migration of immune cells lymphocyte homing and recirculation
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NEUTROPHIL GRANULOCYTES ARE RECRUITED FROM THE BONE NEUTROPHIL GRANULOCYTES ARE RECRUITED FROM THE BONE MARROW RESERVOIRE TO INFECTED TISSUESMARROW RESERVOIRE TO INFECTED TISSUES
LYMPHOCYTE RECIRCULATION
1. Homing – most lymphocytes reside in lymphoid organs, few in circulation2. Recruitment – chemokines and chemokine receptors, chemotaxis
Few antigen-specific lymphocytes should be recruited to the site of antigen entry – ANTIGEN RECOGNITION (lymph node)
The appropriate effector lymphocytes shoud migrate to the site of antigen EFFECTOR/MEMORY CELLS (tissue, lymphoid tissue)
3. MigrationAmong tissues, organsLymph node - Lymph node, Lymph node - TissuesBLOOD CIRCULATION - LYMPHATICS
4. Adhesion molecules HOMING RECEPTORS Antigen independent appearance (dependent on activation state of
lymphocyte SelectinsIntegrinsIg supergene family molecules
LIGANDS FOR VASCULAR ENDOTHELIAL CELL RECEPTORS Adressin ligands
INTERACTION WITH THE EXTRAVASCULAR CONNECTIVE TISSUEBinding, detachement
1. The central lymphoid organs are not connected to lymphatics – Isolated from the environment
2. The spleen has no lymph circulation – immune response to blood borne antigens
3. HEV – high endothelial venules – special entry sites of blood circulating lymphocytes to peripheral lymphoid organs
4. 1 lymph node circle/hour, 25 billion lymphocytes (25x109)/lymph nodes/day
BB TBONE MARROW THYMUS
MALTSALTBALT
HEV
BLOOD
Thoracic ductLymphatics
TISSUES
SPLEEN
LYMPH NODES
MIGRATION OF LYMPHOCYTES IN CENTRAL AND PERIPHERAL LYMPHOID ORGANS
Role of endothelial cells in trafficking and recirculation
Endothelial cells are involved in:Vasomotor tone, vascular permeability, regulation of coagulation, immune
modulation and lymphocyte extravasation
High endothelial venules
Constitutively present insecondary lymphoid tissue
Need to allow egress ofNeed to allow egress ofnaïve cells from the circulationnaïve cells from the circulation
Post-capillary venules
Present in non-lymphoid tissues
Molecules expressed by endothelial cells regulate traffickingand recirculation through lymphoid and non-lymphoid tissues
Post capillary venules in 2º lymphoid tissue are
called HIGH ENDOTHELIAL
VENULES.Specialised to allow
lymphocytes and nothing else into the lymph node
HEV
High endothelial venules
Post capillary venules in other tissues are lined by
simple squamous epithelium
Blood enters lymph node via the arteryPost capillary venules in the paracortex have cuboidal endothelial cellsHIGH ENDOTHELIAL VENULES - specialised properties to allow lymphocytes and
nothing else into the lymph node
NAIVE LYMPHOCYTESHoming to lymphoid tissues Homing receptor on naive lymphocyteL-selectin – carbohydrate binding
Ligand on HEV - mucin-like adressin CD34+ and GlyCAM-1 sulphated sialyl-Lewisx
Lymph node - PNAd – retention (peripheral node addressin)
HIGH ENDOTHELIAL VENULESHEV
Lymphocytes slow down and bind to HEVLFA-1 integrin – ICAM-1/2 Ig family
CCL21 chemokine and CCR7 chemokine receptor
MIGRATION OF LYMPHOCYTES
HEV
CD34
L-selectin
Naive lymphocyteNaive lymphocyte
Naive B lymphocytes migrate to lymph node Naive B lymphocytes migrate to lymph node through HEVthrough HEV
Naive B cells are recruited to HEV by CCL21 Naive B cells are recruited to HEV by CCL21 kemokin produced by stromal cellskemokin produced by stromal cells
CCL21 and CCL19 chemokines produced by CCL21 and CCL19 chemokines produced by dendritic cells target B lynphocytes to lymph dendritic cells target B lynphocytes to lymph
nodesnodes
HOMING OF B LYMPHOCYTES TO HOMING OF B LYMPHOCYTES TO LYMPH NODESLYMPH NODES
Limfocyte Homing I
NAIVE LYMPHOCYTESHoming to lymphoid tissues Homing receptor on naive lymphocyteL-selectin – carbohydrate binding
Ligand on HEV – mucin-like adressin CD34+ and GlyCAM-1 sulphated sialyl-Lewisx PSGL-1Lymph node – PNAd - retention
Limfocita Homing IIExtravasation
HIGH ENDOTHELIAL VENULESHEV
Lymphocytes slow down and bind to HEVLFA-1 integrin – ICAM-1/2 Ig family
CCL21 chemokine and CCR7 chemokine receptor
Homingto
lymphnode
L-se
lect
in
VLA
-4
Homingto inflamed
vascularendothelium
CD
45R
A
CD
45R
O
Differentialsplicing of
CD45 mRNAin naïve & armed
T cells
CD
2
LFA
-1
CD
44
Adhesion molecules
Naïve
Activated
Different adhesion molecules of naive, armed and effector CD4+ T cells
+
-
+ + -+ + -
++ ++ ++ +++-
Associates with TcR and CD4 - phosphatase activity reduces threshold of T cell
signalling
EFFECTOR/MEMORY LYMPHOCYTESReturn to the site of stimulation (antigen)
Mucosal surface- MADCAM-1Retention in spleen, lymph node
LFA-1 – ICAM-1/2integrin – cell and extracellular matrix
Migration through activated endothelial cells of inflammed tissues
Lamina propria in gutMucosal epitheliumDermis in skin
Activated endothel
LFA-1 VLA-4
VCAM-1ICAM-1
Activated/effector/memory lymphocyte
ALTERED EXPRESSION OF CELL SURFACE ADHESION MOLECULES
Adhesion molecules and chemokines controlling T- cell homing toAdhesion molecules and chemokines controlling T- cell homing tolamina proprialamina propria
T-cells activated in mucosal tissue associated lymphoid tissues return to MALT
T-cell activated in mucosal tissue associated lymphoid tissues return to MALT
Naive T cellNaive T cell
Activated T cellActivated T cell
Bél lumen
Nyirok
Mesenteriális nyirokcsomó felé
Izolált limfoid folliculus
Peyer patchM sejt
Kripta
Villus
Epithelium
A BÉLFALHOZ KAPCSOLÓDÓ SZERVEZETT LIMFOID SZÖVET ÉS A BÉLFALHOZ KAPCSOLÓDÓ SZERVEZETT LIMFOID SZÖVET ÉS IZOLÁLT LIMFOID FOLLICULUSIZOLÁLT LIMFOID FOLLICULUS
Lamina propria
1. The central lymphoid organs are not connected to lymphatics – Isolated from the environment
2. The spleen has no lymph circulation – immune response to blood borne antigens
3. HEV – high endothelial venules – special entry sites of blood circulating lymphocytes to peripheral lymphoid organs
4. 1 lymph node circle/hour, 25 billion lymphocytes (25x109)/lymph nodes/day
BB TBONE MARROW THYMUS
MALTSALTBALT
HEV
BLOOD
Thoracic ductLymphatics
TISSUES
SPLEEN
LYMPH NODES
MIGRATION OF LYMPHOCYTES IN CENTRAL AND PERIPHERAL LYMPHOID ORGANS
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