White Blood Cells

White blood cells are also known as leukocytes, they are the essential soldiers in the body's immune system and its defense mechanisms. These specialized cells play a pivotal role in protecting the body against infections, diseases, and foreign invaders. 

Leukocytes are a type of blood cell that forms an integral part of the body's immune system. They are produced in the bone marrow and circulate throughout the bloodstream, ready to defend the body against pathogens such as bacteria, viruses, fungi, and other harmful substances.

The primary function of white blood cells is to combat infections and maintain the body's overall health. They achieve this by identifying and neutralizing foreign invaders, producing antibodies, engulfing and destroying pathogens through phagocytosis, and coordinating immune responses to eliminate threats.

This article discusses the definition, function, laboratory testing, interpretation of test results, related biomarkers, and natural methods to support and optimize white blood cell levels and function.

Definition and Function of White Blood Cells

What are White Blood Cells, or Leukocytes?

White blood cells, or leukocytes, are essential immune cells produced in the bone marrow and present in both blood and lymph tissue. They play a crucial role in protecting the body against infections, diseases, and foreign invaders by mounting inflammatory and cellular responses to injury or pathogens. 

There are several types of white blood cells, including granulocytes (neutrophils, eosinophils, and basophils), and the agranulocytic monocytes and lymphocytes (T cells and B cells), each with distinct functions in immune defense.

Structure

White blood cells can be classified into two main groups: granulocytes and agranulocytes. 

Granulocytes, including neutrophils, eosinophils, and basophils, possess distinctive microscopic granules in their cytoplasm and specific morphological features. 

Agranulocytes, comprising monocytes and lymphocytes, lack granules but contain azurophilic granules. Each type of white blood cell exhibits unique characteristics and functions tailored to its role in immune defense.

Myeloid and Lymphoid Cells

White blood cells can further be categorized into myeloid and lymphoid cells, each encompassing specific subsets with distinct functions within the immune system

Myeloid cells, including neutrophils, basophils, eosinophils, and monocytes, play critical roles in innate immunity and phagocytosis. 

Lymphoid cells are predominantly lymphocytes; lymphocytes are integral to adaptive immunity, orchestrating antigen recognition and immune response regulation. These diverse cell populations collectively contribute to the body's defense against pathogens and maintenance of immune homeostasis.

Function of Leukocytes: What Do Leukocytes Do in the Body?

Diapedesis (Extravasation or Leukocyte Adhesion Cascade)

A hallmark of leukocyte function is white blood cell migration to sites of injury or infection is orchestrated by molecular patterns present on microbes and damaged tissues. 

This process, known as diapedesis, involves the release of cytokines by local inflammatory cells, leading to leukocyte adhesion, rolling, arrest, and eventual migration from inside capillaries out into affected tissues. 

Once at the site of infection, white blood cells recognize and eliminate pathogens through phagocytosis, releasing various substances to combat infections and modulate inflammatory responses.

Functions of Various White Blood Cells

All white blood cells contribute to immune system function, albeit with specific roles and functions unique to each cell type. 

Neutrophils  [8., 14.]

Neutrophils, the most abundant white blood cells, serve as the body's initial defense against bacterial infections.  Their quick response and ability to navigate to infection sites are facilitated by chemical signals in the body. 

Once at the site of infection, neutrophils exert their function by phagocytosis, or engulfing pathogens and destroying them via degranulation, or the release of reactive oxygen species. This process is essential for the resolution of infection and for preventing its spread. 

Neutrophils can also deploy a defensive mechanism known as neutrophil extracellular traps (NETs), where they release nuclear material to ensnare and neutralize pathogens, thereby contributing to host defense against infections.

Additionally, neutrophils play a role in wound healing and tissue repair, clearing away debris and dead cells.

Basophils  [16.]

Basophils are primarily involved in the inflammatory response and allergic reactions. They release histamine, heparin, and other chemical mediators in response to allergens or pathogens, contributing to the dilation of blood vessels, increased vascular permeability, and recruitment of other immune cells to the site of inflammation. 

Eosinophils  [16.] 

Eosinophils participate in immune responses against parasitic infections, allergic reactions, and asthma by releasing toxic proteins and enzymes that help destroy invading pathogens and modulate inflammation. Additionally, they contribute to tissue repair and regeneration after injury.

Monocytes  [16.] 

Monocytes differentiate into macrophages and dendritic cells in the tissue space; these cells are essential for engulfing and digesting pathogens, presenting antigens to other immune cells, and orchestrating immune responses. 

