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VERIFIED CONTENTAuthor: Krzysztof Bialazite

Langerhans cells are cells that play a key role in the skin's immune mechanisms. Langerhans cells colonize our epidermis and recognize the antigens that appear in it. Despite many years of research, Langerhans cells are still considered somewhat mysterious in the scientific world - many questions regarding their origin and exact mechanisms of action still remain unclear. Find out what Langerhans cells are, what their function is in the immune system and what diseases can be associated with Langerhans cell dysfunction.

Langerhans cellsare cells that play a key role in the skin's immune mechanisms. Langerhans cells colonize our epidermis and recognize the antigens that appear in it. In addition to the skin, Langerhans cells are also found in the epithelium of the mouth, respiratory tract and the genitourinary system.

The main role of Langerhans cells is to recognize pathogens that enter our body through natural barriers. In such situations, thanks to the Langerhans cells, the immune system is immediately stimulated. Langerhans cells also play an important role in the mechanisms of immune tolerance.

Langerhans cells - what are they and where are they?

Langerhans cells belong to the population of white blood cells that perform an immune function. The place of their formation is the bone marrow. From there, Langerhans cells end up in the blood, which transports them to the appropriate tissues.

Langerhans cells colonize both our skin and the mucosa epithelium in the oral cavity, nasopharynx, respiratory tract, gastrointestinal tract and genitourinary tract.

Langerhans cells belong to the dendritic cell family. Their name comes from the characteristic protrusions resembling dendrites of nerve cells (these are extensions branching into the shape of the tree crown).

Langerhans cells settle permanently in places of constant contact of our tissues with the external environment. Their location is not accidental - they are cells specialized in performing immune functions.

After contact withWith a foreign substance or pathogen, Langerhans cells "make the decision" whether it is necessary to stimulate the immune system in a given situation.

If so, the process of the immune response and neutralization of the "intruder" begins. If not, the so-called immune tolerance - the immune system does not respond to a given antigen.

Structure of Langerhans cells

Langerhans cells, after leaving the bone marrow, take a small, round shape. Their form drastically changes only when the target tissues are colonized. Then they are significantly enlarged and create characteristic protrusions.

For many years, because of their similarity to nerve cells, Langerhans cells have been viewed as parts of nerve endings located in the skin. It was not until the 1970s that the connections between Langerhans cells and the immune system were discovered, which revolutionized the views on them so far.

Langerhans cells are most often located in the spinous layer of the epidermis.

Our epidermis consists of five layers of cells. These are, in turn (from the inside) the basal layer, the thorny layer, the grainy layer, the light layer and the horny layer.

Langerhans cells inhabit relatively deep layers of the epidermis. Nevertheless, they can exercise precise control over its entire thickness. How?

This is possible due to the aforementioned protrusions that extend to the outermost layer - the horny layer. These protrusions combine into an extensive network that allows you to create an efficient immune barrier.

Looking at Langerhans cells in an electron microscope, we notice very characteristic structures in the shape of tennis rackets. They are the so-called Birbeck granules, which are a specific marker of Langerhans cells.

These "rackets" are probably responsible for the antigen processing in which Langerhans cells specialize. These cells have a wide range of mechanisms that allow them to absorb antigens, analyze them and stimulate or suppress an immune response.

Langerhans cells - functions in the body

Langerhans cells create an extremely interesting immune barrier within our skin and mucous membranes. Let's take a closer look at their functions. Langerhans cells are responsible for the following processes:

  • Langerhans cells - antigen presentation

The most important task of Langerhans cells is the so-called antigen presentation. What is this phenomenon about? It is the process of absorbing, processing, and demonstrating antigens to otherscells of the immune system. Thanks to this, it is possible to stimulate them to a coordinated immune response.

Antigens are specific "labels" of molecules and cells, recognized by cells that patrol the environment of a given tissue. Antigens make it possible to recognize a given object and make a decision whether or not this element is pathogenic.

It is worth remembering that antigens are not only present on the surface of "intruders". Each cell in our body has its own antigens, recognized by the immune system in such a way as not to trigger an inflammatory response against them.

Antigen presentation is critical to effective defense against pathogens. How does this process take place in Langerhans cells?

The first step is to recognize the foreign element. Langerhans cells are equipped with many tools that allow them to "catch" potentially dangerous particles and microbes from the environment.

One of such tools are the so-called pathogen recognition receptors (PRR). Thanks to them, Langerhans cells "know" that they are dealing with a foreign cell with pathogenic properties.

When Langerhans cells recognize a pathogen, they want to immediately warn other cells of the immune system of it. To do this, they must first consume a given object.

Langerhans cells are equipped with a number of mechanisms enabling endocytosis, i.e. the uptake of substances from the external environment. Depending on their needs, they use:

  • phagocytosis ("eating" solid particles)
  • pinocytosis (liquid absorption)
  • endocytosis with the participation of special receptors

During these processes, Langerhans cells have the possibility of a thorough analysis and getting to know the "intruder". Then, the antigens of the microorganism are exposed to the surface of the Langerhans cell. Antigen presentation begins.

