LANGERHANS CELLS: CHARACTERISTICS, MORPHOLOGY, FUNCTIONS - BIOLOGY - 2025

The Langerhans cells are a group of cells of the immune system of mammals with extensive antigen presentation. They are mainly found in tissues that are exposed to the external environment, such as the skin. However, they can also be found in the thymus or tonsils, among other places.

These cells are part of the so-called dendritic cells. They were discovered in 1868 by the then German medical student, Paul Langerhans, hence their name. They were the first dendritic cells described.

Birbeck granules or bodies. Characteristic structures of Langerhans cells. Taken and edited from: Josef Neumüller, Sylvia Emanuela Neumüller-Guber, Johannes Huber, Adolf Ellinger and Thomas Wagner.

They differ from other similar cells by the presence of organelles or Birbeck bodies. The main function of Langerhans cells is to absorb and process external agents, initiating and regulating the immune response.

Langerhans cells (hereinafter CLs) are one of the known dendritic cell varieties, although some authors classify them all as the same. On the other hand, the CLs should not be confused with the islets of Langerhans or with the giant cells of Langhans.

History

Langerhans cells were discovered by the German physician and anatomist Paul Langerhans, when he was just a medical student, in 1868. Langerhans originally pointed out that these were a type of nerve cell or a nerve receptor, due to their close resemblance to dendrites.

They were considered cells of the immune system from 1969, thanks to the research of the eminent Venezuelan dermatologist, Dr. Imelda Campo-Aasen, who during her stay in England determined that the CLs were epidermal macrophages.

Langerhans cells were included within the group of dendritic cells in 1973, thanks to the studies of researchers Ralph Steinman and Zanvil Cohn, who coined the term, to designate some macrophage cells that play a role in the adaptive immune response.

characteristics

They are antigen presenting cells. They are mainly characterized by having cytoplasmic organelles, called Birbeck bodies. They are located in all the epidermal layers (skin), and are more prominent in the spinous stratum, that is, between the granular and basal stratum of the epidermis.

They are also found in tissues such as lymph nodes, in the lining of the oral cavity, tonsils, thymus, vagina, and foreskin. These cells have the particularity of extending their membranous processes between epithelial cells, without altering the optimal functioning of the epithelial barrier.

Longitudinal section of the inner lining of the vagina. Taken and edited from: Jpogi at English Wikipedia.

They appear in the body from week 14 of embryonic development. Once they appear, they occupy the epidermis and the rest of the aforementioned tissues. Within these tissues they replicate and complete their cycle in approximately 16 days.

The CLs represent, in a healthy human, approximately 4% of the total cells of the epidermis. Their distribution and densities vary from one anatomical site to another. It is estimated that in the epidermis there may be more than 400 to 1000 Langerhans cells per square millimeter.

Morphology

When Langerhans cells staining assays are performed, and they are observed using an electron microscope, it can be seen that they are separated from the keratocytes (predominant cells of the epidermis) by a slit.

You can also see the characteristic Birbeck bodies, which are shaped like a cane, tennis racket or hemispherical blister at one end of a straight and flat structure.

There is a group of cells that are identical to Langerhans cells, but do not have the characteristic Birbeck bodies. These are called "indeterminate cells." Scientists consider that a protein called lectin, along with other factors, are responsible for the formation of these granules or bodies.

Langerhans cells are similar to other macrophages. However, they exhibit a varied morphology depending on whether they are immature, mature and even if they have captured an antigen.

Immature Langerhans cells

During their immature stage they show a stellate morphology, with many vesicles. They measure about 10 microns.

Mature Langerhans cells

In the mature stage, Langerhans cells can have a variety of membranous processes (in the plasma membrane). These can have dendrite forms, veil or have pseudopods.

An example of these membranous processes is the veil form. This is formed after the cell captures an antigen during an infection. From then on, the dendritic morphology changes to veil-like projections of the plasma membrane.

Features

CLs fulfill the function in the body of capturing and processing antigens. These cells can move from the skin to the lymphoid tissue, and when they arrive there they begin to interact with lymphocytes (T cells), to initiate the adaptive immune response.

