Functions of macrophages. Tissue macrophages are promonocytes. Macrophage cells. What are they and what functions do they have? Where do macrophages develop?
Literally translated, the definition of "macrophage" has a rather sinister and frightening meaning: "macro" in Greek means "large", and "phagos" means devourer. “Big Eater”... The imagination pictures some kind of monster, but we are just talking about blood cells. However, if we judge macrophages at the cellular level, then they fully justify their name.
What are macrophage cells and where do they come from?
Functions of macrophages:
When a foreign object enters the body, be it a microbe or a foreign body, the immune system immediately “unleashes the dogs” on it: it is attacked by phagocytes. These cells, including macrophages, recognize, capture and devour strangers who threaten the well-being of the internal environment of the body.
In addition, macrophages destroy dead cells that have completed their existence through the process of apoptosis (programmed, natural, normal cell death). Also, the functions of macrophages are to provide antitumor immunity: having detected the appearance of atypical cancer cells in the body, macrophages attack and eat them.
Types of macrophages:
7. Where are the m acrophages of lymph nodes, is clear from the name. It is thanks to them that the lymph nodes are known as filters that cleanse the lymph.
Macrophages and the immune system:
Macrophage cells do not just mindlessly destroy harmful objects: by breaking them down into fragments, they carry out the process of presenting their antigens. Antigens are molecules of harmful particles that indicate their genetic foreignness and cause an appropriate protective reaction from the immune system. By themselves, they do not pose a threat of infection or other negative impact, but they are a mark of a stranger, so the body reacts to their presence with a defensive reaction, as if it were a full-fledged aggressor.
During the process of phagocytosis, macrophages present the antigens of killed “enemies” - they expose them to the surface of their membranes. They also form cytokines - information molecules that carry data about the defeated aggressor.
With this invaluable cargo, macrophages are sent to representatives of another part of the immune system - lymphocytes. They transmit information to them and teach them what to do if a carrier of the same antigen ever enters the body again. As a result, the immune system remains fully combat-ready against it.
Unfortunately, sometimes the personal experience of our macrophages or other phagocytes is not enough for the immune system to work properly and respond correctly to harmful objects. To increase its effectiveness and at the same time improve your overall health, it is recommended to take the drug Transfer Factor. It contains cytokines that carry data about various pathogens, toxins and other harmful agents. The drug trains the immune system to function fully, which immediately and favorably affects the course of existing diseases, the state of metabolism and organ function. The product can be used for therapeutic and prophylactic purposes.
Macrophages(from ancient Greek μακρός - large, and φάγος - eater (synonyms: histiocyte-macrophage, histophagocyte, macrophagocyte, megalophage-eater)), polyblasts, cells of mesenchymal nature in the animal body, capable of actively capturing and digesting bacteria, residues dead cells and other particles foreign or toxic to the body. The term “macrophages” was introduced by Mechnikov.
Macrophages include blood monocytes, connective tissue histiocytes, endothelial cells of the capillaries of the hematopoietic organs, Kupffer cells of the liver, cells of the wall of the lung alveoli (pulmonary macrophages) and the peritoneal wall (peritoneal macrophages).
It has been established that in mammals, macrophage precursors are formed in the bone marrow. The cells of the reticular tissue of the hematopoietic organs, which are combined with macrophages into the reticuloendothelial (macrophagic) system, which performs a protective function in the body, also have active phagocytic properties.
Morphology
The main cell type of the mononuclear phagocyte system. These are large (10 - 24 microns) long-lived cells with a well-developed lysosomal and membrane apparatus. On their surface there are receptors for the Fc fragment of IgGl and IgG3, C3b fragment C, receptors of B and T lymphocytes, complement, other interleukins and histamine.
Tissue macrophages
In fact, a monocyte becomes a macrophage when it leaves the vascular bed and penetrates the tissue.
Depending on the type of tissue, the following types of macrophages are distinguished.
