The immune system of animals is no different from the human IP. Virtually nothing. Well, of course, the features of evolution have developed specific immune responses for different species, because. completely different conditions and habitats of different animals. And herself animal immune system, the principles of its "work", the organs are the same as ours.
And the same vaccination of animals is carried out for the same purpose as ours - it is a preventive measure that allows the animal's body to prepare in advance for a "meeting" with a harmful microorganism (virus, bacterium, fungal spore). And since the immune system of animals is identical to ours, the methods of treatment are the same.
Components and reactions of the immune system
In order for the protection of the immune system to be effective, it is necessary to know well the characteristics of your body, as well as the components of the immune system and the features of its "work".
Imagine that your immune system is equipped with numerous regiments of warriors who are in constant motion. These protectors of our health must be on the alert at all times, every minute, in order to destroy any harmful bacteria, virus, or cancer cell. They are armed with deadly weapons for our enemy and work for absolute destruction. Just imagine - every cell of our body belongs to our internal armed forces!
This army has about a trillion white blood cells and, like any army, has its own units. Lymphocytes belong to the "special forces", and leukocytes are called "infantry". There are also utilizers (cleaners). These are large cells that swallow bacteria, small harmful particles and utilize them. They are called macrophages and phagocytes. That's what the protection of the immune system!
And now consider immune system reactions and her work.
Special Forces lymphocytes specialize mainly in viruses and cancer cells, divided into B-lymphocytes and T-lymphocytes. The former are cells on which an arsenal of weapons accumulates and forms - specific antibodies. They are called specific because on the surface of each antibody molecule there is a peculiar pattern that ideally matches the pattern on the surface of the "enemy" agent, like a key fits a lock. Antibodies, joining the enemy, block it and contribute to its destruction.
There are also B-lymphocytes of memory (archivists), which throughout a person's life store in memory information about all the "enemy" agents who have ever "passed on the case", with whom they had a chance to fight.
Among the T-lymphocytes, an elite unit stands out (snipers capable of independently neutralizing the enemy with an antitoxin shot). There are also T-helpers (helpers that stimulate friends from group B and activate the reproduction of T-killers), T-suppressors (commanders to clear the alarm so that the immune system does not overstrain) and memory T-lymphocytes, which also specialize in remembering information about an already neutralized enemy.
Leukocytes (neutrophils) are both "reconnaissance" and "infantry" rolled into one. Half of them float freely in the blood plasma, "scanning" its composition, looking for foreign cells, destroyed cells of their own body, etc. These cells live only 2-3 days, but against the background of the fight against infection, their life expectancy is reduced to 2-3 hours. The other half of them is not carried by blood, but, as it were, sticks to the walls of blood vessels - these are parietal leukocytes. Hiding on the sidelines, they perform the functions of traffic police. Noticing the disorder in the form of an infection or under the influence of stress, hormones, etc., they rush through the bloodstream to the violator of the order and, having caught up with him, capture, swallow and digest. Each of the leukocytes can neutralize from 5 to 20 microbes, but then he himself dies, defending his fatherland. Neutrophils fight mainly with bacteria and fungi. And so, when all the "subdivisions" are healthy, then the protection of the immune system is reliable and it is almost impossible to make a hole in it.
The reaction of the immune system to the detection of "enemies" and their subsequent destruction is called the immune response. All forms of the immune response can be divided into acquired and innate reactions of the immune system. The main difference between them is that acquired immunity is highly specific with respect to a particular type of antigens and allows them to be destroyed faster and more efficiently upon repeated collision. Antigens are called molecules that cause specific reactions of the immune system, perceived as foreign agents. For example, people who have had chickenpox (measles, diphtheria) often develop lifelong immunity to these diseases. In the case of autoimmune reactions of the immune system, the antigen can be a molecule produced by the body itself.
How to Boost Your Immune System
Faced with some kind of illness, we often think about. To do this, it is necessary to know well what components are necessary for the immune system, in which products they are contained and how they affect the IP. If all this is not a secret for you, then the matter is only in your will, and then how to increase the immune system is not a problem for you.
