Islets of Langerhans: small areas of the pancreas of great importance. melanocytes

Keratinocytes (keratinocytes)

Keratinocytes are the first class of skin cells. On electron microscopy, keratinocytes are presented in the form of fluffy glomerular balls. This figure shows a keratinocyte of the skin of the face at the moment when it is on the basement membrane and. These “balls” form a barrier in relation to the external environment.

The functions of keratinocytes as skin cells are well known to us, so let's consider.

Keratinocytes provide skin sensitivity and transmit sensory stimulus.
Synthesize sensory peptides, just like the cells of the nervous system - neurons.
They transmit sensory temperature sensations, without the participation of a special temperature receptor. The keratinocyte is able to respond to changes in temperature, sensing a difference of less than one tenth of a degree. This means that with a well-developed sensitivity and during training, you can feel the temperature difference, like an experienced mother, putting her hand to the child’s forehead, says: “38.2” - and a thermometer is not needed. The keratinocyte is able to measure the temperature, and when you have compared the result of the measurement with your hand several times with the result of measuring with a thermometer, then you have this connection, and now you are already a “man-thermometer”, he is also a “man-culinary”, he is also a “person-nanny” " etc.
Keratinocytes transmit the sensation of pain.
They transmit osmotic stimuli to the nervous system in response to the amount of salts. Everyone knows that when immersed in salt water, the skin becomes a little loose and macerates. It's such an adaptive mechanism. Grooves on the fingers in the water appear in order to make it less slippery to grab fish with them. And when the fingers become like those of Gollum from The Lord of the Rings, then with a bare hand you can easily grab in the water: fish, stones, algae. This is in some way an atavism and a hunting device that has been preserved in humans. When the salt ratio changes, keratinocytes are able to analyze this, and, with a certain gradient, transmit a stimulus to the nervous system. The nervous system quickly gives back the stimulus, organizing the swelling of the entire epidermis and a little of the upper layer of the dermis, due to the release of special mediators. This increases the volume of the skin, furrows are formed and, please, fish with your bare hands.
Osmotic reactivity has been used in cosmetology for a long time. If the water gradient in the epidermis is up to 90 g/cm², then water-soluble ingredients do not penetrate the skin. When the water gradient rises above 91 g/cm², osmotic sensations appear. Therefore, thanks to the work of keratinocytes, it is possible to achieve the penetration of water-soluble ingredients by changing the osmotic gradient. To raise the water gradient in the epidermis, it is necessary to create contact with something permanently hydrated, such as a sheet mask. After 3.5-4 minutes the water gradient will rise and the water soluble ingredients (like the green tea extract found in the mask) will go in. This is due to the fact that keratinocytes will open channels and water-soluble ingredients will penetrate deep into the epidermal layer. It is safe to say that wet, non-drying masks help carry water-soluble ingredients through at least the entire thickness of the epidermis.
Stimulation of any kind of keratinocyte receptor leads to the release of neuropeptides, in particular substance P, which plays the role of a neurotransmitter that transmits signals to target cells that modulate epidermal functions. Substance P is responsible for increased (redness, itching, peeling).
They interact with neurons in different ways: adenosine triphosphate activation of cells, activation and deactivation of calcium channels. And if the keratinocyte considers it necessary to launch some kind of interaction stimulus, then it will do it by itself opening the calcium channel or closing it. Peptides, which have a pronounced calming effect and are used to create the effect of "serene skin", are able to change the polarization of the membrane, due to which the activation-deactivation of the calcium channel is difficult, and as a result, the nerve stimulus is not transmitted. Against this background, the skin calms down. This is how hibiscus extract and some peptides, such as Skinasensyl, work.
Release neuropeptides (substance P, galanin, CGRP, VIP).

Keratinocytes are completely independent cells. They synthesize the key components for transmitting information themselves and actively broadcast messages to the nervous system. In principle, they largely command the nervous system and ask it what to do. It used to be that something happened on the skin, the stimulus ran, and the nervous system made a decision. But it turns out - no, it was the skin that made the decision and implemented it through the nervous system.

The same ion channels and neuropeptides that keratinocytes use were originally found in the brain, that is, keratinocytes are the neurochemical partners of the brain in the literal sense. Keratinocytes are practically brain cells, but brought to the surface. And the skin, in a certain sense, is able to think and make some life decisions directly with nerve cells on the surface of the skin.

