Immune cell

Cells involved in or related to immune response

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Immune cells refer to cells involved in or related to immune response. include lymphocyte 、 dendritic cell , monocyte/macrophage Granulocyte 、 mast cells Etc. Immune cells can be divided into many types, which play an important role in the human body. Common name of immune cell white blood cell , including congenital lymphocytes, various Phagocyte Equal sum can be identified antigen , generation Specific immune response The lymphocyte of.

Chinese name: Immune cell
Foreign name: immune cell
Commonly known as: white blood cell

Distribution: in vivo
immune organ: Tonsils, lymph nodes, thymus
Immune cell: Phagocyte

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brief introduction

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immune Cells (Immune cell) Common name white blood cell , including lymphocytes and various phagocytes, also specifically capable of recognizing antigen , generation Specific immune response The lymphocyte of. lymphocyte yes immune system The basic ingredients of T lymphocytes 、 B lymphocytes Stimulated by antigen, it is activated, split, proliferate, and generate specificity immune response 。 except T lymphocytes And B lymphocytes, and K lymphocytes and NK lymphocytes , there are four types. T lymphocytes are multifunctional Cell population 。 In addition to lymphocytes, the cells involved in immune response are plasma cells 、 Granulocyte 、 mast cells 、 Antigen-presenting cell and Mononuclear phagocyte Systemic cells^[1] 。

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immune organ

Type: tonsil, lymph node, thymus, spleen, bone marrow, etc.

Function: It is a place where immune cells are generated, matured, or concentrated.

Immune cell

Phagocytes: ① They form the second line of defense of the human body with the bactericidal substances in the body fluid and participate in non-specific immunity.

② It ingests and processes antigens and participates in cellular and humoral immunity.

Lymphocytes: ① T cells

② B cell

Memory cell

Immunoactive substances

Antibodies, lymphokines and lysases.

Types of immune cells

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T lymphocytes

I.e thymus rely on lymphocyte （thymus dependent lymphocyte）。 Also referred to as T cell 。 Multi energy from bone marrow stem cells (In embryonic stage, it comes from yolk sac and liver). At present, it is believed that Embryonic stage and Nascent stage , part of bone marrow Pluripotent stem cell Or pre T cells migrate into the thymus Thymic hormone T cells with immune activity. Mature T cells are distributed to Peripheral immune organ Of Thymus dependent region Settle down and lymph gland , peripheral blood and Tissue fluid Etc recycling , play cellular immunity and Immunomodulation And other functions. T cell recycling is conducive to extensive exposure to Antigenic substance Strengthen immune response and maintain it for a long time Immune memory 。 There are many different markers on the cell membrane of T cells, mainly surface antigens and Surface receptor 。 These surface markers are bound to the cell membrane megalin Molecules.

T cells and B cells (2 sheets)

T cells are very complex, heterogeneous, and constantly renew in the body. They can be different at the same time Developmental stage Or functional subgroups, but at present, the classification principles and nomenclature are confused and have not yet been unified. According to different functions in immune response, T cells can be divided into several subgroups, which are generally recognized as: T helper cells (TH) with assistance humoral immunity And cellular immunity; Inhibitory T cells (TS) with Suppressor cell Immune and humoral immune function; Effector T cell (TE) with release Lymphokine Function of; Cytotoxic T cells (TC) have the function of killing target cells; Tardiness allergy T cells (TD) can participate in type IV allergic reaction; Enlarge T cells (TA), which can act on TH and TS, with enlargement Immune effect The role of; Memory T cells (TM), with memory Specific antigen Stimulating effect. T cells can survive for months to years in vivo. his Memory cell The survival time is longer.

T cells are the main component of lymphocytes, which have a variety of biological functions, such as direct killing Target cell , assist or inhibit B cell Generate antibodies against specific antigens and Mitogen Response and generation of cell factor They are brave fighters against disease infection and tumor formation in the body. T cell The generated immune response is cellular immunity, and there are two main forms of cellular immunity effects: specific combination with target cells, destruction of target cell membranes, and direct killing of target cells; The other is to release lymphokines, and finally Immune effect Expand and enhance.