The three most important antioxidant vitamins are beta-carotene, vitamin C and vitamin E. They are found in brightly colored vegetables and fruits - especially red, purple, orange and yellow hues. To achieve maximum benefits for your body, eat fresh fruits or steamed (in a double boiler). The most famous antioxidants are vitamins A, C, E, as well as glutathione, selenium, vitamin B6. Vitamin E is found in sesame, sunflower, pumpkin, nuts, and 
dandelion, vegetable oils.
Beta-carotene and other carotenoids are found in apricots, mangoes, nectarines, peaches, pink grapefruits, tangerines, asparagus, beets, broccoli, cantaloupe, carrots, corn, green peppers, cabbage and green leafy vegetables, turnips, zucchini, spinach, sweet potatoes (yam), tomatoes and watermelon.
Vitamin C is rich in various berries (especially strawberries), musk and nutmeg melons, grapefruits, kiwi, mangoes, nectarines, oranges, papaya, broccoli, Brussels sprouts, cauliflower and white cabbage, red, green and yellow peppers, peas, sweet potatoes and tomatoes.
Vitamin E is abundant in broccoli, carrots, chard (chard), mustard and green turnips, mangoes, nuts, papaya, pumpkin, red paprika, spinach, and sunflower seeds.
Other foods known for their antioxidant properties include prunes, apples, raisins, plums, red grapes, alfalfa sprouts, onions, eggplant, and legumes.
Quercetin - found in apples, onions, tea leaves, red wine and other foods. Successfully fights inflammatory processes, reduces allergic reactions.
Luteolin - found in abundance in celery and green peppers. As well as quercetin, it has anti-inflammatory properties and protects against diseases of the central nervous system. In particular, one study showed that luteolin is able to combat Alzheimer's disease.
Catechins are most concentrated in tea leaves. Reduce the risk of cancer, heart disease, Alzheimer's disease.
Here you can how to boost immune system. Just don't be lazy, it's your health. And it should also be noted that in conditions of total environmental pollution, we cannot do without immunomodulators. The best one is Transfer Factor. This drug contains small peptide molecules that are carriers of immune memory. This is indeed a unique drug that eliminates all disturbances in the work of our IP at the DNA level. This "algorithm of action" is inherent only to him and therefore its effectiveness is an order of magnitude higher than that of other immunomodulators.
Improving the immune system is not only due to proper nutrition or medication intervention. Improving the immune system is also an active life, active rest. This is the absence of stressful situations and all kinds of negativity in life. Hardening also has a great positive effect on improving the immune system. And one of the hardening methods is a contrast shower. Try it and you will immediately feel the benefits of such methods.
Components of the immune system
And in order to increase the immune system even more effectively, you need to clearly know all the components of the immune system. The fact is that the result of an action is the more effective, the better a person represents or understands the anatomy of this action. So, the components of the immune system:
- The immune system has evolved to protect the macroorganism from pathogenic microbes. Some of them, such as viruses, penetrate the host cells, others, such as many bacteria, multiply extracellularly in tissues or body cavities.
- Lymphocytes and phagocytes are involved in the maintenance of immunity. Lymphocytes recognize the antigens of pathogenic microorganisms. Phagocytes engulf and destroy pathogens themselves.
- The immune response consists of two phases. In the early phase, the recognition of the antigen by specifically reacting lymphocytes and their activation occurs; in the late (effector) phase, these lymphocytes carry out their coordinating function in eliminating the source of foreign antigens from the body.
-Specificity and memory are the two main characteristics of acquired immunity. The immune system responds more effectively to a repeated encounter with the same antigen.
- Lymphocytes are specialized in functions. B cells form antibodies. Cytotoxic T-lymphocytes destroy cells infected with viruses. Helper T-lymphocytes coordinate the immune response by contact intercellular interactions and the release of cytokines into the intercellular environment, which, for example, help B-cells in the formation of antibodies.
-Antigens are molecules recognized by receptors on lymphocytes. B-lymphocytes usually recognize uncleaved antigen molecules, while T-lymphocytes are most often able to recognize antigenic molecules only as fragments on the surface of other cells.
- Recognition of antigen molecules by lymphocytes specific to it entails selective reproduction of lymphocytic clones; clonal expansion is accompanied by differentiation of lymphocytes into effector cells and immunological memory cells.
