Phagocytes are a type of cell that engulf and “eat” other cells. Their role in the immune system came to light through the work of Elie Metchnikoff, a scientist at the turn of the 20th century. He was very famous at the time for his discoveries of what he dubbed “professional” and “unprofessional” phagocytes, although those terms are typically considered outdated now. He was also a strong adherent to Darwinism, and made strong, popular arguments for the public to regularly consume yogurt to protect the bacterial balances in their gastrointestinal tracts. Metchnikoff elucidated how essential the professional phagocytes are for the immune system’s ability to fight off infection. Unprofessional phagocytes are cells that have primary functions other than engulfing and dissolving cells, such as certain skill cells. Professional phagocytes, according to Metchnikoff’s terminology, are cells whose primary function is dedicated to phagocytosis. In other words, their job is to find and destroy pathogenic cells that are dangerous to the organism.
Many cells in the bodies of multicellular organisms engage in phagocytosis, such as certain skin cells. Pathogens are microbes or any other foreign bodies that can cause harm or disease. Sometimes pathogens are not in fact foreign bodies, but malignant – or cancerous – cells already in the body. Phagocytes work to remove all of these kinds of potentially harmful pathogens. Phagocytes are created by cells called haematopoietic stem cells that are present in the bone marrow. These stem cells produce myeloid and lymphoid cells, which in turn give rise to other cells, including the cells fundamental to the immune system. Some of the cells that the myeloid cells give rise to are monocytes and neutrophils. Neutrophils are a type of phagocyte. Monocytes give rise to macrophages, which are another type of phagocyte.
TL;DR (Too Long; Didn't Read)
Phagocytes are a type of cell that engulf and “eat” other cells. Two types of phagocytes are macrophages and neutrophils, which are both essential cells involved in immunity. They are particularly involved in the innate immune system, which is effective from the beginning of an individual’s life. Macrophages and neutrophils bind to shapes called PAMPs on the surfaces of many invasive microbes, and then absorb and dissolve the microbes.
Two Immune Systems
Like other vertebrates, humans have two types of immune systems for protection against pathogens. One of the immune systems is called the innate immune system. The innate immune system is also present in most other life forms. In vertebrates, this system employs phagocytes as one of its lines of defense. The innate immune system is called that because the instructions for its operations are written into species’ genetic codes. This system is effective from the beginning of an individual’s life, and it reacts to pathogens that have been around for millennia. This is in contrast to the adaptive, or acquired, immune system, which is unique to vertebrates, and is their second immune system. It adapts to pathogens that the individual organism is exposed to during life.
The adaptive immune system takes longer to respond to threats than the innate immune system, in part because it is much more specific in its response to threats. The adaptive immune system is the one that humans rely on when receiving vaccinations in order to avoid becoming ill in the future with influenza, smallpox or numerous other infectious diseases. The adaptive immune system is also responsible for the confidence a person has that they will never again become infected with chicken pox, for example, because they were sick with it when they were six years old. In this second kind of immune system, there is a first exposure to an infectious agent, called an antigen, either through illness or vaccination. That first exposure teaches the adaptive immune system to recognize the antigen. If the antigen invades another time in the future, receptors on the surface of the antigen will trigger a series of immune responses tailor-made for that specific strain of infection. Phagocytes, however, are primarily involved in the innate immune system.
The First Line of Defense
Before the phagocytes become involved in the fight against pathogens as part of the innate immune system, the body uses a less costly line of defense that consists of physical barriers and chemical barriers. The environment is full of toxins and infectious agents in the air, water and food. There are a number of physical barriers in the human body that block or expel invaders. For example, both mucus membranes and hairs in the nostrils prevent debris, pathogens and pollutants from entering the airways. The body flushes toxins and microbes out of the body in urine, through the urethra. The skin is coated with a thick layer of dead cells that block pathogens from entering through pores. This layer sheds frequently, which effectively removes any potential microbes and other pathogens clinging to the dead skin cells.
The physical barriers make up one arm of the first line of defense in the innate immune system; the other arm consists of chemical barriers. These chemicals are substances in the body that break down microbes and other pathogens before they can cause harm. Acidity on the skin from oils and sweat prevent bacteria from growing and causing infections. The highly acidic gastric juice of the stomach kills most bacteria and other toxins that might be ingested – and vomiting acts as a physical barrier to remove pathogenic agents such as “food poisoning,” as well. Working together, the ever-vigilant chemical and physical barriers do a great deal to keep out many of the microscopic dangers of the environment that attempt to enter the body and cause harm.