tumor cell

T cells, which are differentiated from lymphoid stem cells in the thymus, are the most numerous and complex type of lymphocytes. According to its function, it can be divided into three subgroups: T helper cells 、 Inhibitory T cells and Cytotoxic T cells 。 Their normal function is very important for human beings to resist diseases. So far, much progress has been made in the research on the evolution of T cells and their relationship with cancer. Hematopoietic stem cells Also called pluripotent stem cells, they are a group of primitive cells existing in hematopoietic tissues blood corpuscle 。 Its biggest feature is that it can replicate and differentiate itself, usually in a quiescent period. When the body needs it, it divides and proliferates, and some of it differentiates into directional stem cells. After being stimulated by certain hormones, it further differentiates into blood cell lines of various systems. There are two ways for further differentiation of lymphoid stem cells. Some stem cells migrate into the thymus, and under the influence of thymic hormone, they proliferate and differentiate into a subgroup of mature lymphocytes, called T lymphocytes. The word "T" of T cells is named after the first Latin letter of "thymus". The second cell group matures and differentiates into another subgroup of lymphocytes, called B lymphocytes, under the action of hormones in organs or tissues similar to the bursa of Fabricius. The word "B" of B cells is named after the first Latin letter of "capsule". The bursa of Fabricius is a unique structure of birds. It is located at the upper back of the cloaca, and its wall is full of lymphoid tissue 。 In humans and mammals, the bursa of fabricius is similar to the bone marrow or the lymphoid tissue in the intestine (collecting lymph nodes, appendix, etc.), and also acts as the bursa of fabricius.

T cells do not produce antibodies, but act directly. Therefore, the immune function of T cells is called "cellular immunity". B cells act by producing antibodies. Antibodies exist in body fluids, so the immune function of B cells is called "humoral immunity". Most antigenic substances are in the process of stimulating B cells to form antibodies; The assistance of T cells is needed. In some cases, T cells can also inhibit B cells. If inhibitory T cells are infected, irradiated Thymic function When the function is reduced due to the influence of disorder and other factors, B cells lose the control of T cells Hyperfunction , a large number of autoantibody And cause various Autoimmune disease 。 For example, systemic lupus erythematosus, chronic active hepatitis, rheumatoid arthritis, etc. Similarly, in some cases, B cells can also control or enhance the function of T cells. It can be seen that all kinds of immune reaction Both cellular immunity and humoral immunity constitute an extremely sophisticated, complex and perfect defense system.

B lymphocytes

It is also called B cell for short. Pluripotent stem cells derived from bone marrow. In birds, it is developed in the bursa of Fabricius, so it is also called bursa dependent lymphocyte/bone marrow dependent lymphocyte (B cell for short), which is derived from the lymphoid stem cells in bone marrow. Compared with T lymphocytes, its volume is slightly larger. This kind of lymphocyte will proliferate and differentiate into a large number of plasma cells after being stimulated by antigen. Plasma cells can synthesize and secrete antibodies and circulate in the blood. B-cell lymphoma is one of the most common lymphocytic leukemia. In mammals, it develops in the bone marrow and other tissues with saclike structure. Also known as bone marrow dependent lymphocytes. Stem cells from bone marrow or Pre-B cell After migrating into bursa of Fabricius or bursa like organ, it gradually differentiated into B cells with immune potential. Mature B cells migrate out of peripheral blood and enter spleen , lymph nodes, mainly distributed in splenic nodules, splenic cords and Lymph node Lymphatic cords and submucosal lymph nodes of the digestive tract, stimulated by antigens, differentiate and proliferate into plasma cells, synthesize antibodies, and play the role of humoral immunity. The number of B cells in bone marrow and collecting lymph nodes is more than that of T cells, the number in blood and lymph nodes is less than that of T cells, and the number in thoracic ducts is less. Only a few participate in recirculation. There are many different markers on the cell membrane of B cells, mainly surface antigens and surface receptors. These surface markers are giant protein molecules that bind to the cell membrane.

B1 cell T cell independent cell. B2 is a T-cell dependent cell. The survival time of B cells in vivo is short, only a few days to several weeks, but their memory cells can exist for a long time in vivo.

