1 chapter 7 cam & lda department of immunology xing-cheng wei ( 韦星呈 ) building of basic...
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Chapter 7
CAM & LDA
Department of ImmunologyXing-cheng WEI ( 韦星呈 )
Building of Basic MedicineRoom 323 Tel.62215671 (office)
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Cell Adhesion Molecules
Leukocyte Differentiation Antigen
Clinical application of CAM and CD
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Sec.1 CAM
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Concept:Concept: The Molecules mediating The Molecules mediating contact and binding between contact and binding between cell and cell or between cells cell and cell or between cells and extracellular matrix.and extracellular matrix.
CAM (cell adhesion
molecule)
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7 Double Signals & Accessory Molecules
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Families of CAMFamilies of CAM -To be grouped according to molecular-To be grouped according to molecularstructures and biological features.structures and biological features.
1. Integrin1. Integrin 2. Selectin 2. Selectin 3. IgSF3. IgSF 4. Cadherin family4. Cadherin family 5. Non-classified molecules5. Non-classified molecules
9 Double Signals & Accessory Molecules
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I. Integrin -making cells adhere to extra-cellular matrix as to form an integration.
•heterodimer and chains
•﹥14 chains8 chains (group)
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Members of Integrin Family (1) Members of Integrin Family (1)
Groups Membersa/b SubunitMW (KDa)
Subunitstructure
Distribution Ligands Bindingdomains
VLA
( 1Group )
Melanoma
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Groups Membersa/b SubunitMW (KDa)
Subunitstructure
Distribution Ligands Binding domains
Continued
Leukocyteadhesion receptor
( 2Group )
Plateletglycoproteins
( 3Group )
Members of Integrin Family (2) Members of Integrin Family (2)
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Groups Membersa/b SubunitMW (KDa)
Subunitstructure
Distribution Ligands Binding domains
4 group
5 group
6 group
7 group
8 group
Members of Integrin Family (3) Members of Integrin Family (3) Continued
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Integrin molecules adhesion to exIntegrin molecules adhesion to extracellular matrix tracellular matrix
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Integrin molecules adhesion to thIntegrin molecules adhesion to the ligands on endothelial cells e ligands on endothelial cells
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APC
T Cell
Integrin molecules adhesion to thIntegrin molecules adhesion to the ligands on APC e ligands on APC
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II. Selectin By adhesion leukocyte-endothelium, a selectin takes part in leukocyte mediated inflammation and lymphocyte homing.
General Structure
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--L-selectin
--E-selectin
--P-selectin
sialyl-Lweis X (sLeX, or CD15s)
Selectin family & the Ligands
Common ligand:
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Members of Selectin FamilyMembers of Selectin Family
Selectins Distribution Ligands Functions
L-Selectin(CD62L) Leucocytes
CD15s(sLex
)DC34GlyCAM-1
Adhesion of leukocyte-endothelium Lymphocyte homing
P-Selectin(CD62P)
PlateletsMegakaryocyte
sActivated endo
thelia
CD15s(sLex)PSGL-1
Adhesion of leukocyte-endothelium Adhesion of leukocyte-platelet
E-Selectin(CD62E)
Activated endothelia
CD15s(sLex
)PSGL-1Myeloid cellsCLAESL-1
Adhesion of leukocyte-endothelium Migration of leukocyte to tissue Metastasis of tumor cell
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Selectin molecule adhesion to the Selectin molecule adhesion to the ligand on endothelial cell ligand on endothelial cell
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III. IgSF -A great number of members.
-Possessing ≥1 Ig domain.
-Mediate cellular adhesion to offer stimulating signals for the cells.
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[Review][Review] Domain of Ig Domain of IgStructure of IgG revealed by X-ray crystallography
[Ig folding]-A globular motif.
-2 Anti-parallel sheet.
- ~ 110AA.
-IgSF: any molecule that contains ≥ 1 Ig folding domain.
