Human Skin Has Its Own Immune System
A revolutionary discovery
reveals intelligent design
in our largest body organ
by Jerry Bergman, PhD
The skin, the largest organ in the human body, covers the entire body. New research has now documented that “The skin — once thought to be a mainly passive barrier — can produce its own antibodies that fight off infections, a pair of studies reported in Nature this week.”[1] This research finding was nothing less than a medical revelation. The specified complexity of the skin’s immune system is illustrated by the observation that
When the immune system sees a friendly bacterium, you would think that it would just give a friendly wave and walk in the other direction, but that’s not at all what happens.” In mice colonized by Staphylococcus epidermidis, a common and harmless bacterium found on human skin, the skin was able to generate antibodies even when other parts of the immune system were disabled. And this surprise power might be harnessed to fight pathogens: when researchers modified S. epidermidis to display part of the tetanus toxin, the skin response protected mice from a lethal dose.[2]
The major problem that an immune system must satisfactorily deal with is that it must kill harmful pathogens without attacking the many helpful microorganisms that inhabit the body. In order to do this it must differentiate between the microbes required for good health, called probiotics, and eliminate the microbes that harm the body, some of which are eventually lethal, called pathogens. It must also not attack the body, causing an autoimmune disease.
Diagram of human skin showing the layers.
From Wiki Commons.
The discovery that the skin also has major immune functions adds one more level of specified complexity to that once-named “simple organ” that enshrouds our body. The skin, properly called the integumentary system, is comprised of the epidermis, the dermis, and the hypodermis of subcutaneous tissue (see illustration, right).
Besides providing a protective physical barrier between the body and the environment, the integumentary system also regulates
the inward and outward passage of water and electrolytes, reducing penetration by destructive chemicals, arresting the penetration of micro-organisms and external antigens, and absorbing radiation from the sun. The skin is important in the regulation of body temperature and is designed, to an extent, to respond to mechanical forces; the epidermis has a degree of mechanical strength to withstand damage and the ability to repair itself if damaged, and the dermis provides elasticity in response to mechanical insults. Antimicrobial peptides (AMPs) provide a chemical barrier to potentially pathogenic micro-organisms. The skin also contains sensory and autonomic nerves and several types of sensory receptors, which detect the incoming stimuli of touch, vibration, pressure, change in temperature (warmth and cold), pain (including heat pain), and itch.[3]
Skin’s New Role
Human skin also has a major role in sociosexual communication and response. To this long, but incomplete list, we now need to add its recently discovered important immunological role. The same concerns that exist for the innate immune system also exist for the skin. The researchers who discovered this new role for skin described this previously unknown level of specified complexity by concluding that
within the skin, host-microbiota symbiosis depends on the remarkable ability of the skin to act as an autonomous lymphoid organ. …. , skin commensals induce the formation of classical germinal centers within the lymph node associated with IgG1 [IgG is the main type of antibody found in blood and extracellular fluid, allowing it to control infection by binding with many pathogen types including viruses, bacteria, and fungi,] … These phenomena are supported by the ability of regulatory T cells to convert into T follicular helper cells. [T cells can wipe out infected or cancerous cells and also direct the immune response by helping B lymphocytes to eliminate invading pathogens] Skin autonomous production of antibodies is sufficient to control local microbial biomass, as well as subsequent systemic infection with the same microbe. Collectively, these results reveal a striking compartmentalization of humoral responses to the microbiota allowing for control of both microbial symbiosis and potential pathogenesis.[4]
The problem is a different set of microorganisms are important for health on the skin epidermis than inside the body. After the gut, more microorganisms live on the skin than anywhere else in the body. These are collectively referred to as the skin microbiota or the skin microbiome. What are called commensals reside on our skin and derive benefits from us, and we benefit from them because they deplete nutrients and produce toxic metabolites preventing the colonization of pathogenic microorganisms. The symbiont microbiota benefits both microorganisms and humans.[5] These symbionts are critically important for skin health. Other skin microbiomes important for health include not only the most well-known bacteria, the Staphylococcus family, but also the bacterial genera Corynebacterium, Dermabacter, Brevibacterium, the Malasezzia fungi, and many others.
