Immunology

Hematopoiesis & Immune cells

Origin, development, and functional classification · USMLE Step 1

Comprehensive notes covering stem cell differentiation, myeloid and lymphoid lineages, and the core functions of leukocytes in innate and adaptive immunity.

🧬 Origin · Hematopoiesis

Hematopoiesis is the lifelong process of blood cell production, differentiation, and maturation from multipotent hematopoietic stem cells (HSCs). It ensures a constant supply of erythrocytes, megakaryocytes, and all leukocyte types.

  • Embryonic – yolk sac (first weeks).
  • Fetal – liver and spleen become dominant during organogenesis.
  • Adult – bone marrow (axial skeleton, proximal long bones) is the primary site throughout life.
⏳ Key transition: Hematopoiesis shifts from yolk sac → liver/spleen → bone marrow. This sequence is high‑yield for understanding developmental anemias and extramedullary hematopoiesis.
Yolk sac Liver / Spleen Bone marrow

Asymmetric division & potency

HSCs undergo asymmetric division: one daughter cell remains a stem cell (self‑renewal), the other becomes a common lymphoid progenitor or common myeloid progenitor. Cytokines and growth factors (SCF, TPO, IL‑3, GM‑CSF) steer differentiation.

🔵 Lymphoid & Myeloid lineages

🔵 Lymphoid

  • Common lymphoid progenitor
  • B lymphocytes (develop in bone marrow)
  • T lymphocytes (migrate to thymus for maturation)
  • Natural killer (NK) cells

Adaptive B and T cells mediate antigen‑specific responses. NK cells are innate large granular lymphocytes that kill virus‑infected and tumor cells without prior sensitization.

🟢 Myeloid

  • Common myeloid progenitor
  • Erythrocytes, megakaryocytes (platelets)
  • Granulocytes: neutrophils, eosinophils, basophils
  • Monocytes / macrophages, dendritic cells, mast cells

Innate Myeloid cells perform rapid, stereotypic responses: phagocytosis, killing of pathogens, antigen presentation, and allergic/inflammatory reactions.


📌 Memory trick:Lymphoid gives Lymphocytes (B, T, NK) ; Myeloid gives the rest — red cells, platelets, granulocytes, monocytes, dendritic cells.”

🩸 White blood cells · morphology & function

Below is a functional summary of the major leukocyte types. Morphologic features (nucleus shape, granules) are key for differential identification.

Cell typeLineageKey morphologyPrimary function
Neutrophil (PMN)MyeloidSegmented (3–5 lobes), pale pink granulesPhagocytosis of extracellular bacteria & fungi; first responder
EosinophilMyeloidBilobed nucleus, large pink/orange granulesHelminth defense; type I hypersensitivity (allergy)
BasophilMyeloidBilobed (often obscured), large deep‑blue granulesAllergic reactions; release histamine, heparin
MonocyteMyeloidKidney‑shaped nucleus, agranularCirculating precursor to macrophage / dendritic cell
MacrophageMyeloidRuffled membrane, vacuoles, irregular shapePhagocytosis, APC, tissue resident (Kupffer, alveolar, etc.)
Dendritic cellMyeloidStellate cytoplasmic projections (“dendrites”)Professional APC; T‑cell activation; bridging innate & adaptive
Mast cellMyeloidSmall nucleus, abundant deep‑blue granulesType I hypersensitivity; parasite defense; tissue resident
B lymphocyteLymphoidLarge nucleus, thin cytoplasmAntibody production (plasma cells), antigen presentation
T lymphocyteLymphoidLarge nucleus, thin rim of cytoplasmCell‑mediated immunity: CD4+ helper, CD8+ CTL
NK cellLymphoidLarge granular lymphocyteInnate killing of virus‑infected cells & tumor cells
🧬 Surface markers (high yield): B cells: CD19, CD20, CD21 · T cells: CD3 (all), CD4 (helper), CD8 (CTL) · NK cells: CD16, CD56.

🧫 B, T, and NK lymphocytes

  • B lymphocytes – mature in bone marrow; express surface immunoglobulin (BCR). Upon activation → plasma cells (antibody factories).
  • T lymphocytes – progenitor migrates to thymus for positive/negative selection; TCR recognition of peptide‑MHC. CD4+ (helper) and CD8+ (cytotoxic).
  • NK cells – large granular lymphocytes; recognize downregulated MHC class I or stress ligands; kill via perforin/granzyme; no rearrangement of antigen receptors.
⚡ Receptor diversity is generated by somatic recombination (V(D)J joining) in B and T cells — a key concept for adaptive immunity. NK cells use germline‑encoded receptors.

📊 WBC differential · reference ranges

Laboratory evaluation includes absolute and relative counts. Shifts in proportions suggest infection, allergy, or hematologic disorders.

Cell typeAdult reference range (%)
Neutrophils (PMNs)50–70
Band cells (immature neutrophils)0–5
Lymphocytes20–40
Monocytes5–10
Eosinophils0–5
Basophils<1
⚠️ Clinical correlate: Neutrophilia (bacterial infection) · Lymphocytosis (viral, pertussis) · Eosinophilia (parasites, allergy) · Basophilia (myeloproliferative).

💎 Clinical pearls & high‑yield facts

  • Plasma cells – terminally differentiated B lymphocytes; eccentrically placed nucleus, prominent Golgi, abundant antibodies.
  • Dendritic cells – most potent APC; express MHC class II and co‑stimulatory molecules.
  • Mast cells vs Basophils – both contain histamine; mast cells are tissue‑resident, basophils circulate.
  • NK cells – lack CD3, do not rearrange antigen receptors; part of innate immunity.
  • Macrophages – arise from monocytes; tissue‑specific names (microglia, Kupffer, alveolar).
🧪 Recall question (USMLE style) +

Which cytokine differentiates the myeloid stem cell into a granulocyte that contains a bilobed nucleus and pink cytoplasmic granules?

  • A. IL‑11
  • B. IL‑5
  • C. Thrombopoietin
  • D. GM‑CSF and IL‑3
  • E. IL‑7
✅ Answer: B. IL‑5 — promotes eosinophil differentiation (bilobed nucleus, pink granules). GM‑CSF/IL‑3 are early myeloid growth factors; IL‑7 drives lymphoid progenitors.
🔬 Exam tip: Eosinophils = IL‑5, bilobed, pink granules; Basophils = IL‑3, bilobed, blue granules; Neutrophils = G‑CSF, multilobed.