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White blood cells, or leukocytes, are immune cells that protect the body against infectious disease and foreign invaders. Produced from hematopoietic stem cells in the bone marrow, they circulate in the blood and lymphatic system. Leukocytes include three main types: granulocytes, lymphocytes, and monocytes. They have nuclei, unlike red blood cells. White blood cell counts, measured in a complete blood count, help indicate health status; too many cells, or leukocytosis, can signal infection or disease, while too few, called leukopenia, suggests weakened immunity. These cells are vital for immunity and overall health.

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Etymology

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 roots leuk- meaning "white" and cyt- meaning "cell". The 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.

Types

Overview

All white blood cells are nucleated, which distinguishes them from the anucleated red blood cells and platelets. Types of leukocytes can be classified in standard ways. Two pairs of broadest categories classify them either by structure (granulocytes or agranulocytes) or by cell lineage (myeloid cells or lymphoid cells). These broadest categories can be further divided into the five main types: neutrophils, eosinophils, basophils, lymphocytes, and monocytes.8 A good way to remember the relative proportions of WBCs is "Never Let Monkeys Eat Bananas".9 These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic. Further subtypes can be classified.

Granulocytes are distinguished from agranulocytes by their nucleus shape (lobed versus round, that is, polymorphonuclear versus mononuclear) and by their cytoplasm granules (present or absent, or more precisely, visible on light microscopy or not thus visible). The other dichotomy is by lineage: Myeloid cells (neutrophils, monocytes, eosinophils and basophils) are distinguished from lymphoid cells (lymphocytes) by hematopoietic lineage (cellular differentiation lineage).10 Lymphocytes can be further classified as T cells, B cells, and natural killer cells.

TypeAppearanceApprox. % in adults See also:Blood valuesDiameter (μm)11Main targets12Nucleus13Granules14Lifetime15
(micrograph)(illustration)
Neutrophil62%12–15MultilobedFine, faintly pink (H&E stain)6 hours – few days(days in spleen and other tissue)
Eosinophil2.3%12–15 (slightly bigger than neutrophils)Bi-lobedFull of pink-orange (H&E stain)8–12 days (circulate for 4–5 hours)
Basophil0.4%12–15 (slightly smaller than neutrophils)Bi-lobed or tri-lobedLarge blueA few hours to a few days
Lymphocyte 30%Small lymphocytes 7–8Large lymphocytes 12–15Deeply staining, eccentricNK-cells and cytotoxic (CD8+) T-cellsYears for memory cells, weeks for all else.
Monocyte5.3%15–3016Monocytes migrate from the bloodstream to other tissues and differentiate into tissue resident macrophages, Kupffer cells in the liver.Kidney shapedNoneHours to days

Neutrophil

Main article: Neutrophil

Neutrophils are the most abundant white blood cell, constituting 60–70% of the circulating leukocytes.17 They defend against bacterial or fungal infection. They are usually first responders to microbial infection; their activity and death in large numbers form 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, which consists of three to five lobes connected by slender strands.18 This gives the neutrophils the appearance of having multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules that are pale lilac when stained. 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.19 Neutrophils are the most common cell type seen in the early stages of acute inflammation. The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours.2021

Eosinophil

Main article: Eosinophil

Eosinophils compose about 2–4% of white blood cells in circulating blood. 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.22

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 parasitic infections. They secrete chemicals that destroy large parasites, such as hookworms and tapeworms, that are too big for any one white blood cell to phagocytize. In general, their nuclei are bi-lobed. The lobes are connected by a thin strand.23 The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin staining.

Basophil

Main article: Basophil

Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing the dilation of blood vessels. Because they are the rarest of the white blood cells (less than 0.5% of the total count) and share physicochemical properties with other blood cells, they are difficult to study.24 They can be recognized by several coarse, dark violet granules, giving them a blue hue. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it.

