T cells are actually acquired immunity that can protect against cytotoxic damaging effects on the body. Alien aggressor cells entering the body cause “chaos”, which outwardly manifests itself in the symptoms of diseases.
Aggressor cells damage everything they can in the body during their activity, acting in their own interests. And the task of the immune system is to find and destroy all foreign elements.
Specific protection of the body from biological aggression (foreign molecules, cells, toxins, bacteria, viruses, fungi, etc.) is carried out using two mechanisms:
When an “aggressor cell” enters the human body, the immune system recognizes foreign and its own modified macromolecules (antigens) and removes them from the body. Also, upon initial contact with new antigens, they are memorized, which facilitates their faster removal in the event of a secondary entry into the body.
The process of memorization (presentation) occurs due to antigen-recognition receptors of cells and the work of antigen-presenting molecules (MHC molecules-histocompatibility complexes).
The functioning of the immune system is determined by the work. These are cells of the immune system that are 
a type of leukocyte and contribute to the formation of acquired immunity. Among them are:
However, in addition to regulating the immune response, T lymphocytes are capable of performing an effector function, destroying tumor, mutated and foreign cells, participating in the formation of immunological memory, recognizing antigens and inducing immune responses.
For reference. An important feature of T cells is their ability to respond only to presented antigens. One T lymphocyte has only one receptor for one specific antigen. This ensures that T cells do not react to the body's own autoantigens.
The diversity of T-lymphocyte functions is due to the presence of subpopulations in them, represented by T-helpers, T-killers and T-suppressors.
Subpopulation of cells, their stage of differentiation (development), degree of maturity, etc. determined using special clusters of differentiation, designated as CD. The most significant are CD3, CD4 and CD8:
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For reference. The function of helpers is carried out through the synthesis of cytokines (information molecules that regulate the interaction between cells).
Depending on the cytokine produced, they are divided into:
T-helper types 1 and 2 always interact antagonistically, that is increased activity of the first type inhibits the function of the second type and vice versa.
The work of helpers ensures interaction between all immune cells, determining which type of immune response will predominate (cellular or humoral).
Important. Disruption of the work of helper cells, namely the insufficiency of their function, is observed in patients with acquired immunodeficiency. Helper T cells are the main target of HIV. As a result of their death, the body's immune response to stimulation of antigens is disrupted, which leads to the development of severe infections, the growth of oncological tumors and death.
These are the so-called T-effectors (cytotoxic cells) or killer cells. This name is due to their ability to destroy target cells. Carrying out lysis (lysis (from the Greek λύσις - division) - dissolution of cells and their systems) of targets carrying a foreign antigen or mutated autoantigen (transplants, tumor cells), they provide reactions of antitumor protection, transplantation and antiviral immunity, as well as autoimmune reactions.
Killer T cells, using their own MHC molecules, recognize a foreign antigen. By binding to it on the cell surface, they produce perforin (cytotoxic protein).
After lysing the “aggressor” cell, killer T cells remain viable and continue to circulate in the blood, destroying foreign antigens.
T-killers make up up to 25 percent of all T-lymphocytes.
For reference. In addition to providing normal immune responses, T-effectors can participate in antibody-dependent cellular cytotoxicity reactions, contributing to the development of type 2 hypersensitivity (cytotoxic).
This may manifest itself drug allergies and various autoimmune diseases (systemic diseases connective tissue, hemolytic anemia autoimmune nature, malignant myasthenia gravis, autoimmune thyroiditis, etc.).
Some have a similar mechanism of action. medicines, capable of triggering the processes of tumor cell necrosis.
Important. Drugs with cytotoxic effects are used in chemotherapy for cancer.
For example, such medications include Chlorbutin. This remedy is used to treat chronic lymphocytic leukemia, lymphogranulomatosis and ovarian cancer.
Most often, a disease such as T-cell lymphoma occurs in older people; it is less often diagnosed in children and adolescents.
The disease usually affects men; cases of morbidity in women are recorded less frequently.
It is known that T-cell lymphoma is epidermotropic in nature (affects skin cells and lymph nodes).
In clinical oncology, it is customary to distinguish the following types:
The causes of the disease are not fully understood, to date, T cell leukemia type 1 (HTLV-1) I is one of the causes of this disease, but the following strains are also considered as an option: Epstein-Barr virus and HHV-6.
