The world we live in can be a messy place. As everything in nature tends to chaos, our lives tend to do the same.
Houses fill up with things, garbage accumulates along the way, it’s a constant job just to keep things collected and tidy.
Interestingly, a similar situation is happening inside our bodies all the time. Cells are dying, bacteria are roaming, and viruses are attempting mass acquisitions.
Our immune system is constantly at work destroying these intruders and cleaning up clutter. One cell in particular, the macrophage, is an integral part of this cleaning process.
We will take a closer look at the work of a macrophage and learn about its importance within the body.
A macrophage is a white blood cell, an important part of the immune system. The term ‘macrophage’ means ‘great eater’.
It is similar to an amoeba, and its function is to cleanse the body of microscopic and invasive debris. A macrophage has the ability to locate and ‘eat’ particles, such as bacteria, viruses, fungi, and parasites.
Macrophages are born from white blood cells called monocytes, which are produced by stem cells in our bone marrow. Monocytes move through the bloodstream and when they leave the blood, they mature into macrophages. They live for months, keeping the organs clean.
Macrophages are innate immune effector cells best known for their role as professional phagocytes, which also include neutrophils and dendritic cells. Recent evidence indicates that macrophages are also key players in metabolic homeostasis.
Macrophages can be found in many tissues, where they respond to metabolic signals and produce pro and / or anti-inflammatory mediators to modulate metabolite programs.
Certain metabolites, such as fatty acids, ceramides, and cholesterol crystals, elicit inflammatory responses through signaling pathways that detect pathogens, implying a poor adaptation of macrophages and the innate immune system to the elevated metabolic stress associated with malnutrition in women. modern societies.
The result of this maladaptation is a direct inflammatory response leading to an unresolved state of inflammation and a collection of metabolic pathologies, including insulin resistance, fatty liver, atherosclerosis, and dyslipidemia.
Interactions with T-cell macrophages
Inflammatory processes are the body’s defense against local disease and damage. Inflammation involves the influx into the organs of immune cells (white blood cells) from the blood.
These cells take care of microbes and repair tissue damage. Two main subtypes of immune cells are T cells and macrophages. T cells are designed to recognize the molecular signatures of particular proteins, such as those of bacteria, to activate an immune response.
Macrophages eat other cells and are able to separate their proteins to present them to T cells. However, if T cells respond to the proteins themselves, inappropriate inflammation can occur that can damage healthy organs.
This is known as an autoimmune disease. Such inflammation is particularly damaging to the eye, as tissue damage and pressure caused by the number of immune cells entering, disrupts the delicate organization of the eye that is required for sight.
Macrophages interact with T cells to cause T cell activation in target organs, and are activated by inflammatory messenger molecules (cytokines) produced by T cells.
Macrophages produce toxic chemicals, such as nitric oxide, that can kill surrounding cells. It has been shown that macrophages stimulated by T cells need to produce a second inflammatory cytokine (TNFα), which is required as a signal to signal macrophages to produce nitric oxide.
Modulation of this is now being used clinically to treat autoimmune inflammatory eye disease. Many other signals (both secreted chemicals and cell surface interactions) also control the outcome of the interaction between macrophages and T cells.
These can be important targets for medical therapy, so the research aims to reveal the details of this inflammatory process, with the long-term goal of identifying novel, more effective, and more specific targets for treating blinding diseases caused by autoimmunity.
When do cells ask for help?
Your cells around the splinter cry out for help, and when the blood vessels let macrophages enter the infected tissue, they also let some blood leak into the area. This extra fluid and the chemicals released by infected cells can cause inflammation. This hurts, but it actually helps your body fight infection better.
- Location: pulmonary alveoli.
- Function: phagocytosis of small particles, dead cells or bacteria.
- Location: liver.
- Function: initiates the immune response and remodeling of liver tissue.
- Location: central nervous system.
- Function: elimination of old or dead neurons and control of immunity in the brain.
- Location: marginal zone of the spleen, red and white pulp.
- Function: removal of old or dysfunctional red blood cells.
This classification is based on macrophage polarization rather than macrophage location.
M1 macrophages: are classically activated, typically by IFN-γ or lipopolysaccharide (LPS), and produce pro-inflammatory cytokines, phagocytose microbes, and initiate an immune response. M1 macrophages produce nitric oxide (NO) or reactive oxygen intermediates (ROI) to protect against bacteria and viruses.
M2 macrophages: are alternately activated by exposure to certain cytokines such as IL-4, IL-10 or IL-13. M2 macrophages will produce polyamines to induce proliferation or proline to induce collagen production. These macrophages are associated with wound healing and tissue repair.
M2 macrophages also contribute to extracellular matrix formation and do not produce nitric oxide or antigen present to T cells. Tumor infiltrating macrophages are typically classified as M2, although some classify them as myeloid-derived suppressor cells (MDSC).