Tissue basophils and blood platelets
Mast cells (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 stored histamine, leukotrienes, interleukins, and prostaglandin D2. In addition, they are capable of synthesizing protease enzymes (chymases and tryptases) de novo. Thanks to this arsenal, mast cells regulate smooth muscle tone, stimulate mucus secretion, affect gastrointestinal motility, and play a key role in allergic reactions and blood clotting.
Platelets (Platelets), in addition to their classic function of stopping bleeding (hemostasis), are actively involved in inflammation and tissue repair processes. Activated blood platelets can directly destroy bacterial cells and interact with leukocytes. They secrete a number of biologically active molecules: adhesion molecules (selectins), serotonin, thromboxane A2 (which causes vascular smooth muscle spasm), as well as chemokines and pro-inflammatory cytokines, including interleukin-1 beta.
Natural killers: guardians of genetic purity
NK cells (Natural Killers) are large granular lymphocytes originating from a lymphoid progenitor. Unlike other lymphocytes, they lack a T-cell receptor, but carry CD16, CD56, and CD94 markers on their surface.
Their main target is cells infected with viruses or intracellular parasites, as well as tumor cells. The prefix "natural" means they do not require additional stimulation to initiate an attack.
The decision to destroy a target is made based on a "signal balance." An NK cell contacts target receptors (such as class I major histocompatibility complex molecules, MHC I) via its own receptors, such as KIR. If the cell is healthy and carries a normal amount of its own MHC I molecules, an inhibitory signal predominates, which blocks the attack. If the MHC I structure is disrupted due to a virus or tumor, or if the density of molecules on the membrane is reduced, the inhibitory signal drops sharply. The activating signal takes over, and the killer releases cytotoxic granules.
In addition to direct destruction, activated NK cells release cytokines, particularly interferon-gamma, performing an important regulatory function.
Mechanisms of cellular killing
There are several pathways by which NK cells destroy targets:
- Antibody-dependent cell-mediated cytotoxicity (ADCC). The killer's surface features a CD16 receptor that binds to the Fc fragment of IgG antibodies coating target cell antigens. The antibody acts as a bridge, triggering a destruction process that combines apoptosis and necrosis.
- Secretory (perforin-granzyme) lysis. The killer releases special proteins into the synapse with the target. Perforins insert into the membrane of the diseased cell and form pores in it. Granzymes enter through these openings, triggering a cascade of reactions leading to DNA fragmentation and cell destruction.
- Non-secretory (receptor-mediated) lysis. Occurs without granule release, purely through contact. The killer's surface bears a Fas ligand that binds to the CD95 receptor (apoptosis receptor) on the target. This immediately provides the cell with a biochemical "suicide" signal.
Dendritic cells
Dendritic cells (Dendritic cells) are the main professional antigen-presenting cells. They got their name from the Greek word dendron (tree) because their immature forms have long, pronounced processes.
Immature forms constantly patrol tissues. They migrate to areas of tumor growth, sites of injury, or paths of pathogen entry. As soon as a cell encounters a foreign antigen, it engulfs it via endocytosis or phagocytosis. This capture triggers maturation. A mature dendritic cell changes shape dramatically: processes smooth out, surface area increases, and it transforms into a veiled cell.
Briefly: answers to topical questions
Where do mast cells form and mature?
Mast cells share a common progenitor with basophils; the exact pathway of development from the common myeloid progenitor is not fully understood.
Features of formation and maturation:
- Spleen — the site of final differentiation for mast cell and basophil precursors.
- Bloodstream — mast cells arrive as immature precursors.
- Tissues — precursors migrate from the blood into tissues, most abundantly into the intestinal mucosa, where their final maturation into mastocytes occurs.
What cytokines do activated NK cells secrete?
Activated NK cells secrete cytokines involved in regulating innate immunity and the cellular response.
These include:
- Interferon-gamma (IFN-γ) — an effector molecule involved in coordinating the immune response.
- Tumor necrosis factor alpha (TNF-α) — a key cytokine of the cellular response.
What pattern recognition receptors (PRRs) do dendritic cells express?
Dendritic cells express pattern-recognition receptors required to recognize microbial products and trigger the maturation process.
Known receptors of this group on dendritic cells include:
- Toll-like receptors (TLR) — expressed on all innate immunity cells and function as homodimers or heterodimers.
- Toll-like receptor 9 (TLR9) — an intracellular receptor whose activation leads to the induction of interferon-alpha secretion.
Secretory lysis is easy to remember with the phrase: "Perforins make PORES, and Granzymes ROB the cell from within."
Class and exam questions
Why do viruses fail to hide from NK cells by reducing MHC I levels?
Viruses often reduce the expression of MHC I molecules on the membrane to become invisible to adaptive immunity. However, for NK cells, this serves as an alarm signal: a drop in MHC I levels reduces the inhibitory signal, which disrupts balance and leads to immediate activation of the killer.
What is the difference between secretory and non-secretory lysis?
During secretory lysis, the NK cell releases perforin and granzyme proteins, which physically punch holes in the target and destroy it from within. Non-secretory lysis occurs without granules—the killer simply connects its Fas ligand to the target's CD95 receptor, triggering programmed cell death (apoptosis).
Why do mast cells synthesize substances de novo if they already have granules?
Granules store rapid-response substances (e.g., histamine) needed for an instant reaction. De novo synthesis allows the production of proteases for later and more prolonged stages of the response.
What role do platelets play in the immune response?
Activated platelets not only stop bleeding, but can also directly destroy bacteria, release the pro-inflammatory cytokine interleukin-1 beta, and recruit other leukocytes to the site of inflammation.
What else to study on this topic
- Cascade of apoptotic reactions induced by granzymes
- The role of interferon-gamma in coordinating the immune response
- Structure and function of Fc receptors (specifically CD16)
- Interaction of innate immunity cells in allergies
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