Erythropoiesis and hemoglobin formation. The modern scheme of hematopoiesis. Regulation of hematopoiesis

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Modern theory hematopoiesis The modern theory of hematopoiesis is based on the unitary theory of A.A. Maksimov (1918), according to which all blood cells originate from a single parent cell, morphologically resembling a lymphocyte. This hypothesis was confirmed only in the 1960s when lethally irradiated mice were injected with donor bone marrow. Cells capable of restoring hematopoiesis after irradiation or toxic effects are called "stem cells"

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Modern theory of hematopoiesis Normal hematopoiesis is polyclonal, that is, it is carried out simultaneously by many clones. The size of an individual clone is 0.5-1 million mature cells. The life span of a clone does not exceed 1 month, about 10% of clones exist up to six months. The clonal composition of the hematopoietic tissue changes completely within 1-4 months. permanent replacement clones is explained by the depletion of the proliferative potential of the hematopoietic stem cell, so the disappeared clones never reappear. Different hematopoietic organs are inhabited by different clones, and only some of them reach such a size that they occupy more than one hematopoietic territory.

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Differentiation of hematopoietic cells Hematopoietic cells are conditionally subdivided into 5-6 sections, the boundaries between which are very blurred, and between the sections there are many transitional, intermediate forms. In the process of differentiation, there is a gradual decrease in the proliferative activity of cells and the ability to develop first into all hematopoietic lines, and then into more and more limited quantity lines.

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Differentiation of hematopoietic cells Department I - totipotent embryonic stem cell (ESC), located at the very top of the hierarchical ladder Department II - a pool of poly- or multipotent hematopoietic stem cells (HSC) HSCs have unique property- pluripotency, i.e., the ability to differentiate into all lines of hematopoiesis without exception. In cell culture, conditions can be created when a colony arising from one cell contains up to 6 different cell lines of differentiation.

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HSC hematopoietic stem cells are formed during embryogenesis and are consumed sequentially, forming successive clones of more mature hematopoietic cells. 90% of clones are short-lived, 10% of clones can function for a long time. HSCs have a high but limited proliferative potential, are capable of limited self-maintenance, i.e., are not immortal. HSCs can undergo approximately 50 cell divisions and maintain the production of hematopoietic cells throughout a person's life.

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Hematopoietic stem cells The HSC division is heterogeneous, represented by 2 categories of progenitors with different proliferative potential. The bulk of HSC is in the G0 resting phase of the cell cycle and has a huge proliferative potential. When leaving dormancy, HSC enters the path of differentiation, reducing the proliferative potential and limiting the set of differentiation programs. After several cycles of division (1-5), HSCs can return to the resting state again, while their resting state is less deep and, if there is a request, they respond faster, acquiring markers of certain lines of differentiation in cell culture in 1-2 days, while the original HSCs need 10-14 days. Long-term maintenance of hematopoiesis is provided by reserve HSCs. The need for an urgent response to a request is satisfied at the expense of the CCM, which have undergone differentiation and are in a state of quickly mobilized reserve.

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Hemopoietic stem cells The heterogeneity of the HSC pool and the degree of their differentiation is established on the basis of the expression of a number of differentiating membrane antigens. Among HSCs, the following were identified: primitive multipotent progenitors (CD34+Thyl+) and more differentiated progenitors characterized by the expression of class II histocompatibility antigen (HLA-DR), CD38. True HSCs do not express lineage-specific markers and give rise to all hematopoietic cell lines. The amount of HSC in the bone marrow is about 0.01%, and together with progenitor cells - 0.05%.

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Hematopoietic stem cells One of the main methods for studying HSCs is the method of colony formation in vivo or in vitro, therefore HSCs are otherwise called “colony forming units” (CFU). True HSCs are capable of forming colonies from blast cells (CFU blasts). This also includes cells that form splenic colonies (CFUs). These cells are able to completely restore hematopoiesis.

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Differentiation of hematopoietic cells III department - As the proliferative potential decreases, HSCs differentiate into polyoligopotent committed progenitor cells that have limited potency, as they are committed to differentiation in the direction of 2-5 hematopoietic cell lines. Polyoligopotent committed precursors of CFU-HEMM (granulocytic-erythrocyte-macrophage-megakaryocytic) give rise to 4 hematopoietic sprouts, CFU-GM - to 2 sprouts. CFU-GEMMs are a common precursor of myelopoiesis. They have CD34 marker, CD33 myeloid lineage marker, histocompatibility determinants HLA-A, HLA-B, HLA-C, HLA-DR.

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Differentiation of hematopoietic cells Cells of the IV department - monopotent committed progenitors are parental for one germ of hematopoiesis: CFU-G for granulocytic, CFU-M - for monocyte-macrophage, CFU-E and BFU-E (burst-forming unit) - precursors of erythroid cells, CFU- Mgcc - precursors of megakaryocytes All committed progenitor cells have a limited life cycle and are not capable of returning to a state of cellular dormancy. Monopotent committed progenitors express markers of the respective cell line of differentiation.

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HSC and progenitor cells have the ability to migrate - out into the blood and return to the bone marrow, which is called the "homing-effect" (home instinct). It is this property that ensures the exchange of hematopoietic cells between dissociated hematopoietic areas, which allows them to be used for transplantation in the clinic.

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Differentiation of hematopoietic cells V department of morphologically recognizable cells includes: differentiating, maturing mature cells of all 8 cell lines, starting with blasts, most of which have characteristic morphological and cytochemical features.

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Regulation of hematopoiesis Hematopoietic tissue is a dynamic, constantly renewing cellular system of the body. More than 30 million cells are formed per minute in the hematopoietic organs. During a person's life - about 7 tons. As they mature, the cells formed in the bone marrow evenly enter the bloodstream. Erythrocytes circulate in the blood - 110-130 days, platelets - about 10 days, neutrophils - less than 10 hours. 1x10¹¹ blood cells are lost daily, which is replenished by the "cell factory" - the bone marrow. With an increase in the demand for mature cells (blood loss, acute hemolysis, inflammation), production can be increased by 10-12 times within a few hours. The increase in cell production is provided by hematopoietic growth factors

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Regulation of Hematopoiesis Hematopoiesis is initiated by growth factors, cytokines, and continuously maintained by a pool of HSCs. Hemopoietic stem cells are stroma-dependent and perceive short-range stimuli received by them during intercellular contact with cells of the stromal microenvironment. As the cell differentiates, it begins to respond to long-range humoral factors. Endogenous regulation of all stages of hematopoiesis is carried out by cytokines through receptors on the cell membrane, through which a signal is transmitted to the cell nucleus, where the corresponding genes are activated. The main producers of cytokines are monocytes, macrophages, activated T-lymphocytes, stromal elements - fibroblasts, endothelial cells, etc.

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Regulation of hematopoiesis HSC renewal occurs slowly and when ready for differentiation (commitment process), they leave the resting state (Go - phase of the cell cycle) and become committed. This means that the process has become irreversible and such cells, controlled by cytokines, will go through all stages of development up to the final mature blood elements.

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Hematopoiesis regulation factors Hematopoiesis regulation factors are divided into short-range (for HSC) and long-range for committed progenitors and maturing cells. Depending on the level of cell differentiation, regulatory factors are divided into 3 main classes: 1. Factors affecting early HSC: stem cell factor (SCF), granulocyte colony stimulating factor (G-CSF), interleukins (IL-6, IL-11, IL -12), inhibitors that inhibit the release of HSC into the cell cycle from a resting state (MIP-1α, TGF-β, TNF-α, acid isoferritins, etc.). This phase of SCM regulation does not depend on the demands of the body.

