adhesion molecules

Adhesion Molecules

Concept Naming RolesClassification

Concept Cell adhesion molecules (CAMs):

proteins which exist in cell surface involve in the binding of cells to each other or to extracellular matrix.

Exist as couples( receptor-ligand) Co-effect with many couples

TCR complex, Co –receptor,

Co-stimulator receptor, immunological synapse

Interactions between B cell and Th cell

B cell activation

B cell Th cell

Ag processing

Th cell

activation

Naming Functions ：ICAM-1 (intercellular adhesion molecules),

LFA-1 (lymphocyte function – associated antigen-1)

VCAM (vascular cell adhesion molecules),

PECAM1(platelet-endothelial-cell adhesion molecule),

CD CD58, CD152

Leukocyte differentiation antigen: Cell surface molecules expressed (or disappeared) on different developmental and differential phases of blood cells .

CD: cluster of differentiation (uses of McAb) CD molecules: The same differentiation antigen

recognized by different monoclone antibodies from different labs is called CD molecule.

Naming by method of identification

CD molecules have a variety of functions

ClassificationMost of the CAMs can be grouped by structure

into five families: Immunoglobulin (Ig) superfamily Integrin family Selectin family Cadherin family Mucin-like family

Others

Ig superfamily CAMs

The structure of these adhesion molecules resemble that of Ig.

Members of the Ig superfamily include the intercellular adhesion molecules (ICAMs), vascular cell adhesion molecule (VCAM-1), platelet-endothelial-cell adhesion molecule (PECAM-1), and neural cell adhesion molecule (NCAM).

Back

Integrins Integrins consist of alpha(1-16) and beta(1 - 8)

chains

VLA-4 (very late antigen-4) （ α4β1 ） ------VCAM-1,

LFA-1 （ α1β2 ） -----ICAM-1, ICAM-2, ICAM-3

举例： LFA-1 （ lymphocyte function associated antigen-1) 分布： thymocyte, T cell, macrophage 配体： ICAM-1 、 2 、 3（表达于APC、内皮细胞）

Selectins The molecule consists of one peptide chain which

has carbohydrate-binding domain. Bing to Sialyl-Lewis (sialyl Louis)

oligosaccharides three family members: endothelial (E)-selectin,

leukocyte (L)-selectin, and platelet (P)-selectin.

Roles— functions of cell adhesion molecules

To mediate the contact and adhesion between cell and cell, or between cell and extracellular matrix resulting to various biologic effects. Cell surface adhesion molecules play vital roles in numerous cellular processes.

1 Involvement in lymphocyte formation and differentiation

2 Involvement in immune response and immune regulation

3 Involvement in inflammation4 Involvement in lymphocyte homing 5 Involvement in regulation of apoptosis

1 Involvement in lymphocyte formation and differentiation

Thymocyte Epithelial cellCD2---------------IFA-3IFA-1-------------- ICAM-1

2 Involvement in immune response and immune regulation Take part in recognition of immnocytes

3 Involvement in inflammation · mediate the adhesion of leukocytes with endothelial cells during inflammation.

Transendothelial migration of leukocytesTransendothelial migration demonstrates cooperativity between leukocyte and endothelial cell adhesion molecules.

(1) rolling, Initial rolling is mediated by binding of E-selectin molecules on the

vascular endothelium to sialylated carbohydrate moieties on mucinlike CAMs.

(2) activation by chemoattractant stimulus, A chemokine such as IL-8 then binds to its receptor on the neutrophil,

triggering an activating signal. This signal induces a conformational change in the integrin molecules, enabling them to adhere firmly to Ig-superfamily molecules on the endothelium

(3) arrest and adhesion, The interaction between integrins and Ig-superfamily CAMs stabilizes

adhesion of the neutrophil to the endothelial cell, enabling the cell to adhere firmly to the endothelial cell.

(4) transendothelial migrationTransmigration of the leukocyte through adjacent endothelial cells in a

process called diapedesis. PECAM-1 is a crucial player in this step.This step is largely unknown.

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4 Involvement in lymphocyte homing · take part in lymphocyte homing and recirculation

Homing receptor on lymphocyte: L-selectin, LFA-1, vascular addressin on HEVs: GlyCAM-1(glycosylation dependent cell adhesion molecules), CD34; ICAM-1

L-selectin ----- GlyCAM-1, CD34

LFA-1 ----- ICAM-1

淋巴细胞定向迁移，分布于淋巴器官和组织的不同部位

HEV are specialized venules found in lymphoid tissues. Lymphocytes migrate from blood into lymphoid tissues by attaching to and migrating across the high endothelial cells of the vessels.

•High endothelial venule，HEV（高内皮毛细血管后微静脉）

Clinical application of CD and adhesion molecules

Elucidating pathological mechanism of disease

Application during diagonosis of disease Application during prevention and

treatment of disease