Human Anatomy - Kotsan I. Y. 2009

Organs of Hematopoiesis and the Immune System
Bone Marrow

The Bone Marrow (medulla ossium) Functions simultaneously as a hematopoietic organ and a primary component of The Immune System. It is subdivided into Cytology/practical/86.html">Red bone marrow (medulla ossium rubra), which in adults is housed within the spongy bone cavities and the epiphyses of long bones, and yellow bone marrow (medulla ossium flava), which occupies the medullary cavities of the diaphyses. The total mass of bone marrow in an adult is approximately 2.5–3 kg, accounting for 4.5–4.7% of total body weight. Roughly half of this volume consists of red bone marrow, with the remainder being yellow bone marrow.

Red bone marrow is composed of a reticular stroma, hemopoietic tissue (myeloid tissue), and lymphoid elements at various stages of maturation. It harbors hematopoietic stem Cells, which serve as precursors for all Blood AND Lymph cells. Branching throughout the red bone marrow are blood capillaries with a diameter of 6–20 µm that supply nourishment, alongside wide capillaries up to 500 µm in diameter known as sinusoids, through whose walls mature formed blood elements (cells) migrate into the bloodstream.

Yellow bone marrow is predominantly composed of adipose tissue that has replaced the reticular stroma. Its characteristic yellowish hue stems from lipid inclusions within degenerated reticular cells, which gives this region of the bone marrow its name. While hemopoietic elements are absent here, in cases of severe blood loss, yellow bone marrow can revert to active red bone marrow.

Development and Age-related Features of the bone marrow. During embryonic development, hematopoiesis initially takes place in the blood islands of the yolk sac (spanning from the 19th day to the beginning of the 4th month of intrauterine life). From the 6th developmental week onward, hemopoiesis shifts to the Liver, and by the 3rd month, it also begins in the Spleen, continuing in these sites until the end of the prenatal period.

Bone marrow begins to form within embryonic bones at the end of the 2nd month of development. Blood Vessels develop within the marrow tissue by the 12th week, and reticular tissue emerges around them, giving rise to the initial hematopoietic islands. From this point onward, the bone marrow begins to function as a blood-forming organ. Starting around the 20th week, the mass of the bone marrow increases rapidly, expanding toward the epiphyses. Bony trabeculae within the diaphyses of long bones are resorbed, forming the medullary cavity. At birth, red bone marrow occupies all medullary cavities. Fat cells within the red bone marrow first appear postnatally (at 1–6 months), and by ages 20–25, yellow bone marrow completely fills the medullary cavities of the diaphyseal regions in long bones. In advanced age, the bone marrow assumes a mucous-like consistency, referred to as gelatinous bone marrow.

Hematopoiesis within the bone marrow, initiated at the 12th week of embryonic development, persists throughout an individual's lifetime. Blood Cells—namely erythrocytes, granulocytes, and platelets—differentiate extravascularly from stem cells. Additionally, stem cells give rise to monocytes (which belong to the macrophage system) and B-lymphocytes, which are Key Components of the immune system. Stem cells also migrate from the bone marrow to the thymus, where they differentiate into T-lymphocytes.

The immune system (from Latin immunitas meaning exemption or release) encompasses the Organs and Tissues responsible for defending the Organism against genetically foreign cells or substances, whether introduced externally or generated internally. The Organs of the immune system serve to "preserve the constancy of the organism's internal environment throughout the individual's life." They generate immunocompetent cells—predominantly lymphocytes, as well as plasma cells (plasmacytes)—incorporating them into immune responses to recognize and destroy cells and foreign substances "bearing the markers of genetically foreign information" (R. V. Petrov). When foreign agents—Antigens—invade the body, protective Proteins known as Antibodies are produced to neutralize them.

The organs of the immune system comprise all structures involved in producing cells that execute the body's defense mechanisms, thereby establishing Immunity—a state of non-susceptibility to agents bearing foreign antigenic properties. These organs are constructed from lymphoid tissue, which functions as a morphofunctional complex of lymphocytes, plasma cells, macrophages, and other cells embedded within a reticular fiber network. The immune organs include the bone marrow, the thymus, Lymph Nodes, the spleen, and aggregates of lymphoid tissue situated within the walls of the hollow organs of the digestive and respiratory tracts (such as the Tonsils, the lymphoid nodules of the Appendix and ileum, and Solitary lymphoid nodules). These organs are classically divided into central and peripheral compartments.

The Central Organs of the Immune System include the thymus and the human equivalent of the bursa of Fabricius (cellular clusters found in the cloacal wall of birds). The bone marrow is generally considered the functional homologue of the bursa of Fabricius in humans, with some evidence also pointing to the lymphoid nodules of the appendix and ileum.