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Regulation of hematopoiesis The activation and functioning of cells depends on many cytokines. The cell begins differentiation only after interacting with growth factors, but they do not participate in the choice of the direction of differentiation. The content of cytokines determines the number of cells produced, the number of mitoses performed by the cell. So, after blood loss, a decrease in pO2 in the kidneys leads to an increase in the production of erythropoietin, under the influence of which erythropoietin-sensitive erythroid cells - the precursors of the bone marrow (BFU-E), increase the number of mitoses by 3-5, which increases the formation of erythrocytes by 10-30 times. The number of platelets in the blood regulates the production of growth factor and the development of cellular elements of megakaryocytopoiesis. Another regulator of hematopoiesis is apoptosis - programmed cell death.

hematopoiesis(syn. hematopoiesis) is a process consisting in a series of cell differentiations that lead to the formation of mature peripheral blood cells. To a large extent, this process has been studied in embryos; in the body of an adult, it can be traced during the restoration of K. after severe cytostatic effects.

In the study of K., the works of A. A. Maksimov, A. N. Kryukov, A. D. Timofeevsky, N. G. Khlopin, A. A. Zavarzin, and A. Pappenheim played an important role. Critical importance in the study of the processes of cell differentiation was used special methods staining of cells in smears developed by P. Erlich and D. L. Romanovsky in the 70s. 19th century

The scheme of hematopoiesis of I. A. Kassirsky and G. A. Alekseev (1967) was the most widespread in the USSR, edges summed up morfol, a stage of studying of this process. It reflected the hypothesis of A. A. Maksimov about the unitary origin of all blood cells - from one type of cells (hemocytoblasts). It was assumed that the close proximity of stromal elements (fibroblasts), which form the cells of the bone marrow, and the hematopoietic cells themselves reflect their histogenetic relationship. This assumption turned out to be wrong. Along with the unitary idea of ​​K., there was also a dualistic hypothesis that allowed for the separate origin of lymphocytes and all other blood elements. The polyphyletic theory of K., representing the origin of many rows of hematopoietic cells independently of each other, is only of historical interest.

The long coexistence of various hypotheses about the origin of blood cells is explained by the fact that visually trace the most initial stages K. was impossible because of the morphs, the similarity of the parent cells of all sprouts of K., and funkts, methods did not exist.

In 1961, Till and McCulloch (J. E. Till, E. A. McCulloch) proposed a method based on the fact that after the introduction of lethally irradiated mice with donor bone marrow, macroscopically visible foci (colonies) of hematopoietic cells develop in their spleens. Using the method of chromosome markers (stably changed after chromosome irradiation), Becker (A. j. Becker, 1963) showed that each such colony is a clone - the offspring of one cell, called the colony-forming unit in the spleen (CFU). When a colony is formed, a single CFU produces several million differentiated progeny cells while simultaneously maintaining its own line of colony-forming cells, which, when the next irradiated mouse is retransplanted, again produce hematopoietic colonies in its spleen. Thus, the existence in the adult organism has been demonstrated special cells, which have the ability for long-term self-maintenance and differentiation into mature blood cells. New clonal research methods made it possible to study the progeny of a single colony-forming cell and directly identify hematopoietic cells - the precursors of different classes, to evaluate their differentiation and proliferative capabilities (see Cell and tissue cultures).

Lymphocyte colonies are not formed in the spleens of irradiated mice after bone marrow injection; therefore, the question of the origin of lymphocytes from a common pluripotent cell, the precursor of both hematopoietic and lymphoid cells, has long been the subject of discussion. Using the method of splenic colonies in combination with the method of radiation markers, it was possible to show that lymphocytes carry the same markers as the hematopoietic cells of splenic colonies. Thus, the presence of a pluripotent cell, common to all sprouts of K., including for lymphocytes, was experimentally confirmed. These cells, called stem cells, turned out to be capable of both self-maintenance and differentiation in all rows of cells (printing table).

The concentration of stem cells in the hematopoietic organs (see) is relatively small - in the bone marrow of mice, their apprx. 0.5%. Morphologically, they are indistinguishable from lymphocytes. Differentiation of the original pluripotent stem cell into the first morphologically recognizable cells of one or another series is a multi-stage process leading to significant expansion the number of each row. On this path, there is a gradual limitation of the ability of precursor cells (this term refers to the entire set of morphologically similar cells of the upper three rows of the K. scheme) to various differentiations and a gradual decrease in their ability to self-maintenance. Stem pluripotent cells have a very high ability to self-maintenance - the number of mitoses performed by each cell can reach 100; most of them are at rest, at the same time in the cycle is approx. 20% cells.

After the existence of stem cells was proved using the method of bone marrow culture for the granulocyte-monocyte germ, and then for the erythrocyte and megakaryocytic germ, poetic-sensitive precursor cells were discovered. The development of methods for cultivating these sprouts made it possible to evaluate both morphological and functional features of the corresponding poetic-sensitive cells. The vast majority of them are in the stage of active proliferation. Morphologically, poetine-sensitive cells, as well as stem cells, are indistinguishable from lymphocytes. The principal feature of the poetic-sensitive cell line is their ability to respond to humoral regulatory influences. It is at the level of these cells that the mechanisms of quantitative regulation of K. are realized, a cut meets the specific needs of the body in the cells of a particular series. In the agar culture of the bone marrow, granulocytes develop sequentially, which are then replaced by monocytes that turn into macrophages. Monocytes appear to replace granulocytes, needing, like the latter, in the so-called. colony-stimulating factor - a putative specific hormonal regulator.

Fibroblast colonies never give rise to hematopoietic cells, and there is never a transformation of hematopoietic cells into fibroblasts.

A significant addition to the concept of lymphocytopoiesis was the discovery of two types of lymphocytes - B- and T-cells, the first of which are responsible for humoral immunity, i.e., the production of antibodies, and the second carry out cellular immunity, participate in the reaction of rejection of foreign tissue (see Immunocompetent cells). It turned out that B-lymphocytes, as a result of antigenic stimulation, can transform from a morphologically mature cell into a blast form and further differentiate into cells of the plasma series. Under the influence of antigenic stimulation, T-lymphocytes are also transformed into a blast form. Thus, which previously seemed to be a single lymph, the row is represented by three rows of cells: B-, T-lymphocytes and plasma cells closely related to B-lymphocytes. In addition, the usual idea of ​​​​a blast cell (a blast is a cell that usually has a narrow cytoplasm, a finely structured nucleus, which is distinguished by the uniformity of the caliber and color of chromatin filaments, often contains nucleoli) as the ancestor of the series turned out to be not entirely accurate for lymphocytes: mature lymphocytes with exposed to specific antigens, they are again able to transform into blast cells. This phenomenon is called the reaction of blastotransformation of lymphocytes (see). Lymphocytes transformed under the action of antigens are called immunoblasts. Arrows had to be introduced into K.'s scheme, indicating the possibility of the transition of morphologically mature lymphocytes into the corresponding blast forms.

Between stem and poetin-sensitive cells are the precursor cells of myelopoiesis and lymphocytopoiesis. The existence of these cells has not been strictly proven, but a number of leukemias have been found, primarily hron, myeloid leukemia, as well as subleukemic myelosis, erythromyelosis, in which the only source tumor proliferation may be cells that are younger (less differentiated) than poetic-sensitive, but more mature than stem cells. The existence of limf, leukemias, represented by both B- and T-lymphocytes at the same time, i.e., arising from their common predecessor, is also shown.

In K.'s scheme, the stem cell and cells of the 2nd and 3rd rows are framed and given in two morphological different options in which they are able to be: lymphocyte-like and blast.

