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Lymphocyte

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Lymphocyte
Scanning electron micrographof a human T cell
Details
SystemImmune system
FunctionWhite blood cell
Identifiers
MeSHD008214
THH2.00.04.1.02002
FMA84065 62863, 84065
Anatomical terms of microanatomy

Alymphocyteis a type ofwhite blood cell(leukocyte) in theimmune systemofmost vertebrates.[1]Lymphocytes includeT cells(for cell-mediated and cytotoxicadaptive immunity),B cells(forhumoral,antibody-drivenadaptive immunity),[2][3]andinnate lymphoid cells(ILCs; "innate T cell-like" cells involved in mucosal immunity and homeostasis), of whichnatural killer cellsare an important subtype (which functions incell-mediated,cytotoxicinnate immunity). They are the main type of cell found inlymph,which prompted the name "lymphocyte" (withcytemeaning cell).[4]Lymphocytes make up between 18% and 42% of circulating white blood cells.[2]

Types

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A stained lymphocyte surrounded byred blood cellsviewed using alight microscope
4D live imaging of T cell nuclear dynamics viewed usingholotomographymicroscopy

The three major types of lymphocyte areT cells,B cellsandnatural killer(NK) cells.[2]

They can also be classified as small lymphocytes and large lymphocytes based on their size and appearance.[5][6]

Lymphocytes can be identified by their large nucleus.

T cells and B cells

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Main articles:T cellandB cell

T cells (thymuscells) and B cells (bone marrow- orbursa-derived cells[a]) are the major cellular components of the adaptive immune response. T cells are involved incell-mediated immunity,whereas B cells are primarily responsible forhumoral immunity(relating toantibodies). The function of T cells and B cells is to recognize specific "non-self" antigens, during a process known asantigen presentation.Once they have identified an invader, the cells generate specific responses that are tailored maximally to eliminate specificpathogensor pathogen-infected cells. B cells respond to pathogens by producing large quantities ofantibodieswhich then neutralize foreign objects likebacteriaandviruses.In response to pathogens some T cells, calledT helper cells,producecytokinesthat direct the immune response, while other T cells, calledcytotoxic T cells,produce toxicgranulesthat contain powerfulenzymeswhich induce the death of pathogen-infected cells. Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form ofmemory cells.Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and are able to mount a strong and rapid response if the same pathogen is detected again; this is known as acquiredimmunity.

Natural killer cells

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Main article:Natural killer cell

NK cells are a part of theinnate immune systemand play a major role in defending the host fromtumorsandvirallyinfected cells.[2]NK cells modulate the functions of other cells, includingmacrophagesand T cells,[2]and distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule calledmajor histocompatibility complex(MHC)class I.NK cells are activated in response to a family ofcytokinescalledinterferons.Activated NK cells releasecytotoxic(cell-killing)granuleswhich then destroy the altered cells.[1]They are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I.

Dual expresser lymphocyte – X cell

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The X lymphocyte is a reported cell type expressing both aB-cell receptorandT-cell receptorand is hypothesized to be implicated in type 1 diabetes.[8][9]Its existence as a cell type has been challenged by two studies.[10][11]However, the authors of original article pointed to the fact that the two studies have detected X cells by imaging microscopy and FACS as described.[12]Additional studies are required to determine the nature and properties of X cells (also called dual expressers).

Development

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Development of blood cells

Mammalianstem cellsdifferentiateinto several kinds of blood cell within thebone marrow.[13]This process is calledhaematopoiesis.[14]All lymphocytes originate, during this process, from a common lymphoid progenitor before differentiating into their distinct lymphocyte types. The differentiation of lymphocytes follows various pathways in a hierarchical fashion as well as in a more plastic fashion. The formation of lymphocytes is known aslymphopoiesis.Inmammals,B cellsmaturein thebone marrow,which is at the core of mostbones.[15]Inbirds,B cells mature in thebursa of Fabricius,a lymphoid organ where they were first discovered by Chang and Glick,[15](B for bursa) and not from bone marrow as commonly believed. T cells migrate to the blood stream and mature in a distinct primary organ, called thethymus.Following maturation, the lymphocytes enter the circulation and peripherallymphoid organs(e.g. thespleenandlymph nodes) where they survey for invadingpathogensand/or tumor cells.

