells requires both antigen presentation and costimulation (B7/CD28). autoreactive cells may have a lower threshold for activation. allelic variants of CTLA-4, and CD40/CD40L variants (higher levels may lead to more activation)
lack of regulatory T cells may contribute to autoimmune disease
CD4+, CD25+, CTLA4+ producing IL4, IL10, and TGFB. require cell contact and CTLA4 for activity. defects in FoxP3, a transcription repressor gene unique to Treg, results in autoimmune disease, mainly in boys.
inflammatory Th 17 cells in autoimmune disease
Helper CD4+ T cells that secrete IL17. proinflammatory binds to IL17 receptor, leading to secretion of cytokines and recruitment of inflammatory cells.
molecular mimicry
may contribute to role of infections. pathogen-derived peptides structurally similar to a self antigen stimulate a T cell response directed against the self-antigen.
infection leading to increased antigen presentation
during infection, Class I and Class II expression may be induced or increased due to interferon gamma production
what is the dominant genetic factor affecting susceptibility to autoimmune disease?
HLA!!
release of sequestered antigens
trauma to sites of immune privelege: normal entry of naive lymphocytes is prevented but self antigens may be exposed to circulation by wound or infection, and effector cells can gain access.
antibody mediated autoimmune diseases
organ-specific and caused by same effector mechanisms as for Type II hypersensitivity reactions
hemolytic anemia
IgG autoantibodies bound to Rh or I antigens may promote antibody dependenct cell mediated cytotoxicity or complement fixation
graves disease
TSH usually induces breakdown of thyroglobulin, releasing T3 and T4, signalling the pituitary to stop releasing TSH. in graves disease, autoantibodies bind TSH receptor of thyroid cells, mimicking action of TSH so more throid hormones are released
myasthenia gravis
ACh binds to ACh receptors on muscle cells, inflow of sodium ions causes contraction. In MG, anto-ACh receptor Ig binds and results in receptor endocytosis and degradation, leading to fewer receptors and decreased sensitivity to stimulation and progressive muscle weakening
IgG mediated disease transferring in utero
antibodies can cross the placenta into the fetus. can be cured by plasmapheresis.
immune-complex mediated autoimmune diseases
type III hypersensitivity effector mechanisms. immune complexes deposit in tissues, fix complement, leading to influx of inflam cells, resulting in tissue damage.
systemic lupus erythematosus (SLE)
immune complexes contain Anti-DNA, anto nucleosome antibodies. Anti-dsDNA titer is diagnostic. butterfly rash, fatigue, headache
T-Cell mediated autoimmune diseases
type IV hypersensitivity effector mechanisms. Antigen specific T cells activated by antigen, as well as other immune cells lead to inflam response.
juvenile diabetes
type 1 diabetes, insulin dependent. beta cells in pancreas make little to no insulin due to destruction by CD8+ T cells. increased thirst and urination, weight loss, nausea, fatigue.
rheumatoid arthritis
antibodies that react with the constant regions of other antibodies and infiltration of the join synovium by inflammatory CD4 and CD8 cells. secretion of TNFa, IL2,6,7, leads to recruitment of effector cells. weakness, fatigue, joint pain
multiple sclerosis
chronic organ specific disease. myelin sheath covering cells of spinal cord and brain destroyed due to CD4 T cells which secrete IFN gamma and activate macrophages. autoantibodies to myelin, proteolipid, etc. weakness, tremors, etc
celiac disease
IgA or IgG antibodies to tissue transglutaminase
treatments for autoimmune diseases
removal of antigen, antibody, or immune complexes. IVIG. NSAIDS, steroids, etc. depletion of immune cells. block interaction of immune cells. repleacement therapy. hormones, diet, exercise
rituximab and infliximab
Rheumatoid arthritis drugs. good success rate