Phagocytes as Sentinels
While the first line of defense consists of physical and chemical barriers, the second line of defense is the point at which the process of phagocytosis becomes involved in fending off threats to the body. Many infectious agents such as viruses and bacteria have molecules on their surfaces with shapes that have remained the same throughout the history of evolution. These shapes are called "pathogen-associated molecular patterns,” or PAMPs. Multiple pathogenic species may share the same PAMP. Unlike the adaptive immune system, which “remembers” the receptor shapes of specific bacteria and viral strains after the first exposure, the innate immune system is non-specific, and only binds to these PAMPs. There are fewer than 200 PAMPs, and cells called sentinels bind to them and then trigger a set of immune reactions. These sentinel cells are macrophages.
Macrophages Are First Responders
One of the first responders of the innate immune system are macrophages, one of the types of phagocytes. They are very non-specific in their targets, but they respond to any of the 100 to 200 PAMPs known to the innate immune system. When a pathogen with a recognizable PAMP binds to a toll-like receptor on the surface of the macrophage, the macrophage’s cell membrane begins to expand in such a way that it engulfs the microbe. The plasma membrane closes so that the microbe, still bound to the toll-like receptor, is held inside a vesicle called a phagosome. Nearby, there is another vesicle inside the macrophage called a lysosome, which is filled with digestive enzymes. The lysosome and the phagosome, which contains the microbe, merge together. The digestive enzymes break down the microbe.
The macrophage uses any parts of the microbe it can and disposes of the rest by expelling the waste via the process of exocytosis. It saves pieces of the microbe called antigen fragments, which are bound to molecules specifically designed to display these fragments. They are called antigen-presenting MHC II molecules, and they are inserted into the macrophage’s cell membrane, as a crucial step in the adaptive immune system. This serves as an activating signal to the cellular players in the adaptive immune system about precisely which strain of pathogen has invaded the body. As part of the innate immune system, however, the macrophage’s primary purpose is to seek and destroy the invaders. Macrophages can be made more quickly by the body than the more specialized cells of the adaptive immune system, but they are not as effective or specialized.
Neutrophils are another type of phagocyte. They were once called microphages by Elie Metchnikoff. Like macrophages, neutrophils are a product of haematopoietic stem cells in bone marrow, which produce myeloid cells. In addition to yielding the monocytes that become macrophages, myeloid cells also yield several other cells that make up the innate immune system, including neutrophils. Unlike macrophages, neutrophils are very small, and they last only a few hours or days. They circulate in the blood only, while macrophages circulate in the blood and tissues. When macrophages respond to pathogens, they release chemicals into the blood stream, particularly cytokines, which alert the immune system to invaders. There are not enough macrophages to battle any infection alone, so neutrophils respond to the chemical alert and work in tandem with macrophages.
The lining of blood vessels is called the endothelium. Neutrophils are so tiny that they slip between the gaps separating endothelial cells, moving in and out of the blood vessels. Chemicals released by the macrophages after binding to a pathogen cause the neutrophils to bind more firmly to the endothelial cells. Once the neutrophils are securely bound to the endothelium, they squeeze their way into the interstitial fluid, and the endothelium dilates. The dilation makes it even more permeable than it was before the macrophages reacted to the pathogens, which allows some blood to flow into the tissues surrounding the blood vessels, making the area red, warm, painful and swollen. The process is known as the inflammatory response.
Sometimes bacteria release chemicals that guide the neutrophils toward them. The macrophages also release chemicals called chemokines that guide the neutrophils toward the site of infection. Like macrophages, neutrophils use phagocytosis to envelope and destroy the pathogens. Once completing this task, the neutrophils die. If there are enough dead neutrophils at an infection site, the dead cells form the substance known as pus. Pus is a sign that the body is healing itself, and its color and consistency can alert a healthcare provider to the nature of the infection. Because neutrophils are so short-lived but so plentiful, they are especially important for fighting acute infections, such as an infected wound. Macrophages, on the other hand, are long-lived and are more useful for chronic infections.
The complement system creates a bridge between the innate immune system and the adaptive immune system. It consists of approximately 20 proteins that are manufactured in the liver, which spend most of their time circulating through the bloodstream in an inactive form. When they come into contact with PAMPs at infection sites they become activated, and once the complement system is activated, the proteins activate other proteins in a cascade. After the proteins activate, they join together to form a membrane-attack complex (MAC), which pushes across the cell membrane of infectious microbes, allowing fluids to flood into the pathogen and cause it to burst. In addition, the complement proteins bind directly to PAMPs, which tags them, allowing phagocytes to more easily identify the pathogens for destruction. The proteins also make it easier for antibodies to find the antigens when the adaptive immune system becomes involved.