Autoimmunity Flashcards
factors contributing to development of autoimmune diseases
immune factors, genetic factors, environmental factors
all autoimmune diseases involve
breakdown of T and B cell tolerance and the production of autoantibody and/or inflammatory autoreactive T cells
breakdown in B cell tolerance
breakdown in: central B cell tolerance, peripheral B cell tolerance
breakdown in central T cell tolerance
defects in AIRE (autoimmunre regulator)
breakdown in peripheral T cell tolerance
insufficient control of T cell costimulation (CTLA-4, B7), lack of regulatory T cells may contribute to autoimmune disease
Th 17
may be link between infection and autoimmunity, helper T cell that secrete IL-17
genetic factors
HLA is the dominant genetic factor affecting susceptibility to autoimmune disease
other factors include AIRE, Fas, FasL, bcl-2, TNF, FoxP3
sympathetic ophthalmia
example of a release of sequestered antigens
trauma to sites of immune privilege - self antigens may be exposed to circulation by wound or infection and effector cells can gain access
celiac disease
example of self proteins may be modified to appear foreign
result is diarrhea, malabsorption of nutrients, IgG or IgA to tissue
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
hashimoto’s disease
infection may lead to increased antigen presentation, upregulation of Class 1 and 2 expression, thyroid gland resembles secondary lymphoid tissue with B and T cells present
additional factors that may contribute to disease mechanisms in genetically susceptible individuals
chemicals, metals, hormones, stress, diet, age
hemolytic anemia
IgG autoantibodies bound to Rh or I antigens may promote antibody dependent cell mediated cytotoxicity (ADCC) or complement fixation.
antibody mediated autoimmune disease (Type 2 hypersensitivity)
Graves disease
autoantibodies bind to the TSH receptor of thyroid cells mimicking the action of TSH so more thyroid hormones are released
can be transferred in utero (to fetus while pregnant)
Myasthenia gravis
anti-acetylcholine receptor antibodies binds to the receptors so muscles cannot contract, leads to muscle weakening
autoimmune diseases that can be transferred in utero
only IgG-mediated diseases (Type 2 and 3 hypersensitivity), T cells cannot cross placenta so no Type 4 hypersensitivity
Systemic Lupus erythematosus (SLE)
type 3 hypersensitivity, immune complex-mediated autoimmune disease, immune complexes contain anti-DNA, anti-nucleosome antibodies, butterfly rash
Juvenile (Type 1) diabetes
type 4 hypersensitivity, beta cells in pancreas produce little or no insulin due to destruction by CD8 cells
Rheumatoid arthritis (RA)
type 4 hypersensitivity, caused by production of antibodies that react with constant regions of other antibodies (rheumatoid factor) and infiltration of joint synovium by inflammatory CD4 and CD8 cells
Multiple sclerosis (MS)
type 4 hypersensitivity, myelin sheath covering cells of spinal cord and brain destroyed due to TH1, macrophages, mast cells, and complement activtation
Treatment for autoimmune diseases
removal of antigen, intravenous IgG, anti-inflammatory drugs, depletion of immune cells, blocking activation of immune cells, replacement therapy, hormones, diet, exercise
