Biological Function of Langerhans Cells - Case Study Example

Describe in Molecular Detail the Biological Function of Langerhans Cells Introduction Langerhans cells are dendritic cells that activate the immune system of the body by combining with antigens by migrating to the local lymph nodes close to the injured or infected part of the skin. LC’s are found in stratum spinosum part of the epidermis and play a key role in protecting the body from bacteria, virus and other infectious invaders. The main function of LCs is to process antigens and present it to T cells to build immune responses. In the process, Langerhans cells combines with several other cells and it has been found that Langerhans cells react only to live infections caused by virus or bacteria and do not respond to artificially imposed sensitizers. The antigen presenting cells move in and out of lymph nodes to initiate immune responses. The interaction of Langerhans cells with immuno competent cells initiates the formation of a number of antibodies in various parts of the human body. Position Langerhans cells(LC) are epidermal dendritic cells that take shape in the bone marrow and moves toward the T cell region of lymph nodes to function as expert antigen presenting cells. Langerhans cells can be identified using a wide range of cell surface markers like ectoenzyme adenosine triphosphatase (ATPase), CD1a antigens and Ia+ (Pérez-Torres, A. & Ustarroz-Cano, M 2001). Paul Langerhans first observed the dendritic Langerhans cells in the skin in 1868. Birbeck et al explained the presence of rod like granules in the cytoplasm of Langerhans cells (Indrasingh. 2006). Ultrastructural detection of Langerhans in the epidermis is performed by the recognition of an exclusive and typical cytoplasmic organelle called the Birbeck granule (BG) (Pérez-Torres, A. & Ustarroz-Cano, M 2001).Langerhans cells belongs to the system of antigen presenting cells and combines with the antigen that moves into the epidermis and the LC presents the combined cells to T-lymphocytes that later creates immune response (Indrasingh. 2006). Dendritic cells (DCs) in the immune system have the natural ability to recognize and seize foreign antigens and effectively provide antigens to T cells. Even though DCs have the capability to present antigens to T cells, cell surface markers, tissue distribution and the ability to assign different methods of adaptive immune responses are responsible for the function of DCs. Paul Langerhans found the presence of DC’s in the skin precisely in the epidermis and the identification of Langerhans cells indicated that it is the only cell in the epidermis to mark MHC class II molecules in normal conditions. After capturing antigen, LCs move towards the lymph nodes and are very effective in providing the T-cells with MHC class II restricted peptides. The T cells then move back to the skin to take part in cutaneous inflammatory responses. These findings show that LCs is crucial to form innate immune reactions in the skin and function to begin the adaptive T cell response in a particular region. Few other features of LC’s include their capacity to show high levels of CD1a which belongs to the family of 1CD1 proteins that share the capability to provide microbial lipid antigens to T cells. Further, LCs is the only known cells to show langerin (CD207), a c-type lectin that is adequate to induce the creation of Birbeck granules. These exclusive features indicate that LC’s are specialized in their ability to express langerin to capture specific antigens when they migrate to the epidermal layers and these antigens are provided to CD1a-restricted T cells to form immune responses (Hunger, et al. 2004). Langerhans cells are dendritic cells characteristic of stratified squamous epithelia and have the distinction for their efficiency in capturing and processing antigens though they are inefficient in providing the mixture to lymphocytes. LCs migrates from the bone marrow by distributing monocytes as intermediates. Langerhans cells migrate from the epidermis after combining with foreign antigens and further penetrate into dendritic cells on the way to peripheral lymphoid organs and give out primary immune responses. The signals controlling the separation of LC into DC’s are performed by a number of cytokines while certain cytokines hinder the migration process. In addition to cytokines, thymic precursors and pro-B cells can lead to the cell migration into DCs. Mucosal stratified squamous epithelia and keratinocytes, the fundamental cell of epidermis can present numerous cytokines that impact the separation of cells and their merger with Langerhans cells. Some of the cytokines that act in the process are TNF-alpha and GM-CSF which maintains the LC in the epidermis. E-cadherin mediates the cell to cell link, and also provides signals from keratinocytes to separate LCs. The separation of LC inside the epithelial micro setting of skin and mucosae usually results from the association of various players that