At the level of poetic-sensitive cells, the differentiation capabilities of cells are further limited. At this and the following morphologically recognizable stages of differentiation, the vast majority of cells are in a state of proliferation.

The last cells capable of dividing among granulocytes are myelocytes, and among erythrokaryocytes - polychromatophilic normocytes. In the process of differentiation, morphologically recognizable cells of the erythrocyte series undergo 5-6 mitoses; granulocytic cells - 4 mitoses; in monocytopoiesis, 7-8 mitoses pass from a monoblast to a macrophage. In megakaryocytopoiesis, several morphologically distinct precursors are distinguished, which, starting from the megakaryoblast, undergo 4-5 endomitoses (nucleus fission without cytoplasm division).

Using the method of cloning and analysis of chromosomal markers, it was shown that phagocytic cells, in particular liver Kupffer cells and all other tissue macrophages, combined into a system of phagocytic mononuclear cells, are derivatives of hematopoietic cells and are the offspring of monocytes, and not reticular cells and not endothelium. The cells of this system have no histogenetic commonality with either reticular or endothelial cells. The main funkts, the characteristics inherent in the cells entering this system, - ability to phagocytosis, pinocytosis, strong sticking to glass. In process of a differentiation in cells of this number there are receptors for immunoglobulins and a complement thanks to what cells acquire ability to active phagocytosis (see).

In erythrocytopoiesis (erythropoiesis), the youngest cell is the erythroblast (also called proerythroblast), which has a blast structure and usually a round nucleus. The cytoplasm is dark blue when stained, is located in a narrow rim, often gives peculiar outgrowths. There is no single nomenclature for erythrokaryocytic cells. Some call them normoblasts, others erythroblasts. Since for other rows the term "blast" is used only for the progenitor cells of one or another germ (hence the name "blast" - germ), all cells that are the offspring of erythroblast should have the ending "cyte" in the name. Therefore, the term "normoblasts" was replaced by "normocytes".

Behind the erythroblast, a pronormocyte appears, which differs from the erythroblast in the coarser structure of the nucleus, although it retains the correct structure of the chromatin filaments. The nucleus diameter is smaller than that of an erythroblast, the rim of the cytoplasm is wider, and the perinuclear zone of enlightenment becomes visible. When studying a myelogram (see), it is easy to confuse a pronormocyte with an erythroblast. Due to the difficulty of separating these cells, some authors propose not to differentiate them at all in practical hematology.

The next - polychromatophilic - normocyte has an even denser nuclear structure; the cytoplasm occupies most of the cell and has a basophilic coloration due to structures containing RNA, and oxyphilic due to the appearance of already enough hemoglobin.

Orthochromic, or oxyphilic, normocyte has a small dense nucleus (like a cherry seed), oxyphilic or basophilic cytoplasm. Normally, there are relatively few oxyphilic normocytes, because, pushing out the nucleus at this stage, the cell turns into an erythrocyte, but in the "newborn" erythrocyte, the remains of basophilia are always preserved due to a small amount RNA, edges disappears during the first day. Such an erythrocyte with remnants of basophilia is called a polychromatophilic erythrocyte. When using a special intravital coloring, the basophilic substance is detected in the form of a mesh; then this cell is called a reticulocyte.

A mature erythrocyte has the shape of a biconcave disc, so it has a central clearing in a blood smear. In process of aging the form of an erythrocyte gradually approaches spherical (see. Erythrocytes).

The youngest cell of thrombopoiesis (thrombopoiesis) is megakaryoblast - a single-nuclear small cell with a large blast nucleus, chromatin threads to-rogo are thicker and coarser than that of erythroblast; 1-2 dark blue nucleoli can be seen in the nucleus. The cytoplasm is grainless, dark blue in color, process, with a narrow rim surrounds the nucleus. A promegakaryocyte results from several endomitoses. The nucleus is polymorphic with a rough chromatin structure; the cytoplasm is dark blue, granular.

A mature megakaryocyte differs from a promegakaryocyte in having a large nucleus. The cytoplasm has a blue-pink color, contains azurophilic reddish granularity. Platelets are formed inside the megakaryocyte (see). In the smear, one can also see disintegrating Megakaryocytes surrounded by heaps of platelets. In thrombocytolytic conditions, platelet detachment can also occur at the promegakaryocyte stage, while platelets are deprived of the azurophilic substance, but they are actively involved in hemostasis.

Leukocytopoiesis (leukopoiesis) includes granulocytopoiesis (granulopoiesis), lymphocytopoiesis (lymphopoiesis) and monocytopoiesis (monopoiesis).

In the granulocytic series, the myeloblast is the first morphologically distinguishable cell. It has a non-structural core, single nucleoli. The shape of the nucleus is round, the dimensions are slightly smaller than those of the erythroblast. Myeloblast differs from undifferentiated progenitor blasts in the presence of granular cytoplasm; the shape of the cell is often round, even.

The next stage of maturation of granulocytes is the promyelocyte - neutrophilic, eosinophilic and basophilic. The round or bean-shaped nucleus of the promyelocyte is almost twice as large as the nucleus of the myeloblast, although this cell is not polyploid; it is often located eccentrically, and the remains of nucleolus can be seen in it. The structure of chromatin already loses the delicate filamentous structure of blast cells, although it does not have a coarse clumpy structure. The area of ​​the cytoplasm is approximately equal to the area of ​​the nucleus; the cytoplasm is abundantly saturated with granularity, which has features characteristic of each row. For the neutrophilic series, the promyelocyte is the most granular cell. Its granularity is polymorphic - large and small, stained with both acidic and basic dyes. In a promyelocyte, granularity is often located on the nucleus. The granularity of an eosinophilic promyelocyte, having the same type of grains characteristic of eosinophils (such as "ketov caviar"), is also stained with both acidic and basic dyes. The basophilic promyelocyte has a large polymorphic basophilic granularity.

Since the transition from a promyelocyte to the next stage of cell maturation - a myelocyte - is not abrupt, an intermediate form has appeared, called the "maternal myelocyte", which in all respects corresponds to the described promyelocyte, but differs from it in a coarser nucleus. In practice, this form is not taken into account; it was not included in the myelogram.

A myelocyte is a cell with a round or oval, often eccentrically located nucleus that has lost any signs of a blast. The cytoplasm is stained in a grayish-bluish tone, its granularity in a neutrophilic myelocyte is smaller than in a promyelocyte. The relative area of ​​the cytoplasm increases. An eosinophilic myelocyte has a characteristic orange-red granularity of the same type, a basophilic myelocyte has a polymorphic large basophilic granularity.

The metamyelocyte is characterized by a bean-shaped large-lumpy nucleus, usually located eccentrically. The area of ​​its cytoplasm is larger than the area of ​​the nucleus and the cytoplasm contains the same granularity as the myelocyte, but in neutrophilic metamyelocytes it is more scarce than in myelocytes.

The monocytic series is represented by fairly simple stages of transition. Normally, it is difficult to distinguish a monoblast from a myeloblast or an undifferentiated blast, but with monoblastic acute or monocytic hron, leukemia, these cells are easy to identify using histochemical staining. The promonocyte has a promyelocyte nucleus, but is devoid of granularity (see Leukocytes).

In the lymphocytic series, a lymphoblast (large lymphocyte) has all the features of an undifferentiated blast, but is sometimes characterized by single large nucleoli. Detection in a smear from limf, node or spleen of a blast without granularity allows us to attribute it to lymphoblasts. An attempt to differentiate a lymphoblast, a monoblast and an undifferentiated blast by the size and shape of the nucleus, by the width of the cytoplasmic rim is not successful, since the lymphoblast under the influence of antigenic stimulation can undergo a variety of changes.

