If you were to look at a sufficiently magnified view of a neuron you would notice it was surrounded by many other processes; some of which are from other neurons, but many of which are non-neuronal cells known as neuroglia. The term neuroglia (also called glia), appropriately named since it literally means “nerve glue”, was first used in 1856 by German neuropathologist Ludwig Virchow. Neuroglia can be distinguished by two different types; macroglia and microglia. Macroglia is futher divided into oligodendroglia and astrocytes. As the name suggests, microglia and macroglia differ in size, but the main reason for the distinction is their different embyological origins. Macroglia develop from the same precursors as neurons, whilst microglia have monocytes as an embryological precursor. Shortly after birth, monocytes will leave the circulatory system and enter the brain, where they develop into microglia. Monocytes are a type of white blood cell and are involved in the body’s immune system. Therefore the connection between microglia and the brain’s immune response should be a matter of course given its origins.

Before discussing the immune function of microglia it is necessary to have some understanding of the body’s immune system response in general. The immune system is mediated by the white blood cells, two of which are monocytes and lymphocytes. The role of monocytes, outside the nervous system, is that of phagocytosis. This means that they will enlarge to become macrophages; scavenger cells that engulf and thereby remove infected cells and other cellular debris. One type of lymphocyte is the B-lymphocyte (B because they are produced in bone marrow), which is vital in synthesizing antibodies, a type of immunoglobulin protein. Antibodies will bind to and deactivate foreign substances, known as antigens. Another type of lymphocyte is the T-lymphocyte (T since it is produced in the thymus). T-cells are similar to B-lymphocytes in that they are also activated by antigens, but differ in their response; they respond by recognising antigens present on cell surfaces and attack the cell whilst secreting chemical messengers designed to mobilise other immune system cells.

Although this arrangement involving lymphocytes and monocytes works quite efficiently within the body, a separate process must be employed within the nervous system due to the inability of the immune system cells to pass through the capillaries of the brain. This is known as the blood-brain barrier and serves to isolate the nervous system. Due to this segregation between brain and body, the nervous system uses microglia as its sole representative of the immune system. Microglia will respond to signals from dying or inflamed nervous tissue; migrating towards the source of the signal and subsequently changing its morphology from a ramified (inactive) state to an amoeboid (active) state engulfing and disposing of the degenerating tissue. This is apparent in samples of brain tissue from patients diagnosed with degenerative disorders of the nervous system since substantial numbers of amoeboid microglial cells are found.

Phagocytosis is not the only function of microglia; microglia also serves to provide chemical signals for other cells, which is extremely important because this acts as a way of opening up the nervous system to other external constituents of the immune system. Activated microglia release substances, called cytokines, which enable immune system cells to communicate both with each other and with other types of cells. In addition to acting as a chemical liaison, cytokines will break down the blood-brain barrier allowing the body’s immune system cells to enter the nervous system. This means that following nervous system injury there will likely be an influx of macrophages originating from outside the nervous system. This has important implications because whilst external immune system cells may target damaged neural cells and help with their disposal, they may also regard healthy tissue as antigens and target it. Consequently, along with providing a beneficial function in the health and maintenance of the nervous system, microglia can paradoxically contribute to and exacerbate disorders associated with nervous system pathology, such as AIDS and Multiple Sclerosis.

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