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