Therefore, the cosmetologist, each time applying something to the skin or using a mesoscooter, must understand what directly affects the nervous system.

melanocytes (melanocytes)

In this figure, an uncharacteristic blue melanocyte is depicted so that it can be better seen. And it is presented in the form of a spider with legs that it can grow. A melanocyte is a mobile cell located on the basement membrane, which can slowly crawl and migrate. If necessary, melanocytes with the help of their legs crawl into those areas in which they are needed.

Normally, melanocytes are distributed evenly over the entire surface of the skin. But the life of any person is arranged in such a way that some parts of the body are much more exposed than other parts, and the third part has never seen the sun. Therefore, melanocytes from the part that has not met the sun slowly migrate to where additional protection is needed. It has practical and aesthetic value. And if you haven’t sunbathed in a thong before the age of sixty, then don’t try it. Because by this age, the melanocytes from the buttocks have already gone on a journey, and in this area the skin will turn red, not golden brown.

The main function of melanocytes is the synthesis of the protective pigment melanin in response to ultraviolet irradiation. The ultraviolet beam hits the skin, and the melanocyte creates a black pea of melanin from tyrosine (amino acids), which it moves to its leg. With this leg, he digs into the keratinocyte, where melanin granules are distilled. Further, this keratinocyte moves up and squeezes out lipids and melanin granules, which spread along the stratum corneum and form an umbrella. In fact, an umbrella is created from the granules at the top, and an umbrella from the melanocytes themselves stuffed with granules - at the bottom. Due to such double protection, ultraviolet rays penetrate into the deep layers of the skin (into the dermis) much less or do not penetrate at all (if there was no radiation). At the same time, ultraviolet does not damage the DNA apparatus and cells, without causing their malignant transformation.
Ultraviolet radiation stimulates melanocytes to synthesize the hormone proopiomelanocortin (POMC), which is a precursor of several bioactive peptides at once. That is, additional peptides appear from it, which will act as neuropeptides - to transmit stimuli to the nervous system. Proopiomelanocortin has analgesic properties.
The hormone adrenocorticotropin, which is produced during times of stress, also synthesizes melanin. If there (for example, regular lack of sleep), then this supports the violation of pigmentation. Any stimulus that increases the amount of adrenocorticotropin will make it difficult and will lead to relapses.
Various types of melanotropin, β-endorphin, lipotropin also activate melanogenesis, stimulating the proliferation of epidermal cells and facilitating the movement of Merkel cells and melanocytes to higher layers of the skin, that is, they help accelerate epidermal renewal. Ultraviolet radiation has both a damaging effect on the skin and some healing effect in the form of stimulation of vitamin synthesis. D, which is necessary for a person to live.
Melanocytes are in constant close contact with sensitive nerve fibers, the so-called C-fibers. E electron microscopy revealed thatthe cell membrane thickens at the fiber and, upon contact with a melanocyte, a synapse is formed.What is a synapse? For neurons. The neuron is characterized by synaptic communication. And as it turned out, melanocytes also have it.Pigmented neurons are exactly the same neurons as in the peripheral nerves, as in the spinal cord and brain, but they have a different function. ToIn addition to being cells of the nervous system themselves, they can synthesize pigment.
Melanocytes belong to the neuroimmune system and are, in a direct sense, sensitive cells that provide a regulatory function in the epidermis. Their way of interacting with nerve fibers is identical to the interaction of neurons. This was one of the reasons for the ban on the widespread use of hydroquinone (a substance found in many whitening products). Hydroquinone causes apoptosis of melanocytes, that is, their final death. And if this is good with respect to hyperpigmented cells, then the death of cells of the nervous system is bad.

Research is currently underway on the harmful effects of hydroquinine on the nervous system. That is why hydroquinone is completely banned in Europe. In America, it is only approved for medical use, and is limited to 4% in the hydroquinone formulation. Doctors usually prescribe 2-4% for a short period of time, since not only its effectiveness, but also the possible development of side effects depends on the duration of hydroquinone use. The use of hydroquinone on the skin is not safe, and for people with black skin is unacceptable. As a result of apoptosis, dark-skinned people develop characteristic blue spots, which, unfortunately, are permanent. For people with fair skin, hydroquinone products should only be used in short courses on prepped skin. Up to three months is the safety limit. American dermatologists prescribe products with hydroquinone - from two to six weeks.

Arbutin is a safe alternative to hydroquinone, since it transforms itself in the skin and turns into hydroquinone already directly inside the skin, without causing apoptosis. Arbutin acts more slowly and less intensely.

Melanocytes are “pigment neurons”, the activity of which directly depends on the state of the nervous system.

