Lecture 3 Flashcards
What is recirculation?
the ability of lymphocytes to repeatedly:
home to secondary lymphoid organs
reside there transiently
and return to the blood
What is leukocyte homing?
cell migration out of the blood and into peripheral tissues, or a site of infection or injury
recruitment of leukocytes and plasma proteins from the blood to sites of infection and tissue injury is a major part of _____
inflammation
What triggers inflammation?
recognition of microbes and dead tissues in innate immune response
A cascade of adhesive and activation events underlies the trafficking of all subsets of circulating lymphocytes which include:
tethering
rolling
adhesion and stop
transmigration in the tissue
How does tethering occur?
through transit interactions of selecting and intern within their ligands
What does rolling allow?
chemokine receptors on leukocytes to bind chemokine expressed on endothelium
endothelial cells in healthy tissues do not express what?
adhesion molecules
_____ provide a low affinity interaction with their ligands
selectins
only _____ endothelial cells express p-selectin and e-selectin
activated
Where is L selectin only expressed?
leukocyts and lymphocytes
L selectin is important for naive T and B lymphocytes for _____ into Las by interacting with _____
homing; HEV (high endothelial venules)
What is the L selectin ligands expressed on HEV called?
peripheral node addressins
What is the distribution of P selectin?
endothelium activated by histamine or thrombin
What is the ligand of P selectin?
Sialyl Lewis X on PSGL-1 and other glycoproteins; neutrophils; monocytes; T cells
What is the distribution of E selectin?
endothelium activated by cytokines
What is the ligand of E selectin?
Sialyl Lewis X on glycoproteins, neutrophils, monocytes, T cells
What is the distribution of L selectin?
neutrophils, monocytes, T cells, B cells
What is the ligand of L selectin?
Sialyl Lewis X/ PNAd on GlyCAM-1 CD34, MADCAM-1 , others; endothelium (HEV)
Integrins provide _____ affinity interaction with their ligands
high
What is the definition of an integrin?
integrate signals triggered by extracellular ligands with cytoskeleton dependent motility, shape change and phagocytic responses
What do integrins do?
mediate adhesion of cells to other cells or to extracellular matrix via various specific ligands
All leukocytes including B and T lymphocytes. monocytes, macrophages, neutrophils, basophils and eosinophils express what?
lymphocyte function associate antigen 1 or LFA-1
What is the distribution of LFA-1?
neutrophils, monocytes, T cells and B cells
what is the ligand of LFA-1?
ICAM-1 and ICAM-2; endothelium
What is the distribution of Mac-1?
neutrophils, monocytes, dendritic cells
What is the ligand of Mac-1?
ICAM-1 and ICAM-2; endothelium
What is the distribution of VLA-4?
monocytes, T cells
What is the ligand of VLA-4?
VCAM-1
What is the distribution of a4B7 integrin?
monocytes, T cells, B cells
What is the ligand of a4B7 integrin?
VCAM-1, MadCAM-1; endothelium in gut and gut associated lymphoid tissues
How are integrins able to respond to intracellular signals?
by rapidly increasing their affinity
Integrin activation occurs in all leukocytes in response to what?
chemokine binding to chemokine receptors
What do chemokines do?
stimulate leukocyte movement and regulate the migration of leukocytes from blood to tissues
How many cysteines in C chemokines?
Single cysteine
What do the cysteines do in CC or B chemokines?
two defining cysteine residues are adjacent
In CXC or alpha chemokines what are the cysteine residues doing?
separated by amino acids
In CX3C chemokines what are the cysteine residues doing?
separated by three amino acids
Do neutrophils and monocytes that Aris in the bone marrow and circulate the blood need to be activated?
no
Dendritic cells bearing Ag enter the lymph node through ______ vessels
lymphatic
L selectin is expressed by both ____ and ____ lymphocytes
B and T
Where are HEV only present?
in secondary lymphoid organs
CCL2 major function
Mixed leukocyte recruitment (monocytes)
CCL5 major function
Mixed leukocyte recruitment
CCL19 major function
T cell and dendritic cell migration into parafollicular zones of lymph nodes
CCL21 function
T cell and dendritic cell migration into parafollicular zones of lymph nodes
CXCL8 function
Neutrophil recruitment
CXCL10 function
Effector T cell recruitment
CXCL12 function
Homing naive B cells to LNs
CXCL13 function
B cell migration into follicles; T follicular helper cell migration into follicles
XCL1 function
T cell and NK cell recruitment
CX3CL1 function
T cell, NK cell, and monocytes recruitment; CTL and NK cell activation
CCL 1 function
Monocyte recruitment and endothelial cell migration
CCL4 function
T cell, dendritic cell, monocyte and NK recruitment, HIV coreceptor