We have reached the stage where the Langerhans cell has engulfed the pathogen and exposed its antigens on its surface. So it's time to present them to other cells of the immune system. Where can you find such cells?

There are relatively few of them in the skin. This is where we come to another extraordinary skill of Langerhans cells.

Well, in order to present the antigen, they can leave the skin and travel to places where cells of the immune system are swarming. Lymph nodes are such places.

Langerhans cells travel from the skin to the lymph nodes via the lymphatic route, using appropriate signaling.There they encounter a lot of lymphocytes - cells specialized in destroying microorganisms.

Langerhans cells present antigens to lymphocytes, which in this way learn to recognize a given pathogen and prepare an immune response against it.

In addition to stimulating the so-called cytotoxic lymphocytes capable of inactivating microorganisms, this process also creates immune memory cells. Thanks to them, the next contact with the same pathogen will trigger a faster and better adjusted immune response.

  • Langerhans cells - tolerogenic properties

The previous paragraph focused on the immunogenic properties of Langerhans cells. Their essence was to stimulate the immune system to fight pathogens. Relatively recently, it was discovered that Langerhans cells are also capable of performing extremely different functions.

Under strictly defined conditions, they acquire tolerogenic properties. Their essence is to suppress the immune response of the organism and develop tolerance to certain antigens.

It turned out that Langerhans cells absorb elements of their own organism (proteins, fragments of dead cells) as often as pathogenic elements. Then they travel with them to the lymph nodes and present them to lymphocytes.

Interestingly, this behavior does not lead to the development of autoimmunity (destruction of the body's own cells by the immune system). On the contrary - the so-called regulatory lymphocytes whose task is to suppress the immune response. This is how our immune system learns to recognize its own antigens.

The same happens with other non-pathogenic foreign objects. In everyday life, our skin comes into contact with a multitude of substances (cosmetics, clothes, jewelry) that should not trigger an inflammatory response. It is thanks to Langerhans cells that it is possible to develop tolerance to this type of antigens.

As you can see, Langerhans cells are constantly balancing between immunogenic and tolerogenic activities.

Maintaining the immune balance in the skin is extremely important. Normal Langerhans cells generate an inflammatory response when it is really needed.

On the other hand, extinguishing an excessive or unnecessary immune response enables the prevention of hypersensitivity reactions.

  • Langerhans cells - wound healing

Any damage to the skin's continuity is associated with the possibility of easier penetration of microorganisms into the body. Wound healing is not only aboutrestoring the proper structure of tissues, but also restoring the continuity of the immune barrier.

Langerhans cells play a significant role in this process. Damage to the epidermal cells leads to an inflammatory environment that allows the local influx of cells of the immune system. This process, coordinated, inter alia, by by Langerhans cells, this is the first stage of wound healing.

At this point, it is worth quoting a scientific study whose aim was to investigate the relationship between the number of Langerhans cells and the efficiency of the healing process.

Scientists carried out a 4-week observation of the wound healing process in patients treated for diabetic foot. The results of the study showed that more Langerhans cells in the vicinity of the wound correlated with better healing outcomes.

More research in this direction is needed to understand the exact mechanisms by which Langerhans cells work in areas of skin damage. Perhaps thanks to them, it will be possible to find ways to use Langerhans cells, for example in the treatment of difficult-to-heal wounds.

Langerhans cells and the SALT and MALT systems

Human skin and mucous membranes constitute a mechanical barrier against the penetration of microorganisms into the body. Their function, however, is not only to create a passive shell. These tissues possess a number of highly developed immune mechanisms that enable them to perform immune functions.

The role of the skin and mucous membranes in the body's defense against pathogens is emphasized by the fact that in modern immunology they have "own" subunits in the organization of the immune system.

These subunits are abbreviated as SALT and MALT. These are the Skin Associated Lymphoid Tissue (Skin Associated Lymphoid Tissue) and the Mucosa Associated Lymphoid Tissue (Mucosa Associated Lymphoid Tissue).

As you can easily guess, Langerhans cells are an important link in both of the above-mentioned systems.

The operation of the SALT and MALT systems is based on the cooperation of epithelial-building cells, antigen-presenting cells (including Langerhans cells) and cells capable of neutralizing pathogens (mainly lymphocytes). Their joint action enables the recognition and processing of antigens directly at the point of entry into the body.

Such effective immune surveillance prevents the penetration of microorganisms from the external environment into deeper tissues and organs.

The role of Langerhans cells in the pathogenesis of diseases

Properly functioning Langerhans cells help maintain a balance between the inflammatory response andtolerance of selected antigens in the skin and mucous membranes.

