What Is White Blood Cells /White blood cells, or leukocytes (Greek; leucko=white and cyte = cell), are part of the immune system participating in both the innate and humoral immune responses. They circulate in the blood and mount inflammatory and cellular responses to injury or pathogens. White blood cells are part of the body’s immune system. They help the body fight infection and other diseases. Types of white blood cells are granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes (T cells and B cells). Checking the number of white blood cells in the blood is usually part of a complete blood cell (CBC) test. It may be used to look for conditions such as infection, inflammation, allergies, and leukemia. Also called leukocyte and WBC.
White blood cells (WBC) are a heterogeneous group of nucleated cells that can be found in circulation for at least a period of their life. Their normal concentration in the blood varies between 4000 and 10,000 per microliter. They play a most important role in phagocytosis and immunity and therefore in defense against infection.
Complete blood count
|Blood component||Abbreviation used||Reference range||SI Reference range|
|White blood cells||WBC||4500-11,000/mm3||4.5-11.0 x 109/L|
|Red blood cells*||RBC||Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million/mm3
|Male: 4.3-5.9 x 1012/L
Female: 3.5-5.5 x 1012/L
|Hemoglobin*||HGB||Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
|Male: 2.09-2.71 mmol/L
Female: 1.86-2.48 mmol/L
|Mean corpuscular volume||MCV||80-100 µm3||80-100 fl|
|Mean corpuscular hemoglobin||MCH||25.4-34.6 pg/cell||0.39-0.54 fmol/cell|
|Mean corpuscular hemoglobin concentration||MCHC||31%-36% Hb/cell||4.81-5.58 mmol Hb/L|
|Platelets||Platelets||150,000-400,000/mm3||150-400 x 109/L|
According to an article in American Family Physician, the normal range (per cubic millimeter) of white blood cells based on age are:
The normal range for pregnant women in the 3rd trimester is 5,800–13,200 per cubic millimeter.
According to the University of Rochester Medical Center (UMRC), these are the normal ranges of WBCs per microliter of blood (MCL):
|Age range||WBC count (per mcL of blood)|
|newborns||9,000 to 30,000|
|children under 2||6,200 to 17,000|
|children over 2 and adults||5,000 to 10,000|
These normal ranges can vary by lab. Another common measurement for the volume of blood is cubic millimeter or mm3. A microliter and cubic millimeter equal the same amount. The types of cells that make up WBCs usually fall within a normal percentage of your overall WBC count.
The normal percentages of the types of WBCs in your overall count are usually in these ranges, according to the Leukemia & Lymphoma Society (LLS):
|Type of WBC||Normal percentage of overall WBC count|
|neutrophil||55 to 73 percent|
|lymphocyte||20 to 40 percent|
|eosinophil||1 to 4 percent|
|monocyte||2 to 8 percent|
|basophil||0.5 to 1 percent|
Higher or lower numbers of WBCs than normal can be a sign of an underlying condition.
Over All Types And Functions
Neutrophils are the commonest type of white blood cell found in a blood smear. They make up 60-70% of the total amount of white blood cells.
Neutrophils (also known as enterocytes or heterophils) are the most abundant type of granulocytes and makeup 40% to 70% of all white blood cells in humans.[rx] They form an essential part of the innate immune system, with their functions varying in different animals.[rx]
They are formed from stem cells in the bone marrow and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.[rx][rx][rx]
Neutrophils have 3 types of granules
- azure granules (lysosomes),
- secretory granules in salmon pink cytoplasm, anti-microbial enzymes.
- have glycoproteins and gelatinase.
- Neutrophils are born in the bone marrow. They circulate in the blood for 6-10 hours and then enter the tissues. They are motile, and phagocytic and will destroy damaged tissue and bacteria. They self-destruct after one burst of activity. They are important in inflammatory reactions.
- These cells are 12 – 17 µm in diameter – larger than neutrophils, and about 3 times the size of a red blood cell. You can see that eosinophils only have two lobes to their nucleus.
- Neutrophils undergo a process called chemotaxis via amoeboid movement, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon-gamma (IFN-γ), C3a, C5a, and Leukotriene B4, which these cells use to direct the path of their migration.
- These cells have large acidophilic specific granules – this stain bright red, or reddish-purple. These granules contain proteins that are ‘destructive’ and toxic. Anti-microbial function highly motile, neutrophils quickly congregate at a focus of infection, attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Neutrophils express[rx] and release cytokines, which in turn amplify inflammatory reactions by several other cell types.
- Neutrophils are phagocytes, capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in opsonins—a process known as antibody opsonization. They can internalize and kill many microbes, each phagocytic event resulting in the formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the “respiratory burst”, although unrelated to respiration or energy production.
