Abstract
This chapter describes white blood cells of the peripheral blood: neutrophils, eosinophils, basophils, monocytes, and lymphocyte subsets. It describes their basic physiology and important disease states associated with defects of each of these entities. Each of these cells arises from a common bone marrow myeloid or lymphoid progenitor to differentiate into their unique types.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Brinkmann V, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.
Papayannopoulos V, et al. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010;191(3):677–91.
Eash KJ, et al. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest. 2010;120(7):2423–31.
Martin C, et al. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity. 2003;19(4):583–93.
Kohler A, et al. G-CSF-mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands. Blood. 2011;117(16):4349–57.
Williams MR, et al. Emerging mechanisms of neutrophil recruitment across endothelium. Trends Immunol. 2011;32(10):461–9.
Phillipson M, Kubes P. The neutrophil in vascular inflammation. Nat Med. 2011;17(11):1381–90.
Ley K, et al. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7(9):678–89.
Jones DH, et al. Quantitation of intracellular Mac-1 (CD11b/CD18) pools in human neutrophils. J Leukoc Biol. 1988;44(6):535–44.
Marchesi VT, Florey HW. Electron micrographic observations on the emigration of leucocytes. Q J Exp Physiol Cogn Med Sci. 1960;45:343–8.
Proebstl D, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med. 2012;209(6):1219–34.
Stark K, et al. Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and ‘instruct’ them with pattern-recognition and motility programs. Nat Immunol. 2013;14(1):41–51.
Kawasaki H, Iwamuro S. Potential roles of histones in host defense as antimicrobial agents. Infect Disord Drug Targets. 2008;8(3):195–205.
Li P, et al. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207(9):1853–62.
Wang Y, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 2009;184(2):205–13.
Yipp BG, Kubes P. NETosis: how vital is it? Blood. 2013;122(16):2784–94.
Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med. 2017;23(3):279–87.
Delgado-Rizo V, et al. Neutrophil extracellular traps and its implications in inflammation: an overview. Front Immunol. 2017;8:81.
Clark SR, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463–9.
Pilsczek FH, et al. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol. 2010;185(12):7413–25.
Yousefi S, et al. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ. 2009;16(11):1438–44.
Pillay J, et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood. 2010;116(4):625–7.
Shi J, et al. Role of the liver in regulating numbers of circulating neutrophils. Blood. 2001;98(4):1226–30.
Furze RC, Rankin SM. The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse. FASEB J. 2008;22(9):3111–9.
Horwitz M, et al. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999;23(4):433–6.
Bellanne-Chantelot C, et al. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood. 2004;103(11):4119–25.
Wetzler M, et al. A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia. Am J Med. 1990;89(5):663–72.
Djaldetti M, Joshua H, Kalderon M. Familial leukopenia-neutropenia in Yemenite Jews. Observations on eleven families. Bull Res Counc Isr Sect E Exp Med. 1961;9E:24–8.
Shaper AG, Lewis P. Genetic neutropenia in people of African origin. Lancet. 1971;2(7732):1021–3.
Reich D, et al. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet. 2009;5(1):e1000360.
Tesfa D, Keisu M, Palmblad J. Idiosyncratic drug-induced agranulocytosis: possible mechanisms and management. Am J Hematol. 2009;84(7):428–34.
Meliconi R, et al. The role of interleukin-8 and other cytokines in the pathogenesis of Felty’s syndrome. Clin Exp Rheumatol. 1995;13(3):285–91.
Liu JH, et al. Chronic neutropenia mediated by fas ligand. Blood. 2000;95(10):3219–22.
Tabor B, et al. Dialysis neutropenia: the role of the cytoskeleton. Kidney Int. 1998;53(3):783–9.
Schwartz J, Weiss ST. Cigarette smoking and peripheral blood leukocyte differentials. Ann Epidemiol. 1994;4(3):236–42.
Parry H, et al. Smoking, alcohol consumption, and leukocyte counts. Am J Clin Pathol. 1997;107(1):64–7.
