Inflammatory response mechanisms

Question 1

under normal circumstance tissues are kept under surveillance by

Answer 1

Dendritic which migrate out of the blood and into the lymphatic system

Question 2

if they encounter no antigens

Answer 2

they return to circulation via the lymphatic system,

Question 3

inflammatory process

Answer 3

1) when an antigen from a pathogen enters the body, it is taken up by an APC
2) processes and presented at the surface as MHC peptide complexes
3) memory T cells encountering this antigen become activated
4) Secreting a number of cytokines e.g. TNF-a which acts on local blood vessels- dilating them
5) The activated vascular endothelium results in a number of inflammatory effects
6) The tight junctions loosen, allowing fluid to pass out of the blood vessels and cause local swelling
7) Leakage of RBC causes the local area to become reddened in appearance
8) Activated endothelium also expresses adhesion molecules, which allows phagocytes to migrate out of the blood vessel
10) These then phagocytose engulf more antigens and macrophages can act as APC
11) Memory and effector T cells also recognise the adhesion molecules expressed by the activated vascular endothelium, and can therefore migrate into the infected tissue continuing the process of inflammation

Question 4

what is the main cytokine released during infammation

Answer 4

TNF-a

Question 5

TNF-a causes

Answer 5

local blood vessel dilation. the activated vascular endothelium results in a number of inflammatory effects:

• tight junction loosen
• activates endothelium also express adhesion molecules which allows phagocytes to migrate out of the blood vessel

Question 6

what occurs when tight junctions loosen

Answer 6

local swelling and leakage of RBC which makes the area appear redder

Question 7

cytokine signalling via JAKSTAT

Answer 7

1) Cytokine receptor consist of 2 chains
2) Each having an extracellular cytokine domain and an intracellular cytoplasmic domain which binds a member tyrosine kinases, called Janus kinases (JAKs)
3) In the absence of the cytokine the two domains remain separate
4) When cytokines bind, stabilisation of the heterodimer occurs, bring the two receptors together- a process called dimerization
5) The JAKs in the cytoplasm are brought together
6) The JAK kinases then auto phosphorylate the cytoplasmic tails of the receptors
7) STAT molecules binding to the phosphorylated cytokine receptor and are then phosphorylated by the JAKs
8) This enables the STATs to dimerise and translocate to the nucleus, where transcription of further cytokines occurs

Question 8

leukocytes can only adhere to

Answer 8

surface of veins and not those of blood vessles- too quickly moving

Question 9

neutrophil rolling

Answer 9

1) Leukocytes are WBCs that help fight infection
2) At sites of injury, infection or inflammation, cytokines are released and stimulate endothelial cells which line adjacent blood vessels
3) The endothelial cells then express surface proteins called selectin
4) Selectins bind to carbohydrates displayed on the membranes of the leukocytes, causing them to stick to the walls of the blood vessels
5) This binding action is of sufficiently low affinity, that leukocytes can literally roll along the surface of the endothelium, binding and unbinding selectins, in search for points to exit the vessel
6) Here they adhere tightly and squeeze between endothelial cells without disrupting the vessel wall
7) They then crawl out of the blood vessel in the adjacent tissue
8) Leukocytes only adhere to the surface of veins and not to those of arteries
a. Some are firmly attached and in the process of crawling through the vessel walls
b. Whereas some have already left the vessel and can be seen in the adjacent tissue

Question 10

how can neutrophils roll

Answer 10

due to the low affinity- binding and unbinding to selctins

Question 11

what do neutrophils bind to during neutrophil rolling

Answer 11

selection molecules

p-selectin and E-selecyin

Question 12

rolling adhesion mechanisms

Answer 12

1) Blood vessel endothelium at sites of infection, express selectin molecules
2) P-selectins and E-selectins
3) Leukocytes such as neutrophils express ligand for selectins in the form the S-lex carbohydrate
4) The binding of the epithelia S-lex is weak and cannot hold the cell against the flow of the blood
5) Instead the leukocyte/ neutrophil rolls along the blood vessel, making and breaking many interactions with the blood vessel selectins

Question 13

lymphocyte homing

Answer 13

1) When a wound occurs, lymphocytes are attracted to migrate from the veins near the site of injury by chemicals, invading bacteria and other lymphocytes
2) Lymphocyte invasion is restricted to the wounded area

Question 14

when does inflammation start

Answer 14

1-3 days

Question 15

what is a ligand for NF-kB receptor

Answer 15

YNF-alpha

Question 16

outline NF-kB pathway

Answer 16

1) TNF-a couples to NF-kB recetor
2) once bound, IKK phosphorylates IKB (inhibitor of NFkB) and it becomes marked for proteasomal degradation- sent to proteasome
3) Once Ikb is degraded, NF-kB is free to translocate to the nucleus and transcribe gene

Question 17

neutrophils only adhere to the walls of

Answer 17

veins and not arteries (blood moves too quick)

Question 18

which selections are expressed on activated endothelium

Answer 18

P-selectin and E-selectin

Question 19

ligand for P-selectin and E-selectin

Answer 19

S-Lec carbohydrate on leucocytes

Question 20

binding of the epithelia to S-lec is

Answer 20

weak and cannot hold the cell against flow of blood