An introduction to chemokines

Question 1

What receptors are responsible for tethering and rolling?

Answer 1

selectins

Question 2

What causes expression of integrins?

Answer 2

selectin signalling and chemokine signalling

Question 3

what are integrins responsible for?

Answer 3

slow rolling and arrest

Question 4

What is the general structure of chemokines?

Answer 4

4 conserved cysteine residues which form 2 disulfide bonds

Question 5

What is the quaternary structure of chemokines?

Answer 5

many chemokines form dimers and higher-order dimers either between the same group or different

Question 6

What is chemokinesis?

Answer 6

non-directional migration of a cell as a result of a chemical stimuluis

Question 7

Where does non-directional migration take place?

Answer 7

in secondary lymphoid organs

Question 8

What is the function of non-directional migration within the SLO?

Answer 8

contributes to rapid scanning for antigens with DCs

Question 9

What signalling contributes significantly to the speed of non-directional migration in SLO?

Answer 9

CCR7

Question 10

What type of migration pathway type is seen in non-directional migration and why?

Answer 10

Levy flight- increases the probability of encountering antigen compared with Brownian motion

Question 11

What is Levy flight?

Answer 11

directionless with large jumps in location

Question 12

What type of receptor do chemokines bind to?

Answer 12

GPCRs

Question 13

What cell types produce chemokines?

Answer 13

epithelial cells; fibroblasts; SM cells and leukocytes etc

Question 14

What can chemokines bind to on the cell surface?

Answer 14

glycosaminoglycans (GAGs)

Question 15

What is the function of chemokine binding to GAGs?

Answer 15

can present chemokines to the GPCRs by increasing the local conc. of protein

Question 16

What chemokines have mucin stalks?

Answer 16

CX3CL1 and CXCL16

Question 17

Wahat is the function of mucin stalks on a chemokine?

Answer 17

tether the chemokines to the producing cell nad promotes the firm adhesion of leukocytes

Question 18

What is a SNP in CX3CR1 associated with?

Answer 18

reduced monocyte adhesion to CX3CL1 and protection from atherosclerosis (can’t extravasate to form macrophage foamy cell)

Question 19

What other roles do chemokines have?

Answer 19

myelopoeisis; angiogeneiss and angiostaiss; homeostasis; bactericidal

Question 20

Give an example of a bactericidal chemokine?

Answer 20

CXCL9 and S.pyogenes

Question 21

What is the function of atypical chemokine receptors?

Answer 21

bind chemokine but don’;t signal- regulate chemokine levels in circulation and in tissues

Question 22

When do chemokines play a detrimental role?

Answer 22

excessive or inadvertent production of chemokines can induce the inflammatory component of several clinically important diseases

Question 23

How is CXCr4 related to tumour cell metastasis?

Answer 23

cancerous mammary cells induce CXCR4 on their surface which results in their recruitment and retainment in organs that produce high levels of CXCL12 where they form metastatic tumours

Question 24

What are hte features of WHIM syndrome?

Answer 24

warts; hypogammaglobulinaemia; immunodeficiency; myelokathexis

Question 25

What causes WHIM sydnrome?

Answer 25

SNPs in the C-terminus of CXCR4 lead to enhanced signalling and leukocyte retention in the bone marrow

Question 26

How is WHIM singalling treated?

Answer 26

CXCR4 antagonist