Epithelioid Cells and Endocytobiosis
The foundation of a specific granuloma is the epithelioid cell. The process of their formation begins when a regular macrophage successfully completes phagocytosis. It destroys the microorganism, processes its antigenic determinants, and triggers a specific immune response.
Following this, the body requires specialized cells that can capture the pathogen but will not digest it. The macrophage transforms into an epithelioid cell, characterized by several distinct features:
- Virtually devoid of lysosomes.
- Lacks a phagocytic vacuole.
- Possesses extremely low bactericidal activity.
As a result, the live microorganism survives inside the cell. This phenomenon is termed endocytobiosis. It is vital for maintaining non-sterile immunity: as long as the pathogen remains inside, it continuously stimulates the immune system. Additionally, epithelioid cells actively secrete interleukin-1 (IL-1), transforming growth factor (TGF), and fibroblast growth factor (FGF), thereby stimulating connective tissue proliferation.
Multinucleated Giant Cells
When epithelioid cells fuse their cytoplasm or undergo multiple nuclear divisions without cellular division, giant cells are formed. They are also capable of selective phagocytosis and endocytobiosis due to their low lysosome content.
Depending on the number and arrangement of nuclei, two main types are distinguished:
- Langhans giant cells: contain up to 20 nuclei arranged peripherally in the cytoplasm in a horseshoe shape.
- Foreign body giant cells: can contain up to 100 nuclei scattered randomly in the central part of the cell.
Architectonics of the Tubercular Granuloma
The tubercular granuloma belongs to the epithelioid cell type. It has a distinct layered structure, with elements arranged strictly from the center to the periphery:
- Central zone: an area of caseous necrosis.
- Inner layer: a palisade of epithelioid cells densely surrounding the necrotic masses.
- Intermediate zone: single (usually 1–3) Langhans giant cells located at the border with the lymphoid cuff.
- Outer cellular cuff: an accumulation of macrophages and sensitized T-lymphocytes.
- Periphery: fibroblasts walling off the inflammatory focus.
An important feature: blood vessels are completely absent inside such a granuloma. A fine network of argyrophilic fibers can only be detected using special staining—silver impregnation.
Morphology of Leprous Granulomas
In leprosy, the microscopic picture directly depends on the clinical form of the disease.
Lepromatous leprosy is characterized by mycobacteria actively destroying cells and spilling into the tissue infiltrate, stimulating immunity. A diagnostic hallmark is the appearance of " lepra cells" (Virchow cells). These are degenerated macrophages whose cytoplasm is packed with large lipid droplets, remnants of destroyed bacteria, and metabolic byproducts. Subsequently, this cellular debris is engulfed by giant cells. Lesions most commonly develop in the skin and peripheral nerves, but can occur in almost any internal organ.
Tuberculoid leprosy proceeds with delayed-type hypersensitivity (DTH). It features classic epithelioid cell granulomas, while the number of detectable mycobacteria is significantly lower than in the lepromatous variant.