The major parts of the immune system From Wikimedia Commons.
The transient microbiota can be isolated and cultured only at certain times, making a complete catalog of skin microbiota difficult. This includes many gram-positive bacteria (meaning they can be identified by a Gram stain test) and the clostridia (anaerobic, rod-like bacteria) that flourish in the perineal area. Very little is known about the function of viruses on normal skin except they are very common.[6] Although once thought to be pathogenic, recent research has found these viruses serve several important functions, including to help keep normal bacteria in check.
For the immune system to attack these bacteria indiscriminately would be catastrophic for human health. Consequently, to keep the skin healthy, the immune system must attack the harmful microbiota, including most commonly Staphylococcus, the Streptococcus species, Yersinia pestis, and the Vibrio vulnificus bacterial family. Normal microbiota also include numerous fungi, viruses, and mites that inhabit the skin of normal, healthy humans.[7] How the skin deals with these must also be considered when attempting to understand the skin’s immune system.
Conversely, some of these same helpful skin bacteria are pathogenic if they invade the body cavity through a break in the skin, such as a cut or an insect bite. Common examples include Staphylococcus aureus, β-hemolytic streptococci, and coryneform (aerobic, rod- and club-shaped) bacteria. Bacteria that are important for health in the body cavity, such as the intestinal bacteria Bacteroides fragilis and Bifidobacterium, but outside of the body they can cause skin disease.[8] Consequently, the skin’s immune system must either ignore or attack very different organisms, depending on their location. Yet this newly discovered immune system must work together with the internal body’s immune system to promote health.
Summary
The skin’s immune system must target some of the same bacteria existing both on the skin and within internal body organs. In contrast, in many cases, it must not attack certain skin bacteria which, if they enter the body cavity due to a cut or an insect bite, the internal body must attack to keep us healthy. The end result is that the skin ignores and attacks a different set of bacteria than does the internal immune system. The research found that the skin produces its own antibodies to help control microbe reproduction. Given that this new, integumentary immune system was recently experimentally documented to exist, the discriminating “ignore or attack” system must be determined for both the internal body bacteria and the skin bacteria. This adds yet another complexity level to the immunology system.
The immune system is by far one of the most complex systems in our body. Having taught human anatomy for over two decades, this fact is obvious to persons attempting to teach immunology, not to mention the challenge faced by students attempting to learn the complex material in this area of anatomy.
References
[1] Guglielmi, Giorgia, “The skin’s ‘surprise’ power: it has its very own immune system,” Nature, 16 December 2024.
[2] Graham, Flora, “Daily briefing: Skin might have an immune system of its own,” Nature, December 2024.
[3] Archer, C.B., “Functions of the Skin,” Chapter 4 in Rook’s Textbook of Dermatology, Volume 1, Eighth Edition, Wiley, New York, NY, 2010.
[4] Gribonika, I., et al. “Skin-autonomous antibody production regulates host-microbiota interactions,” Nature, 11 December 2024.
[5] Gilbert, S.F., et al., “A symbiotic view of life: We have never been individuals,” The Quarterly Review of Biology 87(4): 325-341, December 2012.
[6] Lei, V., et al., “Skin viral infections: Host antiviral innate immunity and viral immune evasion,” Frontiers in Immunology, doi: 10.3389/fimmu.2020.593901, 6 November 2020; Duvic, M., “Human Immunodeficiency Virus and the Skin: Selected Controversies,” Journal of Investigative Dermatology 105(1): 3117-s121.ci, July 1995.
[7] Singal, A., and C. Grover, “Normal Flora of Skin.” Chapter 1 in Comprehensive Approach to Infections in Dermatology, Jaypee Medical Publications, New York, NY, 2016.
[8] Finegold, S.M., “Intestinal bacteria — The role they play in normal physiology, pathologic physiology, and infection,” California Medicine 110(6): 455-459, June 1969.
Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,900 publications in 14 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,800 college libraries in 27 countries. So far over 80,000 copies of the 60 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.