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Haemopoiesis
- 2. Bone Marrow • In adults, bone marrow is the major site of production of various blood cells • In the fetus, blood cells are also formed in the Liver and Spleen • Active cellular marrow is called Red Marrow; whereas inactive marrow that has been infiltrated with fat is called Yellow Marrow • Bone marrow indeed is one of the largest and most active organs in the body !!
- 3. 66x 200x
- 5. From One to Many…
- 7. Hematopoietic Stem Cells (HSCs) • The blood cells begin their lives in the bone marrow from a single type of cell called the pluripotent hematopoietic stem cell, from which all the cells of the circulating blood are eventually derived • As these cells reproduce, a small pool of these cells is maintained throughout life to maintain a continuous supply
- 8. Hematopoietic Stem Cells (HSCs) • The best current source of these stem cells is “Umbilical Cord Blood” • Have you heard of Cord blood banks ??
- 10. Growth Inducers • Growth and reproduction of the different stem cells are controlled by multiple proteins called growth inducers or factors • One of these, interleukin-3, promotes growth and reproduction of virtually all the different types of committed stem cells, whereas the others induce growth of only specific types of cells
- 11. Differentiation Inducers • The growth inducers promote growth but not differentiation of the cells. This is the function of another set of proteins called differentiation inducers • Each of these causes one type of committed stem cell to differentiate one or more steps toward a final adult blood cell
- 12. Red Blood Cells
- 14. RBCs • CFU-E stem cells differentiate into proerythroblast • It divides multiple times, eventually forming many mature red blood cells • In the succeeding generations, the cells become filled with hemoglobin to a concentration of about 34 %, the nucleus condenses to a small size, and its final remnant is absorbed or extruded from the cell
- 16. Regulation of RBCs Production • Tissue Oxygenation Is the Most Essential Regulator of Red Blood Cell Production • The principal stimulus for red blood cell production in low oxygen states is a circulating hormone called erythropoietin, a glycoprotein with a molecular weight of about 34,000 • Erythropoietin is secreted by specialized cells in the Kidney
- 18. Regulation of RBCs Production • When a person moves to an atmosphere of low oxygen, erythropoietin begins to be formed within minutes to hours, and it reaches maximum production within 24 hours • But it takes about 5 days before increased number of RBCs enter the blood • Erythropoietin stimulates the production of proerythroblasts from hematopoietic stem cells in the bone marrow
- 19. Maturation of RBCs • The erythropoietic cells of the bone marrow are among the most rapidly growing and reproducing cells in the entire body • Therefore, their maturation and rate of production are affected greatly by a person's nutritional status • Especially important for final maturation of the red blood cells are two vitamins, vitamin B12 and folic acid
- 20. Maturation of RBCs • Both vitamin B12 and folic acid are essential for the synthesis of DNA because each, in a different way, is required for the formation of thymidine triphosphate, one of the essential building blocks of DNA • Lack of either vitamin B12 or folic acid causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division
- 21. Maturation of RBCs • Furthermore, the erythroblastic cells of the bone marrow, in addition to failing to proliferate rapidly, produce mainly larger than normal red cells called macrocytes and the cell itself has a flimsy membrane and is often irregular, large, and oval instead of the usual biconcave disc
- 24. WBCs • Aside from those cells committed to form red blood cells, two major lineages of white blood cells are formed, the myelocytic and the lymphocytic lineages • The granulocytes, monocytes and megakaryocytes are formed only in the bone marrow • Lymphocytes are produced mainly in the lymphatic tissues- especially the lymph glands, spleen and thymus
- 25. Myeloid stem cell Myeloblast Basophil progenitor Eosinophil progenitor Neutrophil progenitor Basophil granulocyte Eosinophil granulocyte Neutrophil granulocyte Myelopoiesis (1)
- 26. Myeloid stem cell Monoblast Megakaryoblast Megakaryocyte Monocyte Platelets Macrophage Myelopoiesis (2)
- 27. Regulation of WBCs Production • Granulocyte macrophage colony-stimulating factor (GM-CSF) is a protein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts • GM-CSF is a cytokine that functions as a white blood cell growth factor. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes
- 28. Myelopoiesis • The white blood cells formed in the bone marrow are stored within the marrow until they are needed in the circulatory system. Then, when the need arises, various factors cause them to be released • Megakaryocytes are also formed in the bone marrow. These megakaryocytes fragment in the bone marrow; the small fragments, known as platelets (or thrombocytes), then pass into the blood
- 29. Lymphopoiesis Hematopoietic stem cell Pluripotent stem cell Lymphoid stem cell NK cell T lymphocyte B lymphocyte
- 30. Lymphopoiesis • The lymphocytes are mostly stored in the various lymphoid tissues where they undergo maturation, except for a small number that are temporarily being transported in the blood • Their numbers increase in circulation only when required
- 31. T and B Lymphocytes • T and B lymphocytes are indistinguishable histologically • However T and B lymphocytes are very distinct cell lineages and they ‘grow up’ or ‘mature’ in different places in the body. • They are also biochemically distinct and this is reflected in the different markers and receptors present on their cell surfaces
- 32. T Lymphocytes • T cells are formed in bone marrow then migrate to the cortex of the thymus to undergo maturation in an antigen-free environment • Only 2-4% of the T cells succeed. The remaining 96- 98% of T cells die by apoptosis and are phagocytosed by macrophages in the thymus • So many T cells die during the maturation process because there is intensive screening to make sure each T cell has the ability to recognize self (self tolerance)
- 33. T Lymphocytes • Upon maturity, there are several forms of T lymphocytes: • T-helper (needed for activation of other cells such as B cells and macrophages), • T-cytotoxic (which kill virally infected cells), • T-memory (T cells that remember antigens previously encountered), and • T-suppressor cells (which moderate the immune response of other leukocytes) • When T-Cells become activated they undergo a further series of developments
- 34. B Lymphocytes • B cells are formed and mature in bone marrow (and spleen). • These B cells then leave the bone marrow and migrate to peripheral lymphoid tissues, such as a lymph node. Once in a secondary lymphoid organ the B cell can be introduced to an antigen that it is able to recognize. • Through this antigen recognition and other cell interactions the B cell becomes activated and then divides and differentiates to become a plasma cell.
- 35. B Lymphocytes • The plasma cell, is a very active antibody-secreting cell that helps protect the body by attacking and binding to antigen • Some B cells, upon activation, become memory cells. They remain dormant, but upon the attack of same antigen in future can quickly transform into plasma cells and start making antibodies
- 36. Helper T Lymphocytes B Lymphocytes Antibodies Cell-mediated Immunity Antibody-mediated Immunity Cytotoxic T Lymphocytes Cytokines Direct killing of Microbes Bind to invading Antigens
- 37. References Guyton and Hall Textbook of Medical Physiology, 12th edition, 2011 Naish Medical Sciences, 1st edition, 2011