Macrophages

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

In blood, macrophages are not present as such, but in the form of precursors called monocytes; the presence of these circulating cells (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, the appearance in the circulation and the definitive tissue migration (process called diapedesis). At the tissue level, monocytes become larger, increase their lysosomes and differentiate into macrophages, some of which remain fixed at a given site (resident macrophages), while others have the ability to move through amoeboid movements (recruited macrophages). Phenotypically distinct macrophage populations are present in each organ and in 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).

During its existence, a macrophage can eliminate more than 100 bacteria, but if necessary it can also remove larger particles from the tissues, such as aged red blood cells or necrotic neutrophils (neutrophils are another type of white blood cells with phage activity)., therefore similar to that of macrophages, but they are smaller and much more numerous, and they act above all on a blood level). In general, macrophages absorb and digest antigens, or whatever 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 components exposing them on their outer membrane linked to surface receptors (MHC proteins, called "major histocompatibility complex"). These complexes, which are very important for the immune function, act as special "antennae" or "identifying flags" that signal the danger to other immune cells, requiring reinforcements. When they cover this function, macrophages are called antigen-presenting cells ( Antigen-Presenting Cell ).

In addition to presenting antigen to lymphocytes, macrophages produce and secrete a wide range of secretion products (such as some interleukins or TNF-alpha tumor necrosis factor), which allow communication between the various types of lymphocytes; they are therefore able to influence 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, which can recognize antigens and report them as dangerous in the eyes of macrophages. The latter, in fact, are in themselves capable of capturing antigens, recognizing particular surface molecules that bind directly to their specific membrane receptors. At this point the phagocyte literally englobes 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 its dangerousness. This is the case, for example, of the so-called encapsulated bacteria, in which an external polysaccharide capsule masks surface markers. Other bacterial pathogens camouflage their surface with molecules similar to those of white blood cells, thus deceiving the macrophages. While at first escaping the vigilant eyes of macrophages, these antigens are still 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 macrophages to recognize the danger and neutralize them.

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

In addition to large lysosomes, macrophages are markedly larger than the other leukocytes, the Golgi apparatus and the particularly developed nucleus, and the richness of acto-myosin filaments, which give the macrophage a certain motility (migration at infection sites).