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APC
T Cell
IgSF molecules Bind to the ligandsIgSF molecules Bind to the ligandsDuring T cell activationDuring T cell activation
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Members of IgSF (1) Members of IgSF (1)
T cell activation
Distribution Ligands FunctionsIgSF Molecules
Cell adhesion
Th co-receptor, HIV receptor
Tc co-receptor
Accessory signals for T activation
T cell inactivation
Accessory signals for T activation/ inactivation
Accessory signals for T activation/ inactivation
Cell adhesion
Cell adhesion
widespread
widespread
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Lymphocyte adhesion, activation, co-stimulation
IgSF Molecules Distribution Ligands Functions
Cell adhesion, activation,adhesion, killing
Cell adhesion, killing
Cell adhesion, killing;Junction of endothelia
Lymphocyte homing
Cell adhesion;Junction of endothelia
Cell adhesion
Unknown
Members of IgSF (2) Members of IgSF (2)
27 Some IgSF MoleculesSome IgSF Molecules (( T CellsT Cells ) )
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Some IgSF MoleculesSome IgSF Molecules (( B CellsB Cells ))
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Some IgSF MoleculesSome IgSF Molecules (( Ig FcRIg FcR ))
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IV.Functions of
CAM
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Functions of CAMFunctions of CAM
1. 1. Co-receptors & accessory Co-receptors & accessory molecules for activation of molecules for activation of
T and B cells.T and B cells.
2. Interaction of leukocytes 2. Interaction of leukocytes with vascular endothelium with vascular endothelium
in inflammation reactions.in inflammation reactions.
3. Interaction of 3. Interaction of lymphocytes lymphocytes
with vascular endothelium with vascular endothelium
in in Lymphocyte homing.Lymphocyte homing.
Entering Non-
lymphoid Tissues
Entering Lymphoid Tissues
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Co-Receptors & Accessory Co-Receptors & Accessory Molecules for Molecules for T & B Cell T & B Cell
ActivationActivationAPC
T Cell
-Receptor: -Receptor: TCRTCR
-Co-Receptor:-Co-Receptor: CD4,CD8CD4,CD8
-Accessory Mol:-Accessory Mol:
CD28,CD2,etcCD28,CD2,etc
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Interaction of Immune Cell with Interaction of Immune Cell with Vascular Endothelium in Vascular Endothelium in
InflammationInflammationor Lymphocyte Homingor Lymphocyte Homing
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Sec.2 LDA
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LDALeukocyte differentiation
antigen
Distribution:Distribution: -Leucocytes.-Leucocytes. -Non-hemopoietic cells: e.g. vascular-Non-hemopoietic cells: e.g. vascularendothelial cells, fibrocytes, epithelial cells endothelial cells, fibrocytes, epithelial cells and neuro-endocrine cells.and neuro-endocrine cells.
Concept Concept The surface molecules that appear The surface molecules that appear
on oron ordisappear from cell membrane during disappear from cell membrane during
cell cell differentiation, development, differentiation, development,
activation.activation.
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CDCD MoleculesMolecules Cell surface molecules expressed on Cell surface molecules expressed on various cell types in immune system various cell types in immune system that are named uniformly asthat are named uniformly as CDCD(cluster (cluster of differentiation)of differentiation) molecules.molecules. -Surface markers that identify a particular -Surface markers that identify a particular lineage or differentiation stage.lineage or differentiation stage. -Recognized by monoclonal and named with -Recognized by monoclonal and named with CD numbers.CD numbers. -The CD molecules of human named from -The CD molecules of human named from CD1 to CD339 in 14 groups (2004).CD1 to CD339 in 14 groups (2004).
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Groups of Human CD Molecules (2005)
Groups CD Molecules ( examples )
T Lymphocyte
B Lymphocyte
Myeloid cells
Platelet
NK cells
Widespread
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Groups CD Molecules ( examples )
CAM
Cytokine receptors
Endothelial cells
Carbohydrate
Stem cellsProgenitors Stem cells
Continued
DC
Erythrocytes
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[Key Point]
1. Concepts: ① CAM
② LDA
③ CD MoleculesCD Molecules
2. Functions of CAM