Macrophages

Macrophages are highly differentiated immune cells in the various tissues of the organism, where they play the role of "scavengers of the human body". Macrophages are concentrated where there is a need to eliminate a waste, such as a bacteria, a product of tissue breakdown. or a damaged cell.

In the blood, macrophages are not present as such, but in the form of precursors called monocytes; the presence of these cells in circulation (1-6% of the total leukocyte count) is absolutely transient, in the order of about 8 hours, an interval that reflects the time elapsed between their synthesis in the bone marrow, their appearance in the circulation and their definitive migration into tissues (process called diapedesis). At the tissue level, monocytes enlarge, increase their lysosomes and differentiate into macrophages, some of which remain fixed in a specific location (resident macrophages), while others have the ability to move through amoeboid movements (recruited macrophages). Phenotypically distinct populations of macrophages are present in each organ and in the different areas of the spleen and lymph nodes (two of the sites where these cells are most represented, as it is necessary to destroy a large number of particles, toxins and unwanted substances).

Over the course of its existence, a macrophage can eliminate more than 100 bacteria, but if necessary it can also remove larger particles from tissues, such as aged red blood cells or necrotic neutrophils (neutrophils are another type of white blood cell with phage activity. , therefore similar to that of macrophages; however, they are smaller and much more numerous, and act above all in the blood). In general, macrophages incorporate and digest antigens, that is, everything that is foreign to the organism or is recognized as such, therefore worthy of attack and neutralization. Once the antigens have been digested, the macrophages process some of the components by exposing them on their external membrane bound to surface receptors (MHC proteins, called "major histocompatibility complex"). These complexes, very important for the immune function, act as special "antennas" or "identification flags" that signal the danger to other immune cells, requiring reinforcements. When they perform this function, macrophages are called antigen presenting cells (APC, Antigen-Presenting Cell).

In addition to presenting the antigen to lymphocytes, macrophages produce and secrete a wide range of secretion products (such as some interleukins or tumor necrosis factor TNF-alpha), which allow communication between the various types of lymphocytes; they are therefore capable of influencing the migration and activation of other cells of the immune system.

But how does a macrophage manage to identify a cell as dangerous? There are other immune cells, lymphocytes, capable of recognizing antigens and signaling them as dangerous to the eyes of macrophages. The latter, in fact, are in themselves capable of capturing the antigens, recognizing particular surface molecules that bind directly to their specific membrane receptors. At this point the phagocyte literally engulfs and digests the foreign particle. Although the macrophage is able to recognize numerous foreign particles, both organic and inorganic (for example coal and asbestos particles), some substances escape this recognition process, and the macrophage is therefore unable to recognize their danger. This is the case, for example, of so-called capsulated bacteria, in which an external polysaccharide capsule masks the surface markers. Other bacterial pathogens camouflage their surface with molecules similar to those of white blood cells, thus misleading the macrophages. at first in the watchful eyes of macrophages, these antigens are however recognized by lymphocytes, which synthesize antibodies against them. These antibodies bind to the surface of the antigen, as a sort of identifying flag that allows the macrophages to recognize their danger and neutralize them.

After the pathogen has been transformed into food for macrophages, these cells bind, envelop and engulf it, confining it to vesicles called phagosomes. Inside the macrophage the phagosomes merge with the lysosomes, vesicles rich in digestive enzymes and oxidizing agents, such as acid hydrolases and hydrogen peroxide, which kill and demolish what is incorporated. This is how phagolysosomes, otherwise known as "death chambers", are formed.

In addition to the large lysosomes, macrophages are characterized by their clearly superior dimensions compared to other leukocytes, by the Golgi apparatus and the particularly developed nucleus, and by the richness of acto-myosin filaments, which give the macrophage a certain motility (migration at the sites of infection).

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