Leukocytes (White Blood Cells): Types, Functions, Normal Range and Disorders

Introduction to Leukocytes

Leukocytes, also known as white blood cells, are a cellular component of the blood that has a nucleus, absence of hemoglobin, and is capable of motility.

They are part of the immune system and help defend the body against infection and diseases.

• Destroying cancer cells and infectious agents.
• Ingesting foreign materials and cellular debris.
• Producing antibodies.

Leukocytes are produced by bone marrow and found in blood and lymph tissue, spleen, liver, and kidney, which help in regulation of leukocyte production levels.

The normal value of white blood cells ranges from 4000-11000 per microliter.

General Characteristics of Leukocytes

• Belong to at least five different categories and are distinguishable by size, nuclear shape, and cytoplasmic inclusion.
• Different types are involved in different functions.
  • Some recognize intruders.
  • Some kill harmful bacteria.
  • Some synthesize antibodies to protect body against microorganisms including bacteria, viruses, and fungi.

Classification of Leukocytes

In practice, leukocytes are divided into two main groups:

• 1. Granulocytes - those with prominent stainable cytoplasmic granules.

• 2. Agranulocytes - those without prominent stainable cytoplasmic granules and are mononuclear leukocytes.

• Granulocytes include: neutrophils, eosinophils, and basophils.

• Agranulocytes include: monocytes and lymphocytes.

About Granulocytes

• Granulocytes are immune cells that contain granules with enzymes released during allergic reaction, infection, disease, and asthma.
• All granulocytes possess irregular or multilobed nuclei.
• Belong to myeloid lineage of blood cells.

Granulocytes

Neutrophils

Neutrophils are first line of defense in the immune system.

Morphology and Anatomy of Neutrophils

• Generally spherical when at rest, but shape can change to fight infection.
• Size is 12-14 µm diameter.
• Also referred to as polymorphonuclear leukocytes because of irregular segmented multilobed nuclei.
• In females, 3% of nuclei show drum-stick formation, which represents sex chromatin of inactive X chromosomes.
• Clear in color, when react with dye they change color and are visible under microscope.
• Cytoplasm is fine, neutrophilic granules are present, and in Leishman staining, violet color of granules is seen.

Location and Lifespan

• Produced by hematopoiesis in bone marrow.
• Released into peripheral blood and circulate for 7-10 hours before migrating into tissue.
• Lifespan in tissue is only a few days.

Prevalence and Normal Range

• Most common type of white blood cell.
• Consists of 40-75% of all white blood cells in adult body.
• Neutrophil count is part of complete blood count.
• Normal range is 2500-7500 per µl of blood.

Defense Mechanism of Neutrophils

During inflammatory secretion, various substances are generated which serve as chemotactic factors that promote accumulation of neutrophils at inflammatory site.

• Play important role in defense against microorganisms.
• Can phagocytose microbes and small particles in circulation, and after extravasation carry out similar activities in other tissues.
• Actively phagocytic neutrophils can reduce oxygen enzymatically to form reactive oxygen species, including superoxide radicals and hydrogen peroxide, which enhance bacterial destruction.
• After phagocytosis they die. Dead neutrophils, bacteria, tissue debris, and interstitial fluid form characteristic green yellow pus of infected tissue.

Conditions Affecting Neutrophils

• Neutropenia - condition where neutrophil count is too lower than normal, causing repeated infection and swelling.
  • Causes include cancer treatment, infection like hepatitis, tuberculosis, sepsis, Lyme disease, bone marrow disorder, vitamin deficiency, and autoimmune disease.
• Neutrophilia - condition where neutrophil count is higher than normal, also called neutrophilic leukocytosis.
  • Causes include bacterial infection, inflammation, injury, reaction of certain drugs, and immature neutrophils leaving bone marrow too soon.

Functions of Neutrophils

• Migrate to site of infection where they kill or destroy microorganisms by phagocytosis and releasing enzymes.
• Boost immune response of the body.

Eosinophils

Eosinophils are granulocytes that fight against disease and boost inflammation at infection site.