-During the functioning of the immune system, disorders can occur that lead to an immunodeficiency or hypersensitivity state, as well as to autoimmune diseases. 
And in conclusion, I would like to mention the Transfer Factor once again. If you are thinking about how to boost the immune system - learn from the pages of this site as much as possible about Transfer Factor. It was not by chance that we mentioned it, it is a drug of natural origin and, probably, the only one that, when used, does not cause absolutely any side effects (with the exception, of course, of individual intolerance, which is extremely rare). This drug has no age restrictions and is recommended for use by pregnant women and newborns. The use of Transfer Factors has saved thousands of people from the most terrible diseases. There are no immunomodulators similar in effectiveness to it today. So buy this drug and take care of your health.
The immune system consists of various components - organs, tissues and cells, assigned to this system according to the functional criterion (implementation of the body's immune defense) and the anatomical and physiological principle of organization (organ-circulatory principle). In the immune system, there are: primary organs (bone marrow and thymus), secondary organs (spleen, lymph nodes, Peyer's patches, etc.), as well as diffusely located lymphoid tissue - individual lymphoid follicles and their clusters. Lymphoid tissue associated with mucous membranes is especially distinguished (Mucosa-Associated Lymphoid Tussue - MALT).
Lymphoid system- a collection of lymphoid cells and organs. Often the lymphoid system is mentioned as an anatomical equivalent and a synonym for the immune system, but this is not entirely true. The lymphoid system is only a part of the immune system: cells of the immune system migrate through the lymphatic vessels to the lymphoid organs - the place of induction and formation of the immune response. In addition, the lymphoid system should not be confused with the lymphatic system - the system of lymphatic vessels through which the lymph circulates in the body. The lymphoid system is closely connected with the circulatory and endocrine systems, as well as with integumentary tissues - mucous membranes and skin. These systems are the main partners on which the immune system relies in its work.
Organ-circulatory principle of organization of the immune system. The body of an adult healthy person contains about 10 13 lymphocytes, i.e. about every tenth cell in the body is a lymphocyte. Anatomically and physiologically, the immune system is organized according to the organ-circulatory principle. This means that lymphocytes are not strictly resident cells, but intensively recirculate between lymphoid organs and non-lymphoid tissues through the lymphatic vessels and blood. Thus, ≈10 9 lymphocytes pass through each lymph node in 1 hour. The migration of lymphocytes is caused
specific interactions of specific molecules on the membranes of lymphocytes and endothelial cells of the vascular wall [such molecules are called adhesins, selectins, integrins, homing receptors (from the English. home- house, place of residence of the lymphocyte)]. As a result, each organ has a characteristic set of populations of lymphocytes and their immune response partner cells.
The composition of the immune system. According to the type of organization, various organs and tissues of the immune system are distinguished (Fig. 2-1).
. Hematopoietic bone marrow - location of hematopoietic stem cells (HSCs).
Rice. 2-1. Components of the immune system
. Encapsulated Organs: thymus, spleen, lymph nodes.
. Unencapsulated lymphoid tissue.
-Lymphoid tissue of mucous membranes(MALT- Mucosal Associated Lymphoid Tissue). Regardless of localization, it contains intraepithelial lymphocytes of the mucous membrane, as well as specialized formations:
◊ digestive tract-associated lymphoid tissue (GALT) Gut-Associated Lymphoid Tissue). It contains tonsils, appendix, Peyer's patches, lamina propria("own plate") of the intestine, individual lymphoid follicles and their groups;
◊ bronchial and bronchiole associated lymphoid tissue (BALT) Bronchus-Associated Lymphoid Tissue);
◊lymphoid tissue associated with the female reproductive tract (VALT - Vulvovaginal-Associated Lymphoid Tissue);
Nasopharynx-associated lymphoid tissue (NALT) Nose-Associated Lymphoid Tissu e).
The liver occupies a special place in the immune system. It contains subpopulations of lymphocytes and other cells of the immune system, "serving" as a lymphoid barrier the blood of the portal vein, which carries all the substances absorbed in the intestine.
Skin lymphoid subsystem - skin-associated lymphoid tissue (SALT) Skin-Associated Lymphoid Tissue)- disseminated intraepithelial lymphocytes and regional lymph nodes and lymphatic drainage vessels.