Lymphocytes  [16., 17.]

Lymphocytes, a crucial component of the adaptive immune system, are responsible for recognizing and responding to antigens, contributing to long-term immunity.

There are three main types of lymphocytes, each with a specific function in the immune response: B cells, T cells, and natural killer (NK) cells. 

B cells are responsible for producing antibodies, which are proteins that specifically target and neutralize pathogens. 

T cells can be further divided into helper T cells, which assist in orchestrating the immune response, and cytotoxic T cells, which directly kill infected or malignant cells.

NK cells provide rapid responses to virally infected cells and respond to tumor formation, playing a role in the innate immune system by targeting cells that do not display "self" markers correctly

Laboratory Testing for White Blood Cells

A white blood cell count is typically part of a complete blood count (CBC) with differential, which measures the types and numbers of cells in the blood including red blood cells, white blood cells (WBCs), and platelets. 

A complete blood count (CBC) is commonly ordered to assess overall health and detect a wide range of conditions, including infections, anemia, and various blood disorders, by providing information on the quantity and quality of different types of blood cells.

The CBC with differential provides detailed information about the total number of WBCs and breaks down the WBC count into the five major types of white blood cells including lymphocytes, monocytes, neutrophils, eosinophils, and basophils.  An elevated or decreased number of WBCs can signal a problem.

General Lab Test Information and Sample Type

This test is usually conducted using a blood sample obtained via venipuncture, where a healthcare professional collects a small amount of blood from a vein, typically in the arm. The blood sample is then analyzed in a laboratory to determine the amount of white blood cells present in the bloodstream.

No special preparation is typically required for this test, although in certain situations the ordering healthcare provider may request discontinuing certain medications or supplements.

Interpreting Test Results

Reference Range for White Blood Cells

The normal range for leukocyte counts can vary slightly depending on the laboratory and the individual's age.  One reference range is given as: 

Total leukocytes (adults and children >2 years): 5000-10,000/mm3  [13.] 

Clinical Significance of High Levels of White Blood Cells

High levels of white blood cells is also called leukocytosis.  Leukocytosis is considered any finding above 11 x 10^9 cells/L.  [9.]   It may be an incidental finding on blood work, although appropriate workup to discern the cause of the inflammatory response is warranted.  [9.]

Incidental leukocytosis is most often due to benign infectious or inflammatory processes.  [1.]

Determining the type of white blood cell elevated in leukocytosis is important, as it can point to the cause of the elevated white blood cell count:  [9.] 

Neutrophilia: commonly due to stress, infection, inflammation, or medications; may also indicate chronic conditions like rheumatic diseases or Down syndrome.

Leukemoid Reaction: transient neutrophilia (>50 x 10^9 cells/L) in response to infection, sepsis, or solid tumors, distinguishing it from leukemia.

Lymphocytosis: often benign in children but can signify viral infections, hypersensitivity reactions, or malignancies like leukemia or lymphoma.

‍Eosinophilia: linked to neoplastic, inflammatory, infectious, or allergic conditions; medication-induced eosinophilia should be considered.

Monocytosis: associated with chronic infections, autoimmune diseases, or malignancies; persistent monocytosis warrants evaluation for malignancy.

‍Basophilia: occurs in inflammatory conditions, infections, endocrinopathies, or malignancies, sometimes due to allergic reactions or medications.

Causes of leukocytosis include:  [1., 9.]

Acute Leukocytosis

• Leukemoid reaction: some text
  • A leukemoid reaction is a transient condition characterized by a significant increase in white blood cell count, particularly neutrophils, typically exceeding 50 x 10^9 cells/L, in response to various stimuli such as severe infection, inflammation, or other physiological stressors. This reaction can mimic leukemia but is distinguished by the absence of underlying myeloproliferative neoplasms. It usually resolves once the underlying cause is treated or resolved.
• Reactive causes:some text
  • Infection
  • Acute allergies
  • Tissue ischemia
• Drugs: Epinephrine, corticosteroids, NSAIDs, cephalosporin antibiotics, anticonvulsants, beta-agonists, allopurinol, penicillin-derivative antibiotics, illicit substances
• Vaccine administration
• Myocardial infarction
• Hemorrhage
• Acute hemolysis
• Sepsis or septic shock
• Pregnancy

Chronic Leukocytosis

• Smoking
• Obesity
• Chronic allergies
• Autoimmune disorders
• Vasculitis
• Connective tissue disorders
• Malignancy
• Chronic infection
• Asplenia
• Genetic syndromes

Leukocytosis can also be considered respective to bone marrow: for instance, leukocytosis from normally-responding bone marrow may be a response to a variety of factors, while leukocytosis as a response to abnormal bone marrow indicates a malignant or myeloproliferative disorder. 