The prolymphocyte has a relatively homogeneous nucleus structure, often the remains of nucleoli, but it does not have large clumps of chromatin characteristic of a mature lymphocyte (see Lymphocytes).

The plasmablast has a blast nucleus, granular violet-blue cytoplasm. The proplasmocyte, compared with the plasmacyte, has a denser nucleus, usually located eccentrically, with a relatively large blue-violet cytoplasm. The plasma cell is characterized by a wheel-shaped dense nucleus lying eccentrically; the cytoplasm is blue-violet, sometimes with a few azurophilic reddish granules. Both normally and in pathology, it can be multinucleated (see Plasma cells).

Being histogenetically unified, the hematopoietic system in its functioning is characterized by a certain independence of the behavior of individual germs.

Hematopoiesis in the antenatal period

Hematopoiesis in the antenatal period is first detected in a 19-day-old embryo in the blood islands of the yolk sac, in the stem and chorion. By the 22nd day, the first blood cells penetrate into the mesodermal tissue of the embryo, into the heart, aorta, and arteries. On the 6th week K.'s activity in a yolk sac decreases. Completely the first (mesoblastic) period of hematopoiesis, mainly erythrocytopoiesis, ends by the beginning of the 4th month. embryo life. Primitive hematopoietic cells of the yolk sac accumulate hemoglobin and turn into primitive erythroblasts, called megaloblasts by P. Ehrlich.

The second (hepatic) period To. begins after b weeks. and reaches a maximum by the 5th month. K. of this period is predominantly erythroid, although on the 9th week. the first neutrophils are already maturing in the liver. The hepatic period of erythrocytopoiesis is characterized by the disappearance of megaloblasts; while erythrocytes have normal sizes. At the 3rd month In embryonic life, the spleen is included in erythrocytopoiesis, but in humans its role in prenatal K. is limited.

At 4-5 months. the third (bone marrow) period begins. K. Myeloid fetal erythrocytopoiesis is erythroblastic and, like leukocytopoiesis, differs little from adult erythrocytopoiesis.

The general pattern of embryonic erythrocytopoiesis is a gradual decrease in the size of erythrocytes and an increase in their number. Respectively different periods To. (mesoblastic, hepatic and bone marrow) there are three different types of hemoglobin: embryonic, fetal and adult hemoglobin. Basically, the transition from fetal hemoglobin to adult hemoglobin begins at the 3rd week. fetal life and ends after 6 months. after birth.

In the first days, polyglobulia and neutrophilic leukocytosis are observed in newborns. Then the activity of erythrocytopoiesis decreases. It normalizes at the age of 2-3 months. Neutrophilia of the first days of life is replaced by lymphocytosis; only 5 years old leukocyte formula neutrophils begin to predominate.

Regulation of hematopoiesis

Regulation of a hemopoiesis is carried out by hl. arr. in a humorous way. Moreover, for each of the series K., apparently, this path is independent. With regard to erythrocytopoiesis, it is known that the differentiation of poetic-sensitive cells into erythroblasts (with their subsequent differentiation to mature erythrocytes) is impossible without erythropoietin (see). A stimulator for the production of erythropoietin is a drop in oxygen tension in the tissues. For the differentiation of granulocytes in culture, the presence of a colony-stimulating factor, which, like erythropoietin, belongs to alpha2-globulins, is necessary.

In addition to specific hormones such as erythropoietin, other hormones, for example, androgens, also act on K.. They stimulate erythrocytopoiesis by mobilizing endogenous erythropoietin. Mediators (adrenaline, acetylcholine) affect the hematopoietic system, not only causing redistribution shaped elements in the blood, but also through direct impact pas stem cells (adrenergic and cholinergic receptors were found in them).

The question of nervous regulation To. though a plentiful innervation of hemopoietic fabrics cannot but have biol, values. nervous tension, emotional overload leads to the development of short-term neutrophilic leukocytosis without significant rejuvenation of the composition of leukocytes. Slightly increases the level of leukocytes in the blood meal. A similar effect is caused by the introduction of adrenaline. This reaction is based mainly on the mobilization of the vascular granulocytic reserve. In this case, leukocytosis develops within a few tens of minutes. Leukocytosis with a stab shift is caused by the administration of pyrogenal and glucocorticoid steroid hormones, reaching a maximum after 2 hours, and is due to the release of granulocytes from the bone marrow reserve. The content of granulocytes in the bone marrow reserve exceeds their number in the bloodstream by 30-50 times.

Humoral regulation of hematopoiesis is carried out mainly at the level of poetic-sensitive cells. In experiments with uneven irradiation, it was shown that the restoration of hematopoietic cells in the irradiated limb occurs regardless of the composition of the blood and the state of non-irradiated areas of the bone marrow. Bone marrow transplantation under the mouse kidney capsule showed that the volume of bone marrow developing from the transplant is determined by the number of transplanted stromal cells. Consequently, they determine the limits of reproduction of stem cells, from which the bone marrow then develops in the kidney of the recipient mouse. The works of A. Ya. Friedenshtein et al. (1968, 1970) showed the specificity of stromal cells of various hematopoietic organs: spleen stromal cells determine the differentiation of stem cells in the direction of lymphocytopoiesis, bone marrow stromal cells - in the direction of myelopoiesis. At the same time, apparently, there are powerful stimulants, the inclusion of which occurs under unusual conditions (eg, severe anemia), which leads to the development of foci of unusual K. in the spleen, with predominant reproduction of erythrokaryocytes. This is most often seen in childhood. Such foci K., called extramedullary, contain, along with erythrokaryocytes, a small percentage of other elements of the bone marrow - myelocytes, promyelocytes, megakaryocytes. With acute massive or prolonged increased cell loss, K. can follow additional paths in each of the rows. Apparently, there are opportunities for the emergence of special precursor cells of the 3rd row of the K. scheme, which give rise to such shunt pathways of K., which ensure the rapid production of a large number of cells. This is well documented in erythrocytopoiesis, but probably exists in other series as well.

Inclusion of stem cells in a differentiation is most likely random process, the probability to-rogo at stable To. makes approximately 50%. The regulation of the number of stem cells is not general, but local in nature and is provided by mechanisms that function in each specific area of ​​the hematopoietic microenvironment. It is much less clear whether the direction of differentiation of hematopoietic stem cells is regulated. Based on a number of experimental data, it is suggested that the probability of stem cell differentiation in the direction of erythrocytopoiesis, granulocytopoiesis, etc. is always constant and does not depend on external conditions.

There are no facts testifying to the existence of a specialized system that regulates K.. Maintaining a certain amount of mature cells in the blood is carried out by multi-stage transmission of neurohumoral signals. The signal goes to the cell reserve or cell depot, from which erythrocytes are mobilized very quickly when acute blood loss. Then, the production of the corresponding cells at the level of poetic-sensitive elements is stimulated by increasing their number, first without differentiation ("horizontal mitoses"), and then with differentiation. As a result, a category of mature cells is created.