The lymphocytes involved in adaptive immunity (i.e. B and T cells) differentiate further after exposure to anantigen;they form effector and memory lymphocytes. Effector lymphocytes function to eliminate the antigen, either by releasing antibodies (in the case of B cells), cytotoxic granules (cytotoxic T cells) or by signaling to other cells of the immune system (helper T cells).Memory T cellsremain in the peripheral tissues and circulation for an extended time ready to respond to the same antigen upon future exposure; they live weeks to several years, which is very long compared to other leukocytes.[citation needed]

Characteristics

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A scanning electron microscope image of normal circulating human blood showingred blood cells,several types ofwhite blood cellsincluding lymphocytes, amonocyte,aneutrophiland many small disc-shapedplatelets

Microscopically, in aWright's stainedperipheral blood smear,a normal lymphocyte has a large, dark-stainingnucleuswith little to noeosinophiliccytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is approximately the size of ared blood cell(about 7μmin diameter).[13]Some lymphocytes show a clearperinuclear zone(or halo) around the nucleus or could exhibit a small clear zone to one side of the nucleus.Polyribosomesare a prominent feature in the lymphocytes and can be viewed with anelectron microscope.Theribosomesare involved inprotein synthesis,allowing the generation of large quantities ofcytokinesandimmunoglobulinsby these cells.

It is impossible to distinguish between T cells and B cells in a peripheral blood smear.[13]Normally,flow cytometrytesting is used for specific lymphocyte population counts. This can be used to determine the percentage of lymphocytes that contain a particular combination of specific cell surface proteins, such asimmunoglobulinsorcluster of differentiation(CD) markers or that produce particular proteins (for example,cytokinesusing intracellular cytokine staining (ICCS)). In order to study the function of a lymphocyte by virtue of the proteins it generates, other scientific techniques like theELISPOTorsecretion assaytechniques can be used.[1]

Typical recognition markers for lymphocytes[16]
Class Function Proportion (median, 95% CI) Phenotypic marker(s)
Natural killer cells Lysis of virally infected cells and tumour cells 7% (2–13%) CD16CD56but notCD3
T helper cells Release cytokines and growth factors that regulate other immune cells 46% (28–59%) TCRαβ,CD3andCD4
Cytotoxic T cells Lysis of virally infected cells, tumour cells and allografts 19% (13–32%) TCRαβ,CD3andCD8
Gamma delta T cells Immunoregulation and cytotoxicity 5% (2–8%) TCRγδ andCD3
B cells Secretion of antibodies 23% (18–47%) MHC class II,CD19andCD20

In thecirculatory system,they move fromlymph nodeto lymph node.[3][17]This contrasts withmacrophages,which are rather stationary in the nodes.

Lymphocytes and disease

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Several lymphocytes seen collected around a tuberculousgranuloma

A lymphocyte count is usually part of a peripheralcomplete blood cell countand is expressed as the percentage of lymphocytes to the total number of white blood cells counted.

A general increase in the number of lymphocytes is known aslymphocytosis,[18]whereas a decrease is known aslymphocytopenia.

High

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An increase in lymphocyte concentration is usually a sign of aviral infection(in some rare case,leukemiasare found through an abnormally raised lymphocyte count in an otherwise normal person).[18][19]A high lymphocyte count with a lowneutrophilcount might be caused bylymphoma.Pertussis toxin(PTx) ofBordetella pertussis,formerly known as lymphocytosis-promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000 perμlin adults or over 8000 per μl in children. This is unique in that many bacterial infections illustrate neutrophil-predominance instead.