perform varying roles in the process in different pathophysiological and physiological environment (Pieri L, Domenici L & Romagnoli P.2001). Function Langerhans cells act as the most divergent cells in the immune systems of the body. Their function is to seize antigens found in the epidermis and move towards the skin draining lymphoid tissues where they effectively stimulate the effector T cells and the naïve T cells thus starting the immune response in the body. The advanced antigen presenting potential of LC is partially the outcome of maturaitonal phenotypic variations that take place as they migrate from the epidermis. The migration from inhabitant epidermal cell to the lymphoid dendritic cell (DC) is indicated by an enhancement to the expression of cell surface molecules essential for T cell activation like class I and II major histocompatibility complex (MHC), the costimulatory molecules B7–2/CD86 and B7–1/CD80, and the ancilliary molecule ICAM-1/ CD54. One of the reasons for the migration and activation of Langerhancs cells is considered to be the accumulation of class II MHC antigens on the surface of the cell. There is another explaination which indicates that there is an impulsive migration of Ia+ cells from the skin in the ear duirng culture according to the murine model. Though the accurate reason for the beginning of the migration process has not been detected, there are facts that substantiate that the modulation of adhesion molecule expression is assocaited with the reduction in the density of Langerhans cell in the epidermis and the increase in the number of dendritic cell in the nearest draining lymph node (DLN) which is as a result of the contact of LC with the antigen. Therefore the leukocyte function-associated-molecule-1 (LFA-1), 4 integrin and intercellular adhesion molecule-1 (ICAM-1) expression enhances, and the E-cadherin expression reduces. P-glucoprotein also plays a significant role in the migration of dedritic cell from the skin with the translocation of a soluble molecule to the exterior part of the cell. Several cytokines are also caught up during this process that includes tumor necrosis interleukin-1 and factor-. Langerhans cells that are stimulated by factors like tumor necrosis factor- to migrate from the epidermis express CC chemokine receptor 7 and enabe them to be reactive to secondary lymphoid-tissue chemokine that later plays a role in their migration to lymph nodes through the lymphatics. It has been found from research that vaccinia virus decreases the number of epidermal LC. On the other hand systemic infection caused due to the retrovirus Rauscher leukemia has been found to hinder the migration of dendritic cell in reaction to the use of a contact sensitizer in murine model. Moreover, there is no evidence that the movement of LC during the initial stages of immune response to transepidermmally or epidermally obtained replicating protein antigen like virus is gradually erased by the immuno response of the host cells. From the above example it may be substantiated that Langerhans cells move away from the epidermis to the lymph nodes to build immunity in response to the infection caused by a live virus and LC’s do not migrate to draining lymph nodes if the infection is formed by ultraviolet (UV)-inactivated WNV or SFV. Therefore LC migrates to the dendritic lymph nodes to start immune response only in the case of epidermally gained virus infection and does not respond to artificial sensitizers. On acquiring virus through mosquito bites or ticks it is found that vast histocompatibility complex class II+/NLDC145+/E-cadherin+ LC numbers increase in the draining lymph nodes of the infected creature and the increase results in the decrease in the number of LC in the epidermis. LC migrations is related to the formation of leukocytes in the lymph nodes and forms the initial steps in the formation of an immune response. This indicates that LC reach functional maturation in reaction to the virus acquired in the body (Johnston, L.J., Halliday, G.M. & King, N.J.C. 2000). Interaction with other cells Langerhans cells play a significant part in cutaneous immune responses. Ultra structural studies reveal that LCs is present in the human tonsillar epithelium and are responsible to build immune responses. LC’s are ancillary cells of the immune system of the body that has the ability to combine and present antigen to T-lymphocytes to initiate immune response. The presence of typical Birbeck granules in Langerhans and its close association with intraepithelial lymphocytes can be cited in the human tonsillar epithelium. The interaction between LC and immuno-competent cells, T lymphocytes is of much significance to substantiate the cellular interaction in the palatine tonsils. An experiment using conventional electron microscope reveals that Langerhans cells are in apposition with lymphocytes in the Human tonsillar epithelium. A research on tonsillar tissues taken from four patients under tonsillectomy treatment for repeated