Pathology of hematopoiesis

The pathology of hematopoiesis can be manifested by a violation of cell maturation, the release of immature cellular elements into the blood, the appearance in the peripheral blood unusual for this age category cellular elements. Bacterial infection, extensive tissue decay (decaying tumors, cellulitis, etc.), endotoxinemia are accompanied by severe neutrophilic leukocytosis with an increase in the percentage of stab neutrophils, the frequent appearance of metamyelocytes, myelocytes, and promyelocytes in the blood. There is no clear relationship between the degree of leukocytosis and the severity of damage to the body. Leukocytosis depends, on the one hand, on the volume of the bone marrow and vascular granulocytic reserve and on the activity of bone marrow production, on the other hand, on the intensity of consumption of granulocytes in the focus of inflammation. The state opposite to leukocytosis (see) - leukopenia (see), caused primarily by granulocytopenia, may be associated with suppression of granulocyte production as a result of exposure to anti-granulocyte antibodies, bone marrow aplasia of an immune nature, for example, characterized by simultaneous inhibition of granulocytic, erythrocyte and megakaryocytic sprouts, or aplasia of unknown origin (actually aplastic anemia); in other cases, granulocytopenia and leukopenia may be due to increased breakdown of granulocytes in an enlarged spleen (eg, with hron, hepatitis, cirrhosis of the liver). Due to the existence of a bone marrow reserve, a decrease in the number of granulocytes in the blood due to their increased use meets seldom (eg, at extensive drain pneumonia). Leukopenia is common sign tumor replacement of marrow at miliary metastases, at acute leukoses and is occasionally observed at the beginning hron, a lymphocytic leukemia. With leukemia (see) the number of leukocytes in the blood may increase; constantly it happens at hron, leukoses. In acute leukemia, the content of leukocytes in the blood can be different: at the beginning of the process, leukopenia is more often noted, then, as blast tumor cells enter the blood, leukocytosis may occur.

Viral infection, antigenic effects lead to increased production of specific lymphocytic clones, an increase in the level of lymphocytes in the blood. A decrease in the number of platelets (see Thrombocytopenia) is observed with the appearance of autoantibodies to platelets (less often to megakaryocytes), with increased destruction of them by the enlarged spleen. A decrease in platelet count is possible as a result of blood loss, in the event of extensive hematomas, and disseminated intravascular coagulation (consumption thrombocytopenia). An increase in the content of platelets (see Thrombocythemia) is observed in some hron, leukemia (chron, myeloid leukemia, subleukemic myelosis, erythremia), often in cancer. Sometimes, with kidney cancer, cancer cells produce erythropoietin and, possibly, thrombopoietin (see), which is accompanied by sharp rise erythrocyte and platelet counts.

The content of erythrocytes in the blood is determined by the ratio of their decay and production, blood loss, and the body's supply of iron. Iron deficiency leads to a decrease in the level of hemoglobin in erythrocytes with a normal number of them in the blood - a low color indicator. On the contrary, vitamin B 12 deficiency is accompanied by a violation of cell division as a result of violations of DNA synthesis; at the same time, the erythrocytes are ugly, there are few of them, but there is more hemoglobin in them than normal - an increased color indicator (see Hyperchromasia, hypochromasia).

In some cases, reactions of several germs to nonspecific stimulating effects are also possible. For example, the development of a cancerous tumor in the body can lead to an increase in the blood content of both granulocytes and platelets. A similar picture is occasionally observed in sepsis.

To. undergoes deep changes at acute beam influence. These changes in their main manifestations correspond to the changes that often develop during chemotherapy of tumors. Under the influence of ionizing radiation the dividing cells of bone marrow, limf, nodes perish. Mature granulocytes, erythrocytes remain viable even at obviously lethal radiation doses. On the other hand, mature lymphocytes are radiosensitive cells. This explains the rapid decrease in their number in the peripheral blood in the first hours after irradiation. Since erythrocytes in the blood live approx. 120 days, anemia develops in 1 - 1.5 months. after irradiation. By this time in severe cases active K. begins, an increase in the content of reticulocytes is observed, and anemia does not reach a high degree.

In mild cases, restorative reticulocytosis develops after 1.5 months. after irradiation, but anemia is also not deep.

One of the consequences of irradiation is the death of bone marrow cells and the subsequent decrease in cells in the peripheral blood. For manifestations of acute radiation injury, the “dose-effect” formula is specific, characterizing the strict dependence of primary changes on the absorbed dose of ionizing radiation. Bone marrow damage is primary changes, and infections resulting from bone marrow suppression, hemorrhages - to secondary ones; their severity, and the very appearance of damage, is not strictly dose-related. It is conditionally considered that total exposure in a dose of more than 100 rad leads to the development of acute radiation sickness (see). Smaller doses, although they lead to significant death of bone marrow cells, do not represent an immediate danger (radiation damage without a wedge, manifestations). When irradiated at a dose of more than 200 rad, lymphopenia, agranulocytosis, and deep thrombocytopenia develop; anemia usually does not occur. At lower doses, the same disturbances are noted, but to a lesser extent. Total or close to it irradiation of the body in doses of more than 200 rad leads to a maximum drop in the number of leukocytes, platelets and reticulocytes. The time of onset of leukopenia is also strictly dependent on the radiation dose. Here, not only the “dose-effect” pattern is demonstrated, but also the “dose-effect time” pattern, i.e., the duration of clinically detectable damage in acute radiation sickness is determined by the radiation dose.

The pattern of changes in the number of leukocytes in peripheral blood depends on the dose of radiation. These changes are made up of a period of initial rise during the first day, a period of initial decline (5-14 days), a period of temporary rise, which is observed at doses less than 500-600 rad and is absent at higher radiation doses; periods of the main fall and the final recovery, which are observed at doses less than 600 rad (Fig.). The same pattern is observed in platelets and reticulocytes.

The mechanism of fluctuations in the number of leukocytes can be represented as follows. The initial rise is apparently redistributive in nature and usually lasts no more than a day, its height is not related to the radiation dose; only the level of granulocytes increases in the blood and there is no rejuvenation of their composition, which is due to the mobilization of the vascular granulocytic reserve.

After a period of initial rise, a gradual drop in the number of leukocytes begins, reaching a minimum value at different times depending on the dose. The higher the dose, the sooner the moment of maximum decline will come. At radiation doses above 600-1000 rad, this period does not further shorten, although with a decrease in dose it lengthens even at a dose of approx. 80-100 glad falls approximately on the 14th day. The level of fall in the number of leukocytes during the initial decline is dose dependent. The period of the initial decrease in leukocytes should be explained by the consumption of the bone marrow granulocytic reserve (up to 5–6 days) and only partly by the maturation and differentiation of the cells that remained after irradiation (from the moment of irradiation to the end of the initial decrease). Such a conclusion is possible in connection with the preservation of granulocytes in the blood up to 5-6 days. even at such high doses (more than 600-1000 rad), when there are no cells left in the bone marrow capable of any kind of differentiation, but only highly radiosensitive non-dividing mature granulocytes remain. At radiation doses of the bone marrow above 600 rad, almost all cells have gross damage to the chromosomal apparatus and die immediately after the first mitosis within the next few days after irradiation. At smaller doses, a certain part of the bone marrow cells retains the ability to divide and differentiate. The more of them, the later the end of the period of the initial decrease in the number of leukocytes.

The fact that by the 5-6th day. the reserve has been exhausted, which is also confirmed by the fact that these days giant neutrophils begin to appear in the blood - the production of cells of the proliferating pool, apparently irradiated in mitosis. Giant neutrophils are found from the 5th to the 9th day. after radiation exposure in the blood of persons totally irradiated in any dose (these cells are found in the blood even after the action of cytostatics). When irradiated at a dose of more than 600 rad, the release of giant neutrophils immediately precedes the onset of agranulocytosis.

