Langerhans cells are dendritic cells (antigen-presenting immune cells) of the skin and mucosa, and contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as in the mucosa of the mouth, foreskin, and vagina. They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).

A histiocyte is an animal cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell (histio, diminutive of histo, meaning "tissue", and cyte, meaning "cell").

Dendritic cells (DCs) are antigen-presenting cells (also known as "accessory cells") of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.

Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the "dendrites" that give the cell its name (δένδρον or déndron being Greek for "tree"). While similar in appearance, these are structures distinct from the dendrites of neurons. Immature dendritic cells are also called veiled cells, as they possess large cytoplasmic 'veils' rather than dendrites.

Histiocytes are derived from the bone marrow by multiplication from a stem cell. The derived cells migrate from the bone marrow to the blood as monocytes. They circulate through the body and enter various organs, where they undergo differentiation into histiocytes, which are part of the mononuclear phagocytic system (MPS).

However, the term "histiocyte" has been used for multiple purposes in the past, and some cells called "histocytes" do not appear to derive from monocytic-macrophage lines. (The term Histiocyte can also simply refer to a cell from monocyte origin outside the blood system, such as in a tissue (as in rheumatoid arthritis as palisading histiocytes surrounding fibrinoid necrosis of rheumatoid nodules).

Some sources consider Langerhans cell derivatives to be histiocytes. The Langerhans cell histiocytosis embeds this interpretation into its name.

In skin infections, the local Langerhans cells take up and process microbial antigens to become fully functional antigen-presenting cells.

Generally, dendritic cells in tissue are active in the capture, uptake and processing of antigens. Once dendritic cells arrive in secondary lymphoid tissue, however, they lose these properties while gaining the capacity to interact with naive T-cells.

Langerhans cells derive from primitive erythro-myeloid progenitors that arise in the yolk sac outside the embryo in the first trimester of pregnancy, and under normal circumstances persist throughout life, being replenished by local proliferation as necessary. If the skin becomes severely inflamed, perhaps because of infection, blood monocytes are recruited to the affected region and differentiate into replacement LCs. They are similar in morphology and function to macrophages.

Langerin is a protein found in Langerhans cells, and other types of dendritic cells.

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells present antigen (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.

In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ. (The "B" from B cells comes from the name of this organ, where it was first discovered by Chang and Glick, and not from bone marrow as commonly believed).

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind a specific antigen, against which it will initiate an antibody response.

Langhans cells are often found in transbronchial lung biopsies or lymph node biopsies in patients suffering from sarcoidosis.

The morphology of dendritic cells results in a very large surface-to-volume ratio. That is, the dendritic cell has a very large surface area compared to the overall cell volume.

Langhans giant cells (also known as Pirogov-Langhans cells) are large cells found in granulomatous conditions.

They are formed by the fusion of epithelioid cells (macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery.

Although traditionally their presence was associated with tuberculosis, they are not specific for tuberculosis or even for mycobacterial disease. In fact, they are found in nearly every form of granulomatous disease, regardless of etiology.

In terms of the "normal" mechanism of T cell we find that it is a type of white blood cell that has an important role in immunity, and is made from thymocytes One sees in the "partial" disorder of T cells that happen due to cell signaling defects, are usually caused by hypomorphic gene defects Generally, (micro)deletion of 22Q11.2 is the most often seen.

Presentations differ among causes, but T cell insufficiency generally manifests as unusually severe common viral infections (respiratory syncytial virus, rotavirus), diarrhea, and eczematous or erythrodermatous rashes. Failure to thrive and cachexia are later signs of a T-cell deficiency.

The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cells called Langerhans cells, sometimes called Dendritic Cell Histiocytosis. These cells in combination with lymphocytes, eosinophils, and normal histiocytes form typical LCH lesions that can be found in almost any organ. A similar set of diseases has been described in canine histiocytic diseases.

LCH is clinically divided into three groups: unifocal, multifocal unisystem, and multifocal multisystem.