Lymphoproliferative disorders

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Lymphoproliferative disorders(LPD) encompass a diverse group of diseases marked by uncontrolled lymphocyte production, leading to issues like lymphocytosis, lymphadenopathy, and bone marrow infiltration. These disorders are common in immunocompromised individuals and involve abnormal proliferation of T and B cells, often resulting in immunodeficiency and immune system dysfunction. Various gene mutations, both iatrogenic and acquired, are implicated in LPD. One subtype, X-linked LPD, is linked to mutations in the X chromosome, predisposing individuals to natural killer cell LPD and T-cell LPD. Additionally, conditions like common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), and certain viral infections elevate the risk of LPD. Treatment methods, such as immunosuppressive drugs and tissue transplantation, can also increase susceptibility. LPDs encompass a wide array of disorders involving B-cell (e.g., chronic lymphocytic leukemia) and T-cell (e.g., Sezary syndrome) abnormalities, each presenting distinct challenges in diagnosis and management.[20]

Low

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A low normal to low absolute lymphocyte concentration is associated withincreased rates of infection after surgery or trauma.[21]

One basis for low T cell lymphocytes occurs when thehuman immunodeficiency virus(HIV) infects and destroys T cells (specifically, theCD4+subgroup of T lymphocytes, which become helper T cells).[22]Without the key defense that these T cells provide, the body becomes susceptible toopportunistic infectionsthat otherwise would not affect healthy people. The extent of HIV progression is typically determined by measuring the percentage of CD4+T cells in the patient's blood – HIV ultimately progresses toacquired immune deficiency syndrome(AIDS). The effects of othervirusesor lymphocyte disorders can also often be estimated by counting the numbers of lymphocytes present in theblood.

Tumor-infiltrating lymphocytes

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Main article:Tumor-infiltrating lymphocyte

In some cancers, such asmelanomaandcolorectal cancer,lymphocytes can migrate into and attack thetumor.This can sometimes lead to regression of the primary tumor.

Lymphocyte-variant hypereosinophilia

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Main article:Lymphocyte-variant hypereosinophilia

Blood content

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Reference ranges for blood testsof white blood cells, comparing lymphocyte amount (shown in light blue) with other cells

History

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Main article:Lymphocyte T-cell immunomodulator § History

See also

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Notes

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  1. ^The process of B-cell maturation was elucidated in birds and the B most likely means "bursa-derived" referring to thebursa of Fabricius.[7]However, in humans (who do not have that organ), the bone marrow makes B cells, and the B can serve as a reminder ofbone marrow.