The next stage is temporary, so-called. abortive, an increase in the number of leukocytes - is noted at radiation doses of less than 500-600 rad, and at higher doses, the period of the initial drop is directly replaced by a period of the main decrease in the number of leukocytes. The origin of the abortive rise is not fully understood. Its duration is determined by the radiation dose: the higher the dose, the shorter it is; while the level of leukocytes is clearly not related to the dose. The same abortive rise is characteristic of platelets and reticulocytes. With relatively no large doses- OK. 100-200 rad - abortive rise continues until the 20-30th day. and is replaced by a period of the main fall, and at doses of more than 200 rad - agranulocytosis, very low level platelets and the almost complete disappearance of reticulocytes. The final restoration of hematopoiesis (after the period of the main fall) occurs the later, the lower the dose. The duration of the period of the main fall at doses from 200 to 600 glad is approximately the same. The abortive rise is due to the activation of temporary K., possibly coming from the precursor cell of myelopoiesis, which, before it is exhausted, blocks the differentiation of stem cells responsible for the final restoration of K. in the bone marrow. After the period of the main drop in the blood, normalization of the cellular level occurs. In some cases, this recovery is not entirely complete and the level of leukocytes and platelets is slightly reduced.

The discovery of a period of temporary rise in granulocytes, platelets and reticulocytes (but not lymphocytes) with a paradoxical phenomenon of an earlier final restoration of blood composition at high doses of radiation (up to 500 rad) suggested the presence of an inhibitory effect of myelopoiesis precursor cells on stem cell proliferation.

Changes in the composition of the bone marrow in acute radiation sickness have been studied less well than changes in the peripheral blood. The bone marrow is affected by irradiation even at low doses that do not cause acute radiation sickness, although immediately after irradiation it is not always possible to detect a decrease in the number of cells. Important Information about the severity of bone marrow damage gives its cytol, characteristic. Already on the first day after irradiation, the cells of the red row, the percentage of myeloblasts and promyelocytes are significantly reduced. The higher the radiation dose, the more profound these changes. In the following weeks, the emptying of the bone marrow gradually increases. The content of granulocytes is predominantly reduced. The devastation of the bone marrow in the early days ahead of the occurrence of agranulocytosis in the peripheral blood. According to the bone marrow punctate, one can judge the disappearance of foci of hematopoiesis; hematopoietic cells (with moderate damage) are almost absent. Important changes the cellular composition of the bone marrow and peripheral blood were revealed as a result of the use of chromosomal analysis. By the end of the first day, the appearance of mitoses with structural disorders chromosomes - chromosomal aberrations (see Mutation), the number of which is strictly proportional to the radiation dose: at a dose of 100 rad, the number of aberrant mitoses is 20%, at a dose of 500 rad - approx. 100%. The method of determining the number of leukocytes during the period of the primary fall (on the 7-8th day), the time of the beginning of the period of the main fall of leukocytes formed the basis of the biol system, dosimetry during acute radiation exposure.

Significant changes also occur in lymphocytopoiesis. Starting from the first day, the number of lymphocytes in the blood decreases and clearly depends on the radiation dose. After 2 months after irradiation, their content in the blood reaches a normal level. An in vitro study of the chromosomes of peripheral blood lymphocytes stimulated to mitosis by phytohemagglutinin (see), reveals a dose dependence. Lymphocytes in the peripheral blood are in the intermitotic period for many years; therefore, even several years after irradiation, it is possible, by the number of aberrant mitoses in them, to establish the fact of increased exposure in the past and to determine approximately the dose of irradiation. In the bone marrow, cells with chromosomal aberrations disappear after 5-6 days, because as a result of the loss of chromosome fragments during mitosis, they become unviable. When bone marrow cells are stimulated with phytohemagglutinin (PHA), chromosomal damage is detected in them many years after irradiation. These cells were at rest all the years after irradiation, and the response to PHA indicates their lymphocytic nature. The usual analysis of chromosomal aberrations of bone marrow cells is performed without PHA stimulation.

Observations of the restoration of blood composition after acute exposure have shown that the recovery rate is associated not only with the dose of radiation, but also with secondary manifestations of the disease (eg, with inflammatory processes in the skin, in the intestines, etc.). Therefore, at the same dose of radiation, the time of onset of agranulocytosis in different patients is the same, and the elimination of agranulocytosis depends on the degree of damage to other organs.

At hron, radiation sickness, edges arises as a result of repeated repeated exposures organism for months or years in a total dose of more than 200-300 rad, K.'s recovery does not have such a natural dynamics; the death of cells is extended for a long period, during which both recovery processes occur To., and the processes of its further damage. In this case, cytopenia may not develop. Individual signs the asthenic syndrome inherent hron, radiation sickness, can appear at some patients and at radiation in a total dose apprx. 100 rad. In bone marrow at hron, radiation sickness find separate small accumulations of undifferentiated cells, decrease in quantity of cells. Either there are no changes in the blood, or moderate non-progressive cytopenia is noted - granulocytopenia, thrombocytopenia,

Bibliography: Bochkov N.P. and Pyatkin E.N. Factors inducing chromosomal aberrations in humans, in the book: Fundamentals of Human Cytogenetics, ed. A.A. Prokofieva-Belgovskaya, p. 176, M., 1969; Brilliant M. D. and Sparrow-e in A. I. Changes in some indicators of peripheral blood during total irradiation of a person, Probl, gematol, and overflow, blood, t. 17, No. 1, p. 27, 1972, bibliogr.; Zavarzin A. A. Essays on the evolutionary histology of blood and connective tissue, in. 2, M.-L., 1947, bibliography; Kassirsky I. A. and A l of e to-with e e in G. A. Clinical hematology, M., 1970; Maksimov A. A. Fundamentals of histology, parts 1-2, L., 1925; Normal hematopoiesis and its regulation, ed. Edited by N. A. Fedorova. Moscow, 1976. Guide medical issues radiation protection, ed. A. I. Burnazyan, p. 101, M., 1975; FriedensteinA. I. and L and ly to and N and K. S. Bone tissue induction and osteogenic progenitor cells, M., 1973, bibliogr.; KhlopinN. G. General biological and experimental bases of histology, L., 1946; Chertkov I. L. and Vorobyov A. I. Modern scheme of hematopoiesis, Probl, gematol. and transfusion, blood, vol. 18, no. 10, p. 3, 1973, bibliogr.; Chertkov I. L. iFridenstein A. Ya. Cellular bases of hematopoiesis, M., 1977, bibliogr.; Abramson S., Miller R. G. a. P h i 1 1 ip s R. A. The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid svstems, J. exp. Med., v. 145, p. 1565, 1977; Becker A. J., M c C u 1- 1 o c h E. A. a. T i 1 1 J. E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells, Nature (Lond.), v. 197, p. 452, 1963; Becker A. J. a. o. The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony-forming cells of mice, Blood, v. 26, p. 296, 1965; Byron J. W. Manipulation of the cell cycle of the hemopoietic stem cell, Exp. Hematol., v. 3, p. 44, 1975; E b b e S. Megakaryocytopoiesis and platelet turnover, Ser. Haematol., v. 1, p. 65, 1968; Metcalf D. Hemopoietic colonies, in vitro cloning of normal and leukemic cells, B.-N. Y., 1977; Metcalf D. a. Moore M. A. S. Haemopoietic cells, Amsterdam, 1971; Till J. E. a. McCulloch E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells, Radiat. Res., v. 14, p. 213, 1961.

A. I. Vorobyov, I. L. Chertkov.

Hematopoiesis - hematopoietic h- is the process of development of cellular elements, which leads to the formation of mature peripheral blood cells.

The process of hematopoiesis can be depicted as a diagram in which cells are arranged in a certain sequence based on their degree of maturation. According to modern ideas about hematopoiesis, all blood cells come from one, which gives rise to three hematopoietic sprouts: leukocyte, erythrocyte and platelet.

In the scheme of hematopoiesis, blood cells are divided into 6 classes. The first four classes are progenitor cells, the fifth class are maturing cells, and the sixth are mature cells.