Eosinophils are fairly rarely found in blood smears – making up 1-6% of the total white blood cells. Eosinophils, sometimes called eosinophils or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates.[rx] Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.[rx] They form about 2 to 3% of WBCs.
- These cells are born in the bone marrow, and migrate from the peripheral blood system after a few hours, into loose connective tissue in the respiratory and gastrointestinal tracts. They phagocytose antigen-antibody complexes. They also produce histaminase, and aryl sulphatase B, two enzymes that inactivate two inflammatory agents released by mast cells. A high eosinophil blood count may indicate an allergic reaction.
- Eosinophils are also important in killing parasitic worms. They are 14-16 µm in diameter, contain lots of deep blue staining granules (basic) and a bilobed nucleus. The granules contain heparin, histamine, and serotonin. prostaglandins and leukotrienes.
Following activation, eosinophils effector functions include production of the following:
- Cationic granule proteins and their release by degranulation[rx][rx][rx]
- Reactive oxygen species such as hypobromite, superoxide, and peroxide (hypobromous acid, which is preferentially produced by eosinophil peroxidase)[rx]
- Lipid mediators like the eicosanoids from the leukotriene (e.g., LTC4, LTD4, LTE4) and prostaglandin (e.g., PGE2) families[rx]
- Enzymes, such as elastase
- Growth factors such as TGF beta, VEGF, and PDGF[rx][rx]
- Cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, and TNF alpha[rx][rx]
There are also eosinophils that play a role in fighting viral infections, which is evident from the abundance of RNases they contain within their granules, and in fibrin removal during inflammation. Eosinophils, along with basophils and mast cells, are important mediators of allergic responses and asthma pathogenesis and are associated with disease severity. They also fight helminth (worm) colonization and may be slightly elevated in the presence of certain parasites. Eosinophils are also involved in many other biological processes, including postpubertal mammary gland development, oestrus cycling, allograft rejection, and neoplasia.[rx] They have also been implicated in antigen presentation to T cells.[rx]
Eosinophils are responsible for tissue damage and inflammation in many diseases, including asthma.[rx][rx] High levels of interleukin-5 has been observed to up-regulate the expression of adhesion molecules, which then facilitate the adhesion of eosinophils to endothelial cells, thereby causing inflammation and tissue damage.[rx]
An accumulation of eosinophils in the nasal mucosa is considered a major diagnostic criterion for allergic rhinitis (nasal allergies).
Basophils are the rarest type of white blood cell, making up only 1% of the white blood cells found in a blood smear. Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells.[rx] However, they are the largest type of granulocyte. They are responsible for inflammatory reactions during an immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis, and hay fever.[rx] They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, heparin that prevents blood clotting,[rx] although there are less than that found in mast cell granules.[rx] Mast cells were once thought to be basophils that migrated from the blood into their resident tissues (connective tissue), but they are now known to be different types of cells.[rx]
- These cells are involved in immune responses to parasites. They have IgE receptors and the granules are released when the cells bind IgE. These cells also accumulate at sites of infection, and the release of prostaglandins, serotonin, and histamine help to increase blood flow to the area of damage, as part of the inflammatory response. The degranulation-release of histamine also plays a role in allergic reactions such as hay fever.
- Basophils appear in many specific kinds of inflammatory reactions, particularly those that cause allergic symptoms. Basophils contain anticoagulant heparin, which prevents blood from clotting too quickly. They also contain the vasodilator histamine, which promotes blood flow to tissues. They can be found in unusually high numbers at sites of ectoparasite infection, e.g., ticks. Like eosinophils, basophils play a role in both parasitic infections and allergies.[rx] They are found in tissues where allergic reactions are occurring and probably contribute to the severity of these reactions.
- Basophils have protein receptors on their cell surface that bind IgE, an immunoglobulin involved in macroparasite defense and allergy. It is the bound IgE antibody that confers a selective response of these cells to environmental substances, for example, pollen proteins or helminth antigens. Recent studies in mice suggest that basophils may also regulate the behavior of T cells and mediate the magnitude of the secondary immune response.[rx]
This is a photo of a lymphocyte in a blood smear. Most of the lymphocytes are small; a bit bigger than red blood cells, at about 6-9µm in diameter,
The rest (around 10%) are larger, about 10-14µm in diameter. These larger cells have more cytoplasm, more free ribosomes, and mitochondria. Lymphocytes can look like monocytes, except that lymphocytes do not have a kidney-bean-shaped nucleus, and lymphocytes are usually smaller. Larger lymphocytes are commonly activated lymphocytes.
