Macrophage: Structure, Function & Diseases

Macrophages (phagocytes) are white blood cells that are part of the developmentally oldest innate cellular immune system. Macrophages can exit the bloodstream and persist in body tissues as tissue macrophages for several months as a kind of police force on guard. One of their main tasks is to flow around infectious bacteria, degenerate endogenous cells, or toxins in an amoeba-like manner and to phagocytize them, that is, to “eat” them or otherwise render them harmless and transport them away.

What is the macrophage?

Macrophages, also called phagocytes, belong to the phagocytes and thus to the innate cellular part of the immune response. They develop as needed from monocytes, which form in the bone marrow from stem cells and enter the bloodstream. In the presence of a viral or bacterial infection that has been recognized by the immune system, the monocytes move to the vicinity of the site of infection, leave the bloodstream, and differentiate into fully functional macrophages. At the site of infection, they can phagocytose the infectious germs by completely enclosing the particles and biochemically catalytically disassembling them by means of specific enzymes. The macrophages carry the corresponding enzymes in lysosomes, tiny cell organelles. The macrophages are part of the innate, i.e. the genetically fixed immune system. There is a connection to the acquired immune system via the function of antigen presentation by the macrophages, which is particularly triggered by viral infections. The presented antigens are recognized by T-helper cells, which then stimulate the production of specific antibodies. Macrophages can significantly control inflammatory processes in tissues via the secretion of cytokines.

Anatomy and structure

Precursor cells of macrophages are monocytes, which form from stem cells in the bone marrow. Only under the influence of cytokines do monocytes differentiate out into various types of macrophages. In place-bound tissue macrophages that have migrated into the tissue, the morphology depends strongly on the surrounding tissue. Anatomically, a macrophage is virtually equivalent to a unicellular organism with a nucleus, cytoplasm, cytoskeleton, and a multitude of organelles. A macrophage reaches approximately 25 to 50 µm in size. The size of the phagocyte is sufficient to capture about a 5 µm long bacterium and enclose it in one of its phagosomes. To perform its main function, phagocytosis of pathogens or degradation of a substance harmful to the body, the macrophage has lysosomes at its disposal. These are small organelles that contain a number of degradative enzymes that are emptied into the phagosome after the pathogen is captured to initiate and accomplish the actual phagocytosis. Macrophages also have the ability to synthesize lysozyme, which can break glycosidic bonds. Direct contact with lysozyme causes bacteria to dissolve their cell walls.

Function and tasks

One of the main functions and tasks of macrophages is phagocytosis of invading germs or other harmful substances. This includes endogenous degenerated cells (cancer cells) that have been recognized as such by the immune system, as well as endogenous cells that have already died. The macrophages are able to enclose the pathogens in one of their phagosomes and break them down into harmless individual components. Another main task is antigen presentation. In most cases, these are peptide residues, i.e. components of certain proteins of phagocytized germs, which the phagocytic cell “presents” to the outside via a complex mechanism. Certain T-helper cells recognize the presented fragments and induce the synthesis of specific antibodies. In interaction with other components of the immune system such as B and T lymphocytes as well as natural killer cells and fibroblasts, macrophages are capable of producing a variety of cytokines. Cytokines are peptides and proteins with which the immune system controls the very complex immune response. With interleukins, interferons, tumor necrosis factors and other substances assigned to cytokines, the immune system controls the activation and deactivation of immune components as well as the aggressiveness, the strength of the respective immune response including possible fever episodes. Specialized CD-169-positive macrophages in the spleen take on the task of multiplying virus particles in the event of a viral infection in order to accelerate an appropriate immune response.To prevent viruses or virus parts that could escape from the macrophages from causing further infections in the process, the CD-169-positive macrophages are densely surrounded by other macrophages that can immediately destroy the escaped viruses or virus parts in such a case. The immune system also has non-phagocytic macrophages that play an important role in the regeneration of muscle fibers. They produce control proteins that enable the transport of muscle cells and their differentiation.

Diseases

Diseases and conditions directly related to macrophage dysfunction are extremely rare. More common are diseases and symptoms that are due to overreaction of macrophages but are triggered by another disease. This means that the symptoms can be attributed to a natural reaction of the macrophages. A rare disease representing above causal relationship is hemophagocytosis syndrome (HLH). In the presence of this disease, macrophages are so overactivated that they not only phagocytose old red blood cells that need to be disposed of, but also attack healthy cells in a kind of exuberant immune response. The disease, which is often severe, can be inherited, i.e. based on certain genetic defects, but can also be acquired. Triggers can be drugs or infections. A metabolic disease in which the intermediate glucocerebroside is incompletely broken down, this substance accumulates in the lysosomes of the macrophages, causing them to swell. Such altered macrophages are called Gaucher cells, a term derived from the name of the disease Gaucher syndrome. The accumulation of Gaucher cells in the liver, spleen, and bone marrow, as well as in the nervous system and other organs, leads to organ failure if left untreated as the disease progresses.

Typical and common diseases of the blood and erythrocytes.