STEPTRACKERIMMUNOLOGY + HEMATOLOGY | CELLS & ORGANS | HIGH-YIELD REVIEW

Innate Immune Cells

The fast responders — they need no prior exposure, recognize patterns rather than precise antigens, and recruit and instruct the adaptive system.

FOCUS ON
Neutrophils: first to acute bacterial infection; multilobed nucleus; granules (MPO, lysozyme, alkaline phosphatase); hypersegmented in B12/folate deficiency. Monocytes → macrophages: phagocytose, present on MHC II, secrete IL-1, IL-6, TNF-α (fever, acute phase), activated by IFN-γ; names by tissue (Kupffer, microglia, alveolar, osteoclast). Dendritic cells: best APCs; carry antigen to nodes. NK cells: kill cells with ↓ MHC I (virus, tumor) via perforin/granzyme; CD16, CD56; activated by IL-12, IFN-α/β. Mast cells/basophils: IgE-bound FcεRI → histamine (type I). Eosinophils: helminths (major basic protein), allergy; ↑ IL-5; ↓ by steroids.
CELL
FEATURES · MARKERS
FUNCTION
CLINICAL LINK
Neutrophil
Multilobed nucleus; primary (MPO) and specific (lactoferrin, lysozyme) granules; CD16, CD66
Phagocytosis, respiratory burst, NETs; arrive first (hours)
Neutrophilia: bacterial infection, steroids (demargination) · hypersegmented: B12/folate
Monocyte
Kidney-shaped nucleus, frosted cytoplasm; CD14
Circulates, then becomes macrophage or DC in tissue
Monocytosis: TB, chronic infection
Macrophage
CD14, CD68; FcγR, complement receptors, TLRs
Phagocytosis, antigen presentation (MHC II), IL-1/IL-6/TNF-α, IL-12 (→ Th1); granulomas (epithelioid cells, giant cells)
Kupffer (liver), microglia (CNS), alveolar, osteoclast, Langerhans (skin, a DC)
Dendritic cell
Long processes; MHC II, B7 (CD80/86); Langerhans cells have Birbeck granules
Most potent APC → activates naive T cells in lymph nodes; links innate to adaptive
Langerhans cell histiocytosis (CD1a, S-100)
NK cell
Large granular lymphocyte; CD16 (FcγRIII), CD56; no TCR
Kills cells lacking MHC I ("missing self"); ADCC via CD16; makes IFN-γ
Activated by IL-12, IL-15, IFN-α/β · NK deficiency → severe herpesvirus infections
Mast cell
Tissue-resident; FcεRI binds IgE; granules: histamine, heparin, tryptase
Type I hypersensitivity; late-phase leukotrienes, prostaglandins
Cromolyn stabilizes · mastocytosis (KIT D816V, ↑ tryptase)
Basophil
Bilobed nucleus, dark purple granules; FcεRI
Circulating counterpart of mast cell
Basophilia → CML
Eosinophil
Bilobed nucleus, bright red granules; major basic protein, eosinophil peroxidase, cationic protein
Helminth killing (ADCC with IgE), allergy; histaminase limits reactions
Eosinophilia: parasites, asthma, drugs (DRESS), Addison, Churg-Strauss, Hodgkin · ↓ by steroids
Innate lymphoid cells
ILC1, ILC2, ILC3 (lymphoid but no antigen receptor)
Mirror Th1/Th2/Th17 cytokine patterns at barriers
ILC2 in asthma
γδ T cells · NKT cells
Innate-like T cells with limited receptors (CD1d for NKT)
Rapid response at epithelia, lipid antigens
—
Platelets
Release chemokines, CD40L
Contribute to inflammation and NETosis
—

Mechanism — how NK cells decide

Normal cell shows MHC I
→
Inhibitory receptor (KIR) engaged
→
NK cell stays quiet
Virus or tumor ↓ MHC I+ stress ligands
→
No inhibition, activating signals win
→
Perforin + granzyme → apoptosis

Granulocytes compared

CELL
NUCLEUS
GRANULES
↑ IN
Neutrophil
3–5 lobes
Pale, MPO
Bacterial infection
Eosinophil
2 lobes
Red, MBP
Parasites, allergy
Basophil
2 lobes, hidden
Dark purple, histamine
CML
Mast cell
Round
Purple, histamine, tryptase
Mastocytosis

How it's tested

COMMON CONFUSIONNK cells kill cells with too little MHC I; CD8⁺ T cells kill cells displaying foreign peptide on MHC I — tumors that drop MHC I escape T cells but become NK targets.
THE TRAPGlucocorticoids raise the neutrophil count (demargination) but drop eosinophils and lymphocytes.
YOUR APPROACHCell → morphology clue → receptor or marker → main product → disease where it rises or fails.

If you see… think…

First cell at a site of acute bacterial infection → neutrophil
Hypersegmented neutrophils → B12 or folate deficiency
Cytokines causing fever and acute-phase response → IL-1, IL-6, TNF-α
Macrophage activator from Th1 cells → IFN-γ
Best antigen-presenting cell for naive T cells → dendritic cell
Birbeck granules, CD1a ⁺ → Langerhans cell
CD16 ⁺ CD56 ⁺ lymphocyte killing virally infected cells → NK cell
Tryptase elevated after anaphylaxis → mast cell degranulation
Major basic protein → eosinophil (helminths)
Basophilia with leukocytosis → CML