What Is Atypical Lymphocytosis?

Blood cells, also called "blood cells," are cells that exist in the blood and can travel throughout the body with the flow of blood. For mammals, blood cells mainly contain the following three types: Red blood cells: The main function is to carry oxygen. White blood cells: mainly play the role of immunity. When germs invade the human body, white blood cells can pass through the capillary wall, focus on the invading site of the germs, and engulf the germs after being surrounded. Platelets: play an important role in hemostasis. Blood cells make up about 45% of the blood volume and include red blood cells, white blood cells, and platelets. Under normal physiological conditions, blood cells and platelets have a certain morphological structure and a relatively stable number. ^[1]

How blood cells are made

Blood cells derived from bone marrow

Mature erythrocytes have no nucleus and no

1.The proportion of blood cells in whole blood

Instrument introduction

Since the early 1950s

Five blood cell classification technology and its application progress.

Hematology analyzer is one of the most widely used instruments for clinical examination in hospitals. It refers to the analysis of the number and heterogeneity of blood cells in a certain volume. Since the 1990s, with the application of various high and new technologies such as electronics technology, flow cytometry technology, laser technology, electronic computer technology and new fluorescent chemicals in blood cell analyzers, the detection principle of blood cell analyzers has been continuously improved, The measurement parameters continue to increase and the detection level continues to increase. Especially in the five-cell classification technology, it has been developed to use multiple technologies (such as radio frequency, cytochemical staining, flow cytometry, and fluorescent staining technology) to simultaneously detect one white blood cell. Advanced computer technology is used to distinguish and distinguish the cell differences between the respective cells treated by the above methods. Comprehensive analysis of experimental data results in more accurate white blood cell classification results. It provides an important laboratory basis for the diagnosis and treatment of clinical diseases. In recent years. Hematology analyzers that can count five-class counts of white blood cells have been commonly used. This article reviews the current techniques and their latest applications in the five classifications of blood cells.

Principles of the five blood cell classification technology

Flow cytometry

Flow cytometry (FCM) is a comprehensive application of optics, mechanics, fluid mechanics, electronics, computer biology, cell biology, molecular immunology and other subject technologies to make the measured solution flow through the measurement area and detect them one by one A method for rapid quantitative determination and analysis of the physical and chemical characteristics of each cell, thereby allowing high-speed flow of cells or sub-cells.

First, the cells to be tested are pressed into the flow chamber after being processed or stained. At the same time, the buffer solution containing no cells is ejected from the sheath fluid tube under high pressure, and the population direction of the sheath fluid tube is at a certain angle with the flow of the sample to be measured. In this way, the sheath fluid can flow around the sample at high speed to form a circular flow beam. The cells to be tested are arranged in a single row under the wrapping and pass through the detection area in sequence. Under the irradiation of the laser beam, scattered light and excited fluorescence are generated. These two light source signals respectively reflect the size of the cell volume and the internal information. After being received by the photomultiplier tube, it can be converted into an electrical signal, which is then converted by an analog-to-digital converter. The continuous electrical signal is converted into a number that can be recognized by a computer The signal is processed by the computer, and the analysis result can be displayed on the screen.

In order to ensure that the cells pass through the detection area one by one, the sheath flow technique is widely used in flow cytometry. according to

Blood cells derived from bone marrow

One is mitosis (indirect division)

During cell division, special mitochondria appear, so it is called mitosis. Mitosis is the main form of blood cell proliferation. Mitotic cells do not appear in normal human circulating blood. The number of mitotic cells in hematopoietic tissue reflects the extent and state of their proliferation. The division process can be divided into 4 stages, which are mainly manifested in nuclear changes.

(1) Early stage (also known as monofilament stage): When the cell begins to divide, the cell body becomes spherical, the nucleus swells, and nuclear chromatin condenses into a single columnar chromosome. The nuclear membrane and nucleosomes disappear like a silk ball. The cytoplasm staining became lighter, the organelles and inclusions were temporarily hidden, and the centrosome was shown.

(2) Middle stage (also known as single stellate stage): The central body begins to split and gradually goes to the poles, with filaments connected between it, shaped as a spindle, called a spindle. The nuclear chromosomes are arranged like a star or chrysanthemum.

Blood cells are produced in hematopoietic organs, and their main hematopoietic organs are not the same during the embryonic period and at different developmental stages after birth.

Embryonic hematopoietic organs

(1) Mesoderm hematopoiesis: Occurs within 1-2 months of the embryo. The yolk sac is the first place of hematopoietic appearance. Mesoderm mesenchymal cells on the wall of the yolk sac are the basis of the hematopoietic system. Initially, blood cells are generated from the blood islands of the yolk sac. Primitive red blood cells, the blood cells of the embryo.