Morphology and Anatomy of Eosinophils

• Smaller in size, 5-15 µm and motile.
• Present in small numbers in normal blood, ranges 100 to 400 per µl.
• Nucleus has two prominent lobes and appears U-shaped or spectacle-shaped in blood smear.
• Cytoplasm consists of coarse acidophilic granules.

Location and Lifespan

• Produced in bone marrow and then travel to different tissue.
• Generally found in connective tissue of stomach and intestine.
• Total lifespan is a few days, of which 10 hours is spent in circulation and remainder in extracellular tissues.

Prevalence and Normal Range

• Consist of 1-4% of all white blood cells.
• Eosinophil count is part of complete blood count.
• Normal range is 100 to 400 per µl of blood.

Defense Mechanism of Eosinophils

• Level rises in worm infection and certain allergic disorders.
• Thought to have evolved as primary defense by destroying parasitic and cancer cell.
• Contain surface receptor for IgE that binds to IgE-antigen complexes, triggering phagocytosis and release of granule contents.
• Release toxic molecules from granules:
  • Eosinophil cationic protein and major basic proteins which are antiparasitic.
  • Histaminase, which limits inflammatory consequences of mast cell degranulation.

Conditions Affecting Eosinophils

• Eosinopenia - eosinophil count lower than normal range.
  • Common causes are Cushing’s syndrome and sepsis.
• Eosinophilia - eosinophil count higher than normal range.
  • Causes include alcohol intoxication, allergies, gastrointestinal disorder, leukemia, overproduction of cortisol, and parasitic infection.

Functions of Eosinophils

• Killing cells and movement to inflamed areas.
• Trapping substances.
• Anti-bacterial and antiparasitic activity.
• Involvement in immediate allergic reaction.
• Modulating inflammatory reaction.

Basophils

Basophils defend body against pathogens including bacterial, fungal, viral infection, allergens, and parasites.

They release enzymes to prevent blood clots and improve blood flow.

Morphology and Anatomy of Basophils

• Spherical with 10-14 µm in diameter.
• Distinguishing features are large, conspicuous basophilic granules and kidney-shaped nucleus.

Location

• Develop in bone marrow.
• After maturation, flow through bloodstream and migrate to damaged tissue to heal area after injury.

Prevalence and Normal Range

• Form only 0.5 to 1% of total leukocytes.
• Normal range is 25-200 per µl.

Defense Mechanism of Basophils

• Basophilic granules contain heparin, histamine, and several other inflammatory agents.
• Have high-affinity membrane receptors for IgE and are coated with IgE antibodies.
• If receptor binds to its antigen, it triggers degranulation, producing:
  • Vasodilation.
  • Increased vascular permeability.
  • Chemotactic stimuli for other granulocytes.
  • Symptoms of immediate hypersensitivity, for example in allergic rhinitis.
• Histamine improves blood flow by enlarging blood vessels and healing affected area.
• Heparin prevents blood from clotting quickly.

Conditions Affecting Basophils

• Basopenia - body does not synthesize enough basophils.
  • May be seen in hyperthyroidism.
• Basophilia - body produces too many basophils.
  • Conditions include leukemia, polycythemia vera, myelofibrosis, hypothyroidism, and autoimmune disease.

Functions of Basophils

• Protect body from external pathogens, parasites, and allergens.
• Granules contain enzyme that is released and improves blood flow and prevents blood clotting.

Agranulocyte Leukocytes

Monocytes

Monocytes are largest type of white blood cells that reside in blood and tissue to find and destroy microorganisms and eliminate infected cells.

Morphology and Anatomy of Monocytes

• Size is near twice size of red blood cells, 15-20 µm in diameter.
• Form only small proportion, 2-8% with cell count of 100-700 per µl.
• Under microscope, have bilobed nuclei that float in cytoplasm.
• Nucleus changes shape as cell migrates throughout body.
• Shape of nucleus is oval, kidney, or horse-shaped.
• Granules are absent in cytoplasm.

