inflammation and autoimmunity Flashcards
what cells are associated with acute inflammation?
leukocytes (neutrophils)
what cells are associated with chronic inflammation?
lymphocytes and macrophages
5 step process of inflammation?
1- vasodilation
2 - increased vascular permeability
3- increased viscosity of bleed
4- stasis
5- accumulation of neutrophils
3 steps of acute inflammation?
vasodilation - increased blood flow
increased permeability - permits oedema
leukocyte migration
what is margination of leukocytes?
they redistribute along endothelium
what is rolling of leukocytes?
when they adhere transiently to vascular surfaces due to selectins
what happens in adhesion of leukocytes?
firmly adhere to surface due to integrins
how do leukocytes migrate through endothelium?
- interaction mediated by adhesion molecules PECAM-1/ CD81
- release collagenases to pierce basement membrane
what is chemotaxis of leukocytes?
emigrate towards injury, following chemo attractants
exogenous - bacterial products
endogenous - chemical mediators (chemokines)
what happens after recruitment of leukocytes to injury site?
phagocytosis
- engulfment, killing and degradation
effect on body temp of acute inflammation?
increased COX and prostaglandin release from hypothalamus increase body temperature
what classifies a fever?
body temp elevation of 1-4 degrees
what is NF-kB transcription factor?
master regulator of inflammation
regulates expression of cytokines, chemokines, adhesion molecules and enzymes
drugs developing to target NF-kB?
IKK inhibitors
Proteasome inhibitors
inhibitors to block translocation
inhibitors of DNA-binding activity
2 causes of chronic inflammation?
1) persistent infections = microorganisms difficult to eradicate
2) immune-mediated inflammatory diseases = inappropriate activation
3 features of chronic inflammation?
infiltration with mononuclear cells
tissue destruction
attempts at healing
role of macrophages, lymphocytes, plasma cells in chronic inflammation?
macrophages - products eliminate injury agents to initiate repair
lymphocytes - release of cytokines make reaction chronic and severe
plasma cells - produce antibodies
how do cell-derived mediators help inflammation?
produced locally, pre-accumulated and released rapidly
how do plasma protein derived mediators help inflammation?
circulate in plasma and activated at site
how are prostaglandins and leukotrienes made?
generated by several enzymes
what does phospholipase A2 do?
releases arachidonic acid (AA) from phospholipids
what does COX1/2 do?
converts AA into prostaglandins PGG2 PHG2
what does thromboxane synthesase do?
covert PGH2 into thromboxane
what does prostacyclin synthetase do?
convert PGH2 into prostacyclin PGI2
difference between cox 1/2 inhibitors and specific cox 2 inhibitors?
cox2 are selective and cause less GI toxicity
3 properties of NSAIDs to help inflammation?
anti inflammatory - block prostaglandins
analgesic - reduce pain
anti-pyretic - lower temperature
how do lipoxygenase inhibitors work?
block 5-lipoxygenase that produce precursors to leukotrienes
how do glucocorticoids work?
reduce transcription of genes encoding phospholipase A2
reduce cytokines
2 type of autoimmune diseases?
- pathogenic effects of autoantibodies
- T cell-mediated autoimmunity
how does myasthenia gravis cause weakness of skeletal muscle?
antibodies bind to Ach receptor and cause internalisation and removal of muscle surface
how does graves disease cause hyperthyroidism?
antibodies mimic effect of TSH hormone causing excessive secretion
what happens in autoimmune haemolytic anaemia?
autoantibodies damage red blood cells
what do autoantibodies do in lupus?
bind to soluble fragments of DNA which get deposited at susceptible sites
how does insulin-dependent diabetes occur?
cells of pancreas destroyed by CD8 T cells