Class I.- Class of pluripotent progenitor cells

It is represented by stem cells, the number of which in the hematopoietic tissue is a fraction of a percent. These cells are capable of unlimited self-maintenance for a long time (longer than the lifespan of a person). Stem cells are pluripotent, i.e., all hematopoietic sprouts develop from them. Most of stem cells are at rest and only about 10% of them are dividing. During division, two types of cells are formed - stem (self-maintenance) and cells capable of further development (differentiation). The latter constitute the next class.

II. Class of partially determined pluripotent progenitor cells

Represented to a limited extent by pluripotent cells, i.e., cells that can give rise to either lymphopoiesis (the formation of cells of the lymphoid series) or myelopoiesis (the formation of cells of the myeloid series). Unlike stem cells, they are capable of only partial self-maintenance.

Class III. Class of unipotent progenitor cells

In the process of further differentiation, cells called unipotent progenitors are formed. They give rise to one strictly defined series of cells: lymphocytes, monocytes and granulocytes (leukocytes with granularity in the cytoplasm), erythrocytes and platelets.

In the bone marrow, two categories of precursor cells of lymphocytes are found, from which they are formed. B - and T-lymphocytes. B-lymphocytes mature in the bone marrow and are then transported by the bloodstream to the lymphoid organs. Plasma cells are formed from the precursors of B-lymphocytes. Part of the lymphocytes in the embryonic period enters the thymus gland (thymus) through the blood and is designated as T-lymphocytes. Later they differentiate into lymphocytes.

Cells of this class are also not capable of long-term self-maintenance, but are capable of reproduction and differentiation.

All cells of three classes are morphologically non-differentiable cells

Class IV. Morphologically recognizable proliferating cells

Represented by young cells capable of dividing, forming separate rows of myelo and lymphopoiesis. All elements of this series have the ending "blast": plasmablast, lymphoblast, monoblast, myeloblast, erythroblast, megakaryoblast. From the cells of this class, cells of the next class are formed in the process of division.

Class V. Class of maturing cells

It is represented by maturing cells, the names of which have a common ending "cyt". All elements of this class are located in the scheme vertically and in a certain sequence, due to the stage of their development.

The names of the cells of the first stage begin with the prefix "pro" (before): proplasmocyte, prolymphocyte, promonocyte, promyelocyte, pronormocyte, promegakaryocyte. Elements of the granulocytic series go through two more stages in the development process: myelocyte and metamyelocyte ("meta" means after). The metamyelocyte below the myelocyte in the diagram represents the transition from myelocyte to mature granulocyte. The cells of this class also include stab granulocytes. Pronormocytes in the process of erythropoiesis go through the stages of normocytes, which, depending on the degree of saturation of the cytoplasm with hemoglobin, have additional definitions: basophilic normocyte, polychromatophilic normocyte and oxyphilic normocyte. Of these, reticulocytes are formed - immature erythrocytes with remnants of the nuclear substance.

Class VI. class of mature cells

Represented by mature cells incapable of further differentiation with limited life cycle. These include: plasmocyte, lymphocyte, monocyte, segmented granulocytes (eosinophil, basophil, neutrophil), erythrocyte, platelet.

Mature cells move from the bone marrow to the peripheral blood.

An indicator characterizing the state of bone marrow hematopoiesis is a myelogram - a quantitative ratio of cells varying degrees maturity of all hematopoietic sprouts

Ministry of Health and Social Development

GOU VPO Irkutsk State Medical University

V.V.Madayev

Tutorial

Approved by the Federal Migration Service of the Irkutsk Medical University on April 20, 2009.

Protocol No. 9

Reviewer: A.P. Silin, Ph.D. Assistant of the Department of Hospital Therapy of the State Medical University, Chief Hematologist of the Irkutsk Region.

Series editor: Department of Faculty Therapy, Prof., MD Kozlova N.M

Madaev V.V. Leukemias. Irkutsk; twenty13 . 23 p.

The textbook is devoted to the diagnosis and treatment of leukemia and is intended for students of medical universities (pediatric, dental, medical and preventive faculties).

Publisher: Irkutsk Forward LLC

© V.V.Madayev, 2013 Irkutsk State Medical University

Hematopoiesis 4

ACUTE LEUKEMIA 6

Etiology 6

Pathogenesis 7

Bone marrow pathology 8

Diagnostics 10

Treatment 13

CHRONIC LYMPHOLEUKEMIA 14

Diagnostics 14

Treatment 16

CHRONIC MYELOLUKEMIA 17

Diagnostics 17

Treatment 18

APPENDIX 18

LITERATURE 23

ABBREVIATIONS

hematopoiesis

Hematopoiesis is called the development of blood cells, i.e. a process consisting of a series of cellular differentiations that lead to the formation of mature peripheral blood cells. There are embryonic hematopoiesis, which leads to the development of blood as a tissue and occurs in the embryonic period, and postembryonic hematopoiesis, which is a process of physiological blood regeneration.

Hematopoietic organs - red bone marrow, thymus, lymph nodes, spleen, lymphoid formations along the gastrointestinal tract and respiratory system and their main function is the formation of blood cells.

The basis of the genealogical tree of all cellular elements of the blood is a stem pluripotent cell. The main property of a stem cell is the ability to proliferate ( cell division) with differentiation in a certain direction. These cells constitute class I in the hematopoiesis scheme. The P class includes partially determined pluripotent progenitor cells, i.e. progenitor cell for red, leukocyte and megakaryocytic lineages; and progenitor cell for lymphocytes.

Class III - unipotent progenitors includes precursor cells of individual lines of differentiation in the hematopoietic-lymphatic system. The cells of the above three classes are morphologically undifferentiated.

Class IV includes morphologically recognizable proliferating cells, the ancestral elements of all sprouts of the red bone marrow, and these include myeloblast, erythroblast, lymphoblast, monoblast, megakaryoblast, megakaryoblast, plasmablast.

The V class of maturing cells includes transitional elements of all germs (promyelocyte, myelocyte, metamyelocyte, pronormoblast, normoblasts, promegakaryocyte, megakaryocyte, promonocyte, prolymphocyte).

Class VI includes mature cells leukocytes granulocytes - neutrophils (stab and segmented), basophils, eosinophils, agranulocytes - monocytes, lymphocytes; platelets, erythrocytes.

Neutrophils (segmented, stab)

The most important function of neutrophils is phagocytosis. The neutrophil performs this function once in its life, capturing, killing, digesting a microbe or other foreign cell, it dies.

Basophils

The main function - participation in immunological reactions, is associated with specific JgE receptors located on the surface of the basophil, to which JgE is attached.

Eosinophils

The main function is participation in allergic reactions. Eosinophilia is also observed in helminthic invasions and autoimmune diseases.

Picture. Scheme of hematopoiesis.

Lymphocytes

They are divided into T-lymphocytes -70% and B - lymphocytes 30%. In turn, T-lymphocytes are divided into T-killers, T-helpers and suppressors. The main functions of lymphocytes are hematopoietic, trophocytic and immunological, which is carried out by B-lymphocytes responsible for the development of the humoral response in the body, which is expressed in the synthesis of specific antibodies (immunoglobulins) and T-cells responsible for the development of both cellular and humoral immunity using a variety of humoral factors (lymphotoxins, chemotaxis factor, etc.).

Monocytes

The largest leukocytes. Monocytes in the circulating blood represent a mobile pool of relatively immature cells on their way from the bone marrow to the tissues. Moving into the tissue, monocytes turn into macrophages of various types. The most important function of most macrophages is phagocytic, which includes all stages described for neutrophils. Macrophages also synthesize biologically active substances - enzymes, mediators, etc.

One of the most important and complex problems of hematology is the question of the genesis of blood cells.