. peripheral blood - transport and communication component of the immune system.
Central and peripheral organs of the immune system
. central authorities. The hematopoietic bone marrow and thymus are the central organs of the immune system, it is in them that myelopoiesis and lymphopoiesis begin - the differentiation of monocytes and lymphocytes from HSC to a mature cell.
Before the birth of the fetus, the development of B-lymphocytes occurs in the fetal liver. After birth, this function is transferred to the bone marrow.
In the bone marrow, complete "courses" of erythropoiesis (the formation of red blood cells), myelopoiesis (the formation of neutrophils,
monocytes, eosinophils, basophils), megakaryocytopoiesis (formation of platelets), as well as the differentiation of DC, NK cells and B lymphocytes. - Precursors of T-lymphocytes migrate from the bone marrow to the thymus and the mucosa of the digestive tract to undergo lymphopoiesis (extrathymic development).
. peripheral organs. In peripheral lymphoid organs (spleen, lymph nodes, non-encapsulated lymphoid tissue), mature naive lymphocytes come into contact with antigen and APC. If the antigen-recognizing receptor of a lymphocyte binds a complementary antigen in a peripheral lymphoid organ, then the lymphocyte enters the path of further differentiation in the immune response mode, i.e. begins to proliferate and produce effector molecules - cytokines, perforin, granzymes, etc. Such additional differentiation of lymphocytes in the periphery is called immunogenesis. As a result of immunogenesis, clones of effector lymphocytes are formed that recognize the antigen and organize the destruction of both itself and the peripheral tissues of the body where this antigen is present.
Cells of the immune system. The immune system includes cells of various origins - mesenchymal, ecto- and endodermal.
. Cells of mesenchymal origin. These include cells that have differentiated from precursors of lymph/hematopoiesis. Varieties lymphocytes- T, B and NK, which in the process of the immune response cooperate with various leukocytes - monocytes/macrophages, neutrophils, eosinophils, basophils, as well as DC, mast cells and vascular endotheliocytes. Even erythrocytes contribute to the implementation of the immune response: they transport antigen-antibody-complement immune complexes to the liver and spleen for phagocytosis and destruction.
. Epithelium. The composition of some lymphoid organs (thymus, some non-encapsulated lymphoid tissues) includes epithelial cells of ectodermal and endodermal origin.
humoral factors. In addition to cells, "immune matter" is represented by soluble molecules - humoral factors. These are the products of B-lymphocytes - antibodies (they are also immunoglobulins) and soluble mediators of intercellular interactions - cytokines.
THYMUS
in the thymus (thymus) undergoes lymphopoiesis of a significant proportion of T-lymphocytes ("T" comes from the word "Thymus"). The thymus consists of 2 lobes, each surrounded by a connective tissue capsule. Partitions extending from the capsule divide the thymus into lobules. In each thymus lobule (Fig. 2-2), 2 zones are distinguished: along the periphery - cortex, in the center - cerebral (medula). The volume of the organ is filled with an epithelial framework (epithelium), in which are located thymocytes(immature T-lymphocytes of the thymus), DC And macrophages. DCs are located predominantly in the zone transitional between the cortical and cerebral. Macrophages are present in all zones.
. epithelial cells thymus lymphocytes (thymocytes) clasp with their processes, therefore they are called Nurse cells(cells - "nurses" or cells - "nannies"). These cells not only support developing thymocytes, but also produce
Rice. 2-2. The structure of the thymus lobule
cytokines IL-1, IL-3, IL-6, IL-7, LIF, GM-CSF and express adhesion molecules LFA-3 and ICAM-1 complementary to adhesion molecules on the surface of thymocytes (CD2 and LFA-1). In the brain zone of the lobules are dense formations of twisted epithelial cells - Hassall's bodies(thymus bodies) - places of compact accumulation of degenerating epithelial cells.
. thymocytes differentiate from bone marrow HSCs. From thymocytes in the process of differentiation, T-lymphocytes are formed, which are able to recognize antigens in combination with MHC. However, most T-lymphocytes will either not be able to have this property or will recognize self-antigens. To prevent the release of such cells to the periphery in the thymus, their elimination is initiated by induction of apoptosis. Thus, normally, only cells capable of recognizing antigens in combination with “their own” MHCs, but not inducing the development of autoimmune reactions, enter the circulation from the thymus.