They have a small spherical nucleus and has abundant dark staining condensed chromatin. Not much cytoplasm can be seen, and it is basophilic (pale blue/purple staining).
These are the second most common white blood cell (20-50%), and are easy to find in blood smears. Although the cells look similar there are two main types, B-cells and T-cells. B-cells develop in the bone marrow. T cells are born in the bone marrow but are matured in the Thymus. There will be more on this in the section on the immune system.
Lymphocytes are cells that help to regulate the body’s immune system.
The main types of lymphocytes are:
- B lymphocytes (B cells)
- T lymphocytes (T cells)
B lymphocytes are able to release antibodies which are Y-shaped proteins that bind to infected microbes or cells of the body that have become infected.
Antibodies can either neutralize the target microbe or can mark it out for attack by T lymphocytes.
There are a number of different T lymphocytes:
- Helper T cells release a protein called cytokines which help to further direct the response of other white blood cells.
- Cytotoxic T cells (also known as natural killer T cells) are able to release molecules that kill viruses and other antigens.
- Memory T cells will be present after the body has fought off infection and help the body to deal more easily with any future infection of the same type.
- Regulatory T cells (also known as suppressor T cells) help to regulate other T cells to prevent them from targeting the body’s own cells.
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 the MHC I complex of virus-infected or tumor 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.
T lymphocytes and Type 1 Diabetes
In type 1 diabetes, the killer T cells target and kill the body’s own insulin-producing cells. Even if new insulin-producing islet cells are transplanted, the T cells will still try these cells off.
As a result, people who have had islet cell transplants need to take strong anti-immune drugs to preserve the transplanted cells. Researchers have therefore been investigating ways to regulate the immune response in type 1 diabetes.
Bone marrow transplants have had some success in modulating the immune system, however, bone marrow transplants introduce a risk of complications developing.
- The B-cells develop into plasma cells which make antibodies, The T-cells attack viruses, cancer cells, and transplants.
- This is a photo of monocyte in a blood smear. These are the largest type of white blood cells and can be up to 20µm in diameter. They have a large eccentrically placed nucleus, which is kidney bean-shaped. They have abundant cytoplasm and some fine pink/purple granules in the cytoplasm.
Monocytes are the third most common type of white blood cell; about 2-10% of leukocytes are monocytes.
Monocytes can develop into two types of cell:
- Dendritic cells – are antigen-presenting cells that are able to mark out cells that are antigens (foreign bodies) that need to be destroyed by lymphocytes.
- Macrophages – are phagocyte cells that are larger and live longer than neutrophils. Macrophages are also able to act as antigen-presenting cells.
- Monocytes in the circulation are precursors of tissue macrophages that are actively phagocytic. Monocytes circulate in the blood for 1-3 days and then migrate into body tissues, where they transform into macrophages. They will phagocytose dead cells and bacteria. Some monocytes can also transform into osteoclasts.
- Monocytes and their macrophage and dendritic-cell progeny serve three main functions in the immune system. These are phagocytosis, antigen presentation, and cytokine production. Phagocytosis is the process of uptake of microbes and particles followed by digestion and destruction of this material. Monocytes can perform phagocytosis using intermediary (opsonizing) proteins such as antibodies or complement that coat the pathogen, as well as by binding to the microbe directly via pattern-recognition receptors that recognize pathogens. Monocytes are also capable of killing infected host cells via antibody-dependent cell-mediated cytotoxicity. Vacuolization may be present in a cell that has recently phagocytized foreign matter.
- Many factors produced by other cells can regulate the chemotaxis and other functions of monocytes. These factors include most particularly chemokines such as monocyte chemotactic protein-1 (CCL2) and monocyte chemotactic protein-3 (CCL7); certain arachidonic acid metabolites such as Leukotriene B4 and members of the 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid family of OXE1 receptor agonists (e.g., 5-HETE and 5-oxo-ETE); and N-Formylmethionine leucyl-phenylalanine and other N-formylated oligopeptides which are made by bacteria and activate the formyl peptide receptor 1.[rx]
- Microbial fragments that remain after such digestion can serve as antigens. The fragments can be incorporated into MHC molecules and then trafficked to the cell surface of monocytes (and macrophages and dendritic cells). This process is called antigen presentation and it leads to activation of T lymphocytes, which then mount a specific immune response against the antigen.
- Other microbial products can directly activate monocytes and this leads to the production of pro-inflammatory and, with some delay, of anti-inflammatory cytokines. Typical cytokines produced by monocytes are TNF, IL-1, and IL-12. Monocytic cells may contribute to the severity and disease progression in Covid-19 patients.[rx]