8536d_ ch02024-056 9/6/029: 00 PM Page 24 mac85 Mac 85: 365 smm poldsby et al./Immunology 5e: Cells and Organs of the chapter 2 Immune System HE IMMUNE SYSTEM CONSISTS OF MANY DIFFERENT organs and tissues that are found throughout the body. These organs can be classified functionall nto two main groups. The primary lymphoid organs provide appropriate microenvironments for the development and maturation of lymphocytes. The secondary lymphoid organs trap antigen from defined tissues or vascular spaces and are sites where mature lymphocytes can interact effectively with that antigen. Blood vessels and lymphatic systems connect these organs, uniting them into a functional whole Carried within the blood and lymph and populating the Macrophage Interacting with Bacteria uphold various white blood cells, or leuko- cytes, that participate in the immune response. Of these a Hematopoiesis cells, only the lymphocytes possess the attributes of diversity specificity, memory, and self/nonself recognition, the hall- Cells of the Immune System marks of an adaptive immune response. All the other cells a Organs of the Immune System play accessory roles in adaptive immunity, serving to activate lymphocytes, to increase the effectiveness of antigen clear- a Systemic Function of the Immune System ance by phagocytosis, or to secrete various immune-effector a Lymphoid Cells and Organs-Evolutionary molecules. Some leukocytes, especially T lymphocytes, se- Compariso rete various protein molecules called cytokines. These mol ecules act as immunoregulatory hormones and pla important roles in the regulation of immune responses. Th chapter describes the formation of blood cells, the properties contrast to a unipotent cell, which differentiates into a single of the various immune-system cells, and the functions of the cell type, a hematopoietic stem cell is multipotent, or pluripo- lymphoid organs. ent, able to differentiate in various ways and thereby generate erythrocytes, granulocytes, monocytes, mast cells, lympho- cytes, and megakaryocytes. These stem cells are few, normally Hematopoiesis fewer than one HSC per 5 X 10" cells in the bone marrow The study of hematopoietic stem cells is difficult both be All blood cells arise from a type of cell called the hematopoi- cause of their scarcity and because they are hard to grow in etic stem cell(HSC). Stem cells are cells that can differentiate vitro. As a result, little is known about how their proliferation into other cell types; they are self-renewing-they maintain and differentiation are regulated. By virtue of their capacity heir population level by cell division. In humans, for self-renewal, hematopoietic stem cells are maintained at hematopoiesis, the formation and development of red and stable levels throughout adult life; however, when there is an white blood cells, begins in the embryonic yolk sac during the increased demand for hematopoiesis, HSCs display an enor- first weeks of development. Here, yolk-sac stem cells differen- mous proliferative capacity. This can be demonstrated in tiate into primitive erythroid cells that contain embryonic mice whose hematopoietic systems have been completely de hemoglobin In the third month of gestation, hematopoietic stroyed by a lethal dose of x-rays(950 rads; one rad repre- stem cells migrate from the yolk sac to the fetal liver and then sents the absorption by an irradiated target of an amount of to the spleen; these two organs have major roles in radiation corresponding to 100 ergs/gram of target). Such ir hematopoiesis from the third to the seventh months of gesta- radiated mice will die within 10 days unless they are infused tion. After that, the differentiation of HSCs in the bone mar bone-marrow cells from a syngeneic(genetically row becomes the major factor in hematopoiesis, and by birth identical)mouse. Although a normal mouse has 3 X 10 there is little or no hematopoiesis in the liver and spleen bone-marrow cells, infusion of only 10-10 bone-marrow It is remarkable that every functionally specialized, ma- cells(i. e, 0.01%-0.1% of the normal amount)from a donor ture blood cell is derived from the same type of stem cell In is sufficient to completely restore the hematopoietic system,contrast to a unipotent cell, which differentiates into a single cell type, a hematopoietic stem cell is multipotent, or pluripo￾tent, able to differentiate in various ways and thereby generate erythrocytes, granulocytes, monocytes, mast cells, lympho￾cytes, and megakaryocytes. These stem cells are few, normally fewer than one HSC per 5 104 cells in the bone marrow. The study of hematopoietic stem cells is difficult both be￾cause of their scarcity and because they are hard to grow in vitro. As a result, little is known about how their proliferation and differentiation are regulated. By virtue of their capacity for self-renewal, hematopoietic stem cells are maintained at stable levels throughout adult life; however, when there is an increased demand for hematopoiesis, HSCs display an enor￾mous proliferative capacity. This can be demonstrated in mice whose hematopoietic systems have been completely de￾stroyed by a lethal dose of x-rays (950 rads; one rad repre￾sents the absorption by an irradiated target of an amount of radiation corresponding to 100 ergs/gram of target). Such ir￾radiated mice will die within 10 days unless they are infused with normal bone-marrow cells from a syngeneic (genetically identical) mouse. Although a normal mouse has 3 108 bone-marrow cells, infusion of only 104 –105 bone-marrow cells (i.e., 0.01%–0.1% of the normal amount) from a donor is sufficient to completely restore the hematopoietic system, chapter 2 ■ Hematopoiesis ■ Cells of the Immune System ■ Organs of the Immune System ■ Systemic Function of the Immune System ■ Lymphoid Cells and Organs—Evolutionary Comparisons Cells and Organs of the Immune System T       organs and tissues that are found throughout the body. These organs can be classified functionally into two main groups. The primary lymphoid organs provide appropriate microenvironments for the development and maturation of lymphocytes. The secondary lymphoid organs trap antigen from defined tissues or vascular spaces and are sites where mature lymphocytes can interact effectively with that antigen. Blood vessels and lymphatic systems connect these organs, uniting them into a functional whole. Carried within the blood and lymph and populating the lymphoid organs are various white blood cells, or leuko￾cytes, that participate in the immune response. Of these cells, only the lymphocytes possess the attributes of diversity, specificity, memory, and self/nonself recognition, the hall￾marks of an adaptive immune response. All the other cells play accessory roles in adaptive immunity, serving to activate lymphocytes, to increase the effectiveness of antigen clear￾ance by phagocytosis, or to secrete various immune-effector molecules. Some leukocytes, especially T lymphocytes, se￾crete various protein molecules called cytokines. These mol￾ecules act as immunoregulatory hormones and play important roles in the regulation of immune responses. This chapter describes the formation of blood cells, the properties of the various immune-system cells, and the functions of the lymphoid organs. Hematopoiesis All blood cells arise from a type of cell called the hematopoi￾etic 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, hematopoiesis, 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 differen￾tiate into primitive erythroid cells that contain embryonic hemoglobin. 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 gesta￾tion. After that, the differentiation of HSCs in the bone mar￾row becomes the major factor in hematopoiesis, and by birth there is little or no hematopoiesis in the liver and spleen. It is remarkable that every functionally specialized, ma￾ture blood cell is derived from the same type of stem cell. In Macrophage Interacting with Bacteria 8536d_ch02_024-056 9/6/02 9:00 PM Page 24 mac85 Mac 85:365_smm:Goldsby et al. / Immunology 5e: