inflammation and autoimmunity

Question 1

what cells are associated with acute inflammation?

Answer 1

leukocytes (neutrophils)

Question 2

what cells are associated with chronic inflammation?

Answer 2

lymphocytes and macrophages

Question 3

5 step process of inflammation?

Answer 3

1- vasodilation
2 - increased vascular permeability
3- increased viscosity of bleed
4- stasis
5- accumulation of neutrophils

Question 4

3 steps of acute inflammation?

Answer 4

vasodilation - increased blood flow
increased permeability - permits oedema
leukocyte migration

Question 5

what is margination of leukocytes?

Answer 5

they redistribute along endothelium

Question 6

what is rolling of leukocytes?

Answer 6

when they adhere transiently to vascular surfaces due to selectins

Question 7

what happens in adhesion of leukocytes?

Answer 7

firmly adhere to surface due to integrins

Question 8

how do leukocytes migrate through endothelium?

Answer 8

• interaction mediated by adhesion molecules PECAM-1/ CD81
• release collagenases to pierce basement membrane

Question 9

what is chemotaxis of leukocytes?

Answer 9

emigrate towards injury, following chemo attractants
exogenous - bacterial products
endogenous - chemical mediators (chemokines)

Question 10

what happens after recruitment of leukocytes to injury site?

Answer 10

phagocytosis
- engulfment, killing and degradation

Question 11

effect on body temp of acute inflammation?

Answer 11

increased COX and prostaglandin release from hypothalamus increase body temperature

Question 12

what classifies a fever?

Answer 12

body temp elevation of 1-4 degrees

Question 13

what is NF-kB transcription factor?

Answer 13

master regulator of inflammation
regulates expression of cytokines, chemokines, adhesion molecules and enzymes

Question 14

drugs developing to target NF-kB?

Answer 14

IKK inhibitors
Proteasome inhibitors
inhibitors to block translocation
inhibitors of DNA-binding activity

Question 15

2 causes of chronic inflammation?

Answer 15

1) persistent infections = microorganisms difficult to eradicate
2) immune-mediated inflammatory diseases = inappropriate activation

Question 16

3 features of chronic inflammation?

Answer 16

infiltration with mononuclear cells
tissue destruction
attempts at healing

Question 17

role of macrophages, lymphocytes, plasma cells in chronic inflammation?

Answer 17

macrophages - products eliminate injury agents to initiate repair
lymphocytes - release of cytokines make reaction chronic and severe
plasma cells - produce antibodies

Question 18

how do cell-derived mediators help inflammation?

Answer 18

produced locally, pre-accumulated and released rapidly

Question 19

how do plasma protein derived mediators help inflammation?

Answer 19

circulate in plasma and activated at site

Question 20

how are prostaglandins and leukotrienes made?

Answer 20

generated by several enzymes

Question 21

what does phospholipase A2 do?

Answer 21

releases arachidonic acid (AA) from phospholipids

Question 22

what does COX1/2 do?

Answer 22

converts AA into prostaglandins PGG2 PHG2

Question 23

what does thromboxane synthesase do?

Answer 23

covert PGH2 into thromboxane

Question 24

what does prostacyclin synthetase do?

Answer 24

convert PGH2 into prostacyclin PGI2

Question 25

difference between cox 1/2 inhibitors and specific cox 2 inhibitors?

Answer 25

cox2 are selective and cause less GI toxicity

Question 26

3 properties of NSAIDs to help inflammation?

Answer 26

anti inflammatory - block prostaglandins
analgesic - reduce pain
anti-pyretic - lower temperature

Question 27

how do lipoxygenase inhibitors work?

Answer 27

block 5-lipoxygenase that produce precursors to leukotrienes

Question 28

how do glucocorticoids work?

Answer 28

reduce transcription of genes encoding phospholipase A2
reduce cytokines

Question 29

2 type of autoimmune diseases?

Answer 29

• pathogenic effects of autoantibodies
• T cell-mediated autoimmunity

Question 30

how does myasthenia gravis cause weakness of skeletal muscle?

Answer 30

antibodies bind to Ach receptor and cause internalisation and removal of muscle surface

Question 31

how does graves disease cause hyperthyroidism?

Answer 31

antibodies mimic effect of TSH hormone causing excessive secretion

Question 32

what happens in autoimmune haemolytic anaemia?

Answer 32

autoantibodies damage red blood cells

Question 33

what do autoantibodies do in lupus?

Answer 33

bind to soluble fragments of DNA which get deposited at susceptible sites

Question 34

how does insulin-dependent diabetes occur?

Answer 34

cells of pancreas destroyed by CD8 T cells