Macrophage
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A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens |
Macrophages (
Greek: "big eaters",
makros = long, phagein = eat) are
white blood cells, more specifically
phagocytes, acting in the nonspecific defense as well as the specific defense system of vertebrate animals. Their role is to
phagocytize (engulf and then digest) cellular debris and
pathogens either as stationary or mobile cells.
Macrophages are
differentiated from
monocytes, which are eater cells derived from the bone marrow. When a monocyte enters the attacked tissue through the
endothelium of a
blood vessel (a process known as the
leukocyte adhesion cascade), it undergoes a series of changes and becomes a macrophage. The attraction of wandering macrophages to a damaged site occurs through
chemotaxis, triggered by a number of things, depending on circumstances; primarily, damaged cells and pathogens release chemical substances to which macrophages are attracted,
mast cells and
basophils release
histamine and macrophages already at the site release
cytokines to attract more of its kind.
Unlike short-lived neutrophils the life span of a macrophage ranges from months to years, as opposed to just a few days. Macrophages are unable to divide and must mature from monocytes produced in the bone marrow.
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Steps of a macrophage ingesting a pathogen:
a. Ingestion through phagocytosis, a phagosome is formed
b. The fusion of lysosomes with the phagosome creates a phagolysosome; the pathogen is broken down by enzymes
c. Waste material is expelled or assimilated (the latter not pictured)
Parts:
1. Pathogens
2. Phagosome
3. Lysosomes
4. Waste material
5. Cytoplasm
6. Cell membrane |
Phagocytosis
One important main role of macrophage is the removal of
necrotic debris and dust in the case of the
lungs. Removing dead cell material is important in chronic inflammation as the early stages of inflammation are dominated by
neutrophil granulocytes, which are ingested by macrophages if they come of age (see
CD-31 for a description of this process.)
The removal of dust and necrotic tissue is to a greater extent handled by
fixed macrophages, which will stay at strategic locations such as the lungs, liver, neural tissue, bone, spleen and connective tissue, ingesting foreign materials such as dust and pathogens, calling upon wandering macrophages if needed.
When a macrophage ingests a pathogen, the pathogen becomes trapped in a food
vacuole, which then fuses with a
lysosome. Within the lysosome,
enzymes and toxic
oxygen compounds digest the invader. However, some bacteria, such as
Mycobacterium tuberculosis, have become resistant to these methods of digestion. Macrophages can digest more than 100 bacteria before they finally die due to their own digesting compounds.
Macrophages are involved in cell-mediated immunity along with NK cells and cytotoxic T cells.
Role in specific immunity
After digesting a pathogen, a macrophage will present the
antigen (a molecule, most often a protein found on the surface of the pathogen, used by the immune system for identification) of the pathogen to a corresponding
helper T cell. The presentation is done by integrating it into the cell membrane and displaying it attached to a
MHC class II molecule, indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface.
Eventually the antigen presentation results in the production of
antibodies that attach to the antigens of pathogens, making them easier for macrophages to adhere to with their cell membrane and phagocytize. In some cases, pathogens are very resistant to adhesion by the macrophages. Coating an antigen with antibodies could be compared to coating something with
Velcro to make it stick to fuzzy surfaces.
Due to their role in phagocytosis, macrophages are involved in many diseases of the immune system. For example, they participate in the formation of
granulomas, inflammatory lesions that may be caused by a large number of diseases.
Some disorders, mostly rare, of ineffective phagocytosis and macrophage function have been described.
Macrophages are the predominant cells involved in creating the progressive plaque lesions of
atherosclerosis.
When fighting
influenza, macrophages are dispatched to the throat. However, until the killer T cells for the flu virus are found, the macrophages do more damage than help. They not only destroy throat cells infected with the flu virus but also destroy several surrounding non-infected cells.
Macrophages also play a role in
Human Immunodeficiency Virus (HIV) infection. Like
T cells, macrophages can be infected with HIV, and even become a reservoir of ongoing virus replication throughout the body.
As mentioned earlier, a majority of macrophages are stationed at strategic points where microbial invasions or accumulations of dust are likely to occur, each type of macrophage, determined by its location has a specific name:
*Alveolar macrophages/dust cells in the lungs
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Histiocytes in the connective tissue
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Kupffer cells in the liver
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Microglial cells in the neural tissue
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Osteoclasts in the bone
*Sinusoidal lining cells in the spleen
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Tingible body macrophages are found the germinal centers of lymph nodes
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Dendritic cells (including
Langerhans cells)
* A
lipid-laden macrophage is called a "foam cell"