Langerhans cells (Langerhans cells

The most beautiful cells On electron microscopy, Langerhans cells are presented in the form of flowers, inside of which there is a scattering of a beautiful nucleus. They are not only of remarkable beauty, but also of amazing properties, because they belong simultaneously to the nervous, immune and endocrine systems. Such a servant of three masters, who serves all three equally well.

Possess basic antigenic activity. That is, they are able to express antigens and receptors.
When the antigen binds, the Langerhans cell displays its immune activity. It migrates from the epidermis to the nearest lymph node (this is such a fast energetic cell that can move at high speed), transmits information there, providing protective immunity to a specific agent. Suppose Staphylococcus aureus sat on her, she recognized it, rushed to the nearest lymph node, and there was a bell - T-lymphocytes gathered and immediately organized protection against Staphylococcus aureus, ran back after her, and in the epidermis the infection was localized as much as possible, if it was possible immediately destroy. That is why, after mesotherapy and after non-disposable mesoscooters, fortunately, rare clients get infectious.
Langerhans cells are sensitive to temperature changes resulting from fever or inflammation, including changes in skin temperature during the use of certain cosmetic ingredients. A slight increase in temperature activates the immune potential of Langerhans cells and enhances their ability to move. If the skin is prone to inflammatory reactions, then regular use and gentle heat, which is used in the procedure, give a good effect. When using prebiotic therapy, the mask must be used heated, this will give additional activation of Langerhans cells - immunity cells. Naturally, during an extensive inflammatory process, thermal procedures are not needed.
Langerhans cells are involved in the occurrence of itching, and they are the main authors of the phenomenon.
They are characterized by the expression of a large number of neuropeptides and various receptors, which allows them to contact with all cells of the nervous, immune and endocrine systems. , as well as with passive skin cells.
In the hair follicles and sebaceous glands of the skin, an association of Merkel cells and Langerhans cells is observed. At the same time, associated cells are tightly connected with sensory neurons. Normally, Langerhans cells sit on guard in the upper layers of the epidermis, somewhere between . But in hair follicles and sebaceous glands, Langerhans cells bind to Merkel cells, form a two-cell complex, andattached to sensory fibers - C-fibers. And they manage this neuroimmune complex: they grow hair, manage synthesis, sebum and etc. That is, these complexes are closely related to the nervous system and provide an understanding of endocrine stimuli.

Why does the production of sebum and hair growth depend both on the hormonal background and at the same time on the state of the nervous system? Many people have experienced a situation where hair falls out as a result of stress and lack of sleep. But after rest it stops. And against the background of stress, various procedures and ampoules of some expensive drugs have a rather conditional effect. Because the Langerhans cell with the Merkel cell is not so easy to appease, because they are their own mistresses and decide a lot on their own. That is, these are cells that work on three systems at once.

Langerhans cells - belong to the nervous, immune and endocrine systems at the same time.

Merkel cells (Merkel cell s)

Merkel cells on electron microscopy look like small red granules with long tails of a different staining intensity. Tails are sensory fibers that are in constant contact with them. At one time it was believed that the Merkel cell is such a structure with a tail, but then it turned out that the fiber is independent. That is, this is the structure of the skin, and the Merkel cell only uses it.

Merkel cells are located low, unlike all other cells. They are also found in the root zone of the hair follicles.
They synthesize a large number of neuropeptides due to the presence of dense neurosecretory granules (similar to how melanin granules accumulate in melanocytes). With these granules, Merkel cells synthesize a variety of peptides that are actively used. Granules containing neuropeptides are most often located in close proximity to the location of sensory neurons penetrating the epidermis, which may explain the close relationship between the endocrine activity of Merkel cells and the activity of neurons associated with it.
Merkel cells are primarily endocrine cells that transmit endocrine stimuli to the nervous system. Receptors present on the surface of Merkel cells provide autocrine and paracrine activity. In fact, they are more versatile than, say, the thyroid gland or other endocrine organs.
Merkel cells provide interaction with the nervous system both with the help of a large number of different neuropeptides and by synaptic action, like melanocytes. That is, a Merkel cell is also a neuron, but trained to make a hormone.
Clusters or clusters of Merkel cells with sensory neurons have been called Merkel cell neuron complexes. They are slowly adapting mechanoreceptors (SAMs) that respond to pressure. Ruffini bodies also belong to this class.

When doing a massage procedure, when pressing on the skin, a signal is transmitted to a cluster of Merkel cells. If the massage is performed correctly: to observe rhythm, constant pressure with the same force of impact, sustained direction along the lymph flow, moderate temperature, then the Merkel cluster will produce endorphins and the skin will shine.

