An introduction to chemokines Flashcards
What receptors are responsible for tethering and rolling?
selectins
What causes expression of integrins?
selectin signalling and chemokine signalling
what are integrins responsible for?
slow rolling and arrest
What is the general structure of chemokines?
4 conserved cysteine residues which form 2 disulfide bonds
What is the quaternary structure of chemokines?
many chemokines form dimers and higher-order dimers either between the same group or different
What is chemokinesis?
non-directional migration of a cell as a result of a chemical stimuluis
Where does non-directional migration take place?
in secondary lymphoid organs
What is the function of non-directional migration within the SLO?
contributes to rapid scanning for antigens with DCs
What signalling contributes significantly to the speed of non-directional migration in SLO?
CCR7
What type of migration pathway type is seen in non-directional migration and why?
Levy flight- increases the probability of encountering antigen compared with Brownian motion
What is Levy flight?
directionless with large jumps in location
What type of receptor do chemokines bind to?
GPCRs
What cell types produce chemokines?
epithelial cells; fibroblasts; SM cells and leukocytes etc
What can chemokines bind to on the cell surface?
glycosaminoglycans (GAGs)
What is the function of chemokine binding to GAGs?
can present chemokines to the GPCRs by increasing the local conc. of protein
What chemokines have mucin stalks?
CX3CL1 and CXCL16
Wahat is the function of mucin stalks on a chemokine?
tether the chemokines to the producing cell nad promotes the firm adhesion of leukocytes
What is a SNP in CX3CR1 associated with?
reduced monocyte adhesion to CX3CL1 and protection from atherosclerosis (can’t extravasate to form macrophage foamy cell)
What other roles do chemokines have?
myelopoeisis; angiogeneiss and angiostaiss; homeostasis; bactericidal
Give an example of a bactericidal chemokine?
CXCL9 and S.pyogenes
What is the function of atypical chemokine receptors?
bind chemokine but don’;t signal- regulate chemokine levels in circulation and in tissues
When do chemokines play a detrimental role?
excessive or inadvertent production of chemokines can induce the inflammatory component of several clinically important diseases
How is CXCr4 related to tumour cell metastasis?
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
What are hte features of WHIM syndrome?
warts; hypogammaglobulinaemia; immunodeficiency; myelokathexis
What causes WHIM sydnrome?
SNPs in the C-terminus of CXCR4 lead to enhanced signalling and leukocyte retention in the bone marrow
How is WHIM singalling treated?
CXCR4 antagonist