In people suffering T cell lymphoma the focus of the virus can be found in the epidermis, in blood plasma and Langerhans cells. An important role in the development of oncology is played by the immunopathological process in epidermal cells, the key of which is considered to be the uncontrolled proliferation of clonal lymphocytes.
When considering the causes of T-cell lymphoma, it should be mentioned hereditary factor, which carries important role in the formation of this disease.
Considering the hereditary factor in detail, a pattern was discovered in the identification of histocompatibility antigens, namely: HLA A-10 - for slowly flowing lymphomas, HLA B-5 and HLA B-35 - for cutaneous lymphomas high level and HLA B-8 – for the erythrodermic form of mycosis fungoides.
These factors prove the existence of a direct hereditary connection in the formation of the disease. Based on this, T-cell lymphoma can be classified as a multifactorial pathology that originates from the activation of lymphocytes.
One of the widespread diseases in the group of cutaneous T-cell lymphomas is mycosis fungoides; it is registered in 70% of cases. This disease is divided into three forms: classical lymphoma, erythrodermic and decapitated.
The first signs of T-cell lymphoma are an increase in lymph nodes in the neck area, in armpits or in the groin.
A characteristic feature of these manifestations is the painlessness of these formations and the lack of response to antibiotics.
Less common symptoms of T-cell lymphoma are:
In order to correctly diagnose T-cell lymphoma, you should undergo a number of tests, namely:
The key test for diagnosing T-cell lymphoma is a biopsy ( surgical removal lymph node with subsequent study). This fabric is subjected to morphological analysis, which is carried out by a specialist pathologist. The purpose of the study is to detect tumor lymphoma cells; then, if their presence is confirmed, the type of lymphoma should be determined.
There are a number diagnostic studies, one of which is radiation diagnostics. Radiation diagnostics includes x-ray, magnetic resonance and computer examination.
Peculiarity this method consists of identifying tumors in those parts of the body that are not subject to examination by a specialist. This technique is well suited for determining the stage of the disease.
Additional diagnostic methods:
Treatment is prescribed based on the type of lymphoma and general condition patient, for example, slowly progressing lymphomas are not always treated; sometimes it is enough to be constantly monitored by a specialist oncologist or hematologist. In cases where the disease begins to progress (lymph nodes enlarge, body temperature rises, etc.), it is necessary to begin therapeutic treatment as early as possible.
To treat locally advanced stages of lymphoma, radiotherapy is used. In generalized stages of the disease effective technique is chemotherapy.
Used to treat slow progressing lymphomas
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This type of lymphoma, called “indolent”, is difficult to cure, in this case, therapy is aimed at increasing life expectancy and improving the general condition of the patient. An aggressive course requires immediate initiation of therapy (CHOP chemotherapy, in combination with the use of the monoclonal antibody Rituximab).
Extremely aggressive types of lymphomas are treated according to the lymphoblastic leukemia therapy program. The ultimate goal of this method is complete cure and remission, however, this outcome is not always possible, it all depends on the degree of damage to the body and on how early the diagnosis was made. Most effective look Treatment is high-dose chemotherapy followed by hematopoietic stem cell transplantation.
The choice of treatment method is one of the key stages on the path to recovery; here it is necessary to take into account the stage and classification of the disease, the individual characteristics of the patient, etc. To confirm treatment, it is necessary to consult with the patient and his close relatives, so that the therapy method can be the most effective and practical in each specific case.
Video: T-cell lymphomas in detail
The prognosis of T-cell lymphoma directly depends on the degree of the disease, and of course, on how early treatment was started. If the disease begins to be treated at the first or second stage, there is a high probability of obtaining a favorable result, long remission and, as a result, long life. In this case, the probability fatal outcome may only be due to complications or the appearance of other concomitant diseases.
If treatment begins after the formation of tumors, the prognosis is less comforting; on average, life expectancy can be extended by 1-2 years.
Role thymus gland- main organ in immune system was determined only in 1961 thanks to data from R. A. Good and J. F. Miller. Despite the availability of numerous data on the role of the thymus gland in the maturation of the lymphoid system, many aspects of this problem, in particular the transformation of immature prethymic lymphoid cells into immunocompetent T cells with significant functional heterogeneity, have not been fully elucidated.