Location

• Develop in bone marrow and travel to tissue.
• Protect body from infection alongside other cells in immune system.

Prevalence and Normal Range

• Largest type of white blood cell but small proportion.
• Consists of 2-8% of all white blood cells in adult body.
• Monocyte count is part of complete blood count.
• Normal range is 100-700 per µl of blood.

Defense Mechanism of Monocytes

• Actively phagocytic cells and contain numerous lysosomes.
• Phagocytosis is triggered by recognization of opsonized materials.
• Express class II MHC antigen.
• Most monocytes transit via bloodstream from bone marrow to peripheral tissues, where they give rise to macrophage and dendritic cells.
• Different monocyte subsets may target inflamed tissue.
• Dendritic cells recognize antigen of invading germ, then release proteins called cytokines that inform other white blood cells to come to site of infection.
• Macrophages ingest microorganisms and kill it with toxic enzymes within cell, which also helps remove dead cells from tissue.

Conditions Affecting Monocytes

• Monocytopenia - monocyte count too low, occurs as result of decreases in leukocytes.
  • Common causes: aplastic anemia, blood infection, burn injuries, HIV, and reaction to chemotherapy.
• Monocytosis - monocyte count too high.
  • Common causes: autoimmune disease like lupus and rheumatoid arthritis, blood disorders, cancer, cardiovascular disease, infection, and inflammatory disease.

Functions of Monocytes

• Defend body by either killing infectious agents or alerting other blood cells to help destroy them.
• Boost immune response.

Lymphocytes

Lymphocytes are second most numerous type of white blood cell in adulthood and play mandatory role in defense against disease and infection.

• Two types present: T lymphocytes and B lymphocytes.

Morphology and Anatomy of Lymphocytes

• Larger than red blood cells.
• Size varies 6-16 µm, most circulating lymphocytes are 6-8 µm in diameter.
• Have large nucleus almost covering whole cytoplasm.
• Granules are absent in cytoplasm.

Location

• Form in bone marrow.
• After maturation, reach bloodstream and are found in blood and all parts of lymphatic system.
• Some lymphocytes travel to thymus gland which becomes T cell.
• Others travel to lymph nodes and organs which become B cells.

Prevalence and Normal Range

• Normal range is 1500 to 2700 per µl of blood.
• Consists of 20-30% of total population of white blood cells.
• Lifespan ranges from few days to many years.
• Long-lived lymphocytes are necessary for maintenance of immunological memory.

Defense Mechanism of Lymphocytes

Lymphocytes help immune system fight against infection, disease, and cancer. Lymphocytes remember every antigen they come in contact with.

• If same antigen comes again, memory cells recognize it and quickly react.

• Due to this reason, we do not get infection like chickenpox or measles after one-time exposure.

• Vaccination can protect or prevent certain diseases.

• T Cell functions:

  • Different types of T cell help kill infected cell and regulate immune response.
  • Cytotoxic T cell attaches to antigen on infected cell then kills infected cell by making pore in membrane and enzymes are inserted.
  • Helper T cell helps B cell for production of antibodies.

• B Cell functions:

  • Antigen receptors surface present in B cell where antigen attaches.
  • B cells recognize antigen and produce specific antibodies against each one.
  • B cells produce two types of immune response: primary response and secondary response.
  • When antigen attaches to receptor, B cells are stimulated. Some turn into memory cells and some are plasma cells.
  • Plasma cells produce antibodies specific to particular antigen, then primary response is produced.
  • When B cell encounters same antigen again, memory B cell remembers it and multiplies. They turn into plasma cell and immediately produce correct antibody.

Conditions Affecting Lymphocytes

• Lymphocytopenia - low level of lymphocytes.
  • Causes: flu, mild infection, viral infection, tuberculosis, autoimmune disease, blood diseases, radiation and chemotherapy treatment.
• Lymphocytosis - high level of lymphocytes.
  • Causes: viral infection, syphilis, mononucleosis, tuberculosis, hypothyroidism, blood cancer, etc.