References

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  1. ^abcJaneway C,Travers P, Walport M, Shlomchik M (2001).Immunobiology(5th ed.). New York and London: Garland Science.ISBN0-8153-4101-6.
  2. ^abcdeOmman, Reeba A.; Kini, Ameet R. (2020). "Leukocyte development, kinetics, and functions". In Keohane, Elaine M.; Otto, Catherine N.; Walenga, Jeanine N. (eds.).Rodak's Hematology: Clinical Principles and Applications(6th ed.). St. Louis, Missouri: Elsevier. pp. 117–135.ISBN978-0-323-53045-3.
  3. ^abCohn, Lauren; Hawrylowicz, Catherine; Ray, Anuradha (2014)."Biology of Lymphocytes".Middleton's Allergy: Principles and Practice(8th ed.). Philadelphia: Saunders. pp. 203–214.doi:10.1016/B978-0-323-08593-9.00013-9.ISBN9780323085939.Retrieved22 July2020.
  4. ^"NCI Dictionary of Cancer Terms".National Cancer Institute.Retrieved22 July2020.A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. A lymphocyte is a type of white blood cell.
  5. ^van der Meer, Wim; van Gelder, Warry; de Keijzer, Ries; Willems, Hans (July 2007)."The divergent morphological classification of variant lymphocytes in blood smears".Journal of Clinical Pathology.60(7): 838–839.doi:10.1136/jcp.2005.033787.ISSN0021-9746.PMC1995771.PMID17596551.
  6. ^"Lymphocyte - an overview | ScienceDirect Topics".sciencedirect.Retrieved29 May2024.
  7. ^"B Cell".Merriam-Webster Dictionary.Encyclopaedia Britannica.Retrieved28 October2011.
  8. ^Ahmed, Rizwan; Omidian, Zahra; Giwa, Adebola; Cornwell, Benjamin; Majety, Neha; Bell, David R.; Lee, Sangyun; Zhang, Hao; Michels, Aaron; Desiderio, Stephen; Sadegh-Nasseri, Scheherazade (30 May 2019)."A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen".Cell.177(6): 1583–1599.e16.doi:10.1016/j.cell.2019.05.007.ISSN0092-8674.PMC7962621.PMID31150624.
  9. ^"Newly Discovered Immune Cell Linked to Type 1 Diabetes".Johns Hopkins Medicine Newsroom.30 May 2019.Retrieved9 August2020.
  10. ^Japp, Alberto (4 February 2021)."TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes".Cell.184(3): 827–839.doi:10.1016/j.cell.2020.11.035.PMC8016147.PMID33545036.S2CID231809927.
  11. ^Burel, Julie (13 May 2020)."The Challenge of Distinguishing Cell–Cell Complexes from Singlet Cells in Non-Imaging Flow Cytometry and Single-Cell Sorting".Cytometry Part A.97(11): 1127–1135.doi:10.1002/cyto.a.24027.PMC7666012.PMID32400942.
  12. ^Ahmed, Rizwan; Omidian, Zahra; Giwa, Adebola; Donner, Thomas; Jie, Chunfa; Hamad, Abdel Rahim A. (4 February 2021)."A reply to" TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes "".Cell.184(3): 840–843.doi:10.1016/j.cell.2020.11.036.ISSN1097-4172.PMC7935028.PMID33545037.
  13. ^abcAbbas AK, Lichtman AH (2003).Cellular and Molecular Immunology(5th ed.). Saunders, Philadelphia.ISBN0-7216-0008-5.
  14. ^Monga I, Kaur K, Dhanda S (March 2022). "Revisiting hematopoiesis: applications of the bulk and single-cell transcriptomics dissecting transcriptional heterogeneity in hematopoietic stem cells".Briefings in Functional Genomics.21(3): 159–176.doi:10.1093/bfgp/elac002.PMID35265979.
  15. ^abCooper MD(March 2015)."The early history of B cells".Nature Reviews. Immunology.15(3): 191–197.doi:10.1038/nri3801.PMID25656707.
  16. ^Berrington JE, Barge D, Fenton AC, Cant AJ, Spickett GP (May 2005)."Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry".Clinical and Experimental Immunology.140(2): 289–92.doi:10.1111/j.1365-2249.2005.02767.x.PMC1809375.PMID15807853.
  17. ^Al-Shura, Anika Niambi (2020). "Lymphocytes".Advanced Hematology in Integrated Cardiovascular Chinese Medicine.Elsevier. pp. 41–46.doi:10.1016/b978-0-12-817572-9.00007-0.ISBN978-0-12-817572-9.S2CID241913878.
  18. ^ab"Lymphocytosis: Symptoms, Causes, Treatments".Cleveland Clinic.Retrieved22 July2020.
  19. ^Guilbert, Theresa W.; Gern, James E.; Lemanske, Robert F. (2010). "Infections and Asthma".Pediatric Allergy: Principles and Practice.Elsevier. pp. 363–376.doi:10.1016/b978-1-4377-0271-2.00035-3.ISBN978-1-4377-0271-2.S2CID78707217.Lymphocytes are recruited into the upper and lower airways during the early stages of a viral respiratory infection, and it is presumed that these cells help to limit the extent of infection and to clear virus-infected epithelial cells.
  20. ^Justiz Vaillant, Angel A.; Stang, Christopher M. (2023),"Lymphoproliferative Disorders",StatPearls,Treasure Island (FL): StatPearls Publishing,PMID30725847,retrieved7 October2023
  21. ^Clumeck, Nathan; de Wit, Stéphane (2010)."Prevention of opportunistic infections".Infectious Diseases.pp. 958–963.doi:10.1016/B978-0-323-04579-7.00090-3.ISBN9780323045797.S2CID78729807.Retrieved5 January2021.
  22. ^Wahed, Amer; Quesada, Andres; Dasgupta, Amitava (2020). "Benign white blood cell and platelet disorders".Hematology and Coagulation.Elsevier. pp. 77–87.doi:10.1016/b978-0-12-814964-5.00005-x.ISBN978-0-12-814964-5.S2CID241056897.Lymphocytopenia may also be acquired, for example, in patients with HIV infection.
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