If it is wrong to massage: press too hard or vice versa too weakly, do not keep the rhythm, act across, then Merkel cells give a signal. They will signal pain by reducing the synthesis of opiate-like substances, send out vasoactive peptides that dilate blood vessels, causing redness and swelling, to show that something is wrong. During the massage, a neuroendocrine effect occurs.

Properly performed massage gives the production of endorphins and contributes to the fact that the negative epigenetic influences can be partially leveled. In particular, the negative effects of ultraviolet damage can be mitigated. But for this massage should be regular (once a week) and last at least 15 minutes.

Merkel cells are the “master” cells of NISCs (neuroendocrine cells). A feature of Merkel cells is their ability to excite, similar to the ability of neurons. Apparently, Merkel cells are correctly classified as neuron-like cells that are able to respond to a variety of stimuli by direct activation.

Not to be confused with Langerhans cells - epidermal tissue cells.

Islets of Langerhans- accumulations of hormone-producing (endocrine) cells, mainly in the tail of the pancreas. Discovered in 1869 by the German pathologist Paul Langerhans (1849-1888). The islets make up approximately 1-2% of the mass of the pancreas. The pancreas of an adult healthy person has about 1 million islets (with a total weight of one to one and a half grams), which are united by the concept organ of the endocrine system.

History reference

Paul Langerhans, as a medical student working for Rudolf Virchow, in 1869 described clusters of cells in the pancreas that differed from the surrounding tissue, later named after him. In 1881, K. P. Ulezko-Stroganova first pointed out the endocrine role of these cells. The increatory function of the pancreas was proven in Strasbourg (Germany) in the clinic of the largest diabetologist Naunin Mering and Minkowski in 1889 - pancreatic diabetes was discovered and the role of the pancreas in its pathogenesis was first proven. The Russian scientist L. V. Sobolev (1876-1919) in his dissertation “On the morphology of the pancreas during ligation of its duct in diabetes and some other conditions” showed that ligation of the excretory duct of the pancreas leads to complete atrophy of the acinar (exocrine) section, while pancreatic islets remain intact. Based on the experiments, L. V. Sobolev came to the conclusion: “the function of the pancreatic islets is the regulation of carbohydrate metabolism in the body. The death of the pancreatic islets and the loss of this function causes a painful condition - sugar diabetes.

In the future, thanks to a number of studies conducted by physiologists and pathophysiologists in various countries (performing pancreatectomy, obtaining selective necrosis of pancreatic beta cells with the chemical compound alloxan), new information was obtained about the endocrine function of the pancreas.

In 1907, Lane & Bersley (University of Chicago) distinguished between two types of islet cells, which they called type A (alpha cells) and type B (beta cells).

In 1909, the Belgian researcher Jan de Meyer suggested that the secretion product of the beta cells of the islets of Langerhans be called insulin (from lat. insula- islet). However, direct evidence of the production of a hormone that affects carbohydrate metabolism could not be found.

In 1921, in the physiology laboratory of Professor J. Macleod at the University of Toronto, a young Canadian surgeon, Frederick Banting, and his assistant, medical student Charles Best, succeeded in isolating insulin.

In 1962, Marlin et al found that aqueous extracts of the pancreas were able to increase glycemia. The substance that causes hyperglycemia is called "hyperglycemic-glycogenolytic factor". It was glucagon - one of the main physiological antagonists of insulin.

In 1967, Donatan Steiner et al. (University of Chicago) succeeded in discovering proinsulin, a precursor protein to insulin. They showed that the synthesis of insulin by beta cells begins with the formation of a proinsulin molecule, from which the C-peptide and the insulin molecule are subsequently cleaved as necessary.

In 1973, John Ensik (Washington University), as well as a number of scientists from America and Europe, carried out work on the purification and synthesis of glucagon and somatostatin.

In 1976, Gudworth & Bottaggo discovered a genetic defect in the insulin molecule, finding two types of the hormone: normal and abnormal. the latter is an antagonist to normal insulin.

In 1979, thanks to the research of Lacy & Kemp and co-authors, it became possible to transplant individual islets and beta cells, it was possible to separate the islets from the exocrine part of the pancreas and carry out transplantation in the experiment. In 1979-1980. when transplanting beta cells, the species-specific barrier was overcome (cells from healthy laboratory animals were implanted into diseased animals of another species).

In 1990, for the first time, pancreatic islet cells were transplanted to a patient with diabetes mellitus.