T cells that have passed through the thymus acquire the ability to respond to antigens and mitogens (PHA and ConA), settle in the thymus-dependent zones of lymphoid organs (in the paracortical zones of the lymph nodes, periarterial follicles of the spleen) and make up the bulk of the recirculating pool in the peripheral blood with a long life cycle. These cells are called thymus-dependent.
Intrathymic development is ensured various factors: a specific “microenvironment” determined by the stroma of the thymus gland, as well as its hormones, epithelial and mesenchymal cells. A number of active substances are isolated from the thymus gland, differing in activity, molecular weight, resistance to temperature influences. Among them, thymosin, thymopoietin, and thymic humoral factor are described. These substances, in particular thymosin, promote the transformation of T cells into more mature forms.
The mechanism of action of thymosin and other active substances on T cells is not completely clear; it is believed that their point of application is the cell membrane, namely the adenylate cyclase system. Probably, thymosin activates it and increases the concentration of intracellular cAMP and cGMP. These nucleotides are related to the processes of cellular development. The latter are very complex, diverse and require further study.
Among T cells, several subpopulations are distinguished, differing in cortisol sensitivity and differences in antigens and receptors on their surface.
By purpose, T cells are primarily responsible for cellular immunity, but in their functions they are heterogeneous. They consist of several subclasses: cells that recognize antigen; helper cells; killer cells; suppressor cells; memory cells, etc. The question of when T cells divide into different types occurs is very complex and debatable. functional purpose subpopulations. It is unclear what determines the functional direction of development, whether these subpopulations originate from a single precursor or the difference is genetically determined at the level of the stem cell.
All T cell subsets make up about 60-70% of all lymphocytes; about 25% are B cells, or bursa-dependent cells, which have undergone “training” in another central organ of immunity - the bursa of Fabricius (in birds) or its analogues in humans, where they acquire properties distinctive from T cells. It should be noted that a long search for this analogue did not lead to success. This role is assigned to various lymphoid formations - the appendix, tonsils, group lymphatic follicles of the intestines, lymphoid accumulations in the lungs and other organs. After maturation, B lymphocytes move mainly to the splenic follicles and lymph nodes.
Most antigens are thymus-dependent, since the immune response to them requires the participation of T cells; these antigens are complex, have several antigenic determinants with different specificities (tissue, microbial, viral).
The mechanism of antigenic recognition by T cells is very complex and has not been fully studied. The main task of T cells and their receptors is to recognize “self” and “non-self”. antigens. The etiology of T cell receptors that recognize antigens has not been definitively established. The interaction of cellular receptors with antigen is a signal for the initiation of an immune response and cellular differentiation. If the immune response follows the type antibody formation, then the participation of B cells and their transformation into plasma cells requires the participation of T helper cells (Th). The development of cellular reactions carried out by T cells also occurs with the participation of assistants - T amplifiers (Ta).
The mechanism of the helper action of T-lymphocytes (direct contact, or secreted by cells) is very complex and not fully understood. active substances). Activated Th produce specific factors and activate B cells through macrophages. The essence of these factors has not been fully determined. Considering that B cells produce different classes of immunoglobulins, it is possible that different Th subpopulations exist to regulate antibody formation (IgG, IgE).
Gershon in 1969 developed the concept of the suppressive role of T cells (T-suppressors), then it was found that Ts are capable of regulating various phases of the immune response. The role of suppressors is to regulate the level and strength of a specific immune response, ensuring immunological tolerance to some thymus-dependent antigens and to antigens of their tissues. Ts carry receptors for IgG, IgM, and act through soluble mediators. The nature of these factors secreted by Ts is being actively studied. There is no consensus on the mechanisms of Ts induction (direct contact of cells with antigen or feedback signals).
The value of Ts is very high; limiting the immune reaction is no less important for the body than stimulating it. This is especially true for those immune reactions, which can lead to pathology ( autoimmune diseases, diseases)
Killer T cells carry out cellular immune reactions: cytopathogenic effects in transplantation immunity, antitumor immunity, and some types of infections. A subpopulation of killer cells is also an effector of delayed-type hypersensitivity (DTH).
The heterogeneity of the T-cell population in terms of their functional properties explains the extremely complex interaction of cells in the body's reactions to antigen.
It is now obvious that not only T cells, but also B cells are also not a homogeneous mass of cells. B cells are characterized by the presence of immunoglobulins on the surface, which ensure recognition of antigens, under the influence of which B lymphocytes turn into plasma cells that produce antibodies -. Their production for most antigens cannot occur without interaction with T cells. Cellular cooperation is a necessary condition for the development of an immune response.
