Neil V.P. Fernando

THE FINE STRUCTURE OF THE TERMINAL VASCULAR BED. IV. THE VENULES AND THEIR PERIVASCULAR CELLS (PERICYTES, ADVENTITIAL CELLS).

Abstract The fine structure of venules has been described. Venules are larger than capillaries. They are lined by a single layer of endothelium lying on a basement membrane and have an outer discontinuous coat of “perivascular” cells. The interlocking junctions between adjacent endothelial cells are often more complex than in capillaries. Lysosomes, which are not common in endothelium of the other portions of the terminal vascular bed, are common in venules. Pinocytic vesicles may attain a rather large size. The perivascular cells of venules (pericytes or adventitial cells) are similar to those of capillaries, though when stimulated by foreign protein, they show more signs of “activity.” They may become detached and probably can develop into macrophages or into plasma cells. Although continuous with smooth muscle cells in the more proximal and distal parts of the terminal vascular bed, perivascular cells do not have the structural characteristics of typical smooth muscle cells. Intercellularly, one encounters basement membrane , between endothelium and perivascular cells and around the latter. When perivascular cells become detached, the basement membrane around them is no longer demonstrable. Collagen and elastic elements may occur in the wall of venules. In the discussion the significance of venules in inflammation is pointed out, and the nature of the perivascular cells is discussed.

The fine structure of connective tissue: I. The fibroblast☆

Abstract The fine structure of fibroblasts of regenerating tendon, granulation tissue and various other tissues was studied by electron microscopy. The cells were identified as fibroblasts with the light microscope, and then ultrathin sections were prepared for electron microscopy. Fibrcblasts, particularly proliferating ones, are difficult to preserve adequately, swelling and disruption of mitochondria occurring frequently. The findings reported in this paper are based only on the study of adequately preserved material. Fibroblasts as seen by electron microscopy are elongated spindle-shaped or stellate cells, with a slightly indented nucleus. In the resting cell the cytoplasm may taper off into long slender processes. Both resting and proliferating cells contain ergastoplasm (rough-surfaced vesicles of the endoplasmic reticulum), but this is more abundant in proliferating cells. The ergastoplasm sometimes contains an electron dense substance and it may be distended. The periphery of the cell is free of ergastoplasm, but often contains fine filaments. A large Golgi apparatus was always seen in proliferating fibroblasts. Dense, osmiophilic, stellate bodies in the cytoplasm are typical of the fibroblast. Small granules or globules occur in the Golgi region, and somewhat larger ones are found in the periphery of the cytoplasm. Most of the granules resemble secretory granules. Others look like ingested material, or like structures described as lysosomes. A puzzling structure encountered in the Golgi area is a spindle-shaped body containing filamentous material, which stains intensely with phosphotungstic acid.

THE FINE STRUCTURE OF THE LYMPHOID TISSUE DURING ANTIBODY FORMATION.

Abstract The histologic and ultrastructural changes which occur in spleen and lymph nodes of rabbits after primary or secondary antigenic stimulation are described. In the primary response, large pyroninophilic blast cells develop in the periarteriolar lymphcytic sheaths of the spleen. These blast cells migrate toward the periphery of the white pulp as they gradually develop into plasma cells. In lymph nodes, the process begins diffusely in the cortex, and migration occurs toward the medullary cords. Germinal center development lags behind these changes and reaches a peak when plasma cell development in the diffuse lymphoid tissue has been completed. Pyroninophilic blast cells develop in the centers but rarely mature into plasma cells. By using electron microscopy, the large pyroninophilic blast cells can be divided into two types. The cells developing first are characterized by large nuclei and nucleoli, and by numerous free ribosomes in the cytoplasm. These cells have been designated as immunoblasts . The immunoblast becomes a plasmablast by the development of a granular endoplasmic reticulum. By a decrease in the size and an increase in density of the nucleus, together with an enlargement of the Golgi area, the plasmablast becomes a plasma cell. Ultrastructural evidence is presented to show that the immunoblast develops from the lymphocyte, both in the diffuse lymphoid tissue of lymph nodes and periarteriolar lymphoid tissue of the spleen and in the germinal centers. Circumstantial evidence also supports this view.

The fine structure of the terminal vascular bed: II. The smallest arterial vessels: Terminal arterioles and metarterioles☆

Abstract The fine structure of the smallest arterial vessels (terminal arterioles and metarterioles) was described. These vessels have no internal elastic lamina. In these vessels, the number of cytoplasmic organelles varies from one endothelial cell to another. Interesting are the often complex interlocking junctions. The hyaloplasm of endothelial cells is often filamentous. The larger of the vessels without an internal elastic membrane (terminal arterioles) have a continuous media composed of well-differentiated smooth muscle cells with filaments, attachment bodies, and condensation of organelles in circumscribed areas. The smallest vessels (metarterioles) have a discontinuous coat of perivascular cells (pericytes). There are all gradations between these extremes. The intercellular elements between endothelium and the underlying cells, and between the smooth muscle or perivascular cells, consists mainly of basement membrane, with some collagen fibrils and very little elastic tissue. Downstream, there is a gradual transition into capillaries.

