White blood cell
|White blood cell|
White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system that are involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, and several types (including monocytes and neutrophils) are phagocytic. All leukocytes are produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell. They live for about three to four days in the average human body. Leukocytes are found throughout the body, including the blood and lymphatic system.
The number of leukocytes in the blood is often an indicator of disease. In the U.S. there are normally approximately 7000 white blood cells per microliter of blood. They make up approximately 1% of the total blood volume in a healthy adult. An increase in the number of leukocytes over the upper limits is called leukocytosis, and a decrease below the lower limit is called leukopenia. Physical properties of leukocytes (such as volume, conductivity, and granularity) may change. These changes can be due to activation, the presence of immature cells, or the presence of malignant leukocytes in leukemia.
The name "white blood cell" derives from the physical appearance of a blood sample after centrifugation. White cells are found in the buffy coat, a thin, typically white layer of nucleated cells between the sedimented red blood cells and the blood plasma. The scientific term leukocyte directly reflects its description. It is derived from the Greek word leuko- meaning "white" and kytos meaning "hollow vessel", with -cyte translated as "cell" in modern usage. Buffy coat may sometimes be green if there are large amounts of neutrophils in the sample, due to the heme-containing enzyme myeloperoxidase that they produce.
There are several different types of white blood cells. They all have many things in common, but all are distinct in form and function. A major distinguishing feature of some leukocytes is the presence of granules; white blood cells are often characterized as granulocytes or agranulocytes:
- Granulocytes (polymorphonuclear leukocytes): leukocytes characterized by the presence of differently staining granules in their cytoplasm when viewed under light microscopy. These granules (usually lysozymes) are membrane-bound enzymes that act primarily in the digestion of endocytosed particles. There are three types of granulocytes: neutrophils, basophils, and eosinophils, which are named according to their staining properties.
- Agranulocytes (mononuclear leukocytes): leukocytes characterized by the apparent absence of granules in their cytoplasm. Although the name implies a lack of granules these cells do contain non-specific azurophilic granules, which are lysosomes. The cells include lymphocytes, monocytes, and macrophages.
|Type||Microscopic appearance||Diagram||Approx. %
|Diameter (μm)||Main targets||Nucleus||Granules||Lifetime|
|Neutrophil||62%||10–12||Multilobed||Fine, faintly pink (H&E stain)||6 hours–few days
(days in spleen and other tissue)
|Eosinophil||2.3%||10–12||Bi-lobed||Full of pink-orange (H&E stain)||8–12 days (circulate for 4–5 hours)|
|Basophil||0.4%||12–15||Bi-lobed or tri-lobed||Large blue||A few hours to a few days|
|Lymphocyte||30%||Small lymphocytes 7–8 Large lymphocytes 12–15||
||Deeply staining, eccentric||NK-cells and cytotoxic (CD8+) T-cells||Years for memory cells, weeks for all else.|
|Monocyte||5.3%||12–20||Monocytes migrate from the bloodstream to other tissues and differentiate into tissue resident macrophages, Kupffer cells in the liver.||Kidney shaped||None||Hours to days|
Neutrophils defend against bacterial or fungal infection. They are usually first responders to microbial infection; their activity and death in large numbers forms pus. They are commonly referred to as polymorphonuclear (PMN) leukocytes, although, in the technical sense, PMN refers to all granulocytes. They have a multi-lobed nucleus that may appear like multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules that are pale lilac. Neutrophils are active in phagocytosing bacteria and are present in large amount in the pus of wounds. These cells are not able to renew their lysosomes (used in digesting microbes) and die after having phagocytosed a few pathogens. Neutrophils are the most common cell type seen in the early stages of acute inflammation. They make up 60-70% of total leukocyte count in human blood. The life span of a circulating human neutrophil is about 5.4 days.
Eosinophils 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. In general, their nucleus is bi-lobed. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin stain.
Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing vasodilation. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it. They are characterized by their large blue granules.
Lymphocytes are much more common in the lymphatic system than in blood. Lymphocytes are distinguished by having a deeply staining nucleus that may be eccentric in location, and a relatively small amount of cytoplasm. Lymphocytes include:
- B cells make antibodies that can bind to pathogens, block pathogen invasion, activate the complement system, and enhance pathogen destruction.