· Histiocytes - macrophages of connective tissue; component of the reticuloendothelial system.
· Kupffer cells - otherwise endothelial stellate cells of the liver.
· Alveolar macrophages - otherwise, dust cells; located in the alveoli.
· Epithelioid cells - components of granulomas.
· Osteoclasts are multinucleated cells involved in bone resorption.
· Microglia are cells of the central nervous system that destroy neurons and absorb infectious agents.
Macrophages of the spleen
Identification of macrophages
macrophages contain numerous cytoplasmic enzymes and can be identified in tissues by histochemical methods that detect these enzymes. Some enzymes, such as muramidase (lysozyme) and chymotrypsin, can be detected by a labeled antibody test (immunohistochemistry), which uses antibodies against the enzyme proteins. Such monoclonal antibodies against various CD antigens are widely used to identify macrophages.
Functions of macrophages
Macrophage functions include phagocytosis, antigen processing, and interaction with cytokines.
Phagocytosis
· Non-immune phagocytosis: macrophages are able to phagocytose foreign particles, microorganisms and the remains of damaged cells directly, without inducing an immune response. However, phagocytosis of microorganisms and their destruction are greatly facilitated by the presence of specific immunoglobulins, complement and lymphokines, which are produced by immunologically activated T lymphocytes.
· Immune phagocytosis: macrophages have surface receptors for the C3b and Fc fragment of immunoglobulins. Any particles that are coated with immunoglobulin or complement (opsonized) are phagocytosed much more easily than “naked” particles.
· “Processing” of antigens: macrophages “process” antigens and present them to B- and T-lymphocytes in the required form; This cellular interaction involves the simultaneous recognition by lymphocytes of MHC molecules and “processed antigens” found on the surface of macrophages.
· Interaction with cytokines: Macrophages interact with cytokines produced by T lymphocytes to protect the body against certain damaging agents. A typical result of such interaction is the formation of granulomas. Macrophages also produce cytokines, including interleukin-1, interferon-β, and T- and B-cell growth factors. Various interactions of lymphocytes and macrophages in tissues manifest themselves morphologically during chronic inflammation.
The role of macrophages is not limited to the secretion of IL-1. These cells synthesize a number of biologically active substances, each of which makes its own contribution to inflammation. These include: esterases, proteases and antiproteases; lysosomal hydrolases - collagenase, alastase, lysozyme, α-macroglobulin; monokines - IL-1, colony-stimulating factor, fibroblast growth-stimulating factor; anti-infective agents - interferon, transferrin, transcobalamin; complement components: C1, C2, C3, C4, C5, C6; Arachidonic acid derivatives: prostaglandin E2, thromboxane A2, leukotrienes.
Macrophages Monocytes (macrophages) are a type of white blood cell involved in fighting infections. Monocytes, along with neutrophils, are the two main types of blood cells that engulf and destroy various microorganisms. When monocytes leave the blood and enter tissues, they turn into macrophages. Macrophages are close in their functions to monocytes and can fight infections in tissues, as well as perform some other functions, for example, utilize dead cells (scavengers)
Source: "Medical Dictionary"
Connective tissue cells with active mobility and a pronounced ability for phagocytosis - absorption and destruction of foreign cells.
Source: "Medical Popular Encyclopedia"
Medical terms. 2000 .