Cell types

Alpha cells

Main article: alpha cell

Alpha cells make up 15–20% of the islet cell pool and secrete glucagon (a natural insulin antagonist).

beta cells

Main article: beta cell

Beta cells make up 65...80% of the islet cell pool - they secrete insulin (with the help of receptor proteins it conducts glucose into the cells of the body, activates the synthesis of glycogen in the liver and muscles, and inhibits gluconeogenesis).

delta cells

Main article: delta cell

Delta cells make up 3 ... 10% of the islet cell pool - they secrete somatostatin (inhibits the secretion of many glands);

PP cells

Main article: PP cage

PP cells make up 3...5% of the pool of islet cells - they secrete pancreatic polypeptide (suppresses pancreatic secretion and stimulates gastric juice secretion).

Epsilon cells

Main article: Epsilon cell

Epsilon cells make up<1 % пула островковых клеток - секретируют грелин («гормон голода» - возбуждает аппетит).

Islet structure

The pancreatic islet is a complex functional microorganism with a certain size, shape and characteristic distribution of endocrine cells. The cellular architecture of the islet influences the intercellular connection and paracrine regulation, and synchronizes the release of insulin.

For a long time it was believed that the islets of humans and experimental animals are similar both in structure and in cellular composition. Works of the last decade have shown that in adults the predominant type of islet structure is mosaic, in which cells of all types are mixed throughout the islet, in contrast to rodents, which are characterized by a mantle type of cell structure, in which beta cells form the core, and alpha cells cells are on the periphery. However, the endocrine part of the pancreas has several types of organization: it can be single endocrine cells, their small clusters, small islands (diameter< 100 мкм) и крупные (зрелые) островки.

Small islands have the same structure in humans and rodents. Mature human islets of Langerhans have a pronounced ordered structure. As part of such an island, surrounded by a connective tissue membrane, it is possible to identify lobules limited by blood capillaries. The core of the lobules is an array of beta cells, on the periphery of the lobules, in close proximity to the blood capillaries, there are alpha and delta cells. Thus, the cellular composition of an islet depends on its size: the relative number of alpha cells increases with islet size, while the relative number of beta cells decreases.

The skin is the largest specialized human organ, with an area of 2 m 2 and a mass of almost 3 kg. It performs a number of important functions. In particular, the skin is a barrier organ and, most importantly, like the thymus, it is the site where certain types of immune cells mature and immunological reactions take place. In principle, all types of cells capable of carrying out a wide spectrum of immune reactions are represented in the skin barrier. This gives reason to consider the skin as an organ of the immune system.

In the early 80s. In the 20th century, the concept of skin-associated lymphoid tissue (SALT) was formulated, which continues to develop today. In accordance with modern views, along with lymphocytes to the immune system of the skin should be attributed neutrophils, mast cells and eosinophils, Langerhans cells and keratinocytes.

Lymphocytes

Recirculation is characteristic of lymphoid cells - a constant exchange between blood, lymph and organs containing lymphoid tissue. Another feature of this cell population is homing - the settlement of certain areas of lymphoid organs and tissues. Therefore, intradermal lymphocytes differ from those circulating in the peripheral blood. To study the population composition of skin lymphocytes, immunohistochemistry and “skin window” methods were used (determination of the percentage of cells on an imprint from a small area of skin after removal of the surface layer of the epidermis). This made it possible to establish that normally lymphoid cells of the skin are predominantly T-lymphocytes: CD5+ - 19%, CD3+ - 48%, CD25+ - 26%, CD4+ - 33%, CD22+ - 18%. They all share a fairly specific common marker, cutaneous lymphocytic antigen (CLA), which is thought to be a receptor that controls the affinity of T cells for the skin. CLA is an adhesive molecule on the membrane that ensures the binding of the T-lymphocyte to the endothelium of post-capillary skin venules and its passage into the dermis. CLA-positive T cells make up 10-15% of circulating blood cells. The population of CLA-positive T cells is represented by several subpopulations that differ in receptor status and functional activity. All CLA-positive T cells are characterized by the expression of cutaneous T-cell chemoattractant (CTACK), which "attracts" T-lymphocytes from the circulation into the skin, primarily in various inflammatory processes. The totality of clinical and experimental data accumulated today shows that CTACK plays an important role in the immune response of the skin. The most significant is its pathogenetic role as a pro-inflammatory factor in diseases such as atopic and contact dermatitis.

In addition, most T-lymphocytes of normal skin of a healthy person have receptors for other chemokines - biologically active substances that control cell migration, in particular lymphocytes. This contributes to their active participation in various immunological reactions, both physiological and pathological.