K lymphocytes

Also called antibody dependence lymphocyte , pluripotency directly from bone marrow stem cells Derived from, without antigen mark on the surface, but with antibody IgG recipient 。 The corresponding antibody of target cell must exist when killing target cell. The target cell surface antigen binds to the corresponding antibody, and then binds to K cell To trigger the killing effect of K cells. Where combined with IgG antibody All of the target cells have the possibility of being killed by K cells. Therefore, it can also be said that the killing effect of K cells is not Specificity The recognition of target cells completely depends on the specific antibody Identification function 。 K cells account for approximately human peripheral blood Mesolymphocyte 5~10% of the total, but the killing effect is very high. When there is only a small amount of specific antibody in the body, although it can bind to the antigen, it is not enough to activate complement When the system destroys target cells, K cells can play their killing role. K cells are more in peritoneal exudate and spleen, less in lymph nodes, and not in thoracic duct lymph, indicating that K cells do not participate in lymphocyte recycling. But the killing effect of K cells Tumor immunity 、 Antiviral immunity Anti parasite immunity, transplantation rejection and some Autoimmune disease Have an important role in immune response yes Immune protection and Immunopathology Two types. If the target cell is too large (parasite or solid tumor), the phagocyte cannot play a role, or the target cell surface is covered by antibodies, and T cells cannot be approached, K cells can still play a role. The rejection in kidney transplantation and the destruction of the affected organs or tissues of autoimmune diseases may be related to K cells.

NK lymphocytes

Natural killer cell, Natural killer cells ）It is the third group of lymphocytes in parallel with T and B cells. The number of NK cells is small, accounting for about 15% of the total lymphocytes in the peripheral blood spleen There are about 3%~4% in the lungs , liver and intestinal mucosa, but in thymus lymph gland And thoracic duct.

NK cells are large and contain cytoplasmic particles, so they are called Large granular lymphocyte 。 NK cells can kill target cells non-specific and directly. This natural killing activity does not need to be sensitized by antigen in advance, nor does it need antibodies to participate, and there is no MHC restriction.

The target cells killed by NK cells are mainly tumor cells, virus infected cells, larger pathogens (such as fungi and parasites) Allotransplantation An organ, tissue, etc.

NK cell surface NKR can recognize the polysaccharide molecules expressed on the surface of virus infected cells. The killing effect of NK cells is mediated by toxic molecules released after activation, such as perforin, granzyme and TNF - α（ tumor necrosis factor ）Etc.

mast cells

Alkaline cells connective tissue It is called mast cell when it is in the mucosa epithelium. Its structure and function are similar to basophils.

Mast cell is related to blood Basophil Similarly, with strongly basophilic particles Histiocyte 。 Such particles in the blood contain heparin Histamine 、 5-hydroxytryptamine , particles and substances in particles released by cell disintegration can be caused in tissues Immediate anaphylaxis (inflammation). Because it binds to mast cells IgE antibody Contact with antigen makes cells collapse.

Mast cell: the cell is round or oval, the nucleus is small, round or oval, lightly stained, and located in the center of the cell. Cells are often clustered or distributed singly near blood vessels. The cells are round or oval, and the cytoplasm is full of uniform sized, blue purple particles, which are evenly distributed around the nucleus.

Mast cell leukemia (Mast cell leukemia, MCL) is also known as tissue basophilic leukemia. Efrati first proposed the diagnosis of MCL in 1957, and it has been reported since then. MCL accounts for about 15% of malignant mast cell tumors. Many cases are systematic first Mast cell hyperplasia (SMCD), later it will become leukemia, and a few will start with mast cell leukemia.

MCL is the late manifestation of malignant proliferation of mast cells in vivo acute leukemia Similar, but also more specific: because of 16 sex substances in mast cell granules（ histamine The release of heparin, a-TNF, etc. can cause a series of allergic reactions, such as flushing, hypotension, itching or bone pain, headache, Bronchospasm 、 dyspnea ， Peptic ulcer And gastrointestinal bleeding. Abdominal pain, nausea, vomiting and diarrhea may occur during gastrointestinal invasion; Fever, liver, spleen Lymph node enlargement Common; skin Pigmented urticaria Rare.

Patients generally have anemia Thrombocytopenia ； white blood cell The total number is (10-15) x 109/L, and mast cells account for 5%~90%. Bone marrow biopsy It shows that mast cells are significantly increased, sometimes up to 90% (26.2% - 91.8%). Leukemic mast cells are round or quasi round, Chromatin It is fine, nucleolus is clear or unclear, cytoplasm is blue, filled with more or less dark purple red particles and covered on the nucleus, and pseudopodia and phagocytosis are easily seen red blood cell Phenomenon. Hypertrophy of MCL Cell ultrastructure : 1 or more nuclei with occasional obvious nucleoli. The cytoplasm contains mitochondrion 、 Liposome The content of particles is lacking or the particles are full of small particles and typical scroll like characteristics. Granule A can be seen, but no basophil can be seen.

