autoimmunity Flashcards
what is autoimmunity
autoimmunity; caused by loss of tolerance, may or may not cause disease
autoimmunity can be either organ specific or systemic
what are Tregs
Tregs (regulatory T cells); key component of peripheral tolerance and prevention of autoimmune disease
in treg deficient mice large lymph nodes and large spleen develop (lymphadenopathy and splenomegaly), die early
treg deficient humans; develop IPEX(immune dysregulation polyendocrinopathy enteropathy X linked syndrome) caused by mutations in Foxp3 gene
IPEX patients have aggressive autoimmunity and die early, onset occurs within first few days/months of life, over 80% of IPEX patients have type 1 diabetes
what contributes to autoimmune disease
development of autoimmune disease factors; genetic susceptibility, environmental influence, failed immune regulation
genetic susceptibility; largest factor of this is MHC/HLA genes
some specific polymorphisms in genes can contribute to complex diseases
environmental factors; infection (largest factor environmentally), sunlight (can exacerbate lupus), diet, obesity, stress, drugs, microbiome (microbes living on your skin/gut)
microbes activating APCs that are presenting self-antigens is a major problem in autoimmunity, also molecular mimicry; section of microbe looks very similar to self antigen
gender impacts autoimmunity, generally much higher prevalence in women, NOD mice exhibit diabetes much more in females, however if they are bread in germ free conditions (no microbiome present),this difference does not exist, sex bias is microbiome dependent
what are mechanisms of autoimmunity
mechanisms of autoimmunity; autoantibody mediated and T cell mediated
how do autoantibodies cause autoimmunity
autoantibodies may block particular pathways causing pathology e.g myasthenia gravis; autoantibody inhibits binding of Ach to nAchRs in muscle by acting as antagonists
antibodies may also act as agonists e.g graves disease where antibodies act as agonists for TSH receptor (thyroid stimulating hormone)
autoantibodies may also facilitate the phagocytosis of cell attached to autoantibodies by opsonising them, these disease called autoimmune cytopenias, the autoantibodies act as opsonins
describe T cell mediated autoimmunity
multiple sclerosis; T cell driven autoimmune attack of the CNS, CD4 T cell infiltrate CNS and activate macrophages and B cells, cause destruction of myelination
type 1 diabetes; T cell driven attack of beta cells in the pancreas which produce insulin
lupus is a systemic autoimmune disease, autoantibodies act against nuclear components, immune complex depostion occurs and defective clearance of dead cells due to complement defects.