Activated T cells, in addition to the factors secreted by Ts and Th, form a number of mediators - lymphokines, which have different physical and chemical properties. Their role is the involvement of various cells in the immune response - neutrophil granulocytes, macrophages, eosinophilic granulocytes. The participation of these T cells in the immune response is very important. The role of macrophages, which destroy the antigen and convert it into an immunogenic form, is especially important. Macrophages currently include a group of cells capable of phagocytosis, adhering to glass - adherens, phagocytic mononuclear cells, tissue macrophages and monocytes.
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TCR is a heterodimeric protein consisting of two subunits - α and β or γ and δ, presented on the cell surface. The subunits are anchored in the membrane and linked to each other by disulfide bonds.
By their structure, TCR subunits belong to the immunoglobulin superfamily. Each of the subunits is formed by two domains with a characteristic immunoglobulin fold, a transmembrane segment and a short cytoplasmic region.
The N-terminal domains are variable (V) and are responsible for binding antigen presented by molecules of the major histocompatibility complex. The variable domain contains a hypervariable region (CDR) characteristic of immunoglobulins. Due to the extraordinary diversity of these areas, different T cells are able to recognize widest spectrum various antigens.
The second domain is constant (C) and its structure is the same in all subunits of this type in a particular individual (with the exception of somatic mutations at the level of the genes of any other proteins). In the area between the C domain and the transmembrane segment there is a cysteine residue, which forms a disulfide bond between the two TCR chains.
TCR subunits are aggregated with the membrane polypeptide complex CD3. CD3 is formed by four types of polypeptides - γ, δ, ε and ζ. Subunits γ, δ and ε are encoded by closely linked genes and have a similar structure. Each of them is formed by one constant immunoglobulin domain, a transmembrane segment and a long (up to 40 amino acid residues) cytoplasmic part. The ζ chain has a small extracellular domain, a transmembrane segment, and a large cytoplasmic domain. Sometimes, instead of the ζ chain, the complex includes the η chain, a longer product of the same gene obtained by alternative splicing.
Since the structure of the proteins of the CD3 complex is invariant (does not have variable regions), they are not able to determine the specificity of the receptor to the antigen. Recognition is solely a function of the TCR, and CD3 mediates signal transmission into the cell.
The transmembrane segment of each CD3 subunit contains a negatively charged amino acid residue, while the TCR contains a positively charged one. Due to electrostatic interactions, they are combined into a common functional complex of the T-cell receptor. Based on stoichiometric studies and molecular weight measurements of the complex, its most likely composition is (αβ)2+γ+δ+ε2+ζ2.
TCRs consisting of αβ chains and γδ chains are very similar in structure. These forms of receptors are presented differently in different tissues of the body.
The structure of the T-lymphocyte receptor is in many ways similar to the structure of the antibody molecule. T-cell receptor (TCR) molecules consist of two chains - a and p. Each of them contains V- and C-domains, their structure is fixed by disulfide bonds. The variable domains of the a- and p-chains have not 3-4, as in antibodies, but at least 7 hypervariable regions, which form the active center of the receptor. Behind the C domains, near the membrane, there is a hinge region of 20 amino acid residues. It provides the connection of a- and p-chains using disulfide bonds. Behind the hinge region is a transmembrane hydrophobic domain of 22 amino acid residues, which is associated with a short intracytoplasmic domain of 5-16 amino acid residues. Recognition of the presented antigen by the T-cell receptor occurs as follows. MHC class P molecules, like T-lymphocyte receptors, consist of two polypeptide chains - a and p. Their active site for binding the presented antigenic peptides is shaped like a “cleft.” It is formed by helical sections of the a- and p-chains, connected at the bottom of the “gap” by a non-helical region formed by segments of one and the other chain. At this center (cleft), the MHC molecule attaches the processed antigen and thus presents it to T cells (Fig. 63). The active center of the T-cell receptor is formed by the hypervariable regions of the a- and p-chains. It also represents a kind of “gap”, the structure of which corresponds to the spatial structure of the peptide fragment of the antigen represented by the MHC class P molecule to the same extent as the structure of the active center of the antibody molecule corresponds to the spatial structure of the antigen determinant. Each T-lymphocyte carries receptors for only one peptide, that is, it is specific for a specific antigen and binds only one type of processed peptide. The attachment of the presented antigen to the T-cell receptor induces the transmission of a signal from it to the cell genome.