Skin T cells are able to differentiate into cytotoxic or memory cells (CD45RO). Memory cells also express skin lymphocytic antigen (CLA), are formed in the lymph nodes that drain the skin, and return to the skin when inflamed. Normally, they are involved in the formation of immunity in the skin, and in pathology they are involved in the pathogenesis of cutaneous T-cell lymphoma, transplant rejection, atopic dermatitis, etc. . About a third of skin lymphocytes are T-helpers (CD4+). In recent years, it has been shown that this subpopulation of cells is represented by two varieties, Th1 and Th2, which differ primarily in the spectrum of cytokines produced. Normally, there is a certain balance between these cells; in diseases of the skin, the ratio of Th1/Th2 changes. For example, during inflammatory processes, the activity of Th1-lymphocytes increases. Thus, skin lymphocytes represent a heterogeneous cell population that contains recirculating pool cells and specific skin lymphocytes. The latter are characterized by a peculiar set of cellular receptors that determine their affinity for the skin, as well as a certain set of cytokines produced, allowing them to participate in various cellular reactions that provide skin repair.

Neutrophils

Neutrophils are contained in normal skin in small quantities, and in acute inflammatory processes their number increases significantly. In addition, neutrophil granulocytes are involved in the regulation of reparative processes by interacting with other cells (macrophages, keratinocytes). One of the mechanisms of this interaction is the production of neutrophilokins, which stimulate the secretion of growth factors by fibroblasts and lymphocytes, which in turn induce the proliferative activity of regenerating tissue cells.

Mast cells and eosinophils

Mast cells (MC) and skin eosinophils are involved in various pathological processes, primarily in allergic ones. When an allergen is introduced into the skin, it interacts with eosinophils and MCs that carry IgE antibodies on their surface. As a result of this interaction, cell activation and degranulation occurs, followed by the release of various mediators (substance P, interleukins 1 and 6, chemokines). They contribute to the migration of other immunocompetent cells to the focus of the pathological process and support the activity of the inflammatory reaction. The number and functional activity of these cells change differently in various skin diseases. In addition, TK and eosinophils play a role in the pathogenic effects of stress on the skin.

Langerhans cells

Langerhans cells (CL) are specialized cells of the epidermis and make up 2-3% of the total number of its cells. They are one of the forms of dendritic cells of monocyte-macrophage origin and perform the most important immune functions in the body, primarily as antigen-presenting cells. Dendritic cells are a key link between acquired and innate immunity.

During inflammation and other processes associated with antigenic stimulation, CL acquire motor activity, leave the epidermis with the flow of tissue fluid and, moving through the lymph, undergo certain morphological transformations, as a result of which they become the so-called "veil" cells. Reaching the lymph nodes, they actively interact with other immunocompetent cells and present antigens to them. CLs are able to interact with various types of T cells, thus modulating various types of immune responses (inflammation, autoimmunity). In addition, CL is directly involved in the destruction of bacteria in the skin.

Keratinocytes

Keratinocytes should also be attributed to the immune system of the skin. They produce a wide range of regulatory molecules (growth factors, cytokines), which determines their participation in the immune defense of the skin. Violation of the interaction of adhesion molecules on the surface of keratinocytes with lymphocyte receptors is an important mechanism in the pathogenesis of a number of diseases, such as psoriasis.

melanocytes

In recent years, these pigment-producing skin cells have also been referred to as immunocompetent, since they, like keratinocytes, are capable of producing a number of cytokines (interleukins 1, 3, and 6, tumor necrosis factor, transforming growth factor, and others), which act as mediators. immune response in the dermis.

Cytokines - bioregulators of immune responses

The last decades were characterized by a rapid accumulation of data on a new class of immunoregulatory molecules - cytokines. They include a huge number of different substances, including interleukins, which perform a communicative function between immunocytes and have various regulatory effects both within the immune system and in other organs and tissues. At present, most of the known interleukins have been found in the skin: their functions are associated with the skin, and the disruption of production underlies the pathogenesis of a number of skin diseases, in particular psoriasis and atopic dermatitis.

The immune system of the skin in infectious and non-infectious lesions

The immune system of the skin is involved in the implementation of both innate and acquired immunity. Its role is most significant in violation of the integrity of the barrier and the penetration of microorganisms into the dermis. At the same time, SALT reacts as a single functional system. In antigen-presenting cells, antigen processing and presentation occurs, during which CLs turn into dendritic cells and move along the dermis to the lymph nodes. As a result, they acquire the ability to interact with T helper cells, which then activate B cells and partially differentiate into effector lymphocytes and memory cells. Memory T cells carrying CLA are able to migrate from the bloodstream to the epidermis; They are the ones that dominate the skin. As a result of an increase in the number of T-cells in contact with the most "relevant" antigens, an amendment is made to the antigen-recognizing repertoire of T-lymphocytes. This determines the activity of the immune response.