During the existence of the doctrine of blood, several theories of hematopoiesis have changed. For the first time, blood, as a separate tissue of the body, was isolated in 1839 by Schwann. The first division of blood cells - white blood cells - into lymph cells and leukocytes was undertaken in 1845 by the German pathologist Rudolf Virchow. However, by the end of the 19th century, it became known that there are not 2, but 3 types of cells in the blood: leukocytes, erythrocytes and platelets. This raised the question of their origin.

So, theories of hematopoiesis:

Polyphelytic theory. Its founder is the German scientist, Nobel laureate Paul Ehrlich, who in 1878 invented a method for differential staining of blood cells and revealed granularity in leukocytes. Given the morphological differences in cells, he described 8 types of leukocytes:

Nongranular leukocytes

lymphocytes,

mononuclear cells,

transitional cells;

Granular leukocytes

neutrophils,

eosinophils,

fine-grained basophils,

coarse basophils,

β-amphiphilic ("amphi" - on both sides, "philia" - inclination) leukocytes.

Turning to the question of the genesis of these cells, Ehrlich suggested that non-granular leukocytes originate from lymphoid tissue, and granular leukocytes (which he isolated into the system of myeloid cells) originate in BM. Thus, according to his judgments, there are 2 hematopoietic systems - lymphoid and myeloid. Moreover, each of the 8 cells described by him has its own predecessor. That is, the essence of the polyphyletic theory is that each germ of hematopoiesis has its own parent cell.

trialistic theory proposed by Schilling (1919) and Aschoff (1924). According to their beliefs, erythrocytes, granulocytes and platelets are part of myeloid tissue and have 1 precursor cell, which is located in the BM. Lymphoid cells are part of the lymphoid tissue. Monocytes originate from the reticuloendothelial system.

dualistictheory, according to which there are 2 ancestral cells - separately for the myeloid and lymphoid germs of hematopoiesis. It was proposed by Nehely (1900) and Schridde (1923) . It is essentially a confirmation of the 1st theory.

What do these 3 theories have in common?

The assertion that end cells are found in the peripheral blood,

Division of hematopoietic tissue into lymphoid and myeloid,

The absence of an assumption about the existence of one ancestral cell, the same for all germs of hematopoiesis.

Moderate unitary theory(1920, Alexander Nikolaevich Kryukov - the founder of Russian hematology). The essence of the theory is that there are only functional differences between the maternal cells of the myeloid and lymphoid series. Anatomically, it is one - it is (according to Kryukov) a "lymphoidocyte" (or hemocytoblast), which is formed from a reticular cell that has separated from syncytium (hemohytoblast). Those. reticular cell → hemohistoblast → hemocytoblast → cytoblast.

Currently being confirmed unitary theory hematopoiesis, expressed as early as the beginning of the 19th century (in 1916) by the Russian scientist Alexander Alexandrovich Maksimov. The essence of the theory - all blood cells are formed from one stem cell.

According to the modern scheme of hematopoiesis proposed in 1973 by A.I. Vorobyov and I.L. Chertkov all blood cells are divided into 3 big classes:

Ancestral (or stem) cells. They make up 1-2%;

Maturing cells - 25-40%;

Mature cells - 60-75%.

Within these 3 groups, all hematopoietic cells (depending on functional and morphological features) are divided into 6 classes:

I Class: PUCC- pluripotent hematopoietic stem cells. They are located in the CM and (possibly) in the spleen, and can circulate in the peripheral blood. They are absent in the thymus and lymph nodes.

First scientific evidence The existence of stem cells appeared in the 60s of the last century. Thus, in 1960, in the tissue culture laboratory of the University of Toronto, two Canadian researchers, J.E. Till and E.A. McCulloch discovered the property of hematopoietic cells to form colonies in the spleen of lethally irradiated mice. They irradiated animals in lethal dose 6-7 Gy, then they were injected intravenously with BM cells of an intact (non-irradiated) animal. After BM transplantation, foci of hematopoiesis were found in the spleen of irradiated mice in the form of macroscopic colonies of cells: granulocytic, erythroid, megakaryocytic, and mixed. However, colonies of lymphoid cells did not form. With the subsequent introduction of one of these colonies to another lethally irradiated mouse, colonies with three-pronged hematopoiesis again developed in its spleen. Later it was proved that each such colony is the offspring of 1 cell. How? The injected bone marrow cells were “labeled” with low-dose irradiation (2 Gy). This "mark" (ring chromosome) was found in the cells of all colonial lines. This ancestral cell was named - CFU c - colony-forming unit in the spleen. CFUs are categorized as more mature PSKs. In addition, using a chromosomal marker, the ability of CFU c to differentiate into lymphocytes was also detected, since the ring chromosome was detected not only in cells of splenic colonies, but also in lymphocytes of lymph nodes, thymus, and bone marrow of irradiated animals. Finally, it was shown that the culture of KM on agar leads to the formation of granulocytes and monocytes.

PSKK properties:

They have a high (but not unlimited) proliferative potential - they can do no more than 100 mitoses.

They have the ability to differentiate in the direction of all hematopoietic sprouts .

The differentiation of PBSCs (on the path of which no more than 40% of cells enter) is regulated purely locally and does not depend on external influences and the needs of the organism.

% thymidine suicide is 10. This means that 90% of PBSCs are outside the mitotic cycle (in the G 0 stage) and only 10% are in division.

II Class: Semi-stem (partially determined) hematopoietic cells. These include:

CFU-GEMM- a common precursor cell of myelo- and erythropoiesis, giving mixed colonies of granulocytes, erythrocytes, megakaryocytes and macrophages, which differentiates into:

CFU-GM- cells that give colonies of granulocytes and monocytes,

CFU-GE- cells that give colonies of granulocytes and erythrocytes,

CFU-MegE- cells that give colonies of megakaryocytes and erythrocytes,

Common precursor cell of lymphopoiesis - ?

The presence of a common precursor cell for myelopoiesis and erythropoiesis was proven in 1971 by scientists from Nowell and Ford using the example of chronic myelogenous leukemia. Scientists made a curious discovery: in 95% of patients with this pathology, the Philadelphia (Ph) chromosome was found in all blood cells (with the exception of lymphocytes). This made it possible to conclude that there is a progenitor cell that is the same for the three sprouts of myelopoiesis - granulocytes, erythrocytes and megakaryocytes, and separately from this - precursor cells of lymphocytes.

Cell properties:

Reduced proliferative potential and higher proliferative activity compared to PSKC. % thymidine suicide is 30. Ie. 30% of cells are in division, 70% are at rest.

Cell differentiation is regulated by growth factors, the secretion of which depends on the existing demand of the organism. Those. it is no longer a stochastic, but a deterministic process.

III Class: Committed (unipotent) cells- Ancestors of individual sprouts of hematopoiesis. These include:

A) precursor cells of lymphopoiesis:

preT- the ancestor of T-lymphocytes,

preV- the ancestor of B-lymphocytes.

B) myelopoiesis precursor cells:

CFU-G- the ancestor of granulocytes (neutrophils),

CFU-EO- progenitor of eosinophils

CFU-B- the ancestor of basophils,

CFU-M- progenitor of monocytes

CFU Meg- progenitor of megakaryocytes.

C) erythropoiesis precursor cells:

Immature and mature BOE-E- burst-forming units, insensitive to erythropoietin (EP),

CFU-E– EP-sensitive differentiation product BFU-E.

Cell properties:

They have a limited ability to self-sustain (10-15 mitoses), but higher (compared to the previous class of cells) proliferative activity (% thymidine suicide is 60, i.e. 60% of cells are in division, and 40% are in a resting state) .

Cell differentiation is controlled by humoral factors - poetins strictly at the request of the body.