Immune-5 Flashcards
what do immunosuppressive agents do (generally)
inhibit in a controlled fashion one or more steps in the immune response
what are 3 therapy example types of immunosuppressive agents
t-cell directed, b-cell directed, cytokine-directed
what are 3 main examples of small molecule immunosuppressive agents
- glucocorticoids
- calcineurin inhibitors
- mTOR inhibitors
what are GCs (general)
corticosteroid hormones
what are GCs widely used for
their anti-inflammatory and immunosuppressive properties
what kind of effects do GCs have on the immune system (1 word)
pleiotropic (dw)
where are most glucocorticoids inactive
in the extracellular space
how do GCs get into cells
through cell membranes
what do cytosolic (not nuclear) GCs do
exert non genomic effects
what does cytoplasmic cortisol do (2 options)
binds to the GC receptor which translocated to the nucleus to have genomic effects
OR
non genomic effects in the cytoplasm or mito
what are 3 ways that GCs act within the nucleus
- direct binding to GC response elements (inhibit or activate)
- interactions with other transcription factors
- binding to DNA and TFs (Interacts with another TF, they regulate together genes that respond to GCs)
what do GCs do to PRR genes
upregulate the expression
what do GCs do to cytokine receptors
upregulate
what do GCs do to complement factors
upregulate
what do GCs do to genes involved in adaptive immunity
inhibit
what do GCs do to expression of pro-inflammatory cytokines and chemokines
inhibit
what are 3 things that GCs upregulate in innate immunity
- expression of PRR genes
- cytokine receptors
- complement factors
what are 3 things that GCs inhibit in innate immunity
- genes in adaptive immunity
- pro-inflammatory cytokines
- chemokines
what do GCs do to CD4+ T cells and how
suppress their activation indirectly by modulating DC function
what do GCs do to DC maturation + how
inhibit maturation by decreasing expression of MHC class 2 and CD80/86
what do GCs do to DCs in activating T cells + how
reduce their capacity by decreasing production of cytokines that activate T cells
what are 2 things that GCs do to DCs
inhibit maturation and reduce their capacity to activate T cells
what do GCs promote to T cells
the production of anti-inflammatory cytokines (IL-10)
how good are GCs for anti inflammation
good for short term treatment
what happens with chronic GCs for inflammation
side effects and can reduce GC sensitivity
what are 3 uses for GCs
- RA
- Asthma
- MS (not so much anymore)
how are GCs good for RA
they are DMARDs(Disease-modifying anti-rheumatic drugs), GCs + standard therapy can substantially reduce bone erosion
what are calcineurin inhibitors (general what they do)
immunosuppressive drugs that inhibit normal T-cell signal transduction
how do calcineurin inhibitors work
target intracellular Ca++ signalling pathways activated downstream of T cell receptors
what are the structures of calcineurin inhibitors like
they are all structurally unrelated, bind to distinct molecular targets
what does NFAT require to be able to go into the nucleus
it to be dephosphorylated
what does calcineurin usually do and why
dephosphorylates NFAT so it can go into the nucleus and make IL 2
what is cyclosporine A
lipid soluble antibiotic
what does cyclosporine A do once its inside the T cell
forms a complex with immunophilins called cyclophilins (cyclophilin A)