Cluster of Differentiation, CD Tel:8462530; 8462468(lab) E-mail: [email protected] Institute of Immunolgy, weifang Medical University Contents • Human leukocyte differentiation antigen (LDA). • CD molecules • Adhesion molecule. • Clinical application of CD molecule . Section 1 Functional molecule on immunocyte surface and human leukocyte differentiation antigen Electronic microscope image of human T lymphocyte Functional molecule on immunocyte surface Human Leukocyte Differentiation Antigen (LDA) • LDA refer to molecules on cell surface in the differentiation into different lineages, different stages and activation in blood cells. Different differentiation and develop stage Cell activation process L-selectin Rest T cell Activated T cell VLA-4 Classification of LDA • Immunoglobulin superfamily. • Cytokine receptor family. • Type C lectin superfamily. • Integrin family. • TNF superfamily. • TNF receptor superfamily. Cluster of Differentiation: CD • CD: Identified mainly by monoclonal antibody (mAb). One LDA which is recognized by mAb from different labs and whose coding gene and expression profile have been identified, can be designated CD. Cluster of Differentiation: CD • CD1-CD363 • Web site : http://www.hlda8.org Uses of CD moleculers • We can use one or two CD moleculers to classified the lymphocyte precisely. • Based on: some CD moleculer is specific to the cells but some isn’t specific. Section2 Cell adhesion molecules:CAM • Adhesion molecules: mediate the binding of one cell to other cells or to extracellular matrix proteins. Adhesion molecules: mediate the binding of one cell to other cells or to extracellular matrix proteins. Relationship between CD and CAM • They are all the curface molecular . • The denomination of CAM and CD is based on different aspects. • Adhesion molecules are classified by adhesive function. • Most adhesion molecules possess a CD number, however, some do not. Classifications: Based on structural features • Immnoglobulin superfamily. • Cadherins family. • Selectin family. • Integrin family. 1 Immunoglobulin-like adhesion molecules • Include a large group of molecules that are generated from a smaller number of genes by alternative RNA splicing. • The best-studied members of this group are the neural cell adhesion molecules (N-CAMs) which are expressed predominantly in nervous tissue and the intercellular cell adhesion molecules (ICAMs). Neural cell adhesion molecules (N-CAMs) • N-CAM has been found in many different forms. Differing amounts of glycosylation, especially amounts of sialic acid can alter the adhesivity of the molecule. • Alternative splicing of the primary RNA transcript leads to the production of different forms. The following diagram shows four forms of N-CAM. 2 Calcium dependent adhesion molecules (Cadherins) • A family of Ca2+- dependent CAMs. • Ca2+ causes dimerization. • Cadherins cause adhesion via binding to other cadherins in a calcium-dependent manner. Cadherins • Interaction with other cadherins. • Used in organ formation • Primarily link epithelial and muscle cells to their neighbors. • Play critical role during cell development. • E-cadherins hold epithelial cells . • N-cadherins expressed in nervous system are responsible for the specificity of neuronal connections. Cadherins Without cadherins With cadherins Human embryo undergoes compaction with cadherins 3 Selectin family • Selectins are involved in cell extravasation. • Inflammatory signals activate endothelial cells making P-Selectin. • P-Selectin on the surface of endothelial cells binds a specific carbohydrate ligand on leukocytes. • The leukocytes attach to the endothelial wall and roll slowly on it. 3 Selectin family • Selectins are expressed primarily on leukocytes and endothelial cells, is very important in many host defense mechanisms . • Selectins mediate interactions between leukocytes and endothelial cells, promotes rolling of the leukocytes along the endothelium and allows the leukocytes to be stopped in place. Selectin family Molecule L-selectin (CD62L) E-selectin (CD62e) P-selectin (CD62P) Ligands GlyCAM-1 ; CD34 Distribution Leukocytes Cutaneous lymphocyteassociated antigen P-selectin glycoprotein ligand1 Endothelial cells Endothelial cells Platelets Adhesion molecules involved in leukocyte emigration from vessels during inflammation Rolling L-Selectin P-Selectin E-Selectin Stopping Integrins ICAM-1 VCAM-1 Aggregation & Shape Change CD11b CD11a P-Selectin Migration through vessel wall Integrins ICAM-1 VCAM-1 4 Integrin family • Integrins are a diverse and large group of glycoproteins. • The two subunits, alpha and beta, both participate in binding. • Integrins participate in cell-cell adhesion and cells - extracellular matrix such as fibronectin. 4 Integrin family • Integrins facilitate "communication" between the cytoskeleton and extracellular matrix. Interactions of integrins with the extracellular matrix have profound effects on cell function. • Integrins exist in "active" and "inactive" states. a group of integrins responsible for binding of white blood cells to endothelium are normally inactive, allowing the blood cells to circulate freely, but become activated in response to inflammatory mediators, resulting in the white cells being "pulled" from blood into inflammed tissues. βIntegrin family Section 3 Function of Adhesion Molecule • Co-receptor and co-stimulation signal in the recognition of immunocyte. • Adhesion of leukocyte and vascular endothelial cell during the inflammation. • Homing of Lymphocyte. Co-receptor and co-stimulation signal in the recognition of immunocyte Adhesion of leukocyte and vascular endothelial cell during the inflammation Adhesion of leukocyte and vascular endothelial cell during the inflammation Homing of Lymphocyte Section 4 Clinical Application of CD and Adhesion Molecule as well as Their Monoclonal Antibody • Elucidate pathogenesis. • Application in diagnosis. • Application in disease prevention and treatment. Requisition • Master the concept of LDA, CD and adhesion molecule. • Master CD molecules related to T/B cell. • Comprehend classification and functions of adhesion molecules. • Comprehend clinical applications of CD molecule and adhesion molecule .
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