1eye wrote:The other thing I was thinking is, what if what they were doing was being propelled along by some kind of force from inside the vessel, maybe the same thing that make them stay on the vessel? They are single cells, which cannot think or feel. What motivates them? Perhaps it is charge. Perhaps it is magnetism. Something moving along with the blood. I have read about "affinity" but how does it physically work? How do cells follow sources (trails?) of molecules? They have no brains. Without a brain or eyes, how does any single-celled organism find food? Or, in the case of immune cells, find invaders to attack? I bet they are following charge, which changes with blood velocity and direction, and changes with the presence of unwanted visitors.
Any cell biologists care to comment?
That might explain why immune cells might follow myelin, if it's carrying electricity makes them locomote, and electrical transitions make them try to squirt through, which results instead in demyelination.
Let's consider the case of one of the simplest cells, a rod shaped bacterium. It's movement consists of two behaviors, tumbles and glides. Think of a tumble as a random reorientation of direction. A glide is a movement in a particular direction uninterrupted by a tumble. The bacterium can sense the change in concentration of a chemical gradient. If that chemical is food for the bacterium, then it will move up the gradient. However, if that chemical represents a negative stimulus, then the bacterium will move down the gradient. Directed movement occurs in this fashion. In the case of a positive stimulus, such as a food gradient, if the bacterium senses that it is moving away from the food source, or down the gradient, the number of tumbles will be increased and the period between glides and the resulting length of glides will be shortened. In contrast, if the bacterium senses that it's moving towards a food source, then the frequency of tumbles will be reduced. By changing the frequency of tumbles vs. glides, the bacterium minimizes the amount of time it spends travelling in the wrong direction.
Eukaryotic cells, anything other than a bacterium, typically have proteins on their cell surface that are used as molecular receptors. A familiar example of how this works is with the drug Tysabri.
Tysabri prescribing information wrote:Natalizumab binds to the alpha-4-subunit of alpha-4-beta-1 and alpha-4-beta-7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the alpha-4-mediated adhesion of leukocytes to their counter-receptor(s). The receptors for the alpha-4 family of integrins include vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium, and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) present on vascular endothelial cells of the gastrointestinal tract. Disruption of these molecular interactions prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. In vitro, anti-alpha-4-integrin antibodies also block alpha-4-mediated cell binding to ligands such as osteopontin and an alternatively spliced domain of fibronectin, connecting segment-1 (CS-1). In vivo, natalizumab may further act to inhibit the interaction of alpha-4-expressing leukocytes with their ligand(s) in the extracellular matrix and on parenchymal cells, thereby inhibiting further recruitment and inflammatory activity of activated immune cells.
In a nutshell, the Tysabri antibody binds to the cell surface integrin protein on leukocytes and blocks its interaction with the VCAM1 receptor on the endothelium. In the absence of Tysabri, the integrin protein on the leukocyte would be recognized by the VCAM1 receptor on the endothelial cell. This recognition creates a binding event and would signal to the leukocyte that its immune fighting capabilities were needed and the cell would then cross the endothelium. The case of integrin binding to the VCAM1 receptor is just one example. This type of receptor and target activity is quite common.