第七章 白细胞分化抗原和黏附分子

Leukocyte Differentiation Antigen

第一节 白 细 胞 分 化 抗 原

Leukocyte Differentiation Antigen

Cell surface molecules expressed (or disappeared) during different developmental and differential phases, activation or inactivation process of blood cells.

LDAs on different types of cells

Endothelial cell

Tumor cells Glial cell

Neuron

Erythrocyte

Monocyte

Eosinophil

Platelets

Lymphocyte

Neutrophil Basophil

LDA in T cell development

Fayard E. Sci. Signal. 2010

Cluster of Differentiation

The same antigen recognized by different monoclonal antibody from different labs are called CD.

Cell

AntigenX

A B C D E

CD1xx

ImmunophenotypingType of cell CD markers

stem cells CD34+, CD31-

all leukocyte groups CD45+

GranulocyteCD45+, CD15+, CD24+, CD114+, CD182+

MonocyteCD45+, CD14+, CD114+, CD11a, CD91+

T lymphocyte CD45+, CD3+

T helper cell CD45+, CD3+, CD4+

T regulatory cell CD4, CD25, and Foxp3

Cytotoxic T cell CD45+, CD3+, CD8+

B lymphocyteCD45+, CD19+ or CD45+, CD20+, CD24+

Thrombocyte CD45+, CD61+

Natural killer cell CD16+, CD56+, CD3-, CD31, CD30

Adhesion Molecules 第二节 粘附分子

Cell Movement-Chasing

Chemokine gradient

Cell Movement-Basics

Definition--Adhesion Molecule

Cell adhesion molecules (CAMs) are cell surface proteins involved in the interaction of cell-cell or cell-extracellular matrix.

CAMs take effect by the binding of receptor and ligand.

Classification

Integrin familySelectin family Immunoglobulin (Ig) superfamilyCadherin family Mucin-like familyOther adhesion molecules

I. Integrin Family

Consist of α and β chains.

According to β subunits, Integrins are divided into eight groups: β1- β8

b1 Integrin Family

Interaction with ECM

b2 Integrin Family

Integrins promote immune response

II Selectin family

Selectins consist of one peptide chain.

The three family members include: E-selectin, L-selectin, and P-selectin.

Structure

Function

Cell Recruitment Cascade

III Immunoglobulin superfamily(IgSF)

The structure of these adhesion molecules resemble that of Ig;

CD4, CD8, CD2(LFA-2), TCR, MHC I, II molecules;

IgSF family and their ligands

粘附分子的功能

Cell

movement;

Cell activation.

I. CDs in T cell activation

LFA-1ICAM-1

II. CDs in cell movement

CDs and AMs in Medicine第三节临床医学中的分化抗原和粘附分子

I. Anti-CD3 Ab in transplantation

T cell activation in transplantation

Clinical use of humanized CD3-specific antibodies

II. Anti-CD20 and non-Hodgkin’s lymphoma

CD20 expression in B-cell development

III. CD4, co-receptor for HIV

AIDS

The replicative cycle of HIV

CD4/CD8 ratio

I. Targeting Adhesion molecules on tumor cells

Metastatic Process

Dissociation of tumor cells

Intravasation

Survival in circulation

Tumor cell proliferation at metastatic site

Extravasation

Yoon KJ Can. Biol. Ther 2009

Cell adhesion molecules involved in breast cancer metastasis

Drugs target CAMs

II Blocking a4b1 integrin as therapy for MS

Pathophysiology of MS

α4β1 integrin in cell adhesion

Steinmen L Nat. Rev. Drugdisc 2005

Blockade of α4β1 integrin

Key points in the development of Natalizumab

本章重点

名词解释： CD ；

粘附分子的定义；

粘附分子和分化抗原的功能。