See what “Macrophages” are in other dictionaries:
- ... Wikipedia
MACROPHAGES- (from the Greek makros: large and phago eat), vulture. megalophages, macrophagocytes, large phagocytes. The term M. was proposed by Mechnikov, who divided all cells capable of phagocytosis into small phagocytes, microphages (see), and large phagocytes, macrophages. Under… … Great Medical Encyclopedia
- (from macro... and...phage) (polyblasts) cells of mesenchymal origin in animals and humans, capable of actively capturing and digesting bacteria, cell debris and other particles foreign or toxic to the body (see Phagocytosis). To macrophages... Big Encyclopedic Dictionary
- (from macro... and...phage), cells of mesenchymal origin in an animal body, capable of actively capturing and digesting bacteria, the remains of dead cells and other particles foreign and toxic to the body. The term "M." administered.… … Biological encyclopedic dictionary
The main cell type of the mononuclear phagocyte system. These are large (10-24 microns) long-lived cells with a well-developed lysosomal and membrane apparatus. On their surface there are receptors for the Fc fragment of IgGl and IgG3, C3b fragment C, B receptors ... Dictionary of microbiology
MACROPHAGES- [from macro... and phage (and)], organisms that devour large prey. Wed. Microphages. Ecological encyclopedic dictionary. Chisinau: Main editorial office of the Moldavian Soviet Encyclopedia. I.I. Dedu. 1989 ... Ecological dictionary
macrophages- A type of lymphocyte that provides nonspecific protection through phagocytosis and participates in the development of the immune response as antigen presenting cells. [English-Russian glossary of basic terms in vaccinology and... ... Technical Translator's Guide
- (from macro... and...phage) (polyblasts), cells of mesenchymal origin in animals and humans, capable of actively capturing and digesting bacteria, cell debris and other particles foreign or toxic to the body (see Phagocytosis)... ... encyclopedic Dictionary
- (see macro... + ...phage) connective tissue cells of animals and humans, capable of capturing and digesting various particles foreign to the body (including microbes); And. And. Mechnikov called these cells macrophages, in contrast to... ... Dictionary of foreign words of the Russian language
macrophages- ів, pl. (one macroph/g, a, h). Cells of healthy tissue of created organisms, which accumulate and poison bacteria, lattices of dead cells and other foreign or toxic particles for the body. Placenta/rni macrophages/hy macrophages, what... ... Ukrainian Tlumach Dictionary
Books
- Placental macrophages. Morphofunctional characteristics and role in the gestational process, Pavlov Oleg Vladimirovich, Selkov Sergey Alekseevich. For the first time in the world literature, the monograph collects and systematizes modern information about a little-studied group of human placental cells - placental macrophages. Described in detail...
Article for the “bio/mol/text” competition: The immune system is a powerful multi-layered defense of our body, which is amazingly effective against viruses, bacteria, fungi and other pathogens from the outside. In addition, the immune system is able to effectively recognize and destroy transformed own cells, which can degenerate into malignant tumors. However, malfunctions of the immune system (for genetic or other reasons) lead to the fact that one day malignant cells take over. An overgrown tumor becomes insensitive to attacks from the body and not only successfully avoids destruction, but also actively “reprograms” protective cells to meet its own needs. By understanding the mechanisms that tumors use to suppress the immune response, we can develop countermeasures and try to shift the balance toward activating the body's own defenses to fight the disease.
This article was submitted to the competition of popular scientific works “bio/mol/text”-2014 in the “Best Review” category.
The main sponsor of the competition is the forward-thinking company Genotech.
The competition was supported by RVC OJSC.
Tumor and immunity - a dramatic dialogue in three parts with a prologue
It has long been believed that the reason for the low effectiveness of the immune response in cancer is that tumor cells are too similar to normal, healthy ones for the immune system, tuned to search for “strangers,” to recognize them properly. This precisely explains the fact that the immune system most successfully resists tumors of a viral nature (their frequency increases sharply in people suffering from immunodeficiency). However, it later became clear that this was not the only reason.
If this article deals with the immune aspects of cancer, then the work “There are no more terrible claws in the world...” You can read about the features of cancer metabolism. - Ed.
It turned out that the interaction of cancer cells with the immune system is much more diverse. The tumor does not just “hide” from attacks, it can actively suppress the local immune response and reprogram immune cells, forcing them to serve their own malignant needs.
