unwanted immune response against self-tissue Ags that cause chronic inflammatory injury
3 genes commonly mutated in autoimmune diseases
1) CTLA4
2) IL-10
3) FasL
molecular mimicry
activated T cells clear pathogen during infection, but then recognize something similar
in the body that should be recognized as self
chronic, systemic, inflammatory disease that primarily affects synovial membranes of multiple joints in the body
RA
pathogenesis of RA
1) T cell activation by unknown Ag's
2) initiation of inflammatory response
3) cytokine production, synovial inflammation
RA "T cell centric" theory
known association of RA w/ MHC II Ag's
large # CD4+ T cells in RA synovium
RA Macrophage Theory
while T cells may be important in initiating disease, chronic inflammation is perpetuated by macrophages and fibroblasts though T cell INDEPENDENT manner
IL-1 fcn in RA
secreted by macrophages
maintain synovial fibroblast in an activated state
TNF fcn in RA
same as IL-1 fcn -> maintain synovial fibroblast in activated state
GM-CSF fcn in RA
secreted by fibroblasts
promotes maturation of newly recruited monocytes to macrophages
IL-6 fcn in RA
produced by both macrophages & fibroblasts
stimulates B cell maturation to plasma cell
IL-8 fcn in RA
secreted by fibroblasts
recruit neutrophils to site
chronic, inflammatory autoimmune disorder than may affect multiple organ systems
systemic lupus erythematosus
clinical features NOT typically seen in drug-induced SLE
1) renal
2) vasculitis
3) CNS
autoantigens targeted in SLE (4)
1) ssDNA
2) dsDNA
3) histone
4) chromatins
SLE is what type of hypersensitivity rxn?
Type III (immune-complex-mediated)
CD4+ T cell mediated inflammatory disease that targets insulin-producing islet cells
insulin dependent diabetes mellitus
T cell-mediated autoimmune disease targeting the myelin sheath surrounding the nerve fibres
multiple sclerosis
IFN-mechanism of action for MS (4)
1) inhibit leukocyte proliferation
2) inhibit Ag presentation
3) inhibit T-cell migration across BBB
4) modulate cytokine production
natalizumab mech of action for MS
anti-4 integrin mAb binds VLA-4 to mediate CNS migration of lymphocytes
peptide tetramer (GLATiramer) resembling protein found on myelin that diverts autoimmune response away from myelin
fingolimod mech of action for MS
downregulates S1P1 expression on activated T cells to decrease gradient -> cells unresponsive & unable to migrate out of lymph nodes -> reduced lymphocytes in CNS