. hematothymic barrier. The thymus is highly vascularized. The walls of capillaries and venules form a hematothymic barrier at the entrance to the thymus and, possibly, at the exit from it. Mature lymphocytes leave the thymus either freely, since each lobule has an efferent lymphatic vessel that carries lymph to the lymph nodes of the mediastinum, or by extravasation through the wall of postcapillary venules with high endothelium in the cortico-cerebral region and / or through the wall of ordinary blood capillaries.
. Age changes. By the time of birth, the thymus is fully formed. It is densely populated with thymocytes throughout childhood and until puberty. After puberty, the thymus begins to shrink in size. Thymectomy in adults does not lead to serious impairment of immunity, since the necessary and sufficient pool of peripheral T-lymphocytes is created in childhood and adolescence for the rest of life.
THE LYMPH NODES
Lymph nodes (Fig. 2-3) - multiple, symmetrically located, bean-shaped encapsulated peripheral lymphoid organs, ranging in size from 0.5 to 1.5 cm in length (in the absence of inflammation). Lymph nodes through afferent (bringing) lymphatic vessels (there are several of them for each node) drain tissue
Rice. 2-3. The structure of the mouse lymph node: a - cortical and cerebral parts. In the cortical part there are lymphatic follicles, from which the brain cords extend into the brain part; b - distribution of T- and B-lymphocytes. The thymus-dependent zone is highlighted in pink, the thymus-independent zone in yellow. T-lymphocytes enter the parenchyma of the node from post-capillary venules and come into contact with follicular dendritic cells and B-lymphocytes
neve liquid. Thus, the lymph nodes are the "customs" for all substances, including antigens. From the anatomical gates of the node, together with the artery and vein, a single efferent (efferent) vessel emerges. As a result, the lymph enters the thoracic lymphatic duct. The parenchyma of the lymph node consists of T-cell, B-cell zones and brain cords.
. B-cell zone. The cortical substance is divided by connective tissue trabeculae into radial sectors and contains lymphoid follicles, this is the B-lymphocytic zone. The stroma of the follicles contains follicular dendritic cells (FDCs), which form a special microenvironment in which the process of somatic hypermutagenesis of variable segments of immunoglobulin genes, unique for B-lymphocytes, and the selection of the most affinity variants of antibodies (“antibody affinity maturation”) take place. Lymphoid follicles go through 3 stages of development. primary follicle- small follicle containing naive B-lymphocytes. After B-lymphocytes enter into immunogenesis, in the lymphoid follicle appears germinal (germinal) center, containing intensively proliferating B-cells (this occurs approximately 4-5 days after active immunization). This secondary follicle. Upon completion of immunogenesis, the lymphoid follicle is significantly reduced in size.
. T-cell zone. In the paracortical (T-dependent) zone of the lymph node, there are T-lymphocytes and interdigital DCs (they are different from FDCs) of bone marrow origin, which present antigens to T-lymphocytes. Through the wall of postcapillary venules with high endothelium, lymphocytes migrate from the blood to the lymph node.
. Brain cords. Beneath the paracortical zone, there are cords containing macrophages. With an active immune response in these strands, you can see a lot of mature B-lymphocytes - plasma cells. The cords flow into the sinus of the medulla, from which the efferent lymphatic vessel emerges.
SPLEEN
Spleen- a relatively large unpaired organ weighing about 150 g. Lymphoid tissue of the spleen - white pulp. The spleen is a lymphocytic "custom house" for antigens that have entered the bloodstream. Lymphocytes
Rice. 2-4. Human spleen. Thymus-dependent and thymus-independent zones of the spleen. The accumulation of T-lymphocytes (green cells) around the arteries emerging from the trabeculae forms a thymus-dependent zone. The lymphatic follicle and the lymphoid tissue of the white pulp surrounding it form a thymus-independent zone. As well as in the follicles of the lymph nodes, there are B-lymphocytes (yellow cells) and follicular dendritic cells. The secondary follicle contains a germinal center with rapidly dividing B-lymphocytes surrounded by a ring of small resting lymphocytes (mantle)
the spleens accumulate around the arterioles in the form of the so-called periarteriolar clutches (Fig. 2-4).