Seebach JD, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997;107(5):582–91.
Cain DW, et al. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS One. 2011;6(5):e19957.
McCarthy DA, et al. Leukocytosis induced by exercise. Br Med J (Clin Res Ed). 1987;295(6599):636.
Barbosa MD, et al. Identification of the homologous beige and Chediak-Higashi syndrome genes. Nature. 1996;382(6588):262–5.
Durchfort N, et al. The enlarged lysosomes in beige j cells result from decreased lysosome fission and not increased lysosome fusion. Traffic. 2012;13(1):108–19.
Marlin SD, et al. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986;164(3):855–67.
Winkelstein JA, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155–69.
van den Berg JM, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234.
Petersen LC, Bjorn SE, Nordfang O. Effect of leukocyte proteinases on tissue factor pathway inhibitor. Thromb Haemost. 1992;67(5):537–41.
Noubouossie DF, et al. In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps. Blood. 2017;129(8):1021–9.
von Bruhl ML, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–35.
Fuchs TA, Brill A, Wagner DD. Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2012;32(8):1777–83.
Mantovani A, et al. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11(8):519–31.
Scapini P, Bazzoni F, Cassatella MA. Regulation of B-cell-activating factor (BAFF)/B lymphocyte stimulator (BLyS) expression in human neutrophils. Immunol Lett. 2008;116(1):1–6.
Keshari RS, et al. Cytokines induced neutrophil extracellular traps formation: implication for the inflammatory disease condition. PLoS One. 2012;7(10):e48111.
Villanueva E, et al. Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J Immunol. 2011;187(1):538–52.
Soderberg D, et al. Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission. Rheumatology (Oxford). 2015;54(11):2085–94.
Wong SL, et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med. 2015;21(7):815–9.
Schauer C, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014;20(5):511–7.
Antonio N, et al. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. EMBO J. 2015;34(17):2219–36.
Houghton AM, et al. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med. 2010;16(2):219–23.
Deryugina EI, et al. Tissue-infiltrating neutrophils constitute the major in vivo source of angiogenesis-inducing MMP-9 in the tumor microenvironment. Neoplasia. 2014;16(10):771–88.
Blaisdell A, et al. Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells. Cancer Cell. 2015;28(6):785–99.
Zhang DE, et al. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci U S A. 1997;94(2):569–74.
Ackerman SJ. To be, or not to be, an eosinophil: that is the ??? Blood. 2013;122(5):621–3.
Du J, et al. Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein. J Biol Chem. 2002;277(45):43481–94.
Hirasawa R, et al. Essential and instructive roles of GATA factors in eosinophil development. J Exp Med. 2002;195(11):1379–86.
Paul CC, et al. Cooperative effects of interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor: a new myeloid cell line inducible to eosinophils. Blood. 1993;81(5):1193–9.
Collins PD, et al. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med. 1995;182(4):1169–74.
Steinbach KH, et al. Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood. Blut. 1979;39(1):27–38.
Liao W, et al. The eosinophil in health and disease: from bench to bedside and back. Clin Rev Allergy Immunol. 2016;50(2):125–39.
Gleich GJ, Adolphson CR. The eosinophilic leukocyte: structure and function. Adv Immunol. 1986;39:177–253.
Ueki S, et al. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood. 2013;121(11):2074–83.
Farhan RK, et al. Effective antigen presentation to helper T cells by human eosinophils. Immunology. 2016;149(4):413–22.
Duez C, et al. Migration and accumulation of eosinophils toward regional lymph nodes after airway allergen challenge. J Allergy Clin Immunol. 2004;114(4):820–5.
MacKenzie JR, et al. Eosinophils promote allergic disease of the lung by regulating CD4(+) Th2 lymphocyte function. J Immunol. 2001;167(6):3146–55.
Robertson SA, et al. Uterine eosinophils and reproductive performance in interleukin 5-deficient mice. J Reprod Fertil. 2000;120(2):423–32.
Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9–22.
Gotlib J. World Health Organization-defined eosinophilic disorders: 2014 update on diagnosis, risk stratification, and management. Am J Hematol. 2014;89(3):325–37.
Simon HU, et al. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immunol. 2010;126(1):45–9.
Cogan E, Roufosse F. Clinical management of the hypereosinophilic syndromes. Expert Rev Hematol. 2012;5(3):275–89; quiz 290.
Bochner BS, Gleich GJ. What targeting eosinophils has taught us about their role in diseases. J Allergy Clin Immunol. 2010;126(1):16–25; quiz 26–7.
Vivier E, et al. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10.
Moffett A, Colucci F. Uterine NK cells: active regulators at the maternal-fetal interface. J Clin Invest. 2014;124(5):1872–9.
Miller JS, Alley KA, McGlave P. Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitor. Blood. 1994;83(9):2594–601.
Spits H, Lanier LL, Phillips JH. Development of human T and natural killer cells. Blood. 1995;85(10):2654–70.
Poli A, et al. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009;126(4):458–65.
Lieberman J. The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal. Nat Rev Immunol. 2003;3(5):361–70.
Biron CA, et al. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol. 1999;17:189–220.
Martin-Fontecha A, et al. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol. 2004;5(12):1260–5.
Zamai L, et al. Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med. 1998;188(12):2375–80.
Long EO. Regulation of immune responses through inhibitory receptors. Annu Rev Immunol. 1999;17:875–904.
Borrego F, et al. Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol Immunol. 2002;38(9):637–60.
Weis WI, Taylor ME, Drickamer K. The C-type lectin superfamily in the immune system. Immunol Rev. 1998;163:19–34.
Moretta A, et al. Natural killer lymphocytes: “null cells” no more. Ital J Anat Embryol. 2001;106(4):335–42.
Ruggeri L, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110(1):433–40.
De Oliveira LG, et al. Role of interleukin 8 in uterine natural killer cell regulation of extravillous trophoblast cell invasion. Placenta. 2010;31(7):595–601.
Biron CA, Byron KS, Sullivan JL. Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med. 1989;320(26):1731–5.
Mace EM, et al. Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56(bright) subset. Blood. 2013;121(14):2669–77.
Gineau L, et al. Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. J Clin Invest. 2012;122(3):821–32.
Lima M, et al. Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56−/+dim chronic natural killer cell large granular lymphocytosis. Am J Pathol. 2004;165(4):1117–27.
Tse E, Liang RH. Natural killer cell neoplasms. Clin Lymphoma. 2004;5(3):197–201.
Tefferi A, et al. Chronic natural killer cell lymphocytosis: a descriptive clinical study. Blood. 1994;84(8):2721–5.
Hoganson DD, Weenig RH, Warrington KJ. A 61-year-old man with livedo reticularis. Arthritis Rheum. 2008;59(11):1682–4.
Imai K, et al. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356(9244):1795–9.
Sullivan KE, et al. Defective natural killer cell function in patients with hemophagocytic lymphohistiocytosis and in first degree relatives. Pediatr Res. 1998;44(4):465–8.
Fogel LA, Yokoyama WM, French AR. Natural killer cells in human autoimmune disorders. Arthritis Res Ther. 2013;15(4):216.
Nagasawa T. CXCL12/SDF-1 and CXCR4. Front Immunol. 2015;6:301.
Pieper K, Grimbacher B, Eibel H. B-cell biology and development. J Allergy Clin Immunol. 2013;131(4):959–71.
Milne CD, Paige CJ. IL-7: a key regulator of B lymphopoiesis. Semin Immunol. 2006;18(1):20–30.
Middendorp S, et al. Function of Bruton’s tyrosine kinase during B cell development is partially independent of its catalytic activity. J Immunol. 2003;171(11):5988–96.
Melchers F, et al. The surrogate light chain in B-cell development. Immunol Today. 1993;14(2):60–8.