They secrete two chemicals that aid in the body's defenses: histamine and heparin. Histamine is responsible for widening blood vessels and increasing the flow of blood to injured tissue. It also makes blood vessels more permeable so neutrophils and clotting proteins can get into connective tissue more easily. Heparin is an anticoagulant that inhibits blood clotting and promotes the movement of white blood cells into an area. Basophils can also release chemical signals that attract eosinophils and neutrophils to an infection site.25

Lymphocyte

Main article: Lymphocyte

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:

Monocyte

Main article: Monocyte

Monocytes, the largest type of white blood cell, 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 attack 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 not granulated. They also possess abundant cytoplasm.

Fixed leucocytes

Some leucocytes 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.

Disorders

The two commonly used categories of white blood cell disorders divide them quantitatively into those causing excessive numbers (proliferative disorders) and those causing insufficient numbers (leukopenias).26 Leukocytosis is usually healthy (e.g., fighting an infection), but it also may be dysfunctionally proliferative. Proliferative disorders of white blood cells can be classed as myeloproliferative and lymphoproliferative. Some are autoimmune, but many are neoplastic.

Another way to categorize disorders of white blood cells is qualitatively. There are various disorders in which the number of white blood cells is normal but the cells do not function normally.27

Neoplasia of white blood cells can be benign but is often malignant. Of the various tumors of the blood and lymph, cancers of white blood cells can be broadly classified as leukemias and lymphomas, although those categories overlap and are often grouped together.

Leukopenias

Main article: Leukopenia

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.28

Neutropenia

Main article: Neutropenia

Neutropenia can be acquired or intrinsic.29 A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood.30

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.31 One severe consequence of neutropenia is that it can increase the risk of infection.32

Lymphocytopenia

Main article: Lymphocytopenia

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.33 This is not a complete list.

Like neutropenia, symptoms and treatment of lymphocytopenia are directed at the underlying cause of the change in cell counts.

Proliferative disorders

Main article: Leukocytosis

An increase in the number of white blood cells in circulation is called leukocytosis.34 This increase is most commonly caused by inflammation.35 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.36 Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis.

Neutrophilia

Main article: Neutrophilia

Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age.37 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.38

Primary causes39

Secondary causes41

Eosinophilia

Main article: Eosinophilia

A normal eosinophil count is considered to be less than 0.65×109/L.42 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.43 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.44

Counting and reference ranges

Main article: White blood cell differential

The complete blood cell count is a blood panel that includes the overall white blood cell count and differential count, a count of each type of white blood cell. Reference ranges for blood tests specify the typical counts in healthy people.

The normal total leucocyte count in an adult is 4000 to 11,000 per mm3 of blood.

Differential leucocyte count: number/ (%) of different types of leucocytes per cubic mm. of blood. Below are reference ranges for various types leucocytes.45

See also

Wikimedia Commons has media related to Leukocytes.

References

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  11. Daniels VG, Wheater PR, Burkitt HG (1979). Functional histology: A text and colour atlas. Edinburgh: Churchill Livingstone. ISBN 0-443-01657-7. 0-443-01657-7 ↩

  12. Alberts B, Johnson A, Lewis M, Raff M, Roberts K, Walter P (2002). "Leukocyte also known as macrophagesfunctions and percentage breakdown". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9. 0-8153-4072-9 ↩

  13. Alberts B, Johnson A, Lewis M, Raff M, Roberts K, Walter P (2002). "Leukocyte also known as macrophagesfunctions and percentage breakdown". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9. 0-8153-4072-9 ↩

  14. Alberts B, Johnson A, Lewis M, Raff M, Roberts K, Walter P (2002). "Leukocyte also known as macrophagesfunctions and percentage breakdown". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9. 0-8153-4072-9 ↩

  15. Daniels VG, Wheater PR, Burkitt HG (1979). Functional histology: A text and colour atlas. Edinburgh: Churchill Livingstone. ISBN 0-443-01657-7. 0-443-01657-7 ↩

  16. Handin RI, Lux SE, Stossel TP (2003). Blood: Principles and Practice of Hematology (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 471. ISBN 9780781719933. Retrieved 18 June 2013. 9780781719933 ↩

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  45. Specific references are found in article Reference ranges for blood tests#White blood cells 2. /wiki/Reference_ranges_for_blood_tests#White_blood_cells_2 ↩