The “dialogue” between a degenerated cell, out of control, with its offspring (that is, a future tumor) and the body develops in several stages, and if at first the initiative is almost entirely on the side of the body’s defenses, then at the end (in the event of the development of a disease) - goes to the side of the tumor. Several years ago, cancer immunologists formulated the concept of “immunoediting” ( immunoediting), describing the main stages of this process (Fig. 1).
Figure 1. Immunoediting (immunoediting) during the development of a malignant tumor.
The first stage of immunoediting is the process of elimination ( elimination). Under the influence of external carcinogenic factors or as a result of mutations, a normal cell is “transformed” - it acquires the ability to divide indefinitely and not respond to the body’s regulatory signals. But at the same time, as a rule, it begins to synthesize special “tumor antigens” and “danger signals” on its surface. These signals attract cells of the immune system, primarily macrophages, natural killer cells, and T cells. In most cases, they successfully destroy “spoiled” cells, interrupting the development of the tumor. However, sometimes among these “precancerous” cells there are several whose immunoreactivity - the ability to cause an immune response - is weakened for some reason, they synthesize fewer tumor antigens, are less recognized by the immune system and, having survived the first wave of the immune response, continue to divide.
In this case, the interaction of the tumor with the body enters the second stage, the equilibrium stage ( equilibrium). Here the immune system can no longer completely destroy the tumor, but is still able to effectively limit its growth. In such an “equilibrium” (and undetectable by conventional diagnostic methods) state, microtumors can exist in the body for years. However, such latent tumors are not static - the properties of the cells that make them up gradually change under the influence of mutations and subsequent selection: among the dividing tumor cells, those that are better able to resist the immune system receive an advantage, and eventually cells appear in the tumor - immunosuppressants. They are able not only to passively avoid destruction, but also to actively suppress the immune response. Essentially, this is an evolutionary process in which the body unwittingly “brings out” the exact type of cancer that will kill it.
This dramatic moment marks the transition of the tumor to the third stage of development - avoidance ( escape), - in which the tumor is already insensitive to the activity of cells of the immune system, moreover, it turns their activity to its benefit. It begins to grow and metastasize. It is this kind of tumor that is usually diagnosed by doctors and studied by scientists - the two previous stages occur hidden, and our ideas about them are based mainly on the interpretation of a number of indirect data.
Dualism of the immune response and its significance in carcinogenesis
There are many scientific articles describing how the immune system fights tumor cells, but an equally large number of publications demonstrate that the presence of immune system cells in the immediate tumor environment is a negative factor that correlates with accelerated cancer growth and metastasis. Within the framework of the concept of immunoediting, which describes how the nature of the immune response changes as the tumor develops, such dual behavior of our defenders finally received an explanation.
We will look at some of the mechanisms of how this happens, using macrophages as an example. The tumor uses similar techniques to deceive other cells of the innate and acquired immunity.
Macrophages - “warrior cells” and “healing cells”
Macrophages are perhaps the most famous cells of the innate immune system - it was with the study of their abilities for phagocytosis that Metchnikoff began classical cellular immunology. In the mammalian body, macrophages are the combat vanguard: being the first to detect the enemy, they not only try to destroy it on their own, but also attract other cells of the immune system to the battlefield, activating them. And after the destruction of foreign agents, they begin to actively participate in eliminating the damage caused, developing factors that promote wound healing. Tumors use this dual nature of macrophages to their advantage.
Depending on the predominant activity, two groups of macrophages are distinguished: M1 and M2. M1 macrophages (they are also called classically activated macrophages) - “warriors” - are responsible for the destruction of foreign agents (including tumor cells), both directly and by attracting and activating other cells of the immune system (for example, T-killer cells ). M2 macrophages - “healers” - accelerate tissue regeneration and ensure wound healing.