(2) Hematopoietic phase of liver: It occurs in 2-5 months of embryo. The yolk sac is atrophic and degraded, and its hematopoietic function is replaced by the liver. It can differentiate not only primary primordial red blood cells, but also secondary primordial red blood cells. These cells gradually develop into mature red blood cells and enter the blood through sinusoids. At this time, the hematopoietic activity of the liver was very active. The spleen is also involved in hematopoiesis around the 3rd month of the fetus, producing mainly red blood cells, granulocytes, lymphocytes and monocytes. By the fifth month, the spleen's hematopoietic function was gradually reduced, and only lymphocytes and monocytes were produced, and this hematopoietic activity remained for life.

(3) Bone marrow hematopoietic phase: This phase begins at the 4th month of the embryo. The fetus begins to develop bone marrow hematopoietic tissue, initially producing only granulocytes, followed by red blood cells and megakaryocytes. At the same time as bone marrow hematopoiesis, thymus and lymph nodes also begin to produce blood. The thymus produces lymphocytes and maintains this function after birth; lymph nodes mainly produce lymphocytes and plasma cells, and are also involved in the production of red blood cells at an early stage.

The above three stages are intertwined with each other, which is actually difficult to separate.

Hematopoietic organs after birth

(1) Bone marrow: Bone marrow is the only hematopoietic organ that produces red blood cells, granulocytes, and megakaryocytes after birth. It also produces lymphocytes and monocytes. From newborn to 4-year-old child, whole body bone marrow has active hematopoietic function. At the age of 5-7 years, fat cells begin to appear between the hematopoietic cells of the tubular bone. With age, the range of red pulp in tubular bones gradually decreases, fat tissue gradually increases, and bone marrow turns yellow, called yellow bone marrow. Although hematopoietic is no longer in the yellow pulp, it still retains potential hematopoietic function. About 18-20 years old, the red pulp is limited to flat bones such as skull, sternum, spine, and sacrum, as well as the proximal ends of humerus and femur. The red pulp accounts for about half of the total bone marrow. Hematopoietic activity of the red pulp will continue for life, but its activity may decrease slightly with age.

The bone marrow is a kind of spongy, gelatinous or fatty tissue, which is enclosed in the hard bone marrow cavity. Divided into red pulp (hematopoietic cells) and yellow pulp (adipocytes), normal adult bone marrow weight is 1600 grams-3700 grams, about 3.4%-5.9% of the total body weight, of which the weight of red pulp is about 1,000 grams.

The bone marrow has a complex and rich vascular system. In human bone marrow, the capillaries that supply the entire bone marrow cavity rely mainly on nutritional arteries. All arteries of the bone marrow are accompanied by nerve bundles. Nerve fibers originate from the spinal nerve and enter the bone marrow cavity from the nutrition hole together with the arteries. They are distributed in the bone marrow cavity in parallel with the nutrition arteries and terminate in smooth muscle fibers of the arterial wall. The blood sinuses of the bone marrow are filled with parenchymal cells, that is, hematopoietic cells. The differentiation of bone marrow hematopoietic stem cells into the red, granulocytic, and megakaryotic systems is related to the hematopoietic microenvironment. The hematopoietic microenvironment may be composed of blood vessels, macrophages, nerves, and Matrix, etc. In terms of its function, the hematopoietic microenvironment should include all factors that affect hematopoietic effects. Among them, vascular factors are very important, because various hematopoietic substances and their stimulating substances must enter the bone marrow through blood vessels in order to create blood. There is a barrier between the hematopoietic site and the blood circulation, the bone marrow blood barrier, which has the function of controlling blood cells in and out of the bone marrow.

(2) Thymus: After birth to old age, the thymus has undergone certain changes. After puberty, hematopoietic activity gradually disappears and is replaced by adipose tissue.

The thymus is not only one of the important hematopoietic organs during the embryonic period, but also has an active hematopoietic function after birth. Especially within two years after birth, the glandular tissue grows rapidly and the hematopoietic activity is also vigorous. The thymus is separated by connective tissue into many incomplete leaflets. The peripheral part of the leaflet is called the cortex, and the central part is called the medulla. The cortex is full of dense lymphocytes. The shallowest layer is more primitive lymphocytes, the middle layer is medium-sized lymphocytes, and the deep layer is small lymphocytes. From shallow to deep, stem cells proliferate and differentiate into thymus-dependent lymphocytes (T cells). process. Although the adult thymus atrophies, it can reproduce itself because the T cells have settled in the surrounding lymphatic tissue. In addition to transporting T lymphocytes to surrounding lymphoid tissues, the thymus also secretes thymosin from epithelial reticulum. Stem cells are induced to differentiate and mature into immune-active T lymphocytes under the action of thymic hormones.