Rolli V, et al. Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol Cell. 2002;10(5):1057–69.
Monroe JG, et al. Positive and negative selection during B lymphocyte development. Immunol Res. 2003;27(2–3):427–42.
Pereira JP, Xu Y, Cyster JG. A role for S1P and S1P1 in immature-B cell egress from mouse bone marrow. PLoS One. 2010;5(2):e9277.
Pereira JP, et al. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nat Immunol. 2009;10(4):403–11.
Cerutti A, Cols M, Puga I. Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol. 2013;13(2):118–32.
Pillai S, Cariappa A. The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol. 2009;9(11):767–77.
Nutt SL, et al. The generation of antibody-secreting plasma cells. Nat Rev Immunol. 2015;15(3):160–71.
Parker DC. T cell-dependent B cell activation. Annu Rev Immunol. 1993;11:331–60.
Bruton OC. Agammaglobulinemia. Pediatrics. 1952;9(6):722–8.
Yel L. Selective IgA deficiency. J Clin Immunol. 2010;30(1):10–6.
Scollay R, et al. The role of the thymic cortex and medulla in T cell differentiation. Adv Exp Med Biol. 1985;186:229–34.
Klein L, et al. Positive and negative selection of the T cell repertoire: what thymocytes see (and don’t see). Nat Rev Immunol. 2014;14(6):377–91.
Ding L, Shevach EM. Activation of CD4+ T cells by delivery of the B7 costimulatory signal on bystander antigen-presenting cells (trans-costimulation). Eur J Immunol. 1994;24(4):859–66.
Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591–619.
Halle S, Halle O, Forster R. Mechanisms and dynamics of T cell-mediated cytotoxicity in vivo. Trends Immunol. 2017;38(6):432–43.
Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014;14(6):392–404.
Ziegler SF. Division of labour by CD4(+) T helper cells. Nat Rev Immunol. 2016;16(7):403.
Leavy O. Regulatory T cells: developing diversity. Nat Rev Immunol. 2016;16(1):2–3.
Fischer A. Severe combined immunodeficiencies. Immunodefic Rev. 1992;3(2):83–100.
Couedel C, et al. Analysis of mutations from SCID and Omenn syndrome patients reveals the central role of the Rag2 PHD domain in regulating V(D)J recombination. J Clin Invest. 2010;120(4):1337–44.
Okoye AA, Picker LJ. CD4(+) T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol Rev. 2013;254(1):54–64.
Ochs HD, Oukka M, Torgerson TR. TH17 cells and regulatory T cells in primary immunodeficiency diseases. J Allergy Clin Immunol. 2009;123(5):977–83; quiz 984–5.
Costantino CM, Baecher-Allan C, Hafler DA. Multiple sclerosis and regulatory T cells. J Clin Immunol. 2008;28(6):697–706.
Grinberg-Bleyer Y, et al. Could we cure type 1 diabetes by stimulating T(reg)? Med Sci (Paris). 2011;27(5):471–2.
Richetta AG, et al. CD4+ CD25+ T-regulatory cells in psoriasis. Correlation between their numbers and biologics-induced clinical improvement. Eur J Dermatol. 2011;21(3):344–8.
Bao W, et al. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood. 2010;116(22):4639–45.
Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol. 2005;6(4):353–60.
Curiel TJ. Tregs and rethinking cancer immunotherapy. J Clin Invest. 2007;117(5):1167–74.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Gollamudi, J., Huang, A.Y., Stavrou, E.X. (2019). Physiological Roles of Leukocytes and Disorders. In: Lazarus, H., Schmaier, A. (eds) Concise Guide to Hematology. Springer, Cham. https://doi.org/10.1007/978-3-319-97873-4_19
Download citation
DOI: https://doi.org/10.1007/978-3-319-97873-4_19
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-97872-7
Online ISBN: 978-3-319-97873-4
eBook Packages: MedicineMedicine (R0)