Leukocytosis in normally responding bone marrow: Infection, inflammation (tissue necrosis, infarction, burns, arthritis), stress (overexertion, seizures, anxiety, anesthesia), drugs (corticosteroids, lithium, beta agonists), trauma (splenectomy), hemolytic anemia

Leukocytosis in abnormal bone marrow: Acute leukemias, chronic leukemias, myeloproliferative disorders

Clinical Significance of Low Levels of White Blood Cells

Leukopenia, a decrease in the circulating white blood cell (WBC) count to < 4000/mcL (< 4 × 109/L), can result from various causes:  [6., 7., 12.] 

Infection or treatment like chemotherapy or radiation therapy: infections, chemotherapy and radiation therapy can all deplete the WBC supply by impairing bone marrow function.

Hematopoietic stem cell abnormalities: certain conditions or abnormalities affecting bone marrow production of white blood cells can hinder normal WBC growth/maturation in the bone marrow.  This is seen in myelodysplastic syndrome and leukemia.

In leukemia or myeloproliferative disorders, leukopenia arises due to the disruption of normal white blood cell (WBC) production in the bone marrow. This disruption occurs because of the overproduction of abnormal white blood cells or their precursor cells, which leads to overcrowding of the bone marrow and suppression of normal hematopoiesis. 

As a result, there is a decrease in the production of mature, functional white blood cells including neutrophils, lymphocytes, monocytes, eosinophils, and basophils.  Alterations in red blood cell and/or platelet count may also be seen.

Neutropenia: neutropenia, where the neutrophil count drops below 1.5 x 10^9/L, is the most common form of leukopenia.

Related Biomarkers

Further testing for white blood cells will depend on which type of white blood cell is out of range.  Additional assessment for white blood cells may include: 

• A peripheral blood smear, ideally with a manual differential for the analysis of abnormal cells

• CD4 Count: This test measures the number of CD4 T cells in the blood, a specific type of lymphocyte that HIV primarily targets and destroys. A CD4 count is crucial for assessing the immune function of individuals infected with HIV and guiding treatment decisions, including when to start antiretroviral therapy.
• HIV Viral Load: This test measures the amount of HIV RNA in the blood and is used alongside CD4 counts to monitor the effectiveness of HIV treatment. A lower viral load indicates successful suppression of the virus, while an increase can signal treatment failure or resistance.

• Antinuclear Antibodies (ANA): ANA testing is often used when autoimmune diseases are suspected. These antibodies, which target the body's own tissues, are commonly found in conditions like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome.
• Rheumatoid Factor (RF) and Anti-CCP: These are specific antibodies tested for in the diagnosis of rheumatoid arthritis. RF is found in about 80% of people with RA, while anti-CCP is more specific and can indicate the likelihood of developing RA.

• C-reactive Protein (CRP): Beyond its role in diagnosing autoimmune diseases, CRP is a broad biomarker for inflammation and can indicate inflammatory illnesses, infections, and chronic diseases.
• Erythrocyte Sedimentation Rate (ESR): Similar to CRP, ESR is another non-specific marker of inflammation. High levels may suggest an ongoing inflammatory process, but like CRP, ESR must be interpreted in the context of other clinical findings.

Natural Ways to Support Healthy White Blood Cells

Maintain a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to provide essential vitamins and minerals necessary for white blood cell production and function.  [5.]

Ensure adequate intake of vitamin D, which plays crucial roles in supporting immune function and white blood cell production.  [2.] 

Incorporate immune-boosting foods such as garlic, ginger, turmeric, and medicinal mushrooms like reishi and shiitake into your diet.  [4.] 

Get regular exercise to enhance circulation and promote the movement of white blood cells throughout the body.  [11.]

Practice good hygiene habits, including regular handwashing, to reduce the risk of infections that can compromise white blood cell function. 

Get sufficient sleep to allow your body to rest and regenerate, supporting optimal immune function and white blood cell production.  [3.] 

Limit alcohol consumption, as it can impair immune function and reduce white blood cell counts.  [15.] 

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