The thymus serves as the site for the differentiation of T-lymphocytes (thymus-dependent cells), which develop from stem cells migrating into the organ from the bone marrow. Conversely, the bursal equivalent mediates The formation of B-lymphocytes (bursa-dependent, meaning their differentiation is independent of the thymus). Subsequently, these two lymphocyte populations enter the bloodstream and populate the peripheral immune organs, which encompass the tonsils, lymphoid nodules lining the hollow visceral organs, lymph nodes, and the spleen.

T-lymphocytes populate the thymus-dependent zones of lymph nodes (the paracortical zone), the spleen (the periarterial regions of lymphoid nodules and the periarterial lymphoid sheaths), and mediate both cellular immunity—via the proliferation and deployment of sensitized (hypersensitized) lymphocytes—and humoral immunity through the Synthesis of specific antibodies.

B-lymphocytes serve as precursors to antibody-producing cells, namely plasma cells and highly active lymphocytes. They migrate to the bursa-dependent areas of the LYMPH NODES AND spleen. B-lymphocytes are principally responsible for humoral immunity, wherein the primary roles are played by blood, lymph, and glandular secretions containing the antibodies that participate in immune reactions.

Under a Light Microscope, T- and B-lymphocytes are indistinguishable from one another. Transmission Electron Cell/15.html">Microscopy reveals that lymphocytes possess microscopic cytoplasmic projections on their surface known as microvilli. These projections bear receptors—sensitive structures capable of recognizing antigens, which are complex molecules that trigger an Immune Response within the organism. This response involves The production of antibodies by the Cells of the lymphoid tissue. The density of such surface receptors on B-lymphocytes is 100 to 200 times greater than on T-lymphocytes.

The Anatomy of the immune system's organs reveals several overarching patterns. Some are characteristic of all immune organs, others are exclusive to the central organs, and still others are specific to the peripheral Organs of Immunogenesis.

The first common characteristic across all organs of the immune system is that their functional parenchyma consists of lymphoid tissue. A second shared morphological feature is their early embryonic emergence during Organogenesis. A third hallmark is their morphological and functional maturity by the time of birth. Fourthly, these organs achieve their maximal development—quantitatively in terms of mass, dimensions, number of lymphoid nodules, and the presence of germinal centers—during childhood and adolescence. Finally, a fifth common feature is their relatively early age-related involution.

The central organs of the immune system are distinguished by several key features: first, their anatomical Location in areas exceptionally well-shielded from external environmental influences. The bone marrow is encased within the medullary cavities of bones, while the thymus is situated in the thoracic cavity posterior to the broad and robust Sternum. Second, both the bone marrow and the thymus serve as sites where lymphocytes differentiate from precursor stem cells. Third, within these central organs, lymphoid tissue is embedded within a specialized microenvironmental niche—reticular Connective Tissue in the bone marrow and Epithelial Tissue in the thymus.

Peripheral immune organs are characterized by the further differentiation of lymphoid tissue, marked initially by the appearance of clusters of lymphoid-Lineage cells—pre-nodular aggregates—which subsequently mature into structured lymphoid nodules. The highest degree of structural differentiation within these organs is signaled by The Emergence of germinal centers within the lymph nodes. Such centers develop within the nodules in response to prolonged or robust antigenic stimulation. The appearance of germinal centers reflects, on the one hand, The impact of potent and diverse environmental factors, and on the other hand, a high level of activity in the body's defense systems.

A second characteristic feature of peripheral immune organs is their strategic placement along pathways where genetically foreign substances might enter the body, or along the transit routes of such substances generated internally. The tonsils, which form the pharyngeal lymphoid ring (Pirogov-Waldeyer's ring), encircle the entrance to the Pharynx from the oral and nasal cavities. Numerous small clusters of lymphoid tissue, known as lymphoid nodules, are scattered throughout the mucous membranes of the digestive, respiratory, and urinary tracts. Large and prominent aggregations of lymphoid tissue are situated within the walls of the small and large intestines, flanking the ileocecal valve amidst distinct microbial environments. In the Small Intestine, these appear as Aggregated lymphoid follicles (Peyer's patches) alongside numerous solitary lymphoid nodules. On the opposite side of the ileocecal valve lie the cecum and appendix, rich in lymphoid follicles. Lymph nodes are positioned directly along the lymphatic drainage routes from various organs and tissues, including the body's outer coverings—the Skin and mucous membranes. The spleen, interposed along the vascular pathway between the arterial and venous systems, stands as the sole organ dedicated to "monitoring" the blood. Within the spleen, the functions of recognizing and clearing senescent erythrocytes are carried out by the periarterial lymphoid sheaths, ellipsoid capillaries, uniquely structured splenic sinuses, and the red pulp (splenic parenchyma).

For a Description of the thymus, refer to the chapter "Endocrine Organs"; for the lymph nodes, see the chapter "Lymphatic system."