chapter13

Kuby Immunology, Sixth Edition

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C HAPTER 13: L EUKOCYTE A CTIVATION AND M IGRATION P AGE 1 I. C ELL  A DHESION  M OLECULES  (CAM S ) A. R OLES   OF  C ELL  A DHESION  M OLECULES 1) Stabilization of cell-cell interactions Used by leukocytes to interact with tissue cells Leukocyte adhesion to vascular endothelial cells Also increase the strength of functional interactions between cells of the immune  system 1. T H    APCs 2. T H    B cells 3. CTLs   target cells 2) Signaling 3) Migration at sites of inflammation 4) Recirculation of lymphocytes 5) Localization of cells to tissues or compartments within tissues Also play vital roles in embryogenesis, homeostasis, thrombosis, wound  healing, and tumor metastasis
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C HAPTER 13: L EUKOCYTE A CTIVATION AND M IGRATION P AGE 2 ✼β G ENERAL  S TRUCTURE   OF  A DHESION  M OLECULES   B. C ELL  A DHESION  M OLECULE  F AMILIES 1) Selectin Family      (Receptor for Mucin-specific binding) Specialized for mediating  capture/tethering  and  rolling Always  active for binding Responsible for the initial stickiness of leukocytes to vascular endothelium Selectin examples: 1. L-selectin (CD62L) 2. P-selectin (CD62P) 3. E-selectin (CD62E)
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C HAPTER 13: L EUKOCYTE A CTIVATION AND M IGRATION P AGE 3 Expressed by: Mediates Binding of: L-selectin (CD62L) *expressed by circulating leukocytes Leukocytes (constitutively) Macrophages Monocytes Eosinophils Neutrophils Lymphocytes of HEV Inflamed endothelium P-selectin (CD62P) *expressed on vascular endothelial cells during inflammation Inflamed endothelium Activated platelets Neutrophils Monocytes TH1 E-selectin (CD62E) *expressed on vascular endothelial cells during inflammation Inflamed endothelium Neutrophils Monocytes TH1 L-selectin almost  ALWAYS  expressed on  circulating leukocytes P-selectin rapidly expressed once endothelial cell  is activated P-selectin expressed before E-selectin because it  is already formed; stored in granules E-selectin expression occurs hours later because  it requires synthesis of new proteins which in turn  requires stimulation by cytokines
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C HAPTER 13: L EUKOCYTE A CTIVATION AND M IGRATION P AGE 4 2) Mucin-like Family      (Selectin Ligand) Serine- and threonine-rich proteins Heavily glycosylated, fucosylated, sialyated, and sulfated Present carbohydrate ligands to selectins Mucin-like examples: 1. G     lycosylation-dependent  CAM-1  ( GlyCAM-1 ) 2. CD34 3. PSGL-1 4. MAdCAM-1 5. C     utaneous  L ymphocyte  A ntigen- 1  ( CLA-1 ) Selectin            Mucin L-selectin GlyCAM-1 CD 34 P-selectin PSGL-1 E-selectin CLA-1
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C HAPTER 13: L EUKOCYTE A CTIVATION AND M IGRATION P AGE 5 3) Integrin Family      (Receptor for Ig-binding) Mediate firm  adhesion/arrest ALL are heterodimers containing an  α  and
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