The presence of a large number of M1 macrophages in the tumor inhibits its growth, and in some cases can even cause almost complete remission (destruction). And vice versa: M2 macrophages secrete molecules - growth factors, which additionally stimulate the division of tumor cells, that is, they favor the development of malignancy. It has been experimentally shown that M2 cells (“healers”) usually predominate in the tumor environment. Even worse: under the influence of substances secreted by tumor cells, active M1 macrophages are “reprogrammed” into the M2 type, stop synthesizing antitumor cytokines such as interleukin-12 (IL12) or tumor necrosis factor (TNF) and begin to release molecules into the environment , accelerating the growth of the tumor and the germination of blood vessels that will provide its nutrition, for example, tumor growth factor (TGFb) and vascular growth factor (VGF). They stop attracting and initiating other cells of the immune system and begin to block the local (antitumor) immune response (Fig. 2).
Figure 2. M1 and M2 macrophages: their interaction with the tumor and other cells of the immune system.
Proteins of the NF-kB family play a key role in this reprogramming. These proteins are transcription factors that control the activity of multiple genes required for M1 activation of macrophages. The most important members of this family are p65 and p50, which together form the p65/p50 heterodimer, which in macrophages activates many genes associated with the acute inflammatory response, such as TNF, many interleukins, chemokines and cytokines. The expression of these genes attracts more and more immune cells, “highlighting” the area of inflammation for them. At the same time, another homodimer of the NF-kB family - p50/p50 - has the opposite activity: by binding to the same promoters, it blocks their expression, reducing the degree of inflammation.
Both activities of NF-kB transcription factors are very important, but the balance between them is even more important. It has been shown that tumors specifically release substances that disrupt p65 protein synthesis in macrophages and stimulate the accumulation of the p50/p50 inhibitory complex. In this way (in addition to a number of others), the tumor turns aggressive M1-macrophages into unwitting accomplices of its own development: M2-type macrophages, perceiving the tumor as a damaged area of tissue, turn on the restoration program, but the growth factors they secrete only add resources for tumor growth. This completes the cycle - the growing tumor attracts new macrophages, which are reprogrammed and stimulate its growth instead of destruction.
Reactivation of the immune response is a current direction in anticancer therapy
Thus, in the immediate environment of tumors there is a complex mixture of molecules, both activating and inhibiting the immune response. The prospects for the development of a tumor (and therefore the prospects for the survival of the organism) depend on the balance of the ingredients of this “cocktail”. If immunoactivators predominate, it means that the tumor has not coped with the task and will be destroyed or its growth will be greatly inhibited. If immunosuppressive molecules predominate, this means that the tumor was able to pick up the key and will begin to progress rapidly. By understanding the mechanisms that allow tumors to suppress our immune system, we can develop countermeasures and shift the balance toward eliminating tumors.
Experiments show that the “reprogramming” of macrophages (and other cells of the immune system) is reversible. Therefore, one of the promising areas of onco-immunology today is the idea of “reactivating” the patient’s own cells of the immune system in order to enhance the effectiveness of other treatment methods. For some types of tumors (for example, melanomas) this allows achieving impressive results. Another example discovered by Medzhitov's group is the common lactate, a molecule that is produced when there is a lack of oxygen in fast-growing tumors due to the Warburg effect. This simple molecule stimulates the reprogramming of macrophages, causing them to support tumor growth. Lactate is transported into macrophages through membrane channels, and potential therapy is to block these channels.
This article will discuss the mechanism of immunity formation, that is, the body’s properties to protect its cells from foreign substances (antigens) or pathogens (bacteria and viruses). Immunity can be formed in two ways. The first is called humoral and is characterized by the production of special protective proteins - gamma globulins, and the second is cellular, which is based on the phenomenon of phagocytosis. It is caused by the formation in organs of endocrine and special cells: lymphocytes, monocytes, basophils, macrophages.
Macrophage cells: what are they?
