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Langerhans cell

Medically Reviewed by Anatomy Team

Table of Contents

Langerhans cells are a specialized subset of dendritic cells located primarily in the epidermis of the skin. Discovered by Paul Langerhans in 1868, these cells play a crucial role in the immune system by serving as antigen-presenting cells (APCs) that bridge innate and adaptive immunity.[2] Their strategic location in the skin, the body’s largest organ and primary barrier, highlights their importance in immune surveillance, pathogen recognition, and inflammation regulation.

Structure and Anatomy

Langerhans cells are irregularly shaped cells that reside within the basal and suprabasal layers of the epidermis. Their structural and ultrastructural features reflect their specialized immune functions.

Location

  • Found predominantly in the epidermis, particularly in areas frequently exposed to environmental pathogens, such as the hands, feet, and face.[3]
  • Also present in mucosal tissues, including the oral cavity, vaginal mucosa, and respiratory tract.

Cytological Features

  • Dendritic Morphology:
    • Langerhans cells have long, slender dendritic processes that extend between keratinocytes to sample antigens.
    • These processes enable them to interact extensively with surrounding cells and capture environmental antigens.
  • Nucleus:
    • Large, irregularly shaped nucleus with prominent nucleoli.
    • Reflects the cell’s active role in transcription and protein synthesis.

Birbeck Granules

  • A hallmark feature of Langerhans cells, visible under electron microscopy.
  • These are tennis racket-shaped organelles involved in antigen processing and presentation.
  • Believed to play a role in the internalization and degradation of pathogens.[5]

Development and Maturation

Langerhans cells are derived from bone marrow precursors and belong to the mononuclear phagocyte system.

Origin

  • Arise from hematopoietic stem cells in the bone marrow.
  • Differentiate into monocyte-like precursors that migrate to the skin during fetal development.

Maintenance

Unlike many immune cells, Langerhans cells are self-renewing and maintain their population independently of circulating monocytes under steady-state conditions.[7]

Maturation

  • In their immature state, Langerhans cells reside in the epidermis, where they are highly phagocytic.
  • Upon encountering antigens, they undergo maturation, which includes upregulation of major histocompatibility complex (MHC) molecules and co-stimulatory proteins.
  • Mature Langerhans cells migrate to regional lymph nodes to activate T cells.

Function

Langerhans cells serve as sentinels of the immune system, detecting and responding to pathogens, allergens, and damaged cells. Their primary roles include antigen capture, processing, and presentation.

Antigen Capture and Processing

  • Phagocytosis and Endocytosis:
    • Langerhans cells engulf pathogens, allergens, and dead cells through phagocytosis.
    • Internalized antigens are processed within endosomes and presented on MHC molecules.
  • Birbeck Granules:
    • Facilitate the degradation of antigens into smaller peptides suitable for presentation.

Antigen Presentation

  • Langerhans cells present processed antigens to naïve T cells in the lymph nodes.
  • MHC class I molecules present intracellular antigens to CD8+ T cells, while MHC class II molecules present extracellular antigens to CD4+ T cells.[8]

Role in Immune Responses

  • Initiation of Adaptive Immunity:
    • By activating T cells, Langerhans cells link innate and adaptive immune responses.
  • Tolerance Induction:
    • In non-inflammatory conditions, they promote immune tolerance, preventing overreaction to harmless antigens like self-proteins and commensal microbes.

Communication with Other Cells

Langerhans cells interact with keratinocytes, melanocytes, and dermal dendritic cells to modulate local immune responses.

Role in Skin Immunity

The strategic placement of Langerhans cells in the epidermis enables them to serve as the first line of defense against environmental insults.

Pathogen Recognition

  • Detect pathogens through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs).
  • Respond to bacterial, viral, and fungal infections by capturing antigens and initiating immune responses.

Regulation of Skin Inflammation

  • Modulate inflammatory responses by releasing cytokines and chemokines.
  • Maintain skin homeostasis by promoting tolerance to non-pathogenic stimuli.[1]

Role in Wound Healing

Langerhans cells contribute to wound healing by regulating the recruitment of immune cells to injured areas.

Clinical Significance

Langerhans cells are implicated in various dermatological and systemic conditions. Understanding their behavior is essential for diagnosing and treating these disorders.

Infections

  • Viral Infections:
    • Act as reservoirs for viruses like HIV, capturing and presenting the virus to T cells, which can exacerbate the infection.
  • Fungal Infections:
    • Langerhans cells play a critical role in recognizing fungal antigens and mounting an immune response.

Autoimmune Diseases

  • Dysregulation of Langerhans cells can lead to autoimmune skin conditions, such as psoriasis and vitiligo.
  • Aberrant antigen presentation may trigger inappropriate immune responses against self-antigens.[4]

Allergic Reactions

  • Overactivation of Langerhans cells can cause hypersensitivity reactions, including allergic contact dermatitis.
  • These cells play a key role in recognizing allergens and initiating inflammatory cascades.

Langerhans Cell Histiocytosis (LCH)

  • A rare disease characterized by the abnormal proliferation of Langerhans cells.
  • Symptoms can range from localized skin lesions to systemic involvement, affecting bones, lungs, and other organs.[6]

References

  1. Abbas, A. K., Lichtman, A. H., & Pillai, S. (2021). Cellular and Molecular Immunology (10th ed.). Elsevier. ISBN 9780323757485.
  2. Kumar, V., Abbas, A. K., & Aster, J. C. (2020). Robbins and Cotran Pathologic Basis of Disease (10th ed.). Elsevier. ISBN 9780323531139.
  3. Murphy, K., Weaver, C., & Janeway, C. (2016). Janeway’s Immunobiology (9th ed.). Garland Science. ISBN 9780815345053.
  4. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2014). Molecular Biology of the Cell (6th ed.). Garland Science. ISBN 9780815344643.
  5. Delves, P. J., Martin, S. J., Burton, D. R., & Roitt, I. M. (2017). Roitt’s Essential Immunology (13th ed.). Wiley-Blackwell. ISBN 9781118415770.
  6. Male, D., Brostoff, J., Roth, D. B., & Roitt, I. M. (2012). Immunology (8th ed.). Elsevier Health Sciences. ISBN 9780702046636.
  7. Arstila, T. P., & Gran, B. (2010). The Lymphoid System in Immunity, Infection, and Inflammation. Springer. ISBN 9789048138071.
  8. Hall, J. E. (2020). Guyton and Hall Textbook of Medical Physiology (14th ed.). Elsevier. ISBN 9780323672801.