Neutrophils

Polymorphonuclear Leukocytes

the nucleus appears to have multiple lobes or segments

Granulocytes that have granules

neutrophil , basophil. Eosinophil, Mast cell

Why do neutrophils not recirculate? 

When the neutrophils enter the tissue they are locked there → doing their job they apoptose

Endothelial cells

• Tightly connected to one another

• Create a barrier between components of the blood and tissue 

Chemokine effects on selectins and integrins 

• selectin and integrin activation/upregulation

• Direct movement of leukocytes. Leukocytes chemokine receptor used to sense chemokines moves toward higher concentration of chemokine

Chemokine receptors 

G protein-coupled receptor that leads to activation of intercellular proteins and actin polymerization

Intergrins

Leads to strong attachment

Anatomy of an integrin

Structure of intergins (how do they become activated?)

• Heterodimers with beta and alpha subunit 

• Have inactive and active conformation → active when chemokine receptors engage w. Chemokines  

• Leading to adhesion and attachment

HEV sialomucin

negatively charged, sugar-rich glycoproteins expressed on high endothelial venules (HEVs)

High Endothelial venules (HEV) [what receptor do they express and what do htey recognize]

specialized blood vessels with endothelial cells that are only present in secondary lymphoid organs; they express CD34 which only B cells and T cells can recognize

How T cells stick 

• T cell story

  • 1. T cells use L-selectin to bind HEV sialomucin (rolling)

  • 2. T cells use CCR7 (not expressed on B cells or neutrophils) to recognize chemoattractant CCL21 expressed by High

  • Endothelial Venules (HEV), which are special blood vessels that run through lymph nodes

  • 3. CCR7 activates the integrin LFA1 to cause sticking/adhesion to HEV

  • Transendothelial migration occurs

Natalizumab [what intergrin does it block]

is a monoclonal antibody medication that blocks immune cells from entering tissues, especially the brain and gut, to reduce harmful inflammation

• mAb that blocks alpha-4 integrin 

  • Blocking integrin → less leukocyte trafficking → less inflammation

  • Helps patients with autoimmune diseases (like multiple sclerosis)

•  What is the fatal effect

Genetic deficiency in Mac-1 integrin [what health condition results]

• Prevents neutrophil adhesion → neutrophil can’t reach the site of infection

• High number of neutrophils remain in circulation (Rolling BUT NO Arrest)

• Recurrent bacterial infections 

Neutrophils vs T cells

Five Hallmarks of Inflammation 

Heat

Redness

Swelling

Pain

Loss of Function

Neutrophils after killing

• Programmed cell death

do leukocytes and endothelial cells both have selectin and ligand

Leukocytes + endothelial cells BOTH have selectins + ligands. KO of either = impaired migration

chemotaxis

the mobile response a cell has towards a chemical that has attractive properties to it

CCR7

expressed on T cells

CCL21 expressed by HEV