The T-dependent zone of the coupling directly surrounds the arteriole. B-cell follicles are located closer to the edge of the sleeve. The arterioles of the spleen flow into sinusoids (this is already red pulp). The sinusoids terminate in venules that drain into the splenic vein, which carries blood to the portal vein of the liver. The red and white pulp is separated by a diffuse marginal zone inhabited by a special population of B-lymphocytes (B-cells of the marginal zone) and special macrophages. Marginal zone cells are an important link between innate and adaptive immunity. This is where the very first contact of organized lymphoid tissue with possible pathogens circulating in the blood takes place.
LIVER
The liver performs important immune functions, which follows from the following facts:
The liver is a powerful organ of lymphopoiesis in the embryonic period;
Allogeneic liver transplants are less strongly rejected than other organs;
Tolerance to orally administered antigens can only be induced with a normal physiological blood supply to the liver and cannot be induced after portocaval anastomosis surgery;
The liver synthesizes acute phase proteins (CRP, MBL, etc.), as well as proteins of the complement system;
The liver contains various subpopulations of lymphocytes, including unique lymphocytes that combine characteristics of T and NK cells (NKT cells).
Cellular composition of the liver
Hepatocytes form the liver parenchyma and contain very few MHC-I molecules. Normally, hepatocytes almost do not carry MHC-II molecules, but their expression may increase in liver diseases.
Kupffer cells - liver macrophages. They make up about 15% of the total number of liver cells and 80% of all macrophages in the body. Macrophage density is higher in periportal areas.
Endothelium sinusoids of the liver does not have a basement membrane - a thin extracellular structure consisting of different types of collagens and other proteins. Endothelial cells form a monolayer with lumens through which lymphocytes can directly contact hepatocytes. In addition, endothelial cells express various scavenger receptors. (scavenger receptors).
Lymphoid system The liver, in addition to lymphocytes, contains the anatomical division of the lymph circulation - the space of Disse. On the one hand, these spaces are in direct contact with the blood of the sinusoids of the liver, and on the other hand, with hepatocytes. Lymph flow in the liver is significant - at least 15-20% of the total body lymph flow.
stellate cells (Ito cells) located in the spaces of Disse. They contain fat vacuoles with vitamin A, as well as α-actin and desmin characteristic of smooth muscle cells. Star cells can transform into myofibroblasts.
LYMPHOID TISSUE OF MUCOUS MEMBRANES AND SKIN
Non-encapsulated lymphoid tissue of the mucous membranes is represented by the pharyngeal lymphoid ring of Pirogov-Waldeyer, Peyer's patches of the small intestine, lymphoid follicles of the appendix, lymphoid tissue of the mucous membranes of the stomach, intestines, bronchi and bronchioles, organs of the genitourinary system and other mucous membranes.
Peyer's patches(Fig. 2-5) - group lymphatic follicles located in lamina propria small intestine. The follicles, more precisely the T cells of the follicles, are adjacent to the intestinal epithelium under the so-called M cells ("M" from membranous, these cells do not have microvilli), which are the "entrance gates" of the Peyer's plaque. The bulk of lymphocytes is located in B-cell follicles with germinal centers. T-cell zones surround the follicle closer to the epithelium. B-lymphocytes make up 50-70%, T-lymphocytes - 10-30% of all cells of the Peyer's patch. The main function of Peyer's patches is to support the immunogenesis of B-lymphocytes and their differentiation.
Rice. 2-5. Peyer's patch in the intestinal wall: a - general view; b - simplified diagram; 1 - enterocytes (intestinal epithelium); 2 - M-cells; 3 - T-cell zone; 4 - B-cell zone; 5 - follicle. Scale between structures not maintained
roving to plasma cells producing antibodies - mainly secretory IgA. The production of IgA in the intestinal mucosa accounts for more than 70% of the total daily production of immunoglobulins in the body - in an adult, about 3 g of IgA every day. More than 90% of all IgA synthesized by the body is excreted through the mucous membrane into the intestinal lumen.
intraepithelial lymphocytes. In addition to organized lymphoid tissue in the mucous membranes, there are single intraepithelial T-lymphocytes disseminated among epithelial cells. On their surface, a special molecule is expressed that ensures the adhesion of these lymphocytes to enterocytes - integrin α E (CD103). About 10-50% of intraepithelial lymphocytes are TCRγδ + CD8αα + T-lymphocytes.