In non-infectious skin lesions, such as trauma, the immune system is actively involved in the healing of the skin wound. Skin wound healing is a dynamic interactive process involving mediators, blood cells, extracellular matrix and mesenchymal cells, which consists of three phases: inflammation, granulation tissue formation and tissue remodeling. Inflammation is the response of the body in general and the skin in particular to injury. The leading role in its development belongs to blood cells - neutrophils. They not only participate in hemostasis, but also secrete biologically active substances.

As a result, monocyte-macrophages are activated, which serve as a link between inflammation and regeneration. Activation of these cells leads to the induction of epidermal proliferation. It should be noted that re-epithelialization begins within a few hours after injury. Initially, it occurs due to the reduction of intracellular tonofilaments, which increases the migration ability of epidermal cells. Approximately four days later, a newly formed stroma (granulation tissue) is determined in the wound. Under the influence of various cytokines produced by immunocompetent cells, fibroblast differentiation, collagen synthesis, and vascular neoformation occur in it. Cytokines, including growth factors (epidermal, transforming, platelet, endothelial, and others) take an active part in these processes. Collagen metabolism, the appearance of myofibroblasts in the granulation tissue, the proliferation of keratinocytes, and a number of other cellular events that complete the “maturation” of the granulation tissue lead to the formation of a skin scar, which indicates the restoration of tissue integrity and the completion of the reparative process.

Thus, all types of immune response are present in the skin - innate and acquired (adoptive), cellular and humoral. Due to this, both a nonspecific protective function (immunoglobulins, lysozyme, lactoferrin, defensins, phagocytosis) and primary recognition of an antigen with its subsequent presentation and proliferation of antigen-specific T cells are possible. As a result, both cytotoxic reactions and antibody formation are carried out in the dermis. It should be emphasized that the peculiarity of the skin as an immune organ is the relative predominance of innate immunity over acquired, and in turn, cellular factors prevail in the system of innate immunity of the skin. Analysis of numerous scientific data suggests that immune responses are related to most of the physiological and pathological processes occurring in the skin.

SALT dysfunction

Based on extensive experimental and clinical material, it has been shown that impaired SALT functions - T-cell reactivity, cytokine production, chemokine expression on cells, intercellular interactions, and other immunological reactions - lead to the development of a number of diseases, any of which is accompanied by a change in the appearance of the skin. These can be inflammatory skin diseases (boils, acne), atopic dermatitis, psoriasis, T-cell cutaneous lymphoma. It is known that age-related changes in the skin are also associated with changes in its immunological functions. In aging skin, mononuclear infiltration, a decrease in the number of Langerhans cells, and a change in the production of cytokines by immunocompetent cells that affect the proliferation and differentiation of skin cells are observed.

The variety of cells that make up the immune system of the skin, as well as the variety of their functions, explain the fact that at the skin level, all types of immunopathological syndromes (immunodeficiency, autoimmune, allergic, lymphoproliferative) can manifest. Immunodeficiency syndrome is manifested, for example, by furunculosis and other purulent-inflammatory processes. With defects in phagocytosis, the skin becomes susceptible to many bacterial and fungal infections, but the immune response to any antigen is impaired as antigen presentation suffers.

Allergic (hyperergic) syndrome is quite common and occurs with contact and atopic dermatitis. The phenomena of hyperergy are also characteristic of psoriasis. Autoimmune syndrome also has skin manifestations (scleroderma, systemic lupus erythematosus). An example of a lymphoproliferative syndrome is T-cell lymphoma of the skin (mycosis fungoides).

Diagnosis of all these conditions is based on clinical signs. For example, for an immunodeficiency disease, these will be criteria such as a recurrent course of an infectious skin lesion, its protracted course despite adequate pharmacotherapy, a tendency to generalization of the infectious and inflammatory process in the skin, resistance to antimicrobial therapy, the predominance of necrotic changes over inflammatory ones in the lesion, discrepancy between local and systemic manifestations of skin infection. There are no specific tests characterizing the state of skin immunity in practical medicine. A dermatologist can focus on standard immunological blood counts. In scientific research, morphological (histological) assessment of immunocompetent skin structures, the “skin window” method, and some others are used.

How to improve skin immunity?