(3) Spleen: The spleen is the largest lymphoid organ in the human body, and its essence is divided into two parts: red pulp and white pulp. The white pulp includes lymphatic sheaths around the central artery and nodules of the spleen. Around the central artery is the thymic-dependent region of the spleen, which is predominantly T lymphocytes. The spleen nodules are lymph nodules in the spleen. There are germinal centers in the nodules, mainly B lymphocytes. In addition to producing lymphocytes and monocytes, the spleen also has the function of storing blood and destroying senescent red blood cells.

(4) Lymphatic agglomeration of the appendix and ileum, where stem cells of the bone marrow aggregate, which can induce the proliferating stem cells to differentiate into bone marrow-dependent lymphocytes (B cells) and spread in the surrounding lymphoid organs.

(5) Lymph nodes: Divided into the cortex of the surrounding part and the medulla of the central part. The center of the superficial cortical lymphoid follicles is the site of B cell proliferation, called the germinal center or response center; the deep cortex is mainly composed of T cells migrated from the thymus, called the thymus-dependent region; under the stimulation of the antigen, T lymphocytes Can proliferate, produce a large number of sensitized small lymphocytes, and directly affect antigens through blood flow. The medulla is mainly composed of myelin (lymph) and lymphatic sinus. The main components of myelin are B lymphocytes, plasma cells, and macrophages.

The above (2), (3), (4), (5) sites are hematopoietic of lymphoid organs. Lymphatic organs are divided into central lymphatic organs and peripheral lymphoid organs. Lymphoid tissues in the thymus and bone marrow belong to central lymphoid organs, which are the focus of lymphatic directional stem cells. Lymph nodes, spleen, and other lymphoid tissues are peripheral lymphoid organs, and are the sites where differentiated T cells and B cells are located.

(6) Reticuloendothelial system (RES): Reticulocytes including spleen and lymph nodes, endothelial cells covering the liver, bone marrow, adrenal cortex, sinusoidal space of the anterior pituitary gland, and free tissue cells in other organs. Its main cell component is reticulocytes, which can differentiate into phagocytic reticulocytes. Monocytes in the blood, which enter the reticular tissue after the myeloid formation, are tissue cells; under certain conditions, they can be transformed into free phagocytic cells with phagocytosis, forming a so-called monocyte-macrophage system.

Under normal circumstances, babies 2 months after birth will never have extra bone marrow hematopoiesis. In pathological conditions, hematopoietic foci can occur in tissues other than bone marrow, such as the spleen, liver, and lymph nodes. This is called extramedullary hematopoietic. This is because these sites retain mesenchymal cells with hematopoietic capacity and restore their hematopoietic function during the embryonic period. .

The average lifespan of red blood cells is about 120 days. Although aging red blood cells have no morphological specificity, their functional activities and physical and chemical properties have changed, such as reduced enzyme activity, hemoglobin degeneration, increased cell membrane fragility, and surface charge changes. As a result, the ability of cells to combine with oxygen is reduced and Easily broken. Aging red blood cells are mostly swallowed by macrophages in the spleen, bone marrow, and liver. At the same time, the same amount of red blood cells are produced and released by the red bone marrow into the peripheral blood, maintaining a relatively constant number of red blood cells.

Red blood cells have electrorheological properties, and the nature and quantity of their surface charges are closely related to blood rheological properties, cell-to-cell interactions, and the lifespan of red blood cells. In 1959, Piper treated human red blood cells with neuraminidase. As a result, the electrophoresis rate of red blood cells decreased significantly. Further research confirmed that this was related to the glycoprotein or glycolipid sialic acid or N-acetylneuraminic acid on the surface of red blood cells. The resulting carboxyl group is the main charged group that determines the negative charge on the red blood cell surface. The content of sialic acid released by human or mammalian red blood cells treated with neuraminidase has a significantly positive correlation with the decrease of the red blood cell electrophoresis rate. In addition, through the method of the degree of binding of charged groups and cations and the corresponding changes in spectroscopy, it was found that the partial charge of red blood cells is also related to the amino group and phosphate group. When the latter decreases, the electrophoretic rate of red blood cells There may be some decline.