Your browser is too old
We can't provide a great video experience on old browserUpdate now
Formation and development of red and white blood cells is Hematopoiesis. All blood cells arise from a type of cell called the hematopoietic stem cell (HSC). Stem cells are cells that can differentiate into other cell types; they are self-renewing—they maintain their population level by cell division. In humans, haematopoiesis, the formation and development of red and white blood cells, begins in the embryonic yolk sac during the first weeks of development. Here, yolk-sac stem cells differentiate into primitive erythroid cells that contain embryonic haemoglobin. In the third month of gestation, hematopoietic stem cells migrate from the yolk sac to the Fetal liver and then to the spleen; these two organs have major roles in hematopoiesis from the third to the seventh months of gestation. After that, the differentiation of HSCs in the bone marrow becomes the major factor in hematopoiesis, and by birth there is little or no hematopoiesis in the liver and spleen.
Haematopoiesis is regulated at the genetic Level. The development of pluripotent hematopoietic stem cells into different cell types requires the expression of different sets of lineage-determining and lineage-specific genes at appropriate times and in the correct order. The proteins specified by these genes are critical components of regulatory networks that direct the differentiation of the stem cell and its descendants. Much of what we know about the dependence of hematopoiesis on a particular gene comes from studies of mice in which a gene has been inactivated or “knocked out” by targeted disruption, which blocks the production of the protein that it encodes. If mice fail to produce red cells or particular white blood cells when a gene is knocked out, we conclude that the protein specified by the gene is necessary for development of those cells. Knockout technology is one of the most powerful tools available for determining the roles of particular genes in a broad range of processes and it has made important contributions to the identification of many genes that regulate haematopoiesis.
Programmed cell death, an induced and ordered process in which the cell actively participates in bringing about its own demise, is a critical factor in the homeostatic regulation of Cells undergoing programmed cell death often exhibit distinctive morphologic changes, collectively referred to as apoptosis. These changes include a pronounced decrease in cell volume, modification of the cytoskeleton that results in membrane blebbing, a condensation of the chromatin, and degradation of the DNA into smaller fragments. Following these morphologic changes, an apoptotic cell sheds tiny membrane-bounded apoptotic bodies containing intact organelles. Macrophages quickly phagocytose apoptotic bodies and cells in the advanced stages of apoptosis. This ensures that their intracellular contents, including proteolytic and other lytic enzymes, cationic proteins, and oxidizing molecules are not released into the surrounding tissue. In this way, apoptosis does not induce a local inflammatory response.
Cells of the Immune System
Lymphocytes constitute 20%–40% of the body’s white blood cells and 99% of the cells in the lymph. There are approximately 1011 lymphocytes in the human body. These lymphocytes continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs, thereby integrating the immune system to a high degree. The lymphocytes can be broadly subdivided into three populations—B cells, T cells, and natural killer cells—on the basis of function and cell-membrane components. Natural killer cells (NK cells) are large, granular lymphocytes that do not express the set of surface markers typical of B or T cells. Resting B and T lymphocytes are small, motile, nonphagocytic cells, which cannot be distinguished morphologically. B and T lymphocytes that have not interacted with antigen—referred to as naive, or unprimed—are resting cells in the G0 phase of the cell cycle. Known as small lymphocytes, their cytoplasm forms a barely discernible rim around the nucleus. Small lymphocytes have densely packed chromatin, few mitochondria, and a poorly developed endoplasmic reticulum and Golgi apparatus. The naive lymphocyte is generally thought to have a short life span. Interaction of small lymphocytes with antigen, in the presence of certain cytokines, induces these cells to enter the cell cycle by progressing from GO into G1 and subsequently into S, G2, and M. As they progress through the cell cycle, these cells have a higher cytoplasm: nucleus ratio and more organellar complexity than small lymphocytes. Lymphoblasts proliferate and eventually differentiate into effector cells or into memory cells. Effector cells function in various ways to eliminate antigen.
The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues. During haematopoiesis in the bone marrow, granulocyte-monocyte progenitor cells differentiate into promonocytes, which leave the bone marrow and enter the blood, where they further differentiate into mature monocytes. Monocytes circulate in the bloodstream for about 8 h, during which they enlarge; they then migrate into the tissues and differentiate into specific tissue macrophaged into dendritic cells. Differentiation of a monocyte into a tissue macrophage involves a number of changes: The cell enlarges five- to tenfold; its intracellular organelles increase in both number and complexity; and it acquires increased phagocytic ability, produces higher levels of hydrolytic enzymes, and begins to secrete a variety of soluble factors. Macrophages are dispersed throughout the body. Some take up residence in particular tissues, becoming fixed macrophages, whereas others remain motile and are called free, or wandering, macrophages. Free macrophages travel by amoeboid movement throughout the tissues.
