Lecture 6 - Autoimmune Disorders Flashcards
(44 cards)
what are the targets for autoimmune disorders?
protein antigens or nucleic acids
how do self-reactive T or B cells form?
gene rearrangement created lymphocytes that are specific for self-antigens
how are self-reactive lymphocytes removed?
destroyed or down regulated
where does central self tolerance occur?
thymus or bone marrow
what is the mechanism of central self tolerance?
clonal deletion
what are the mechanisms of peripheral central tolerance?
anergy, cell death and immune deviation
where do T cells form and develop?
originate in bone marrow but develop in thymus
what cells undergo positive selection?
only cells that bind to self MHC with low affinity
what cells undergo negative selection?
cells that bind with high affinity to self MHC and peptides
what cells undergo apoptosis in central tolerance?
cells that fail to interact with any MHC or peptides
how are T reg cells made?
some self-reactive T cells that encounter self antigens in the thymus develop into T reg cells
what happens to B cells that recognise self antigens?
they are deleted or become self tolerant
what us clonal deletion?
physical elimination of a cell
what is Clonal anergy?
lack of co-stimulation or low affinity antigen binding leads to cells not being activated through signalling blocks or inhibitory receptors
what is regulation in peripheral tolerance?
regulation or suppression caused by inhibition of cellular activites by interaction with other cells such as T reg cells
what is immune privilege?
limited lymphatic drainage with low levels of MHC expression and expression of FasL to kill infiltrating T cells
what happens to B cells that are exposed to lots of soluble antigen?
down regulate surface IgM and become anergic, up regulate fasmolecules to cause apoptosis
how do B cells change their antigen specificity?
when binding to an antigen with low affinity they re-express their RAG-1 and RAG-2 genes which cause DNA recombination
what is susceptibility phase?
before onset of disease, influences by genetic factors that effect tolerance induction, regulation and HLA associations
what is the initiation phase?
hidden epitopes revealed or new ones created
how are new epitopes created?
post translational modification, proteolytic cleavage of intracellular antigens
what is the propagation phase?
corresponds with the onset of clinical disease, tissue damage provides antigen to further drive immune responses
what is the regulation/resolution phase?
immunoregulatory pathways that result in natural inhibition or resolution of the disease, quite rare
what are the factors associated with organ specific autoimmunity?
affects one organ yet can be directed against multiple antigens on that organ