Histology

Histology is a branch of biology that is responsible for studying the composition, growth, structure and characteristics of the tissues of all living organisms. In the case of Langerhans cells, reference will be made to animal epithelial tissue, especially that of humans.

Epidermis

Langerhans cells are in the epidermis. In this thin layer of the skin, these cells represent a small portion of predominant cells such as keratocytes. They also share the epithelium with two other types of cells called melanocytes and Merkel cells.

Dermis

The dermis is another layer of the skin in which Langerhans cells are also present. Unlike what happens in the epidermis, here the CLs are accompanied by a different group of cells, called mast cells, histocytes, fibrocytes and dermal dendrocytes.

Diseases

Sexually transmitted diseases

Even though Langerhans cells have the function of capturing and processing antigens, there is a great debate regarding its effectiveness as a barrier against sexually transmitted diseases, caused by viruses such as HIV (Acquired Immunodeficiency Virus) or HPV (virus of human papilloma).

Some researchers suggest that these cells can become reservoirs and even vectors for the spread of these diseases; but, on the other hand, others have evaluated the efficiency of the Langerin protein, present in CLs and other macrophages, pointing to it as a successful natural barrier against diseases such as HIV-1.

Langerhans cell histiocytosis

It is known as a very rare type of cancer that is attributed to the proliferation of abnormal Langerhans cells. These cells come from the bone marrow and can travel from the skin to the node or lymph node.

Symptoms manifest as bone lesions to diseases that affect other organs, even the body in general.

The diagnosis of the disease is made through a tissue biopsy. In this, CLs with characteristics very different from the usual ones should appear, such as, for example, granular cytoplasm with pink coloration and cell margin different from normal.

As a treatment for this disease, it has been proposed to apply radiation of about 5 to 10 Gray (Gy) in children and 24 to 30 Gy in adults. In systemic pathologies, chemotherapy and cream steroids are generally used on skin lesions. The disease has a high survival rate, with 10% mortality.

High-power micrograph of Langerhans cell histiocytosis. Taken and edited from: Nephron

Other pathologies

Exposure of the epidermis to the external environment and the great variety of factors that can affect the correct homeostasis, can trigger a low efficiency of the functions of the Langerhans cells.

This low efficiency could allow parasites, fungi, bacteria, allergens, among others, to enter the body through the epithelium, capable of causing damage to the individual.

Uses in medicine

Today's medicine does not seem to know borders, every day new treatments for diseases are discovered, from bioactive substances, cells and organisms that you never imagined could be so important in the field of medicine.

Langerhans cells have been used experimentally as modulators of the immune response, either to generate the response, enhance it or prevent it.

Treatment of melanomas

It is known from a large number of successful trials in both animals and humans, in the treatment of melanomas (skin cancer). In these tests, Langerhans cells have been obtained from the same patients and have been stimulated under controlled conditions.

Once the CLs have been appropriately stimulated, they are reimplanted in the patient, in order to generate an antitumor immune response. The results of these tests, according to some authors, are quite encouraging.

Treatments against

Leishmania sp., Is a genus of protozoan that causes the skin disease, known as leishmaniasis. This disease manifests as skin ulcerations that heal spontaneously. Critical or fatal manifestations of the disease show not only ulcerations, but inflammation of the liver and spleen.

A group of researchers discovered that DNA and / or RNA sequences can be inserted to modify Langerhans cells, in order to encode and express antigens of interest and produce substances that enhance the immune response necessary to fight diseases such as leishmaniasis.

Other treatments

Currently there are trials to develop and modify Langerhans cells and even other dendritic cells, in order to create and enhance immune responses, not only for melanomas and leishmaniasis, but also for skin allergies and even autoimmune diseases.

On the other hand, it is worth mentioning that it has been discovered that the presence of certain chemical elements and compounds, found in hot springs and sulfur waters, also known medicinal waters, improves the immune response of CLs. Because of this, they are sometimes used in the treatment of psoriasis and atopic dermatitis.

References

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5. M. Begoña, M. Sureda & J. Rebollo (2012). Dendritic cells I: basic aspects of their biology and functions. Immunology.
6. Embryologic, histologic, and anatomic aspects: Langerhans cells. Recovered from derm101.com.
7. Langerhans cell histiocytosis. Recovered from en.wikipedia.org.