Langerhans cells

These are dendritic skin cells and contain Birbeck granules which is an organelle. In almost all the layers of the epidermis, langerhans cells are found. In the stratum spinosum they are the most prominent. Also, in the papillary dermis they occur. They are also found in the mucosa of the vaginal epithelium, mouth, foreskin, and around blood vessels. They can be found in other tissues such as in lymph nodes. Studies have even shown that in the epidermis of hair follicles, the population of langerhans cells are high.

What are langerhans cells?

Paul Langerhans described langerhans cells. These are dendritic, mobile cells and make up 3-6 percent of the epidermal cells. They are antigen presenting cells that are located in the suprabasal layers of the epidermis. They show a stellate appearance and they present very closely to keratinocytes.

Morphology of langerhans cells

The nucleus of the langerhans cells is indented or lobulated. Their cytoplasm is electron-lucent and does not contain tonofilaments and melanosomes. Langerhans cells contain Birbeck granules that are unique, tennis racket shaped, and initially a specific cytoplasmic marker was used to identify them. Still it is unclear as to what is the function of these granules but most likely they may be involved in receptor mediated endocytosis and enable transportation of materials into the extracellular space.

Langerhans cells have been named after the person who discovered it, Paul Langerhans. He was the first person to describe these cells and to state its location. By the fourteenth week of fetal life their appearance begins in the human skin. They originate in the bone marrow and then proceed towards the epidermis, thymus, dermis, lymph nodes, epithelia of the oral mucous membrane and the lymph nodes. It has been estimated that their cycle of replication takes 16 days and they replicate within the epidermis. Based on their location their distribution varies. Into the epidermis fine unmyelinated nerve fibers ascend and they touch the langerhans cells so that between the nervous system and the immune system a link can be created. The function of langerhans cells can be modulated by the nerves.

There is a lot of similarity between the langerhans cells and the macrophages. For presentation of antigen to lymphocytes langerhans posses cell surface HLADR. Langerhans cells can be recognized by immunohistochemical techniques since they are able to express CD1a and S 100. Morphologically, langerhans cells are quite distinct and in various chemical processes that play a crucial role. They play an important role in allograft rejection, allergic contact dermatitis, immune tolerance and surveillance. It is believed that the specificity of lectin to bind with langerin is responsible for inducing the formation of Birbeck granules.

When langerhans cells were stained by hematoxylin and eosin, then it was found that a cleft separated the langerhans cells from the adjacent kerationocytes. In fact, this cleft was formed by shrinkage hence it is more of an artifact. Electron microscopy is the most reliable means of identifying the cells. When under electron microscope, the characteristics of the granules within the cytoplasm are revealed, and at one end of the liner plate-like structure the hemispherical bleb is displayed.

Where do langerhans cell originate?

According to early studies when allogenic bone transplant was done within a few weeks, the donor cells replaced the langerhans cells. From this it was concluded that from a mobile pool of bone marrow derived precursors the langerhans cells were derived. Later using the model of human skin, experiments were done in which the human skin model was grafted on the mouse. For the life of the graft, the langerhans cells persisted even though there was epidermal turnover and there was no human precursor circulating. Also, it was shown that when at the center of a normal graft of human skin a wound was created, from the non-injured areas the langerhans cells originated and the wounded areas was repopulated by them. Studies in murine have found that in mouse and man there are similarities with respect to mobilization and migration of langerhans cells suggesting chances of extrapolation.

Self-reproducing potential of langerhans cells

When on epidermal cell suspension flow, cytometric studies were performed. It was found that in different phases of the cell cycle langerhans cells could be found. Further studies showed that these cells are actively cycling cells and they pass through the cell division process. Under steady conditions throughout life they form a stable self-reproducing population of cells. When there is an exaggerated loss of langerhans cells, then along with the skin even the langerhans cells precursor are recruited.

Functions of langerhans cell

Usually langerhans cells are actively involved in capturing the antigen, in its uptake and in its processing. When they reach the secondary lymphoid tissue they gain the capacity to interact with T cells and lose their other properties.

These dendritic cells have been derived from the primitive erythro-myeloid progenitors and in the first trimester of pregnancy they arise outside the yolk sac. They can persist throughout their life if the condition persists. If necessary by local proliferation they may get replenished. If due to infection the skin becomes severely inflamed, then to the affected region blood monocytes are recruited and they differentiate into langerhans cells. A protein found in these cells is known as langerin and this protein is also found in other dendritic cells.

In the skin of the digestive, respiratory, and urinogenital tracts, langerhans cells are present. Even in other tissues such as lymph nodes they are present. When langerhans cell histiocytosis develops at that time particularly, they are found in the lymph nodes. Antigens are harmful substances and against them antibodies are produced by the immune system. These dangerous antigens are kept away by the langerhans cells.