The immune system distinguishes between "self" and "foreign" and destroys potentially dangerous foreign molecules and cells from the body. The immune system also has the ability to detect and destroy pathologically altered cells of its own tissues. Any molecule recognized by the immune system is considered an antigen (AG).
The skin, cornea and mucous membrane of the respiratory tract, gastrointestinal tract form a physical barrier, which is the first line of defense of the human body. Some of these barriers have active immune functions:
- Outer, keratinized epidermis: skin keratinocytes secrete antimicrobial peptides (defensins), and sebaceous and laryngeal glands secrete microbial-suppressing substances. Many other immune cells are present in the skin.
- Respiratory, gastrointestinal, and urogenital mucosa: The mucosa contains antimicrobial agents such as lysozyme, lactoferrins, and secretory immunoglobulin A (SlgA).
When immune barriers are violated, 2 types of immunity are realized: innate and acquired. Many molecular constituents are involved in both innate and adaptive immunity.
innate immunity
Innate (natural) immunity does not require a prior encounter with antigens. Thus, he immediately responds to the aggressor. It recognizes mainly molecules of widely presented antigens, and not specific to a given organism or cell. Its components are:
- phagocytic cells,
- antigen presenting cells
- natural killer cells
- polymorphonuclear leukocytes.
Phagocytic cells (blood neutrophils and monocytes, macrophages and tissue dendritic cells) engulf and destroy invading antigens The attack of phagocytic cells is facilitated when antigens are covered by antibodies (AT), which is part of acquired immunity, or when complement proteins (which are part of a less specific innate defense system) opsonize AG. AG-presenting cells present fragments of engulfed AG to T-lymphocytes and are part of the acquired immunity. Natural killer cells destroy virus-infected cells and certain tumor cells.
acquired immunity
Acquired immunity requires prior encounter with antigens, i.e. it needs time to develop after the initial encounter with a new aggressor. What follows is a quick response. The system remembers previous contacts and is AG-specific. Its components are:
- T cells.
- In cells.
Acquired immunity derived from certain T-cell immune responses is called cell-mediated immunity. Immunity derived from B-cell reactions is called humoral immunity, because Soluble Ag-specific antibodies are secreted into the cells. B cells and T cells work together to destroy foreign elements. Some of these cells do not directly destroy foreign matter, but instead activate other white blood cells that recognize and destroy foreign matter.
immune response
Successful immune defense requires the activation, regulation and implementation of the immune response.
Activation. The immune system is activated by foreign antigen, which is recognized by circulating antigen or cellular receptors. These receptors can be highly specific or low specific. Low-specific receptors recognize common groups of ligands included in the structure of microbial pathogenicity factors, such as gram-negative bacterial lipopolysaccharides, gram-positive bacterial peptidoglycans, bacterial flagellins, unmethylated cytosine-guanosine dinucleotides (CpG motifs), and viral double-banded DNA. Activation also occurs if AT-AG complexes and the microorganism complement bind to cell surface receptors for the Fc fragment of IgG or for complement C fragments.
Recognized AG, AG-AT complexes or complement-microorganism undergo phagocytosis. Most microorganisms are destroyed by phagocytosis, others (for example, mycobacteria) inhibit the ability of phagocytes to completely destroy them, although they do not prevent absorption. In such cases, cytokines produced by T-lymphocytes, in particular IgG, y (IFN-γ), stimulate the production of lytic enzymes and other microbicidal substances by phagocytes that kill microorganisms.