For any TCR to function, it requires contact with the CD3 molecule. It consists of 5 subunits, each of which is encoded by its own gene. All subclasses of T lymphocytes have CD3 molecules. Thanks to the interaction of the T-cell receptor with the CD3 molecule, the following processes are ensured: a) removal of TCR to the surface of the T-lymphocyte membrane; b) imparting an appropriate spatial structure to the T-cell receptor molecule; c) reception and transmission of a signal by the T-cell receptor after its contact with the antigen into the cytoplasm, and then into the genome of the T-lymphocyte through the phosphatidylinositol cascade with the participation of intermediaries.
As a result of the interaction of the MHC class P molecule carrying the antigenic peptide with the T-lymphocyte receptor, the peptide is inserted into the “gap” of the receptor, which is formed by the hypervariable regions of the a- and p-chains, while contacting both chains
VEGETATIVE (AUTONOMOUS) NERVOUS SYSTEM
The autonomic nervous system, like the entire nervous system, consists of neurons and their processes - nerve fibers. For vegetative nervous system characterized by a two-neuron structure. The first neurons of the autonomic nervous system are located in the brain (middle and medulla oblongata) and spinal cord, where they form clusters - autonomic nuclei. The axons of the first neurons (nerve fibers) leave the central nervous system and end in special nodes (ganglia) located near spinal column, near internal organs or in their walls, on second neurons. The axons of the second neurons go to the innervated organ.
Nerve fibers of the autonomic nervous system emerge from the brain or spinal cord as part of some cranial and spinal nerves and approach the cells vegetative nodes. They are called preganglionic. Postganglionic nerve fibers, in turn, depart from the nodes, which innervate internal organs. Fibers of the autonomic nervous system form vegetative fibers near organs and in their walls. nerve plexuses. These plexuses contain neurons. The autonomic nuclei, located in the brain and spinal cord, constitute the central part of the autonomic nervous system, and ganglia and fibers are its peripheral part.
The autonomic nervous system is divided into two divisions: sympathetic and parasympathetic. Each of them is characterized by its own characteristics. Higher nerve centers The autonomic nervous system is located in the hypothalamus: in the anterior nuclei - the centers of the parasympathetic, in the posterior nuclei - the centers of the sympathetic departments.
The sympathetic division of the autonomic nervous system includes the lateral horns of the spinal cord (sympathetic neurons of these horns, constituting the central part of the sympathetic division of the autonomic nervous system), the borderline sympathetic trunk, sympathetic nerve plexuses and sympathetic nerve fibers.
The sympathetic division of the autonomic nervous system has the following structural features:
1) is formed by nerve fibers extending in symmetrical pairs on both sides of the spinal cord from neurons of the thoracic and lumbar segments (from the first thoracic to the second - fourth lumbar). The processes of the cells of the lateral horns emerge from the spinal cord as part of the corresponding spinal nerves, separate from them and approach the border sympathetic trunk;
2) ganglia are located far from the innervated organs in the form of a chain on both sides of the spinal cord (borderline sympathetic trunk) or in the form of a cluster far from the spinal cord (solar plexus, etc.);
3) preganglionic fibers are short;
4) postganglionic fibers are long.
Sympathetic innervation is universal; sympathetic nerves innervate the tissues of all organs, skeletal muscles and blood vessels. The transmission of impulses from the postganglionic fiber to the organ is carried out using a mediator norepinephrine
Sympathetic nerve fibers stimulate the heart (increase and increase contractions), sweat glands, muscle metabolism, constrict blood vessels, inhibit activity digestive system(weaken juice secretion and inhibit motor skills), dilate the pupils, relax the wall bladder etc.
Fibers cervical spine the sympathetic trunk innervates the blood vessels and organs of the neck and head, to which the branches approach carotid arteries: throat, salivary glands, lacrimal glands, dilator muscle, etc. Fibers thoracic, from which the greater and lesser splanchnic nerves depart, innervate thoracic aorta, esophagus, bronchi and lungs. Fibers of the lumbar and pelvic regions, solar plexus innervate all organs abdominal cavity, fibers of the hypogastric plexus - pelvic organs.
