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Innate Immunity Cells

For medical students2 min readUpdated 2026-10-10

Cells of the innate immune system form the first and fastest line of defense against infections and tissue damage. They do not require prior antigen exposure, act instantaneously, and comprise a diverse range of elements—from tissue-patrolling dendritic cells to natural killer cells and platelets.

NK cellsDestroy tumors and virally infected cells without prior sensitization, accounting for 10–12% of lymphocytes.
PlateletsBesides stopping bleeding, they can directly destroy bacteria and release cytokines.
Dendritic cellsProfessional antigen-presenting cells that change shape upon maturation.
Mast cellsReside in barrier tissues and store histamine in granules for rapid response.

Mast Cells and Platelets

Mast cells are located predominantly in barrier tissues such as the skin and mucous membranes. Their main feature is the presence of large granules containing preformed histamine, leukotrienes, interleukins, and prostaglandin D2. In addition, they can synthesize protease enzymes (chymase and tryptase) de novo. Through this arsenal, mast cells regulate smooth muscle tone, stimulate mucus secretion, influence gastrointestinal motility, and play a key role in allergic reactions and hemostasis.

Platelets, beyond their classic function of arresting bleeding (hemostasis), actively participate in inflammation and tissue repair. Activated platelets can directly destroy bacterial cells and interact with leukocytes. They secrete a range of biologically active molecules: adhesion molecules (selectins), serotonin, thromboxane A2 (which induces vascular smooth muscle spasm), as well as chemokines and proinflammatory cytokines, including interleukin-1 beta.

Natural Killer Cells: Guardians of Genetic Integrity

NK cells (Natural Killer cells) are large granular lymphocytes derived from a lymphoid progenitor. Unlike other lymphocytes, they lack a T-cell receptor but express surface markers CD16, CD56, and CD94.

Their primary targets are cells infected with viruses or intracellular parasites, as well as tumor cells. The term "natural" indicates that they do not require prior stimulation to initiate an attack.

The decision to destroy a target is based on a "signal balance." An NK cell contacts target receptors (such as major histocompatibility complex class I molecules, MHC I) via its receptors, such as KIR. If the target cell is healthy and expresses a normal level of self MHC I, an inhibitory signal predominates, blocking the attack. If MHC I is altered or downregulated due to viral infection or tumorigenesis, the inhibitory signal drops sharply. The activating signal prevails, and the killer cell releases cytotoxic granules.

In addition to direct destruction, activated NK cells secrete cytokines, notably interferon-gamma, fulfilling an important regulatory function.

Mechanisms of Cellular Cytotoxicity

There are several pathways by which NK cells destroy target cells:

  1. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC). The killer cell surface bears the CD16 receptor, which binds to the Fc region of IgG antibodies coating target cell antigens. The antibody acts as a bridge, triggering a destruction process combining apoptosis and necrosis.
  2. Secretory (Perforin-Granzyme) Lysis. The killer cell releases specialized proteins into the immunological synapse. Perforins insert into the target cell membrane and form pores. Granzymes enter through these pores, triggering a cascade of reactions leading to DNA fragmentation and cell lysis.
  3. Non-Secretory (Receptor-Mediated) Lysis. This occurs without granule exocytosis, solely through cell-to-cell contact. The killer cell expresses Fas ligand, which binds to CD95 (the Fas death receptor) on the target. This immediately delivers an apoptotic "suicide" signal to the target cell.

Dendritic Cells

Dendritic cells are the primary professional antigen-presenting cells. They derived their name from the Greek word dendron (tree) because their immature forms possess long, distinct cytoplasmic projections.

Immature dendritic cells continuously patrol tissues, migrating to sites of tumor growth, tissue damage, or pathogen entry. Upon encountering a foreign antigen, the cell engulfs it via endocytosis or phagocytosis. This uptake triggers maturation. A mature dendritic cell undergoes a dramatic morphological change: its processes flatten, surface area increases, and it transforms into a veiled cell.

Mnemonic

Secretory lysis is easily remembered by: "Perforins punch the PORES, while Granzymes GRAB the cell from the inside."

Frequently asked questions

Where do mast cells originate and mature?

Mast cells share a common progenitor with basophils; the exact developmental pathway from the common myeloid progenitor is not fully elucidated.

Developmental features:

  • Spleen: Site of final differentiation for certain mast cell and basophil precursors.
  • Bloodstream: Mast cells circulate as immature precursors.
  • Tissues: Precursors migrate from the blood into tissues (predominantly the intestinal mucosa), where they undergo terminal maturation into mast cells.
What cytokines are secreted by activated NK cells?

Activated NK cells secrete cytokines involved in regulating innate immunity and cell-mediated responses.

These include:

  • Interferon-gamma (IFN-γ): An effector molecule involved in coordinating the immune response.
  • Tumor necrosis factor-alpha (TNF-α): A key cytokine in cellular immunity.
What pattern recognition receptors (PRRs) do dendritic cells express?

Dendritic cells express pattern recognition receptors necessary for detecting microbial components and initiating maturation.

Prominent PRRs expressed by dendritic cells include:

  • Toll-like receptors (TLRs): Expressed on innate immune cells, functioning as homodimers or heterodimers.
  • Toll-like receptor 9 (TLR9): An intracellular receptor whose activation induces interferon-alpha secretion.
Why can't viruses hide from NK cells by downregulating MHC I?

Viruses frequently downregulate surface MHC I expression to evade adaptive immunity. However, for NK cells, this serves as an alarm signal: reduced MHC I levels diminish the inhibitory signal, disrupting the balance and leading to immediate killer cell activation.

What is the difference between secretory and non-secretory lysis?

In secretory lysis, the NK cell releases perforin and granzyme proteins that physically puncture the target and destroy it from within. Non-secretory lysis occurs without granules—the killer cell simply engages its Fas ligand with the target's CD95 receptor, triggering programmed cell death (apoptosis).

Why do mast cells synthesize molecules de novo if they already store preformed granules?

Granules store rapid-response mediators (such as histamine) required for an immediate reaction. De novo synthesis allows the generation of proteases and other mediators for later, prolonged stages of the inflammatory response.

What role do platelets play in the immune response?

Activated platelets not only arrest bleeding but can also directly destroy bacteria, release the proinflammatory cytokine interleukin-1 beta, and recruit other leukocytes to the site of inflammation.

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