Topic 2 lecture note..

progenitors to bone marrow stroma. Production of T cells in the adult is 4-dependent,
and precursors for both T and B cells require 4-integrins for normal development within
the bone marrow. Antibodies against 47 or MAdCAM-1 block the binding of
mesenteric lymph node lymphocytes to Peyer’s patch (PP) HEV in vitro, and the homing
of lymphocytes to the gut and lamina propria in vivo. Hence 47 is critical for the
homing of lymphocytes to the gut, and mucosal sites which are normally chronically
inflamed. 4 integrins have an ability to compensate for the lack of LFA-1 in facilitating
the migration of lymphocytes to peripheral lymph nodes in LFA-1-deficient mice.41
also participates in lymphocyte recirculation through bone marrow.
4 integrins, and their ligands are highly expressed on pathogenic leukocytes, and
diseased tissues at sites of chronic inflammation, and hence are major targets for the
treatment of many of the major chronic inflammatory disease. The 4-integrin ligands
VCAM-1 and MAdCAM-1 are expressed on follicular dendritic cells, and may deliver
signals via 4 integrins during antigen presentation, leading to costimulation of T cell
proliferation.
Ig CAMS
LFA-1
ICAM-3
CD50
Leukocytes activated resting activated HEV
endothelium endothelium endothelium
activated leuk resting lymph/mono macrophage
ICAM-1 (CD54)
Intercellular adhesion molecule-1(ICAM-1) is a single chain 80-114 kDa protein with
five Ig-like domains, a single transmembrane region, and a short cytoplasmic domain. It
can bind to LFA-1, Mac-1, fibrinogen, hyaluronan, and CD43. Resting leukocytes
express little or no detectable ICAM-1, but expression is induced following activation.
Resting endothelial cells have low levels of ICAM-1, and activation with inflammatory