Functions of Lymphocytes

• T cell attacks and kills infected cell and tumor cell and also regulates body’s immune system.
• B cells synthesize antibodies against virus, bacteria, and other foreign antigens.

Physiological Variation of Leukocytes

• Age: In infants, more than 20,000 WBC per microliter is present. In children, level ranges from 10,000 to 15,000 per microliter (original text mentions 10,000 to 10,000).
• Sex: Male has greater WBC count than female.
• Emotional stress: Emotional stress increases leukocyte count.
• After exercise: Leukocyte count increases after exercise.
• Sleep: Leukocyte count decreases during sleep.
• Pregnancy: During pregnancy, leukocyte count increases.

Summary

Leukocytes or white blood cells are nucleated, hemoglobin-free motile cells produced in bone marrow and found in blood, lymphoid tissue, spleen, liver and kidney, with normal range 4000-11000 per microliter. They are classified into granulocytes with prominent granules and agranulocytes without prominent granules. Granulocytes include neutrophils 40-75% which are 12-14 µm polymorphonuclear cells showing drum-stick in females, circulating 7-10 hours and forming green-yellow pus, eosinophils 1-4% which are 5-15 µm bilobed cells with acidophilic granules in stomach and intestine releasing cationic protein and histaminase against parasites, and basophils 0.5-1% which are 10-14 µm cells with kidney-shaped nucleus releasing heparin and histamine via IgE mediated degranulation. Agranulocytes include monocytes 2-8% which are largest 15-20 µm cells giving rise to macrophages and dendritic cells presenting antigen via MHC II, and lymphocytes 20-30% which are 6-16 µm cells comprising T cells and B cells providing cell-mediated and humoral immunity with long-lived memory. Disorders include neutropenia, neutrophilia, eosinopenia, eosinophilia, basopenia, basophilia, monocytopenia, monocytosis, lymphocytopenia and lymphocytosis. Physiological variations occur with age, sex, stress, exercise, sleep and pregnancy.

References

1. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 10th Edition. Elsevier. Chapter 2, Cells and Tissues of Immune System.
2. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. 6th Edition. Garland Science. Chapter 24, Innate Immunity.
3. Lodish H, Berk A, Kaiser CA, Krieger M, Bretscher A, Ploegh H, Amon A. Molecular Cell Biology. 8th Edition. W.H. Freeman. Chapter 24, Immunology.
4. Campbell NA, Urry LA, Cain ML, Wasserman SA, Minorsky PV, Reece JB. Biology. 12th Edition. Pearson. Chapter 43, Immune System.
5. Tortora GJ, Derrickson B. Principles of Anatomy and Physiology. 15th Edition. Wiley. Chapter 19, Blood.
6. Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J. Hematology: Basic Principles and Practice. 7th Edition. Elsevier. Chapter 30, Morphology of White Blood Cells.
7. Bain BJ. Blood Cells: A Practical Guide. 5th Edition. Wiley Blackwell. Chapter 2, White Blood Cells.
8. NCERT. Biology Textbook for Class XI. Reprint 2023-24. National Council of Educational Research and Training. Chapter 18, Body Fluids and Circulation.
9. Guyton AC, Hall JE. Textbook of Medical Physiology. 14th Edition. Elsevier. Chapter 34, White Blood Cells and Inflammation.
10. Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 10th Edition. Elsevier. Chapter 3, Leukocytes in Inflammation.
11. Parham P. The Immune System. 5th Edition. Garland Science. Chapter 2, Innate Immunity.
12. Kindt TJ, Goldsby RA, Osborne BA. Kuby Immunology. 7th Edition. W.H. Freeman. Chapter 2, Cells of Immune System.
13. Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology. 9th Edition. Garland Science. Chapter 2, Innate Immunity and Leukocytes.
14. Borregaard N. Neutrophils, from Marrow to Microbes. Immunity. 2010. Volume 33.
15. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: Changing Perspectives in Health and Disease. Nature Reviews Immunology. 2013. Volume 13.