Hematology

White Blood Cells

Leukocytes — neutrophils, lymphocytes, monocytes, eosinophils, basophils — patrolling and defending against infection and cancer

White blood cells (leukocytes) are the cellular arm of immunity, derived from hematopoietic stem cells in bone marrow. Five major types in normal CBC differential. Neutrophils (40-70%): first responders to bacterial infection, phagocytose and kill via reactive oxygen species and granule enzymes; live ~1 day. Lymphocytes (20-45%): T cells (CD4 helper, CD8 cytotoxic), B cells (antibody producers), NK cells (innate cytotoxic). Monocytes (2-10%): differentiate into tissue macrophages and dendritic cells; phagocytose, present antigen, release cytokines. Eosinophils (1-6%): parasitic infections, allergy, asthma. Basophils (<1%): allergic reactions, release histamine. Total WBC normal range 4,000-11,000/µL. Patterns of differential abnormality (leukocytosis, leukopenia, left shift, lymphocytosis) localize disease.

  • Total WBC normal4,000-11,000/µL
  • Neutrophils40-70% (most numerous)
  • Lymphocytes20-45% (T, B, NK)
  • Monocytes2-10% (become tissue macrophages)
  • Eosinophils1-6% (parasites, allergy)
  • Basophils<1% (rarest)

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Why white blood cells matter

  • Infection diagnosis. Leukocytosis with left shift suggests bacterial; lymphocytosis suggests viral; eosinophilia suggests parasites or allergy.
  • Sepsis recognition. WBC <4,000 or >12,000 is a SIRS criterion; band count and morphology refine severity.
  • Cancer diagnosis. Leukemias present with abnormal counts and blasts; flow cytometry classifies lineage.
  • Chemotherapy management. Nadir neutrophil counts predict febrile neutropenia risk; G-CSF prophylaxis adjusted accordingly.
  • HIV monitoring. CD4 count tracks disease progression; <200 defines AIDS and prophylaxis triggers.
  • Allergy and asthma. Eosinophil count and IL-5 biology guide biologic therapies (mepolizumab, benralizumab, dupilumab).
  • Immunodeficiency. SCID, CGD, hyper-IgM, common variable immunodeficiency present with characteristic infection patterns and lab abnormalities.

Common misconceptions

  • High WBC always means infection. Stress, exercise, glucocorticoids, leukemia, and trauma also elevate WBC.
  • Normal WBC excludes infection. Sepsis can present with leukopenia; immunocompromised patients may not mount leukocytosis.
  • All lymphocytes look the same. Atypical/reactive lymphocytes signal viral infection; lymphoblasts signal acute leukemia.
  • Eosinophilia is benign allergy. Sustained eosinophilia warrants workup for parasites, malignancy, or DRESS.
  • Macrophages and monocytes are identical. Monocytes are circulating precursors; macrophages are tissue-resident derivatives with diverse phenotypes.
  • Granulocytes refer to all leukocytes. Granulocytes specifically are neutrophils, eosinophils, and basophils.

Frequently asked questions

How do neutrophils kill bacteria?

Neutrophils circulate ~6-8 hours then enter tissues following chemokine gradients (IL-8/CXCL8). At infection sites they phagocytose bacteria and fuse phagosomes with primary granules (myeloperoxidase, defensins) and secondary granules (lactoferrin, lysozyme). NADPH oxidase generates superoxide → hydrogen peroxide → hypochlorous acid (oxidative burst). They can also release neutrophil extracellular traps (NETs) — DNA webs decorated with antimicrobial proteins. Chronic granulomatous disease impairs NADPH oxidase and causes recurrent bacterial/fungal infections.

What's the difference between T and B lymphocytes?

B cells differentiate into plasma cells producing antibodies (humoral immunity); they recognize native antigen via membrane-bound IgM/IgD. T cells recognize antigen as peptides on MHC molecules. CD4 T helper cells respond to MHC II (on antigen-presenting cells) and direct other immune cells via cytokines; subsets include Th1 (IFN-γ, intracellular pathogens), Th2 (IL-4/13, parasites and allergy), Th17 (IL-17, neutrophil recruitment), Treg (immune suppression). CD8 cytotoxic T cells respond to MHC I and kill virus-infected or tumor cells via perforin/granzyme.

What does a left shift mean?

Increased percentage of immature neutrophils (band cells) in peripheral blood, classically associated with bacterial infection or sepsis. Reflects bone marrow demand exceeding supply of mature neutrophils. Severe shifts include myelocytes and metamyelocytes ("leukemoid reaction"). Distinguish from chronic myeloid leukemia by basophilia, splenomegaly, and Philadelphia chromosome (BCR-ABL). Toxic granulation, Döhle bodies, and vacuolation in neutrophils also suggest severe infection.

Why might lymphocytes be elevated?

Viral infections (CMV, EBV mononucleosis, HIV, COVID-19) commonly cause lymphocytosis with reactive (atypical) lymphocytes — large with abundant cytoplasm, indented nuclei. Pertussis classically causes marked absolute lymphocytosis. Chronic lymphocytic leukemia (CLL) presents with sustained lymphocytosis in older adults; flow cytometry shows clonal CD5+ B cells. Acute lymphoblastic leukemia (ALL) shows blasts. Lymphocytopenia: HIV, sepsis, glucocorticoids, chemotherapy, radiation.

When do you see eosinophilia?

Mnemonic NAACP: Neoplasm (Hodgkin, eosinophilic leukemia), Allergy/asthma, Adrenal insufficiency, Connective tissue disease (eosinophilic granulomatosis with polyangiitis), Parasites (especially helminths — Strongyloides, schistosomiasis, hookworm). Drug reactions (DRESS — Drug Reaction with Eosinophilia and Systemic Symptoms — can be life-threatening). Hypereosinophilic syndrome with persistent count >1,500/µL can damage heart and other organs. Imatinib treats some forms.

What is neutropenia and why is it dangerous?

Absolute neutrophil count <1,500/µL, severe <500/µL, profound <100/µL. Causes: chemotherapy (most common), drugs (clozapine, methimazole, sulfa, ticlopidine), bone marrow disease (aplastic anemia, MDS, leukemia), autoimmune (Felty syndrome), infection, ethnic/benign in some populations. Severe neutropenia with fever (febrile neutropenia) is a medical emergency — empiric broad-spectrum antibiotics (cefepime, piperacillin-tazobactam) within 1 hour. G-CSF (filgrastim) accelerates neutrophil recovery.

How are monocytes and macrophages related?

Monocytes circulate in blood, then enter tissues to differentiate into resident macrophages (Kupffer in liver, alveolar in lung, microglia in brain, osteoclasts in bone) or dendritic cells (skin Langerhans, lymph node DCs). Macrophages phagocytose pathogens, debris, apoptotic cells; present antigen on MHC II to CD4 T cells; release cytokines (TNF-α, IL-1, IL-6) driving inflammation. Polarization: M1 (pro-inflammatory, classical) vs M2 (anti-inflammatory, tissue repair). Monocytosis: chronic infections (TB, endocarditis), CMML, autoimmune disease.