- T cells:
- CD4+ helper T cells: T cells displaying co-receptor CD4 are known as CD4+ T cells. These cells have T-cell receptors and CD4 molecules that, in combination, bind antigenic peptides presented on major histocompatibility complex (MHC) class II molecules on antigen-presenting cells. Helper T cells make cytokines and perform other functions that help coordinate the immune response. In HIV infection, these T cells are the main index to identify the individual's immune system integrity.
- CD8+ cytotoxic T cells: T cells displaying co-receptor CD8 are known as CD8+ T cells. These cells bind antigens presented on MHC I complex of virus-infected or tumour cells and kill them. Nearly all nucleated cells display MHC I.
- γδ T cells possess an alternative T cell receptor (different from the αβ TCR found on conventional CD4+ and CD8+ T cells). Found in tissue more commonly than in blood, γδ T cells share characteristics of helper T cells, cytotoxic T cells, and natural killer cells.
- Natural killer cells are able to kill cells of the body that do not display MHC class I molecules, or display stress markers such as MHC class I polypeptide-related sequence A (MIC-A). Decreased expression of MHC class I and up-regulation of MIC-A can happen when cells are infected by a virus or become cancerous.
Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an extra role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed. This causes an antibody response to be mounted. Monocytes eventually leave the bloodstream and become tissue macrophages, which remove dead cell debris as well as attacking microorganisms. Neither dead cell debris nor attacking microorganisms can be dealt with effectively by the neutrophils. Unlike neutrophils, monocytes are able to replace their lysosomal contents and are thought to have a much longer active life. They have the kidney shaped nucleus and are typically agranulated. They also possess abundant cytoplasm.
Some leukocytes migrate into the tissues of the body to take up a permanent residence at that location rather than remaining in the blood. Often these cells have specific names depending upon which tissue they settle in, such as fixed macrophages in the liver, which become known as Kupffer cells. These cells still serve a role in the immune system.
- Dendritic cells (Although these will often migrate to local lymph nodes upon ingesting antigens)
- Mast cells
There are two major categories of white blood cell disorders: proliferative and leukopenias. In the proliferative disorders there is an increase in the number of white blood cells. This increase is commonly reactive (ex. due to infection) but may also be cancerous. In leukopenias there is a decrease in the number of white blood cells. Both proliferative disease and leukopenias are quantitative[disambiguation needed] disorders of white blood cells. Qualitative[disambiguation needed] disorders of white blood cells are another category. These are disorders in which the number of white blood cells is normal but the cells do not function normally.
A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen.
Neutropenia can be acquired or intrinsic. A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. The following list of causes is not complete.
- Medications - chemotherapy, sulfas or other antibiotics, phenothiazenes, benzodiazepines, antithyroids, anticonvulsants, quinine, quinidine, indomethacin, procainamide, thiazides
- Toxins - alcohol, benzenes
- Intrinsic disorders - Fanconi's, Kostmann's, cyclic neutropenia, Chediak-Higashi
- Immune dysfunction - disorders of collagen, AIDS, rheumatoid arthritis
- Blood cell dysfunction - megaloblastic anemia, myelodysplasia, marrow failure, marrow replacement, acute leukemia
- Any major infection
- Miscellaneous - starvation, hypersplenism
Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity. Treatment is also aimed at the underlying cause of the neutropenia. One severe consequence of neutropenia is that it can increase the risk of infection.
Defined as total lymphocyte count below 1.0x109/L, the cells most commonly affected are CD4+ T cells. Like neutropenia, lymphocytopenia may be acquired or intrinsic and there are many causes. This is not a complete list.