tonsillitis were separated using dissecting microscope and set in phosphate shielded glutaraldehyde formalin mixture at a level of pH 7.2 -7.4 for four hours. The tissue was then washed using phosphate buffer and later set in one percent Osmic acid for duration of 90 minutes and it was washed again with phosphate buffer, dried in graded alcohols, clarified in propylene oxide and fixed in araldite. The tissue was further divided using a glass knife and observed through a Philips E.M.201 at 60Kv. It was observed that Langerhans cells are present in the tonsillar epithelium of human beings as pale staining cells without desmosomes, tonofilaments and the nuclei of these cells were indented. These Langerhans cells comprised mitochondria, free ribosomes, Golgi bodies and electron accumulated lysosome like structures. The cytoplasm comprised Birbeck granules which looked like rod and tennis racket shape and horse shoes. It was also observed that there was a close association between the two lymphocytes in the exterior epithelium of palatine tonsil and the Langerhans cells. In certain places the dendritic process of LC was in apposition to the lymphocytes. The evidence of LC in the epithelium of tonsil has been substantiated by Mausle et al in 1971 through the Zinc Iodide Osmium method. The presence of dendritic cells in the tonsillar epithelium of human being was explained due to their capability to combine peanut agglutinin, lectin and its response to a wide range of monoclonal antibodies. The evidence of Langerhans cells in the palatine tonsil of human beings leads to the conclusion that LC functions as antigen presenting cells due to its close link with lymphocytes. There is also evidence that LCs is in close contact with lymphocytes in cellular hyper sensitivity. A study by Ozbilgin et al states that, though several antigen presenting cells are found in the hypertrophy pharyngeal tonsils of kids, only dendrite cells are in opposition with immuno-competent cells and related antigen presenting cells. The sites of interaction between lymphocytes and antigen presenting cells (macrophages, dendritic cells) and the palatine tonsil of human beings can be found by observing through acid-phosphatase histochemistry and pre-fixed immunoelectron microscopy. The ultra structural description of close apposition between lymphocytes and LC indicates the functional relationship in the formation of local immune reactions (Indrasingh. 2006). Conclusion It may be concluded that Langerhans cells are important components of the human immune system. These cells are vigilant and stimulate the formation of immune response soon after the skin is attacked by a foreign body. LCs move from the epidermis to the lymph node to present antigens to the T cells to initiate responses. Several cytokines, receptors and molecules play intermediary roles in moving the LCs from epidermis to lymph nodes. By presenting antigens, LCs enables the body to build response and protects the body from serious infection and serves as reservoir in the case of HIV virus and eliminates a case of infection. After completing its task in the lymph nodes, Langerhans cells move back to the epidermis. Langerhans cells are receptive only to live infections and they combine with antigen only if the attack is cause by a live bacteria or virus. This is evident by comparing its performance by imposing artificial sensitizers to the skin and has resulted in no response from the Langerhans cells. The interaction with lymphocytes results in competent immune responses in various parts of the body. Therefore Langerhans cells are essential and significant to protect the body from epidermal infections. Reference Hunger, et al. 2004. Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. Journal of Clinical Investigation Vol. 113. Iss. 5 p.701-708. Available: http://www.jci.org/articles/view/19655. Accessed on October 29, 2008 Indrasingh. 2006. Apposition of Langerhans cells and lymphocytes in Human tonsillar epithelium: An Ultrastructural study. J.Anat.Soc. India 55 (2) 24-26. Available: http://medind.nic.in/jae/t06/i2/jaet06i2p24.pdf. Accessed on October 29, 2008 Johnston, L.J., Halliday, G.M. & King, N.J.C. 2000. Langerhans Cells Migrate to Local Lymph Nodes Following Cutaneous Infection with an Arbovirus. Journal of Investigative Dermatology Vol. 114, 560–568. Available: http://www.nature.com/jid/journal/v114/n3/full/5603309a.html. Accessed on October 29, 2008 Pérez-Torres, A. & Ustarroz-Cano, M 2001 Demonstration of Birbeck (Langerhans cells) granules in the normal chicken epidermis. Journal of Anatomy Vol:199 p.493-497. Available: http://journals.cambridge.org/action/displayAbstract;jsessionid=225372B93041D312E2F87D62D8718EB3.tomcat1?fromPage=online&aid=88009. Accessed on October 29, 2008 Pieri L, Domenici L & Romagnoli P.2001. Langerhans cells differentiation: a three-act play. Ital J Anat Embryol. Vol.106(1):47-69. Available: http://www.ncbi.nlm.nih.gov/pubmed/11410998. Accessed on October 29, 2008 Read More