Organs of the Immune System
A number of morphologically and functionally diverse organs and tissues have various functions in the development of immune responses. These can be distinguished by function as the primary and secondary lymphoid organs. The thymus and bone marrow are the primary (or central) lymphoid organs, where maturation of lymphocytes takes place. The lymph nodes, spleen, and various mucosal associated lymphoid tissues (MALT) such as gut-associated lymphoid tissue (GALT) are the secondary (or peripheral) lymphoid organs, which trap antigen and provide sites for mature lymphocytes to interact with that antigen. In addition, tertiary lymphoid tissues, which normally contain fewer lymphoid cells than secondary lymphoid organs, can import lymphoid cells during an inflammatory response. Most prominent of these are cutaneous-associated lymphoid tissues. Once mature lymphocytes have been generated in the primary lymphoid organs, they circulate in the blood and lymphatic system, a network of vessels that collect fluid that has escaped into the tissues from capillaries of the circulatory system and ultimately return it to the blood.
The thymus is the site of T-cell development and maturation. It is a flat, bilobed organ situated above the heart. Each lobe is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of connective tissue called trabeculae. Each lobule is organized into two compartments: the outer compartment, or cortex, is densely packed with immature T cells, called thymocytes, whereas the inner compartment, or medulla, is sparsely populated with thymocytes. The role of the thymus in immune function can be studied in mice by examining the effects of neonatal thymectomy, a procedure in which the thymus is surgically removed from new-born mice. These thymectomized mice show a dramatic decrease in circulating lymphocytes of the T-cell lineage and an absence of cell-mediated immunity. Other evidence of the importance of the thymus comes from studies of a congenital birth defect in humans (DiGeorge’s syndrome) and in certain mice (nude mice) in which the thymus fails to develop. In both cases, there is an absence of circulating T cells and of cell-mediated immunity and an increase in infectious disease.
Secondary and Tertiary Lymphoid organs
As blood circulates under pressure, its fluid component (plasma) seeps through the thin wall of the capillaries into the surrounding tissue. Much of this fluid, called interstitial fluid, returns to the blood through the capillary membranes. The remainder of the interstitial fluid, now called lymph, flows from the spaces in connective tissue into a network of tiny open lymphatic capillaries and then into a series of progressively larger collecting vessels called lymphatic vessels.
Various types of organized lymphoid tissues are located along the vessels of the lymphatic system. Some lymphoid tissue in the lung and lamina propria of the intestinal wall consists of diffuse collections of lymphocytes and macrophages. Other lymphoid tissue is organized into structures called lymphoid follicles, which consist of aggregates of lymphoid and nonlymphoid cells surrounded by a network of draining lymphatic capillaries. Until it is activated by antigen, a lymphoid follicle—called a primary follicle—comprises a network of follicular dendritic cells and small resting B cells. After an antigenic challenge, a primary follicle becomes a larger secondary follicle—a ring of concentrically packed B lymphocytes surrounding a center (the germinal center) in which one finds a focus of proliferating B lymphocytes and an area that contains nondividing B cells, and some helper T cells interspersed with macrophages and follicular dendritic cells
Lymph nodes are the sites where immune responses are mounted to antigens in lymph. They are encapsulated bean shaped structures containing a reticular network packed with lymphocytes, macrophages, and dendritic cells. The spleen plays a major role in mounting immune responses to antigens in the blood stream. It is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity. While lymph nodes are specialized for trapping antigen from local tissues, the spleen specializes in filtering blood and trapping blood-borne antigens; thus, it can respond to systemic infections. Unlike the lymph nodes, the spleen is not supplied by lymphatic vessels.
Functions and Evolution
The many different cells, organs, and tissues of the immune system are dispersed throughout the body, yet the various components communicate and collaborate to produce an effective response to an infection. An infection that begins in one area of the body initiates processes that eventually involve cells, organs, and tissues distant from the site of pathogen invasion. Consider what happens when the skin is broken, allowing bacteria to enter the body and initiate infection.
The tissue damage associated with the injury and infection results in an inflammatory response that causes increased blood flow, vasodilation, and an increase in capillary permeability. Chemotactic signals are generated that can cause phagocytes and lymphocytes to leave the blood stream and enter the affected area. Factors generated during these early stages of the infection stimulate the capacity of the adaptive immune system to respond. Langerhans cells (dendritic cells found throughout the epithelial layers of the skin and the respiratory, gastrointestinal, urinary, and genital tracts) can capture antigens from invading pathogens and migrate into a nearby lymphatic vessel, where the flow of lymph carries them to nearby lymph nodes.