Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that secrete large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Plasma cells originate in the bone marrow; B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell. Once released into the blood and lymph, these antibody molecules bind to the target antigen (foreign substance) and initiate its neutralization or destruction.
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.
A lymphocyte is one of the subtypes of white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (Phagocytes) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte".
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.
Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs. They develop from bone marrow hematopoietic stem cells and constitute < 0.4% of peripheral blood mononuclear cells (PBMC).
In humans they exhibit plasma cell morphology and express CD4, HLA-DR, CD123, blood-derived dendritic cell antigen-2 (BDCA-2), Toll-like receptor (TLR) 7 and TLR9 within endosomal compartments, but do not express high levels of CD11c or CD14, which distinguishes them from conventional dendritic cells or monocytes, respectively. Mouse pDC express CD11c, B220, BST-2/Tetherin (mPDCA) and Siglec-H and are negative for CD11b.
As components of the innate immune system, these cells express intracellular Toll-like receptors 7 and 9 which detect ssRNA and unmethylated CpG DNA sequences, respectively. Upon stimulation and subsequent activation, these cells produce large amounts (up to 1,000 times more than other cell type) of type I interferon (mainly IFN-α (alpha) and IFN-β (beta)), which are critical pleiotropic anti-viral compounds mediating a wide range of effects.
The number of circulating pDCs are found to be decreased during chronic HIV infection as well as HCV infection.
Basophils are a type of white blood cells. Basophils are the least common of the granulocytes, representing about 0.5 to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They can perform phagocytosis (cell eating), produce histamine and serotonin that induce inflammation, and heparin that prevents blood clotting. It used to be thought that basophils that have migrated from blood into their resident tissues (connective tissue) are known as mast cells, but this is no longer thought to be the case.
Basophils were discovered in 1879 by German physician Paul Ehrlich, who one year earlier had found a cell type present in tissues that he termed "mastzellen" (now mast cells). Ehrlich received the 1908 Nobel Prize in Physiology or Medicine for his discoveries.
The name comes from the fact that these leukocytes are basophilic, i.e., they are susceptible to staining by basic dyes, as shown in the picture.
Langhans cells are often found in transbronchial lung biopsies or lymph node biopsies in patients suffering from sarcoidosis.
The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.
Memory T cells are a subset of infection- and cancer-fighting T cells (also known as a T lymphocyte) that have previously encountered and responded to their cognate antigen; thus, the term antigen-experienced T cell is often applied. Such T cells can recognize foreign invaders, such as bacteria or viruses, as well as cancer cells. Memory T cells have become "experienced" by having encountered antigen during a prior infection, encounter with cancer, or previous vaccination. At a second encounter with the invader, memory T cells can reproduce to mount a faster and stronger immune response than the first time in the immune system responded to the pathogen which is entered into the body. This behaviour is utilized in T lymphocyte proliferation assays, which can reveal exposure to specific antigens.
Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age. Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation.
Primary causes
- Conditions with normally functioning neutrophils – hereditary neutrophilia, chronic idiopathic neutrophilia
- Pelger–Huet anomaly
- Down syndrome
- Leukocyte adhesion deficiency
- Familial cold urticaria
- Leukemia (chronic myelogenous (CML)) and other myeloproliferative disorders
- Surgical removal of spleen
Secondary causes
- Infection
- Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease, Crohn's disease, ulcerative colitis, granulomatous infections (for example, tuberculosis), and chronic hepatitis
- Cigarette smoking – occurs in 25–50% of chronic smokers and can last up to 5 years after quitting
- Stress – exercise, surgery, general stress
- Medication induced – corticosteroids (for example, prednisone, β-agonists, lithium)
- Cancer – either by growth factors secreted by the tumor or invasion of bone marrow by the cancer
- Increased destruction of cells in peripheral circulation can stimulate bone marrow. This can occur in hemolytic anemia and idiopathic thrombocytopenic purpura
Eosinophils compose about 2-4% of the WBC total. This count fluctuates throughout the day, seasonally, and during menstruation. It rises in response to allergies, parasitic infections, collagen diseases, and disease of the spleen and central nervous system. They are rare in the blood, but numerous in the mucous membranes of the respiratory, digestive, and lower urinary tracts.
They primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections. They secrete chemicals that destroy these large parasites, such as hook worms and tapeworms, that are too big for any one WBC to phagocytize. In general, their nucleus is bi-lobed. The lobes are connected by a thin strand. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin staining.
The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. Lymphocytes can be identified by their large nucleus.
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.
The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.
T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.