- Inherited immune deficiency - severe combined immunodeficiency, common variable immune deficiency, ataxia-telangiectasia, Wiskott-Aldrich syndrome, immunodeficiency with short-limbed dwarfism, immunodeficiency with thymoma, purine nucleoside phosphorylase deficiency, genetic polymorphism
- Blood cell dysfunction - aplastic anemia
- Infectious diseases - viral (AIDS, SARS, West Nile encephalitis, hepatitis, herpes, measles, others), bacterial (TB, typhoid, pneumonia, rickettsiosis, ehrlichiosis, sepsis), parasitic (acute phase of malaria)
- Medications - chemotherapy (antilymphocyte globulin therapy, alemtuzumab, glucocorticoids)
- Major surgery
- Miscellaneous - ECMO, kidney or bone marrow transplant, hemodialysis, kidney failure, severe burn, celiac disease, severe acute pancreatitis, sarcoidosis, protein-losing enteropathy, strenuous exercise, carcinoma
- Immune dysfunction - arthritis, systemic lupus erythematosus, Sjogren syndrome, myasthenia gravis, systemic vasculitis, Behcet-like syndrome, dermatomyositis, Wegener granulomatosis
- Nutritional/Dietary - alcohol abuse, zinc deficiency
Like neutropenia, symptoms and treatment of lymphocytopenia are directed at the underlying cause of the change in cell counts.
An increase in the number of white blood cells in circulation is called leukocytosis. This increase is most commonly caused by inflammation. There are four major causes: increase of production in bone marrow, increased release from storage in bone marrow, decreased attachment to veins and arteries, decreased uptake by tissues. Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis.
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.
- 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
- Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease[disambiguation needed], 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
A normal eosinophil count is considered to be less than 0.65×109/L. Eosinophil counts are higher in newborns and vary with age, time (lower in the morning and higher at night), exercise, environment, and exposure to allergens. Eosinophilia is never a normal lab finding. Efforts should always be made to discover the underlying cause, though the cause may not always be found.
- LaFleur-Brooks, M. (2008). Exploring Medical Language: A Student-Directed Approach (7th ed.). St. Louis, Missouri, USA: Mosby Elsevier. p. 398. ISBN 978-0-323-04950-4.
- Maton, D., Hopkins, J., McLaughlin, Ch. W., Johnson, S., Warner, M. Q., LaHart, D., & Wright, J. D., Deep V. Kulkarni (1997). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1.
- "Vital and Health Statistics Series 11, No. 247 (03/2005)" (PDF). Retrieved 2014-02-02.
- Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter (2002). "Leukocyte functions and percentage breakdown". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9.
- Gartner, L. P., & Hiatt, J. L. (2007). Color Textbook of Histology (3rd ed.). Philadelphia, PA: SAUNDERS Elsevier. p. 225. ISBN 978-1-4160-2945-8.
- "White Blood Cells". Wisc-online.com. Retrieved 2013-12-07.
- Daniels, V. G., Wheater, P. R., & Burkitt, H. G. (1979). Functional histology: A text and colour atlas. Edinburgh: Churchill Livingstone. ISBN 0-443-01657-7.
- Handin, Robert I.; Samuel E. Lux, Thomas P. Stossel (2003). Blood: Principles and Practice of Hematology (2nd ed.). Philadelphia: Lippincott Williams and Wilkins. p. 471. ISBN 9780781719933. Retrieved 2013-06-18.
- Wheater, Paul R.; Stevens, Alan (2002). Wheater's basic histopathology: a colour atlas and text. Edinburgh: Churchill Livingstone. ISBN 0-443-07001-6.[dead link]
- Pillay, J.; Den Braber, I.; Vrisekoop, N.; Kwast, L. M.; De Boer, R. J.; Borghans, J. A. M.; Tesselaar, K.; Koenderman, L. (2010). "In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days". Blood 116 (4): 625–7. doi:10.1182/blood-2010-01-259028. PMID 20410504.
- Vinay Kumar et al. (2010). Robbins and Cotran pathologic basis of disease. (8th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 1416031219.
- Kenneth Kaushansky et al., ed. (2010). Williams hematology (8th ed.). New York: McGraw-Hill Medical. ISBN 0071621512.
- Richard A. McPherson, Matthew R. Pincus, Naif Z. Abraham Jr. et al. (ed.). Henry's clinical diagnosis and management by laboratory methods (22nd ed.). Philadelphia, PA: Elsevier/Saunders. ISBN 1437709745.
- Lee Goldman; Andrew I. Schafer (eds.). Goldman's Cecil medicine (24th ed.). Philadelphia: Elsevier/Saunders. ISBN 1437716040.
- Atlas of Hematology
- Leukocytes at the US National Library of Medicine Medical Subject Headings (MeSH)