Unifocal LCH, also called "Eosinophilic Granuloma" (an older term which is now known to be a misnomer), is a slowly progressing disease characterized by an expanding proliferation of Langerhans Cells in various bones. It can be a monostotic (involving only one bone) or polyostotic (involving more than one bone) disease. It typically has no extraskeletal involvement, but rarely an identical lesion can be found in the skin, lungs, or stomach. When found in the lungs, it should be distinguished from Pulmonary Langerhans cell hystiocytosis—a special category of disease most commonly seen in adult smokers. This primary bone involvement helps to differentiate Eosinophilic Granuloma from other forms of Langerhans Cell Histiocytosis (Letterer-Siwe or Hand-Schüller-Christian variant.

Clonal hypereosinophilia, also termed Primary hypereosinophelia or clonal eosinophilia, is a grouping of hematological disorder characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell, in the bone marrow, blood, and/or other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

The clone of eosinophils bear a mutation in any one of several genes that code for proteins that regulate cell growth. The mutations cause these proteins to be continuously active and thereby to stimulate growth in an uncontrolled and continuous manner. The expanding population of eosinophils, initially formed in the bone marrow may spread to the blood and then enter into and injure various tissues and organs.

Clinically, clonal eosinophilia resembles various types of chronic or acute leukemias, lymphomas, or myeloproliferative hematological malignancies. However, many of the clonal hypereosinophilias are distinguished from these other hematological malignancies by the genetic mutations which underlie their development and, more importantly, by their susceptibility to specific treatment regiments. That is, many types of these disorders are remarkably susceptible to relatively non-toxic drugs.

One classification system for lymphomas divides the diseases according to the size of the white blood cells that has turned cancerous. The large-cell lymphomas have large cells. A large cell, in this context, has a diameter of 17 to 20 µm. Other groups of lymphomas in this system are the small-cell lymphomas and mixed-cell lymphomas.

Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia. These former symptoms are due to release of a substance called histamine from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly is characteristic. The mast cells release also many anticoagulants like heparin which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.

The disease in the lungs is characterized by enlargement of the tracheobronchial lymph nodes and infiltration of the lungs, sometimes leading to lung lobe consolidation and pleural effusion. Signs and symptoms include cough, loss of appetite, weight loss, anemia, and difficulty breathing. Seizures and rear limb weakness can be seen. Invasion of the bone marrow can cause pancytopenia. Diagnosis requires a biopsy.

Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs "de novo" but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

A similar disease is diffuse histiocytic sarcoma, a term used to designate a localized histiocytic sarcoma that has spread throughout the body.

Another disease of histiocytic origin that affects Bernese Mountain Dogs is systemic histiocytosis. This condition generally begins as lesions on the eyelids, nasal mucosa, and skin, especially the scrotum. It progresses to a more generalized disease affecting the lymph nodes, bone marrow and spleen. Other signs and symptoms include weight loss and loss of appetite. It also has a very poor prognosis.

The T-cell lymphomas are four types of lymphoma that affect T cells. These account for about one in ten cases of non-Hodgkin lymphoma.

They can be associated with Epstein Barr virus and Human T-cell leukemia virus-1.

Hematopoietic stem cells give rise to: 1) myeloid precursor cells that differentiate into red blood cells, mast cells, blood platelet-forming megakaryocytes, or myeloblasts, which latter cells subsequently differentiate into white blood cells viz., neutrophils, basophils, monocytes, and eosinophils; or 2) lymphoid precursor cells which differentiate into T lymphocytes, B lymphocytes, or natural killer cells. Malignant transformation of these stem or precursor cells results in the development of various hematological malignancies. Some of these transformations involve chromosomal translocations or Interstitial deletions that create fusion genes. These fusion genes encode fusion proteins that continuously stimulate cell growth, proliferation, prolonged survival, and/or differentiation. Such mutations occur in hematological stem cells and/or their daughter myeloid precursor and lymphoid precursor cells; commonly involve genes that encode tyrosine kinase proteins; and cause or contribute to the development of hematological malignancies. A classic example of such a disease is chronic myelogenous leukemia, a neoplasm commonly caused by a mutation that creates the "BCR-ABL1" fusion gene (see Philadelphia chromosome). The disease is due to conversion of the tightly regulated tyrosine kinase of ABL1 protein to being unregulated and continuously active in the BCR-ABL1 fusion protein. This Philadelphia chromosome positive form of chronic myelogenous leukemia used to be treated with chemotherapy but nonetheless was regarded as becoming lethal within 18-60 months of diagnosis. With the discovery of the uncontrolled tyrosine kinase activity of this disorder and the use of tyrosine kinase inhibitors. Philadelphia chromosome positive chronic myelogenous eukemia is now successfully treated with maintenance tyrosine kinase inhibiting drugs to achieve its long-term suppression.

