22 April, 2007

Multiple Sclerosis

On any other day one would find them standing close by, snug up against each other and glued in place to create an impenetrable wall. But today something is odd. As blood pulses, pushing at them from one side, they begin to lose grip, just a little bit, but it's enough. The endothelial cells panic. Normally it is their given purpose to protect the precious brain matter on the other side of the capillary, and they are failing. Collectively, they don't know what is going on, so they signal for help individually. Cell surface proteins are changed from cadherins to integrins and cytokines are wafted out into the blood, calling for macrophages to come and see what is wrong.

That was their first mistake.

As they always do, the macrophages quickly come sailing down the bloodstream, slowing down and rolling along the sides of the capillary until they reach the distressed endothelial cells, where they squeeze themselves between the loosened cells. Normally, macrophages cannot penetrate the tight barrier presented by the endothelial cells in the blood-brain barrier, but this is different.

Letting them cross was their second mistake, but it was one they could hardly help since something seems to be wrong with their adhesion factors in the first place.

Inside the densely packed brain matter, the macrophages are confused. This is tissue they've never seen before, it is strange and alien to them, usually closed off but suddenly opened wide for them to see. The macrophages know that that which is strange and alien means danger to the organism, and as such, they mount their normal innate immune response. The funny-tasting brain matter is blasted with oxidative chemicals as yet more cytokines are wafted out through the bloodstream.

Soon the side of the weakened capillary is crawling with immune cells. In addition to macrophages, there are now monocytes, neutrophils, natural killer cells, and dendritic cells. All that the former can do is blast the weird tissue with yet more chemicals and try to eat it, but it is the latter cells, the dendritic cells, whose appearance is most ominous.

The dendritic cells busily set up shop, ingesting pieces of the brain matter and swooping back out in the bloodstream. There they sneak out of postcapillary venules into lymph nodes and other lymphatic organs and, like mother birds regurgitating food for their young, spit those pieces of brain matter back up so that the developing, naive T cells and B cells can see and and feel it and memorize one simple fact: THIS IS OUR ENEMY!

The T cells and B cells go wild and proliferate all over the place. The B cells swell with antigens against the brain matter, and so does the blood serum. The T cells migrate to the site of weakened blood-brain barrier and join the macrophages and others in bombarding the brain matter with pro-inflammatory chemicals in a concerted effort to destroy it. The B cells' antigens mark the brain matter for destruction, and phagocytosis sets in.

The oligodendrocytes of the brain matter are confused, hurt, and reeling from the sudden onslaught of the immune system. Collectively, they teeter on the edge between survival and apoptosis, and unfortunately many of them fall to apoptosis, disrupting the normal course of electrical signalling in that part of the brain.

Eventually, the endothelial cells of the blood-brain barrier recover and rejoin to once again deny the immune system access to the brain matter. So the immune system lurks outside, ready and muttering to itself, while the brain matter inside ineffectually tries to heal itself, recovering to some degree, but nonetheless still bearing deep scars.

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