Topic 2 lecture note..

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L-selectin PNAd, others All leukocytes, but naive T cells > memory T cells PSGL-1 P-selectin All leukocytes, but eosinophils > neutrophils CLA E-selectin Skin-homing memory T cells Sialyl-dimeric Lex E-selectin All leukocytes, but neutrophils > eosinophils 41 integrin VCAM-1, others All leukocytes except neutrophils 47 integrin MAdCAM-1, others All leukocytes except neutrophils E7 integrin E-cadherin Intraepithelial lymphocytes Chemokine receptors CCR3 Eotaxin 1-3, others Eosinophils, basophils, mast cells; some TH2 cells CCR4 TARC, MDC Skin-homing memory T cells CCR5 MIP-1 TH1 cells CCR6 MIP-3 Memory T cells CCR7 SLC (CCL21), Naive B and T cells MIP-3 (CCL19) CCR8 I-309 TH2 cells CCR9 TECK Gut-homing memory T cells CCR10 CTACK Skin-homing memory T cells CXCR3 Mig, IP-10, I-TAC TH1 cells CXCR5 BLC (CXCL13) Naive B cells PNAd, Peripheral lymph node addressin; PSGL-1, P-selectin glycoprotein ligand-1; CLA, cutaneous lymphocyte antigen; Lex, Lewis X; VCAM-1, vascular cell adhesion molecule-1; MAdCAM-1, mucosal addressin adhesion molecule-1; TARC, thymus- and activation-related chemokine; MDC, macrophagederived chemokine; MIP, macrophage inflammatory protein; SLC, secondary lymphoid tissue chemokine; TECK, thymus-expressed chemokine.
Guidance of neutrophils to sites of sterile inflammation A multistep cascade of molecular events guides the recruitment of neutrophils to sites of sterile injury ie tissue injury in the absence of infection. Neutrophils contribute to the clearance of debris from necrotic sites. They have an arsenal of destructive molecules hence collateral tissue destruction needs to be avoided. Steps: 1. ATP released from necrotic cells at the wound site activates the NLRP3 inflammasome via the P2X7 receptor in inflammatory cells (macrophages) resulting in release of IL-1. 2. IL-1 upregulates ICAM-1 on the vascular endothelium, leading to M2 integrin-mediated adhesion of neutrophils to microvascular endothelia near the wound site within 30-60 minutes of injury. 3. The chemokine MIP-2 (CXCL2) released at the wound site forms a chemoattractant gradient that surrounds but not does completely reach the injured area. It is maximal at 100-150 m from the injury border. 4. Neutrophils migrate via an intravascular route to the site of injury. 5. MIP-2 attacts neutrophils up to the injury border (but what attracts neutrophils into the necrotic lesion?). 6. Necrotic cells release mitochondria-derived formylated peptides, which over-ride MIP-2 and guide neutrophils directly into the injury site via formyl peptide receptor 1 signalling. This focuses the innate immune response on sites of damage rather than healthy tissue. Did this pathway evolve to limit collateral damage by allowing neutrophils to remain intravascular during migration to the wound via healthy tissue? The pathway has been established in liver, but also applies to skin. Figure MIP-2 expression (red) and PECAM-1+ endothelium (blue) were visualized 2.5 hours after injury.
Page 1 and 2: Cell adhesion: Roles in lymphocyte
Page 3 and 4: compartmentalized cells such as mac
Page 5 and 6: cytokines such as IL-1, IFN-, and T
Page 7 and 8: L-Selectin The smallest of the vasc
Page 9 and 10: Mucins Selectin ligands are mucins.
Page 11 and 12: Rolling Once leukocytes are capture
Page 13 and 14: targeted mice lacking CD18. This su
Page 15 and 16: CD73 is a glycosylphosphatidylinosi
Page 17: Poorly characterized **************
Page 21 and 22: Peyer’s patches. Mice deficient i
Page 23 and 24: Sunshine, vitamin D3, and dendritic
Page 25 and 26: Vitamin A and dendritic cells impri

Topic 2 lecture note..

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