Nerd Boosts

EV-D68–Nerd boost

EV-D68 (as discussed in the main post) is a virus in the same family as the polio virus and coxsackievirus (which can cause meningitis).  The innate immune system is critical in preventing viral infections from getting out of control and talking with the adaptive immune system if they do get out of hand.  Let’s say you were given pictures of a villain and a superhero, but you don’t recognize either of them.  Chances are that based off of clues in the expressions on their faces, physical features, or background colors you would be able to pick who was good and who was bad.

Captain Marvel

Doctor Sivana

Cells of the innate immune system recognize viruses and bacteria using similar mechanisms. They see very broad features that are common to lots of different types of viruses or lots of different types of bacteria.  These broad features are called Pathogen Associated Molecular Patterns (PAMPs) and are recognized by innate immune cells using Pattern Recognition Receptors (PRR).  For enterovirus, the PAMP is double stranded RNA (dsRNA).  RNA is in our own cells as well and is used to make proteins, but we don’t generally have it in this double stranded form so it’s seen as foreign. Innate immune cells recognize this RNA with a PRR molecule called TLR3.  Binding of dsRNA to TLR3 starts a series of actions that tells cells to go into anti-viral mode partly through telling the cell to make the cytokine called Interferon.  (This cytokine was also discussed in the nerd boost about Ebola).  EV-D68 interrupts these events from occurring by cutting up one of the “signaling molecules” that allows the cell to go from recognizing the danger to producing the Interferon.  This disruption prevents the anti-viral mode from going into full action.

Luckily this virus hasn’t proven to be deadly and only causes a few days of cold-like symptoms.  This is an indication that most likely the immune system adjusts and the T cells and B cells of the adaptive immune system are able to eventually take over and get rid of the virus.

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Dr. Jekyll–Nerd Boost

The transition of microglia from Dr. Jekyll to Mr. Hyde (as discussed in the main post) is influenced by many other cells in the brain.  Some cells, including the nerve cells, can actively prevent microglia from becoming the more inflammatory Mr. Hyde.  In a healthy brain, the nerve cells are helping themselves by keeping the microglia in a more supportive role.  As these nerve cells die off in ALS however, the brakes are released and microglia are able to become more destructive.  As discussed in the main post, Regulatory T cells help to keep microglia in a protective state during early stages.  But as the disease progresses, other T cells seem to take over and influence microglia to become inflammatory and destructive.  

Astrocytes

Mr. Hyde microglia release lots of damaging, inflammatory molecules into the brain, which then have effects on other cells besides just the nerve cells.  The astrocytes pictured above are not immune cells but play an important role in protecting nerve cells in the healthy brain and helping them to communicate their messages. Astrocytes are located near the Blood-Brain-Barrier which puts them in a prime location to influence cells outside of the brain (those immune cells that are in the bloodstream).  The communication between microglia and astrocytes amps up the inflammation and leads to the recruitment of immune cells into the brain where access would normally be forbidden.

Involvement of immune cells in ALS is very complicated with lots of different types of cells talking to one another. While Regulatory T cells try to maintain a “civil” conversation, the interaction of all of these cells ends up being very heated and damaging to the motor neurons.  ALS is not exactly an immune-mediated disease,  but the inflammation that results can lead to its progression.

References can be found here and here.

Hijacked by Ebola–Nerd boost

This aside is a “nerd boost” for the main article found here.

Those immune cells infected by Ebola are monocytes, macrophages, and dendritic cells. These are all cells whose mission is to respond quickly to invasions by foreigners. Monocytes circulate throughout your bloodstream and once they enter into tissue (be it lung, liver, heart, or spleen), they morph into either macrophages (literally “big eaters”) or dendritic cells (very good at presenting evidence of infection to other immune cells).   Within these tissues, macrophages and dendritic cells are situated at prime locations to monitor the entry of foreign pathogens (including Ebola).

One of the cytokines (again the words used for communication) normally produced upon infection by viruses is called Interferon.   Interferons tell infected cells to slow down or stop the process of making DNA and protein so that the virus can’t hijack those functions to make more virus. Interferons also tell infected cells to identify themselves to immune cells so that if needed those cells can be killed. They do this by displaying bits of the virus on the cell surface.  Kind of like waving a red flag to attract the attention of immune cells (particularly T cells) that are well-suited for eliminating infections.  Ebola prevents these defense mechanisms from happening by making proteins, VP35 and VP24, which blocks the functions of Interferons.

The dendritic cells mentioned above are also severely impaired during infection.  The Interferon discussed would normally help the dendritic cells to act as the pep rally for the troops (specifically those T cells).  But by interfering with Interferon production, Ebola forces the dendritic cell to communicate a message of “No problem here” instead of “Danger!  Danger!”.

Interrupting all of these levels of the immune system creates a very deadly virus.