The pathology of the immune system leads to the development of an immune-dependent pathology. Therefore, the need to stimulate skin immunity when it is suppressed is pathogenetically justified. For these purposes, drugs such as Polyoxidonium and Likopid can be recommended. Some immunomodulators (for example, Riboxin) can be used both for systemic and local use, including in mesotherapeutic techniques. At the same time, intradermal injections affect mainly the immune system of the skin, and systemic use leads to the activation of lymphopoiesis in the thymus and lymph nodes. In other words, the choice of the method of administration of the drug (local or systemic) should be based on the nature of immune disorders - both in the skin and in the body as a whole.

Nonspecific adaptogens (vitamin-microelement complexes, aralia tincture, etc.) also have a moderate immunotropic effect. We have found immunoactive properties in organic silicon, which is widely used in mesotherapy practice. In the treatment of diseases caused by increased reactivity of the immune system (psoriasis, lymphomas), immunosuppressants (cyclosporine) are used. The latest achievement of immunopharmacology is the use of monoclonal (highly specific) antibodies as inhibitors of the immune system.

Improving the immune status of the skin, it should be remembered that the immune system of the skin, morphologically represented by SALT, on the one hand, is a fairly autonomous part of the body's immune system, on the other hand, has close morphofunctional and regulatory relationships with it. Violations of normal immune reactions in the skin lead to the development of many dermatological diseases and the vast majority of aesthetic problems, including premature skin aging. Not surprisingly, the skin is a target for immunotherapeutic interventions, in particular immunomesotherapy. We plan to consider this issue in more detail in future publications.

Literature

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Pancreatic tissue is represented by two types of cell formations: the acinus, which produces enzymes and is involved in the digestive function, and the islet of Langerhans, whose main function is to synthesize hormones.

There are few islands in the gland itself: they make up 1-2% of the total mass of the organ. The cells of the islets of Langerhans differ in structure and function. There are 5 types. They secrete active substances that regulate carbohydrate metabolism, digestion, and may be involved in response to stress reactions.

What are the islets of Langerhans?

The islets of Langerhans (OL) are polyhormonal microorganism consisting of endocrine cells located along the entire length of the pancreatic parenchyma, which performs exocrine functions. Their bulk is localized in the tail section. The size of the islets of Langerhans is 0.1-0.2 mm, their total number in the human pancreas is from 200 thousand to 1.8 million.

Cells form separate groups, between which pass capillary vessels. From the glandular epithelium of the acini, they are delimited by connective tissue and fibers of nerve cells passing in the same place. These elements of the nervous system and the cells of the islet form the neuroinsular complex.

The structural elements of the islets - hormones - perform intrasecretory functions: they regulate carbohydrate and lipid metabolism, digestion processes, and metabolism. A child has 6% of these hormonal formations in the gland from the total area of the organ. In an adult, this part of the pancreas is significantly reduced and amounts to 2% of the surface of the gland.

Discovery history

Clusters of cells that differ in their appearance and morphological structure from the main tissue of the gland and are located in small groups mainly in the tail of the pancreas were first discovered in 1869 by the German pathologist Paul Langerhans (1849-1888).

In 1881, the outstanding Russian scientist, pathophysiologist K.P. Ulezko-Stroganova (1858-1943) carried out fundamental physiological and histological work on the study of the pancreas. The results were published in the journal "Vrach", 1883, No. 21 - the article "On the condition of her rest and activity." In it, she for the first time at that time expressed a hypothesis about the endocrine function of individual formations of the pancreas.

Based on her work in 1889-1892. in Germany, O. Minkowski and D. Mering found that when the pancreas is removed, diabetes mellitus develops, which can be eliminated by transplanting a part of a healthy pancreas under the skin of the operated animal.

Domestic scientist L.V. Sobolev (1876-1921) was one of the first, on the basis of his research work, to show the importance of the islets discovered by Langerhans and named after him in the production of a substance related to the onset of diabetes mellitus.

Later, thanks to a large number of studies conducted by physiologists in Russia and other countries, new scientific data on the endocrine function of the pancreas were discovered. In 1990, transplantation of the islets of Langerhans to humans was performed for the first time.

Types of islet cells and their functions

OL cells differ in morphological structure, functions performed, and localization. Inside the islets, they have a mosaic arrangement. Each island has an ordered organization. In the center are the cells that secrete insulin. Along the edges are peripheral cells, the number of which depends on the size of the OB. Unlike acini, OL does not contain its own ducts - hormones enter the blood immediately through the capillaries.

There are 5 main types of OL cells. Each of them synthesizes a certain one, regulating digestion, carbohydrate and protein metabolism:

α-cells;
β cells;
δ cells;
PP cells;
epsilon cells.