Langerhans cell dysfunction may underlie some dermatological, immune and even neoplastic diseases. Here are their examples:

  • Langerhans cell histiocytosis

Langerhans cell histiocytosis is an oncological disease associated with the excessive multiplication of Langerhans cells. These cells can accumulate in various organs - the skin, bones, lymph nodes and internal organs.

Langerhans cell histiocytosis is usually diagnosed in children, although it is also seen in adults.

Langerhans cells can multiply in a specific place (then we are talking about a localized form) or occupy numerous locations (it is called a multifocal form).

The localized form usually has a good prognosis, and in rare cases may even heal itself.

The multifocal form requires aggressive treatment, mostly with chemotherapy. This variant of the disease is also associated with a worse prognosis.

  • Langerhans cells and contact eczema

Contact eczema is caused by the skin being oversensitive to certain external factors. The substances that most often cause contact eczema include: nickel, chromium, some dyes and preservatives, and cosmetic ingredients.

The particles of these substances, thanks to their small size, are able to penetrate the subsequent layers of the epidermis. At some point, their "meeting" with Langerhan's cells occurs.

Langerhans cells absorb these molecules (in a form bound to proteins), and then present them on their surface. In this way, they "teach" lymphocytes to recognize the above substances.

At the moment of repeated contact with them (e.g. regular wearing of a given jewelry), an immune response is triggered. Local inflammation develops, manifested by the formation of itchy, reddened papules and vesicles.

At this point, it is worth emphasizing that despite the frequent contact of human skin with the substances described above, the symptoms of contact eczema appear relatively rarely.

The tolerance of the above antigens in most people is probably due to the tolerogenic properties of Langerhans cells.

  • Langerhans cells and dermatological diseases

Langerhans cells appear to play an important role in the pathogenesis of certain skin diseases, such as atopic dermatitis and psoriasis. Immune regulation disorders for whichLangerhans cells respond, contribute to the development of inflammatory dermatological diseases.

It seems that the activity of Langerhans cells in the above-mentioned diseases is shifted towards pro-inflammatory activity; however, their tolerogenic activity is weakened.

The confirmation of these dependencies may be the fact that photochemotherapy is successfully used in the treatment of both psoriasis and atopic dermatitis. It is treatment by means of irradiation with the use of ultraviolet radiation. Such irradiation soothes skin changes.

It is suspected that one of the mechanisms of photochemotherapy is the reduction in the number and weakening of the function of Langerhans cells, which contributes to the inhibition of excessive immune response.

  • Langerhans cells and graft versus host (GvHD)

Graft versus Host Disease is one of the possible complications of bone marrow transplantation and blood transufusion. Its essence is the rejection of the recipient's organs by the transplanted donor leukocytes.

In the course of the disease, one of the most frequently rejected organs is the skin. The exact role of Langerhans cells in graft-versus-host pathogenesis is still unknown.

Research conducted in animals so far shows that reducing the number of Langerhans cells in the transplant recipient reduces the risk of developing a graft-versus-host reaction.

  • Langerhans cells and HIV infection

For many years in the scientific world, Langerhans cells were thought to be the first target of HIV attack. It has also been hypothesized that HIV-infected Langerhans cells carry it to the lymph nodes, contributing to the spread of infection to other cells of the immune system.

The latest scientific reports refute the above theories, however. Langerhans cells are now considered to be an immune barrier: they do absorb HIV particles, but block its further transmission.

It also appears that virus-activated Langerhans cells induce a favorable immune response in the initial phase of infection.

  • Langerhans cells and skin cancer

Langerhans cells perform immunological supervision over the microorganisms that appear in our skin. In addition, they are also able to recognize cancer cells and trigger an immune response against them.

In studies of skin cancer, it has been shown that the number of Langerhans cells in the vicinity of the tumor is significantly reduced. During the process of neoplasm, the presentation of antigens by Langerhans cells is also impaired.

Understanding the role of Langerhans cells in anti-cancer defense initiated a series of scientific studies aimed at finding the use of these cells in cancer therapy.

Langerhans cells - clinical application

Langerhans cells are the subject of scientific research aimed at their use in anti-cancer therapy.

An example of a method that uses Langerhans cells is percutaneous immunization, which is - to put it simply - an anti-cancer vaccine.

The idea is the subcutaneous administration of tumor cell antigens (e.g. proteins characteristic of melanoma cells). These antigens would be processed by Langerhans cells and then presented to other cells of the immune system. In this way, the immune system would be stimulated to fight cancer.

Research into percutaneous immunization in cancer therapy is still ongoing - hopefully the hopes related to this method will be confirmed in clinical experiments.

About the authorKrzysztof BialaziteA medical student at Collegium Medicum in Krakow, slowly entering the world of constant challenges of the doctor's work. She is particularly interested in gynecology and obstetrics, paediatrics and lifestyle medicine. A lover of foreign languages, travel and mountain hiking.

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Immune system