Paul Langerhans was a twenty-one-year-old German medical student when he discovered these cells. These cells belong to the dendritic family and they are present in almost all the epidermal layers of the body. These cells are found throughout the body. Since they are immune cells, to the immune system they present antigens. Whenever pathogens and other foreign material are present in the skin then the immune system is made alert by these dendritic cells such as langerhans cells. These dendritic cells are present in the skin since the skin acts like a barrier against infection. Originally, langerhans cells were believed to be a part of the nervous system and and they only made the immune system alert about the antigens. But later it was found that in two ways langerhans cells could dampen the skin reaction to infection. They would do this by providing protection to the skin against any infection and secondly they would stimulate allergic reactions.

Special immune cells such as T cells and B cells are sent by the langerhans cell as soon as they sense any danger in the skin. Any foreign material such as bacteria and viruses are captured by these immune cells. Constantly langerhans cells keeps monitoring the environment of the skin any if there is any foreign invader then that information is brought by the immune cells after which to either form a scar tissue or by creating an allergic reaction. By doing this they can fight off invaders and also provide protection from infection.

At present the physiological role of langerhans cells is under a lot of debate. First, it was found that these are antigen presenting cells and the cutaneous antigens are locally processed by them. Then for effective antigen presentation to the T cells they migrate from the skin into the draining lymph node. As they journey to the lymph node, their surface phenotype changes and they begin to mature. At the same time, they down regulate the antigen processing so that the ability to co-stimulate with the T cells is improved.

In murine models in whom langerhans cells were deficient, the antigen specific T cell activation was found to be intact thus the biological significance of this pathway was questioned. However, in these studies the results found were inconsistent. Here many factors may have affected the results such as the site of challenge, the mode of langerhans cell depletion, the antigen dosage, etc…To date no model have used a strictly epidermotropic pathway to show the redundancy of langerhans cells in inducing immunity.

Since it was found that the murine carcinogenesis promoted unexpectedly by the langerhans cells expressing ligans for cytotoxic T cells thus from this a novel role of langerhans cell was suggested. From these data it suggests that the migration of the langerhans cells from the skin to the draining lymph nodes takes place in a steady state and the induction and tolerance to cutaneous antigens is maintained. From this a working hypothesis is being emerged in which in sustaining cutaneous immunological tolerance a more important role is being played by the langerhans cells and the DCs that are located in the dermis may be involved in the cutaneous immune activation. It could so happen that depending on the environmental context any one of the two roles can be played by langerhans cells.

Immunoregulation and langerhans cells

Although the major function of the epidermis is to synthesize keratin, it is known to play an immunoregulatory role in the immune defense system of the host. Melanocytes are dendritic cells present in the human epidermis and apart from this there are other dendritic cells in which pigment is not manufactured. They are distributed far towards the skin surface. The function of langerhans cells remained to be obscured after their discovery till later it was realized that in the immunologic mechanism langerhans cells play a vital role.

When the morphology of langerhans cells was studied under the electron microscope, it was found that there is are Birbeck granules that are a unique, tennis racked shaped organelle. Langerhans cells are like sentinel cells and whenever the skin encounters any foreign material, langerhans are the first ones to come into their contact. The dendritic processes of these cells create a large surface area which enhances their ability to function effectively. On the langerhans cells there are specialized receptors that enable them to recognize the pathogens and to the lymphoid system information is conveyed. To this foreign material then the body will mount immunologic response.

First, it was thought that keratinocytes are involved only in the process of synthesis of keratin but now it has been found that a number of immunostimulatory peptides of high molecular weight are secreted by these keratinocytes and these peptides are termed as cytokines. The epidermal langerhans cells secrete one of these epidermal cell derived thymocyte activating factor. It is involved in the systemic reaction of the body towards injuries and infections and also the immune response of the lymphoid system is enhanced by them.

Since every few minutes through the skin the whole blood volume gets circulated thus there can be a profound influence of the of the immunoregulatory substances released by the epidermal cells on the capacity of the body to produce an immune response to the pathogens to cancerous growths.

Skin conditions

According to research, any virus in the surrounding area can be identified and attacked by the langerhans cells so that the infection can be prevented. This role that langerhans cells play in creating an immune response against various diseases makes them very important. For immunotherapy, langerhans cells can be like potential targets. The mechanism that is involved in many skin disorders is the following:

• Psoriasis - skin cells accumulate with this condition and they form scales. This condition is accompanied by dry patches, itchiness, and redness.
• Lupus - with this condition the body tissue is attacked by its own immune system; hence this is an inflammatory disease.
• Skin cancer - in the U.S. this form of cancer is very common. The skin cells grow abnormally.

Topical vaccines may be developed and administered through the skin. The main focus is that in the skin containing antigens, langerhans cells are directly loaded. In order to inhibit melanoma growth, research is trying to look for ways in which vaccines can be given through barrier disrupted skin.

Article resources:

https://www.ncbi.nlm.nih.gov/pubmed/19388527

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424941/

https://www.verywellhealth.com/langerhans-cell-1069348

https://www.derm101.com/inflammatory/embryologic-histologic-and-anatomic-aspects/langerhans-cells/