Cytochemistry Features: SBB and toluidine blue Colorable, specific esterase 、 acid phosphatase Positive staining, lysozyme Weakly positive; Peroxidase And. Non specific esterase was negative.

Immunophenotype: malignant mast cells express CD9, CD33, CD44 and CDll7, but not monocyte Related antigens CDl4, CDl5 and basophil related antigen CDll6 CDwl7、CDl23/IL-3RCK。 It also lacks 0116 (CM-CSm) and skin mast cell marker antigen CD88. HLA-D, DR and CDl, Cm, CD4, 07, CDl0, CDl9, TdT are all negative, and MCG-35 has a higher effect on mast cell granules Specificity The cultured mast cells were strongly positive.

Travis et al. put forward the diagnostic criteria for MCL in 1986: ① peripheral blood mast cells 10%; ② Leukemia cells are characterized by atypical mast cells (immature mast cells); ③ Leukemia cells have the histochemical characteristics of mast cells (metachromatic particles, positive specific esterase, negative Pox, etc.). Clinical manifestations include mast cell hyperplasia and leukemia. Differential diagnosis: It should be differentiated from systemic mast cell hyperplasia and malignant mast cell hyperplasia.

Treatment: At present, there is no successful treatment plan, and the survival period is very short（ Median survival 5 months). Splenectomy It can temporarily relieve symptoms, and the hemogram can temporarily rise, but the survival period of patients is significantly shortened (average 2 months). At the beginning of the 21st century Life Ark Project Great progress has been made in the research and treatment of systemic mast cell hyperplasia.

Monocyte phagocyte system

Mononuclear phagocyte system macrophage Macrophage system is a cell system with strong phagocytosis and defense function in the body. It includes macrophages, monocytes and immature monocytes scattered in various organs and tissues of the body. It originates from hematopoietic stem cells and develops in bone marrow Immature monocyte They develop into monocytes, stay in the blood for 12~102 hours, enter connective tissue and other organs along the blood stream, and transform into macrophages.

The cytoplasm contains rich lysosomes, mitochondria and rough Endoplasmic reticulum Small processes and membrane folds were formed on the cell surface. At rest, it is called fixed macrophage, with Chemotactic factor It becomes a wandering macrophage and can Deformation movement And phagocytosis. Human macrophages can live for months to years. Many diseases can cause a large number of proliferation of mononuclear phagocyte system, manifested as enlargement of liver and spleen lymph nodes. Its function is to phagocytosis and remove bacteria, foreign bodies and aging dead cells in the body; Activate T B. Lymphocyte immune response. Can be secreted under the stimulation of bacteria or other factors acid hydrolase 、 neutral protease , lysozyme and other endogenous pyrogens^[2] 。

Separation technology

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Isolation of lymphocytes

Take 1ml of heparin anticoagulant solution and dilute it with Hanks solution 1:1, and slowly drip along the pipe wall with 2ml of lymph Cell separation In the test tube (note not to mix with the separating solution, and then centrifugate horizontally at 2000r/min for 20min. The tube is divided into four layers, from top to bottom, which are plasma, mononuclear cells, granular white blood cells, and red blood cells (Figure 2-1). Use capillary tube to stretch into mononuclear cell layer (located on the interface between cell separation solution and plasma), and gently suck out all cells along the tube wall. Then the cells were washed twice with Hanks solution and centrifuged at 2000r/min for 10min each time. Finally, the cells were prepared into 2 × 106/m1 cell suspension with RPMI l640 culture medium for standby.

Separation of T cells and B cells

Pass lymphocyte suspension through nylon cotton column, B cell Adhering to nylon cotton, T cells do not adhere. First, the nylon cotton column is eluted with RPMI l640 medium. The cell suspension flowing down contains rich T cells. Then repeatedly squeeze the nylon column, squeeze out the B cells adhered to the nylon cotton, and elute with a small amount of RPMI l640 medium. This cell suspension contains rich B cells. The length of nylon column (plastic tube) and the number of nylon cotton depend on the number of isolated cells.

Isolation of CD4 and CD8 cells

⑴ Separation of CD4 cells: pass a certain amount of T cell suspension through a SephDdex C-10 column, and then use a small amount of RPMll640 to culture and wash. The harvested cell suspension contains about 85% of CD4 cells.

