By Nathaniel Vorhees
The human immune system is a fascinating and multifaceted system that is critical to our health and response to disease. Broadly, it can be divided into adaptive and innate immunity both serving specific and necessary roles. The adaptive immune system is often viewed as the star of the show as it can create specialized defense strategies against specific pathogens. On the other hand the innate immune system displays a swift and broad response to pathogens, acting as our body’s first line of defense. These brave soldiers work to block pathogens from entering our body, eat and destroy those that have successfully entered the body, and will work to activate and recruit the adaptive immune counterpart when the invasion becomes too strong. While often overshadowed by adaptive immunity, the innate immune system is the body’s formidable defender and research continues to unveil its hidden complexities to improve our disease prevention and overall health.
The first act of defense that the immune system has is a number of barriers to physically block pathogens from entering the body. While these barriers, such as the skin, are critical and without them the body would be exposed to an overwhelming excess of pathogens, unfortunately, they are not foolproof. Pathogens are still able to find ways to enter the body, leading to infection.
To defend against invading pathogens, the innate system has a dynamic cellular defense network. The key cell types in this multifunctional system are phagocytes, granulocytes, and innate lymphoid cells. Three main phagocytes include macrophages, dendritic cells, and neutrophils (which are also a granulocyte).
Figure 1. Cartoon figures of different immune cells
Macrophages: “Pac-Man” of the immune system with great debris and pathogen clearance capability
Dendritic Cells: Great communicators that work to activate T cells, which are targeted assassins against specific viruses.
Neutrophils: Super fast short lived cells that aim to eat bacteria.
Mast, Basophil, and Eosinophil: are Granulocytes, commonly responding to allergies
NK Cells: Natural Killer Cells, particularly excel in one area, killing infected cells.
Macrophages can be considered the “Pac-man of the immune system” as they engulf or “eat” bacteria, fungi, and dead/damaged cells. While debris clearance, or the removal of unwanted materials in the body, is a leading responsibility of macrophages, it is far from their only function. Macrophages continuously survey their environment working to detect any foreign substances. Upon detection of an intruder, macrophages are able to become activated and enlarged and will release inflammatory signals, called cytokines, to recruit more cells to the area of damage/infection. The recruitment of other innate immune cells and collaboration with the adaptive immune system makes macrophages a communicative cell type with a wide range of functions; researchers continue to discover how versatile these cells truly are.
Antigen presentation can be highly complex, however at its simplest form, antigen presentation is similar to a “wanted poster” of a pathogen to the immune system allowing the adaptive cells to recognize what it is fighting against. Dendritic cells (DCs) are known as professional antigen-presenting cells and they are the best activator of T Cells, which each fight off specific viruses. The constant surveillance of dendritic cells allows for fast recognition of pathogens and escalates the speed of adaptive immunity when it is necessary. Lastly, neutrophils are short-lived phagocytes/granulocytes that are specialized to eat and kill bacteria. Neutrophils are best suited when there is an urgent need to kill bacteria as they can very quickly mobilize to the site of infection with signals such as certain cytokines and begin to phagocytose infected cells upon arrival.
Granulocytes are most prominent in allergy reactions and common infections. They are white blood cells filled with small granules – tiny sacs containing an assortment of enzymes, which are proteins that help start a reaction, and other substances. As foot soldiers of the immune system, granulocytes are always ready to fight off germs and infections. In action, certain granulocytes will release the contents from their granules, including proteins, enzymes, and cytokines that can lead to a strong localized reaction by recruitment of more immune cells. In an overreaction, granulocytes are capable of inducing anaphylaxis, a hypersensitive allergic response in which the body responds excessively. This can cause inflammation, redness, swelling, and even closure of airways, sometimes threatening lives. While this hypersensitivity is possible, mast cells are still important components of the immune system and help mediate wound healing and can also have an opposite function to suppress the immune system at times when it is acting excessively.
The predominant innate lymphoid cell is the Natural Killer cell. As their name suggests, natural killer cells work to kill infected cells. They are regulated by signals like cytokines that may tell the natural killer cell “eat me, I’m infected!” or “I’m healthy, don’t eat me!” The mechanism of killing is different than phagocytes, rather than eating the infected or damaged cell, natural killer cells release a protein that makes a hole in the outer layer of the infected cell into which it inserts granzymes leading to the cell dying.
Overarchingly, the innate immune system is a highly dynamic and multifaceted system that works as the first line of defense against foreign substances to block, recognize, and kill infected cells and recruit the adaptive immune response by means of antigen presentation. While often immune therapies target the adaptive immune response with thoughts to manipulate the antibody response and T Cell regulation, the innate immune system’s role in health maintenance and disease clearance should not be understated.
