Immune 77: Squeezing the most killing out of neutrophils

Immune reviews research showing that the migration of neutrophils between endothelial cells activates bactericidal function via mechanosensing.
Show notes at www.microbe.tv/immune/immune-...
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[@DudeFun-yi7nu]

Thank goodness for science, changing the world one informed conversation at a time.

[@margaritaalvarez8462]

So cool! Thumbs up for the neutrophil necklace, I wish we could have gotten a close up look at it, lol.

[@brucethomas471]

I really enjoyed this episode. Lots applies to me. Thanks for helping me understand more!❤️

[@danell1s]

Great to know more about the cells they're counting before my chemotherapy hits them again. I guess that's why it causes joint pain - lots of neutrophils dying as they try to reproduce.

[@wallacegrommet9343]

Advancing human knowledge of every aspect of biology is the work is essentialto humanity

[@muscovyducks]

this was probably the most critical treatment of a pub I've heard so far on microbetv. interesting to hear them dive into the details and peek behind the curtain a bit.

[@bizzystradlin7751]

Thanks!

[@lesfaby8997]

24:48 Glossary ROS: Reactive oxygen species

[@wallacegrommet9343]

Endogenous pesticides

[@ralphhancock7449]

I always wonder if there are times when the blood is too crowded with immune system cells. What would be a good source of information about that?

[@immunominuteswithcindyleif5123]

The body is good at maintaining the right number of cells, but in cases when there is cancer of an immune cell like a B cell leukemia, the body can't maintain the right number. The excess number of cells can make the blood very thick and can lead to rare problems such a stroke or difficulty breathing. Even if the blood doesn't thicken, too many cells in the blood can cause pain, fever, and other generalized symptoms. It is important to note that during infection, there can be a normal elevation of immune cells in the blood. For example, during bacterial infection many neutrophils are recruited from the bone marrow to the blood and this can be measured by complete blood counts (CBC) and is called neutrophilia. Neurophilia should naturally resolve as the infection clears.

[@ShonMardani]

Where do neutrophils die and what happens to their body?

[@wallacegrommet9343]

Circulating blood leukocytes have short life expectancies and end their lives by committing programmed cell death or apoptosis. Apoptosis is an active form of cell death that is initiated by a number of stimuli and is intricately regulated. Apoptosis in both excessive and reduced amounts has pathological implications. Basically, they are broken down carefully by chemical catalysis and their useful components are reused in new cells. The process is careful to not allow these nutrients to feed pathogens or overload the body with an excess of circulating cell material.

[@spamletspamley672]

How do the neutrophils know where they need to squeeze through the tight junctions (or are they just loosened where needed?). Could it be that the squeezing acts to burst vessicles of different reagents, allowing their mixing to create the free radicals. Like breaking a vial of water inside a bag of metabisulphite to release sulphur dioxide, when you are out of range of what you want to sterilise.

[@immunominuteswithcindyleif5123]

Great questions. Neutrophils use sophisticated molecular interactions to attach to and find the junctions between cells. They express a molecule called PECAM on their surface that binds to PECAM on the part of the endothelial cell at the junction. That molecule ratchets the neutrophil between the cells. Their vesicles, which carry lots of antibacterial molecules, are very small and don't break when they squeeze through as far as I know. But when the cell traverses the endothelium, it activates signals that then mobilize those effector mechanisms so they can be deployed against the bacteria that the neutrophil finds and eats.

[@spamletspamley672]

Thank you for replying, Cindy. I wondered how the neutrophil knows where it is needed. Do the epithelial cells over infected areas relax their PECAM in a kind of 'waiving for help' that the neutrophil's counterpart then grabs and gets pulled in? (Looking at the Wiki on CD21, I'm put in mind of hands reaching and clasping each other! I'm always filled with wonder at how all this vast amount of molecular machinery ever came to be! And equally amazed at how anyone ever found so much of it and worked out what it does AND then thought to write it up in Wikipedia for us! It is all quite miraculous! If only I could read and retain it all! :O This was quite a magical episode. Thank you. xx

[@spamletspamley672]

Sorry: CD31, not 21.

[@immunominuteswithcindyleif5123]

@@spamletspamley672 you are quite close! The neutrophils carry a hook that grabs onto a catch that the endothelial cells put out. They know to put out the catch because macrophages that detect infection secrete cytokines to activate the endothelial cells. This happens close to the site of infection. That’s how the neutrophils sense where to exit the blood. It is all quite amazing and magical 😊

[@spamletspamley672]

@@immunominuteswithcindyleif5123 Just thinking about the seemingly infinite number of complex reactions even to work one cell makes my brain hurt (Not to mention the equally infinite number of lucky chances that had to succeed just to make a planet for life to evolve on! It just seems too crazy to be possible: but here we are. :O )