⑵ CD8 cell separation: use Tris buffer solution to dilute sheep anti mouse IgG (the concentration is 10 μ g/ml), coat the surface of a plate, and then place it at 4 ℃ overnight. Antibodies not coated are washed with PBS. Then mark it with anti CD8 monoclonal antibody Add 3m1 of T cells (cell concentration is 1 × l07/m1) to the above plate, place it at 4 ℃ for 2 hours, gently clean the cells that have not adhered with PBS, and then add 10m1 PBS to the capillary tube for blowing. Collected Exfoliative cell After washing, it is suspended in RPMI l640 medium for standby. CD4 cells can also be separated by this method.

Isolation of mononuclear macrophages

Monocyte macrophage It has the characteristic of adhering to the surface of plastic or glass, while lymphocytes have no such characteristic. Therefore, these two types of cells can be separated. The method is described as follows. Add the cell suspension to be separated (such as the peritoneal fluid of real animals) into a plastic or glass plate of appropriate size and place it at 37 ℃ C02 Incubate in the incubator for 1 hour, then gently rinse the surface of the plate with RPMI 1640 medium to remove the non adherent cells, and then gently scrub the surface of the plate with cells with the above medium to collect the adherent monocyte macrophages. If you want to obtain mononuclear macrophages with high purity, you can repeat the above process.^[3]

transfer

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Unlike most types of cells that maintain homeostasis in situ and perform physiological functions, the migration of immune cells in adult higher multicellular organisms is one of the basic attributes of immune cells throughout their life and closely related to their various behavioral functions. Except that the progenitor cells of some immune cells will migrate and settle down in some organs or tissues during embryonic development, most types of immune cells constantly migrate between different lymphoid organs/tissues, between lymphoid organs/tissues and non lymphoid organs/tissues, as well as within organs/tissues, Ensure the development and differentiation of immune cells and the play of various immune functions. Lymphatic circulation and blood circulation are the main routes of immune cell migration between organs/tissues. Different tissue microenvironments with different characteristics are important external conditions for regulating immune cell migration and playing specific immune functions.^[4]

Improve immune cells

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With sleep

Sleep is closely related to human immunity. The famous immunologist found through the "self sleep" test that good sleep can significantly increase the number of two kinds of lymphocytes in the body. The research of medical experts shows that the human body will produce a kind of Parietal acid Sleep factor, which promotes white corpuscle The number of macrophages is increased, and the detoxification function of the liver is enhanced, thus eliminating the invading bacteria and viruses.

Keep an optimistic attitude

It can maintain the human body in an optimal state. Especially in today's society, people face great pressure Psychological pressure Will lead to Human immune system Inhibitory hormone The ingredients increase, so it is vulnerable to colds or other diseases.

Limit drinking

Do not drink more than 100ml of low alcohol liquor, 250ml of yellow rice wine and 1 bottle of beer every day, because alcohol will have a negative impact on every part of the human body. Even if drinking wine can reduce cholesterol, it should be limited to one cup a day. Excessive drinking will give blood and heart And other organs.

Take part in sports

Three studies conducted by experts pointed out that the number of immune cells will increase after 30 to 45 minutes of exercise every day, five days a week and lasting for 12 weeks, Resistance It also increased relatively. Exercise as long as the heart rate can accelerate, walking after dinner is very suitable.

Vitamin supplement

Take proper vitamin and mineral supplements every day. Experts pointed out that the physical resistance to foreign aggression weapons, including interferon The number and vitality of various immune cells are related to vitamins and minerals.

Improve the internal ecological environment

use Microecological preparation The research and use of improving immunity have a long history. Research shows that the intestinal tract Bifidobacterium 、 Lactobacillus The beneficial flora represented by Immunogenicity It can stimulate the division and reproduction of lymphocytes responsible for human immunity, and can also mobilize Nonspecific immunity Systematically, we can "eat" all kinds of pathogenic foreign microorganisms, including viruses, bacteria, chlamydia, etc., to produce a variety of antibodies and improve human immunity. For healthy people, we might as well "diet" and eat more lactobacillus drinks; The healthy marginal population can use microecological agents to adjust the internal microecological balance.

scientific research

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On November 10, 2022, the British journal Nature published One Non viral engineered immune cells can be used for personalized treatment of cancer Research^[5] 。

In September 2023, it was learned from the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences that Chinese researchers successfully constructed the human immune system development map with the widest coverage of tissues, the longest time span, and the highest sampling density for the first time, and found that immune cells are "new" Type "- microglia like cells.^[6]

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