Monopoiesis, Lymphopoiesis, and Megakaryopoiesis 1 Monopoiesis 2 Monopoiesis system consists of monocytes, macrophages, and their precursors. ► Monopoiesis is the formation of mature monocytes from monoblasts. ► Primary function of a monocyte is as a “scavenger” cell. Monoblast ► Mononuclear Promonocyte Monocyte 3 Monoblasts ► Monoblast has large, eccentrically placed nucleus. ► Nucleus may be minimally indented with 1-2 nucleoli. ► Fine lacy nuclear chromatin in nucleus. ► Cytoplasm is deep blue and lacks granules. ► N:C ratio is 4:1. ► Cells are non-motile and nonphagocytic. ► Give rise to promonocytes. 4 Promonocytes Promonocytes have large indented or folded nuclei with fine chromatin and irregular margins. May have nucleoli. ► N:C ratio is 3:1 or 2:1. ► Promonocytes slightly motile. Are rarely phagocytic. ► Will not be required to identify these cells on peripheral blood smear. ► 5 Monocytes ► ► ► ► 1 of 3 Promonocytes develop into monocytes. Enter into peripheral bloodstream for short period of time. Then migrate into tissues to be transformed into tissue macrophages. Is large cell (15-18μm). Is larger than mature neutrophil. Have abundant cytoplasm in relation to nucleus. N:C ratio is 2:1 or 1:1. Cytoplasm turns dull gray-blue (dove gray). 6 Monocytes ► ► ► See numerous fine, small reddish or purplish granules in cytoplasm, giving it a "ground glass" appearance. Occasionally see digestive vacuoles. In disease states, may see phagocytized erythrocytes, nuclei, cell fragments, bacteria, fungi, or pigments. Nucleus frequently kidney shaped, deeply folded or indented; may occasionally be lobular. Nucleus has brainlike convolutions. Has large, delicate chromatin network. 2 of 3 7 Monocytes 3 of 3 Shape of monocyte variable. May see blunt pseudopods. ► Monocytes have three morphological characteristics: brainlike nuclear convolutions, blunt pseudopods, and dull gray cytoplasm. ► Account for 2-9% of total leukocytes. ► 8 Macrophages ► ► As monocytes move into surrounding tissues, are converted into macrophages. Macrophages normally do not re-enter bloodstream. Are phagocytic cells. Macrophages also called histiocytes. 9 Lymphopoiesis 10 Lymphopoiesis Development from lymphoblast to a mature lymphocyte. ► Primary function of lymphocytes is to protect against viral infections. ► Lymphoblast Prolymphocyte Lymphocyte 11 Lymphoblast ► Lymphoblast contains large round nucleus with small amount of basophilic cytoplasm. ► Nuclear chromatin strands are thin, loose, and evenly stained. One or more nucleoli visible. 12 Prolymphocytes ► Prolymphocytes have intermediate chromatin clumping. Parachromatin (reddish purple color) may be present in nucleus. Nucleoli may or may not be present. 13 Lymphocytes ► ► ► ► The lymphocyte progenitor cell can differentiate into either Blymphocytes (B-cells) or Tlymphocytes (T-cells). T-cells differentiate in thymus and B-cells differentiate in bone marrow. Do have a third class of lymphocytes - null cells. Will not differentiate different classes of lymphocytes on peripheral blood smear. 14 Reactive Lymphocytes 1 of 3 ► Reactive or atypical lymphocytes. ► After exposure to antigen, lymphocytes transform into immunologically competent cells. ► Nucleus and cytoplasm enlarge. Size varies, but are usually large cells with abundant cytoplasm. 15 Reactive Lymphocytes 2 of 3 ► Nucleus may be indented, oval, or irregularly shaped with intermediate chromatin pattern. Rarely see blast-like nucleus with visible nucleoli. ► See varying degrees of basophilia. May see distinctive reddish granules. 16 Reactive Lymphocytes 3 of 3 ► Cytoplasm may contain vacuoles or appear bubbly. ► Cell may have scalloped edges. ► Primarily see in viral infections. 17 Plasma Cell Formation 18 Plasmablasts and Proplasmacytes ► Plasmablast is similar in appearance to other blast forms. ► N:C ratio is 4:1. ► Nucleus appears round with fine, linear chromatin patterns and very visible nucleoli. ► Seen in multiple myeloma patients. ► Will not be required to identify plasmablasts or proplasmacytes in peripheral blood. 19 Plasmacytes or Plasma Cells 1 of 3 ► Are end stage of B-cell development. Not seen in peripheral blood of healthy individuals. ► Nucleus usually round or oval with slightly irregular margins. 20 Plasmacytes or Plasma Cells 2 of 3 ► Cytoplasm non-granular and stains deep, vibrant blue (cornflower or larkspur blue). Cytoplasm adjacent to nucleus is pale with perinuclear clear zone. ► At cell periphery, have secretory vesicles. May see fibrin strands in cytoplasm. 21 Plasmacytes or Plasma Cells 1 of 3 ► Nucleus relatively small, round or oval, and eccentrically placed. Nuclear chromatin is clumped. ► Produce immunoglobulins (antibodies). ► Always put up for pathologist review if found in peripheral blood. 22 Megakaryopoiesis 23 Megakaryopoiesis ► Will cover this material in MLAB 1227 Coagulation. Are responsible for morphological characteristics of mature platelet. ► Are cytoplasmic fragments. Have no nucleus, Resemble broken pieces of china. Are often purple in color. 24 25 Bone-Derived Cells ► Not responsible for this section. 26 Molecular Hematology 27 Introduction to Cell Cycle ► When stimulated by hematopoietic growth factors, cells undergo continuous generative cycle (G cycle) in which cells divide, differentiate, or remain dormant. ► Bone marrow contains cell populations in all phases of cell development. ► Cell cycle is divided into five phases: G0, G1, S, G2, and M. G0 is resting or dormant phase after cell division. G1 is postmitotic rest phase. S is synthesis of DNA phase. G2 is premitotic rest phase. M is mitosis phase. 28 Multipotential Stem Cells – Colony Forming Units ► All cells derived from pluripotential stem cell which has capacity for continuous selfreplication and differentiation into multipotential stem cell and lymphoid stem cell which lack self-replication ability. ► Multipotential stem cell becomes committed to progenitor cells for each of the cell lines. 29 Colony-Stimulating Factors and Interleukins ► Each cell line dependent on cytokines. Cytokines are soluble mediators secreted by cells for purpose of cell-to-cell communication. ► Act on multipotential cells to stimulate their proliferation and differentiation. ► Two types of cytokines are colonystimulating factors or growth factors and interleukins. 30 Trends in Therapeutic Manipulation of Hematopoiesis ► This section will be covered in MLAB 1335. 31 1. Study Questions 2. Homework Assignment 3. Exam for Unit I will be on Sept 13 32