Some hematological malignancies exhibit increased numbers of circulating blood eosinophils, increased numbers of bone marrow eosinophils, and/or eosinophil infiltrations into otherwise normal tissues. These malignancies were at first diagnosed as eosinophilia, hypereosinophilia, acute eosinophilic leukemia, chronic eosinophilic leukemia, other myeloid leukemias, myeloproliferative neoplasm, myeloid sarcoma, lymphoid leukemia, or non-Hodgkin lymphomas. Based on their association with eosinophils, unique genetic mutations, and known or potential sensitivity to tyrosine kinase inhibitors or other specific drug therapies, they are now in the process of being classified together under the term clonal hypereosinophilia or clonal eosinophilia. Historically, patients suffering the cited eosinophil-related syndromes were evaluated for causes of their eosinophilia such as those due to allergic disease, parasite or fungal infection, autoimmune disorders, and various well-known hematological malignancies (e.g. Chronic myelogenous leukemia, systemic mastocytosis, etc.) (see causes of eosinophilia). Absent these causes, patients were diagnosed in the World Health Organization's classification as having either 1) Chronic eosinophilic leukemia, not otherwise specified, (CEL-NOS) if blood or bone marrow blast cells exceeded 2% or 5% of total nucleated cells, respectively, and other criteria were met or 2) idiopathic hypereosinophilic syndrome (HES) if there was evidence of eosinophil-induced tissue damage but no criteria indicating chronic eosinophilic leukemia. Discovery of genetic mutations underlining these eosinophilia syndromes lead to their removal from CEL-NOS or HES categories and classification as myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of "PDGFRA, PDGFRB, FGFR1," and, tentatively, "PCMA-JAK2". Informally, these diseases are also termed clonal hypereosinophilias. New genetic mutations associated with, and possibly contributing to the development of, eosinophilia have been discovered, deemed to be causes of clonal eosinophilia, and, in certain cases, recommended for inclusion in the category of myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of "PDGFRA, PDGFRB, FGFR1," and, tentatively, "PCMA-JAK2". Many of the genetic causes for clonal eosinophilia are rare but nonetheless merit attention because of their known or potential sensitivity to therapeutic interventions that differ dramatically form the often toxic chemotherapy used to treat more common hematological malignancies.

Most commonly histiocytomas are found in young dogs and appear as a small, solitary, hairless lump, although Shar Peis may be predisposed to multiple histiocytomas. They are most commonly found on the head, neck, ears, and limbs, and are usually less than 2.5 cm in diameter. Ulceration of the mass is common. Diagnosis is made through cytology of the mass. Cytology reveals cells with clear to lightly basophilic cytoplasm and round or indented nuclei with fine chromatin and indistinct nucleoli.

Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas. The islets containing the pancreatic β-cells, and in some cases, the exocrine tissues, become infiltrated by T and B lymphocytes, macrophages and dendritic cells. This innate immune cell and lymphocyte infiltration can result in destruction of the insulin producing beta cells of the islets, and clinical diabetes. Insulitis is often studied in the multiple low dose streptozotocin (MLDS) mouse model or the non-obese diabetic (NOD) mouse model of type 1 diabetes. The chemokine family of proteins may play a key role in promoting leukocytic infiltration into the pancreas prior to pancreatic beta-cell destruction.

X-type histiocytoses are a clinically well-defined group of cutaneous syndromes characterized by infiltrates of Langerhans cells, as opposed to Non-X histiocytosis in which the infiltrates contain monocytes/macrophages. Conditions included in this group are:

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.