Macrophages, together with other protective cells (monocytes), are the main structures of phagocytosis - the process of capturing and digesting foreign substances or pathogenic agents that threaten the normal functioning of the body. The one described was discovered and studied by the Russian physiologist I. Mechnikov in 1883. He also established that cellular immunity includes phagocytosis - a protective reaction that protects the cell genome from the damaging effects of foreign agents called antigens.
You need to understand the question: macrophages - what kind of cells are they? Let us recall their cytogenesis. These cells are derivatives of monocytes that have left the bloodstream and entered the tissues. This process is called diapedesis. Its result is the formation of macrophages in the parenchyma of the liver, lungs, lymph nodes and spleen.
For example, alveolar macrophages first come into contact with foreign substances that enter the lung parenchyma through special receptors. These immune cells then absorb and digest antigens and pathogens, thereby protecting the respiratory organs from pathogens and their toxins, as well as destroying particles of toxic chemicals that enter the lungs with a portion of air during inhalation. In addition, it has been proven that in terms of the level of immune activity, alveolar macrophages are similar to protective blood cells - monocytes.
Features of the structure and functions of immune cells
Phagocytic cells have a specific cytological structure, which determines the functions of macrophages. They are capable of forming pseudopodia, which serve to capture and envelop foreign particles. The cytoplasm contains many digestive organelles - lysosomes, which ensure the lysis of toxins, viruses or bacteria. Also present are mitochondria that synthesize molecules of adenosine triphosphoric acid, which is the main energy substance of macrophages. There is a system of tubes and tubules - the endoplasmic reticulum with protein-synthesizing organelles - ribosomes. The presence of one or more nuclei, often of irregular shape, is required. Multinucleated macrophages are called symplasts. They are formed as a result of intracellular karyokinesis, without separation of the cytoplasm itself.
Types of macrophages
The following must be taken into account when using the term “macrophages”, that this is not one type of immune structure, but a heterogeneous cytosystem. For example, there are fixed and free protective cells. The first group includes alveolar macrophages, phagocytes of the parenchyma and cavities of internal organs. Also, fixed immune cells are present in osteoblasts and lymph nodes. The storage and hematopoietic organs - liver, spleen and - also contain fixed macrophages.
What is cellular immunity
Peripheral immune hematopoietic organs, represented by the tonsils, spleen and lymph nodes, form a functionally unified system responsible for both hematopoiesis and immunogenesis.
The role of macrophages in the formation of immune memory
After contact of the antigen with cells capable of phagocytosis, the latter are able to “remember” the biochemical profile of the pathogen and respond by producing antibodies to its re-entry into a living cell. There are two forms of immunological memory: positive and negative. Both of them are the result of the activity of lymphocytes formed in the thymus, spleen, plaques of the intestinal walls and lymph nodes. These include derivatives of lymphocytes - monocytes and cells - macrophages.
Positive immunological memory is, in essence, a physiological rationale for the use of vaccination as a method of preventing infectious diseases. Since memory cells quickly recognize the antigens contained in the vaccine, they immediately respond with the rapid formation of protective antibodies. The phenomenon of negative immune memory is taken into account in transplantology to reduce the level of rejection of transplanted organs and tissues.
The relationship between the hematopoietic and immune systems
All cells used by the body to protect it from pathogenic pathogens and toxic substances are formed in the red bone marrow, which is also a hematopoietic organ. or thymus, which belongs to the endocrine system, functions as the main structure of the immune system. In the human body, both the red bone marrow and the thymus are essentially the main organs of immunogenesis.
Phagocytic cells destroy pathogens, which is usually accompanied by inflammatory phenomena in infected organs and tissues. They produce a special substance - platelet activating factor (PAF), which increases the permeability of blood vessels. Thus, a large number of macrophages from the blood reach the location of the pathogenic pathogen and destroy it.
Having studied macrophages - what kind of cells they are, in what organs they are produced and what functions they perform - we were convinced that, along with other types of lymphocytes (basophils, monocytes, eosinophils), they are the main cells of the immune system.