The fine structure of connective tissue: II. The plasma cell☆

Abstract The fine structure of plasma cells in lympho-reticular and connective tissue is described. When observed with the light microscope, mature plasma cells have a basophilic cytoplasm, a perinuclear clear area, and an eccentric dense nucleus. With the electron microscope, a well developed ergastoplasm and a large Golgi apparatus are characteristic of the cell. Immature plasma cells have well developed nucleoli, a relatively high nucleo-cytoplasmic ratio, and more abundant free RNP particles. In plasma cells, the ergastoplasmic sacs may be flat or dilated. When dilated they may contain a finely floccular substance, small dense bodies, large dense bodies (Russell bodies), or crystals. The Golgi area of plasma cells consists of small vesicles, flat or dilated tubules, round or irregular structures with a dense periphery and an obscured limiting membrane, and dense homogeneous globules. The latter are similar to, though much smaller than, the bodies or globules which occur occasionally in the rough surfaced vesicles (Russell bodies). Histochemical, in vitro , immuno-fluorescent studies and other evidence indicates that plasma cells produce antibody and other globulins. This theory is supported by the electron microscopic findings.

The fine structure of the terminal vascular bed I. Small arteries with an internal elastic lamina

Abstract The fine structure of small arteries characterized by a single layer of well-differentiated smooth muscle cells and an internal elastic lamina has been described. The endothelium consists of relatively tall cells with complex junctions, sometimes with a well-developed Golgi area, and with a variable number of rough-surfaced vesicles, multivesicular bodies, and fine filaments in the hyaloplasm. The internal elastic lamina is made mainly of an interrupted elastic membrane but also contains collagen, basement membrane, and sometimes ground substance. Phosphotungstic acid stains the elastica intensely. The media is composed of a layer of closely packed, well-differentiated smooth muscle cells , which have their organelles more or less restricted to circumscribed areas of the cytoplasm. The intervening portions of the cytoplasm are occupied by delicate filaments. Attachment bodies are present at the cell border. Contraction of a vessel may cause the muscle to appear to have more than one layer. The smooth muscle cells are surrounded by basement membrane , which often appear to enclose collagen fibrils and fragments of elastic fibers.

The fine structure of lymphoid tissue

Abstract The fine structure of the lymphoid tissue is described. Six cell types can be identified and described with reasonable accuracy: reticular cells, macrophages, littoral cells, stem cells, lymphocytes, and plasma cells. The reticular cell resembles the fibroblast in having a pale elongated nucleus, branching cytoplasmic processes, a varying amount of ergastoplasm, and often an organelle-free portion at the cell border (ectoplasm), with delicate filaments. Marcophages may resemble reticular cells in shape or may be more rounded. The pale nucleus is elongated or kidney-shaped and contains a small nucleolus. The nucleus is often eccentric. In the cytoplasm there may be varying amounts of phagocytosed material and lysosomes. There are usually many smooth-surfaced vesicles, and the ergastoplasm is often confined to a more or less circumscribed area. Characteristic are the numerous fingerlike processes at the cell border, which may interdigitate with those of neighboring cells. Littoral cells resemble reticular cells and ordinary vascular endothelial cells. They show little or no phagocytosis under normal conditions, but may pick up certain substances, e.g., carbon, just like ordinary macrophages. The lymphocyte nucleus is more or less rounded, most dense in the small lymphocyte, and least densc in the lymphoblast. Lymphoblasts and medium lymphocytes have nucleoli. The nucleo-cytoplasmic ration of small lymphocytes is the greatest of any cell. The cytoplasm is pale and contains a moderatc number of free ribonucleoprotein granules (ribosomes), well-formed mitochondria, and a small Golgi region. In addition, particularly in the medium lymphocytes, the cytoplasm has bodies which probably correspond to the Gall bodies of light microscopy. Plasma cells are characterized by a well-developed ergastoplasm that fills the cytoplasm to its margins, a large and complex Golgi apparatus, fingerlike cytoplasmic processes, and a densc eccentric nucleus. Immature plasma cells have a prominent nucleolus. The variants of the reticular cell are discussed, as is the evidence for and against the existence of a primitive multipotent reticular cell. A cell referred to as a “stem cell” is described. It is found occasionally in normal lymphoid tissue but frequently soon after antigenic stimulation. Its significance and the origin of lymphocytes and plasma cells are discussed. Extracellular elements in the spleen consist of reticular fibers and basement membranes. The latter support the littoral cells of the sinusoid. The reticular fibers of light microscopy are made up of delicate collagen fibrils, an occasional elastic fiber, and an interfibrillar ground substance.