A second regimen under evaluation is R-EPOCH (rituximab with etoposide-prednisone-vincristine-doxorubicin-cyclophosphamide), which demonstrated a 5-year progression-free survival (PFS) of 79% in a phase II trial. A phase III trial, CALGB 50303, is now comparing R-EPOCH with R-CHOP in patients with newly diagnosed DLBCL.
One area of active research is on separating patients into groups based on their prognosis and how likely they are to benefit from different drugs. Methods like gene expression profiling and next-generation sequencing may result in more effective and more personalized treatment.
The germinal center subtype has the best prognosis,with 66.6% of treated patients surviving more than five years. The IPI score is used in prognosis in clinical practice. Lenalidomide has been recently shown to improve outcomes in the non-germinal center subtype. Ratios of immune effectors such as CD4 and CD8 to immune checkpoints such as PD-L1 and M2 macrophages are independent of and additive to the cell of origin and IPI in DLBCL, and are applicable to paraffin-embedded biopsy specimens. These findings might have potential implications for selection of patients for checkpoint blockade and/or lenalidomide within clinical trials.
For children with diffuse large B-cell lymphomas, most studies have found 5-year survival rates ranging from about 70% to more than 90%.
One study has suggested improved overall survival in response to chemotherapy for African Americans.
Basophils contain large cytoplasmic granules which obscure the cell nucleus under the microscope when stained. However, when unstained, the nucleus is visible and it usually has two . The mast cell, another granulocyte, is similar in appearance and function. Both cell types store histamine, a chemical that is secreted by the cells when stimulated. However, they arise from different branches of hematopoiesis, and mast cells usually do not circulate in the blood stream, but instead are located in connective tissue. Like all circulating granulocytes, basophils can be recruited out of the blood into a tissue when needed.
The lymphoma is more common in the young and in males.
A 2008 study found an increased risk of ALCL of the breast in women with silicone breast implants (protheses), although the overall risk remained exceedingly low due to the rare occurrence of the tumor.
Histologic transformation to diffuse large B-cell lymphoma (DLBCL) can occur in up to 12% of cases. After transformation, neoplastic cells carry monoclonal immunoglobulin gene rearrangements. Histological transformation may lead to poor prognosis and therefore repeat biopsy is required at relapse.
One study found a transformation rate of 7.6%, and suggested that prior exposure to chemotherapy and a presentation with splenic involvement were associated with increased risks of transformation.
Breast implant-associated ALCL is a recently recognized lymphoma and definitive management and therapy is under evaluation. However, it appears that removal of the implant, and resection of the capsule around the implant as well as evaluation by medical and surgical oncologists are cornerstones. Still under evaluation is the extent of capsulectomy: partial versus complete capsulectomy; similarly it is not defined the significance of replacement of the implant in the affected breast, or the removal of contralateral implant. Similarly, the value of radiation therapy and chemotherapy are under evaluation.
Currently, there is a drug, LDK378, undergoing Phase III clinical trials at Vanderbilt University that targets ALK positive small cell lung cancer, and has showed clinical promise in its previous clinical trials. Because approximately 70% of ALCL neoplasms are also ALK positive, there is hope that similar highly selective and potent ALK inhibitors may be used in the future to treat ALK positive cases of ALCL.
After leaving the bone marrow, the B cell acts as an antigen presenting cell (APC) and internalizes offending antigens, which are taken up by the B cell through receptor-mediated endocytosis and processed. Pieces of the antigen (which are now known as "antigenic peptides") are loaded onto MHC II molecules, and presented on its extracellular surface to CD4+ T cells (sometimes called "T helper cells"). These T cells bind to the MHC II-antigen molecule and cause activation of the B cell. This is a type of safeguard to the system, almost like a two-factor authentication method. First, the B cells have to encounter a foreign antigen, and are then required to be activated by T helper cells before they differentiate to specific cells.
Upon stimulation by a T cell, which usually occurs in germinal centers of secondary lymphoid organs like the spleen and lymph nodes, the activated B cell begins to differentiate into more specialized cells. Germinal center B cells may differentiate into memory B cells or plasma cells. Most of these B cells will become plasmablasts (or "immature plasma cells"), and eventually plasma cells, and begin producing large volumes of antibodies. Some B cells will undergo a process known as affinity maturation. This process favors, by selection for the ability to bind antigen with higher affinity, the activation and growth of B cell clones able to secrete antibodies of higher affinity for the antigen.
Of all cancers involving the same class of blood cell (lymphoproliferative disorders), 22% of cases are follicular lymphomas.
Chemotherapy with CHOP, infusional EPOCH, hyperCVAD, and CODOX-M/IVAC is often used. The prognosis is generally poor, for example 6 to 7 months and 14 months.