As long as the AG undergoes rapid phagocytosis and is completely destroyed (not a frequent case), the acquired immune response works. It originates in the spleen for circulating antigens, in the lymph nodes for tissue antigens, and in mucosal-associated lymphoid tissues (eg, tonsils, adenoids, Peyer's patches) for mucosal antigens. For example, Langerhans dendritic cells phagocytose antigens in the skin and migrate to local lymph nodes where antigen-derived peptides are expressed on the cell surface of major histocompatibility complex (MHC) class II molecules that present the CD4 peptide to helper cells (TH). When the T helper cell works with the MHC-peptide complex and receives co-stimulatory signals, it becomes activated and expresses receptors for the cytokine IL-2 and secretes several cytokines. Each set of T-helper cells secrete different combinations of substances, thus influencing the nature of the immune response.
Regulation. The immune response must be regulated to prevent extreme harm to the body (eg, anaphylaxis, significant tissue damage). Regulatory T cells help control the immune response through the secretion of immunosuppressive cytokines such as IL-10 and transforming growth factor-β (TGF-β) or through a poorly understood cell contact mechanism. These regulatory cells prevent the occurrence of an autoimmune response and, apparently, contribute to the implementation of responses to non-self (foreign) AG.
Completion. Completion of the immune response occurs when the antigen is separated or removed from the body. Without antigenic stimulation, cytokine secretion ceases and activated cytotoxic cells undergo apoptosis. Apoptosis marks the cell for immediate phagocytosis, which prevents the loss of cellular content and the development of inflammation. T cells and B cells differentiated into memory cells escape this fate.
Geriatric component
With age, the immune system becomes less effective, namely:
- It weakens its ability to recognize its own from the foreign, increasing the frequency of autoimmune disorders.
- Macrophages destroy bacteria, cancer cells and other antigens less intensively, which explains the increase in cancer cases among the elderly.
- T-cells are not able to quickly respond to hypertension.
- The number of lymphocytes capable of responding to new antigens decreases.
- The aging body produces less complement in response to bacterial infections.
- Fewer antibodies are produced in response to hypertension, and antibodies have less ability to attach to hypertension, which explains the increased incidence of pneumonia, influenza, infective endocarditis and tetanus and the increased risk of death from these pathologies in the elderly. These changes may also partly explain the ineffectiveness of vaccinations among the elderly.
Components of the immune system
The immune system is made up of cellular and molecular components that work together to destroy antigens.
Antigen presenting cells
Although some antigens can directly stimulate an immune response, a T-dependent adaptive immune response usually requires the presence of antigen presenting cells (APCs), which present antigen peptides in complex with MHC molecules. Intracellular antigens (for example, viral ones) can be converted and presented to CD8 receptors of Tc-lymphocytes by any nuclear cells. With the help of coding proteins that interfere with this process, some viruses (for example, cytomegalovirus) avoid destruction. Intracellular AG must be converted into a peptide and presented in complex with MHC class II molecules on the APC surface for recognition by helper cells carrying CD4 cells.
Monocytes in the bloodstream are the precursors of tissue macrophages. Monocytes migrate to tissues where, after 8 hours, they develop into macrophages under the influence of macrophage colony stimulating factor (M-CSF) secreted by various cell types (eg, endothelial cells, fibroblast cells).
Macrophages are activated by IFN-y and granulocyte-macrophage colony-stimulating factor (GM-CSF). Activated macrophages destroy intracellular organisms and secrete IL-1 and tumor necrosis factor-alpha (TNF-α). These cytokines potentiate the secretion of IFN-γ and GM-CSF and increase the expression of adhesion molecules on the surface of endotheliocytes, facilitating the influx of leukocytes to the site of infection and the destruction of the pathogenic factor. Depending on the gene expression profile, macrophages were classified into subtypes.
Dendritic cells are present in the skin (Langerhans cells), lymph nodes, and tissues throughout the body. Dendritic cells in the skin are borderline APCs; they capture AG, deliver it to local lymph nodes, where they activate T-lymphocytes.
However, they have receptors for the Fc fragment of IgG and complement, which allows them to bind immune complexes and present them to B-lymphocytes of the germinal centers of secondary lymphoid organs.
Polymorphonuclear leukocytes
Polymorphonuclear leukocytes (PMNs) are also called granulocytes because they their cytoplasm contains specific granules.
They are present in the circulating blood and have a segmented nucleus, with the exception of mast cells, which are permanently present in tissues and are functionally similar to circulating basophils.
Neutrophils make up 40-70% of all leukocytes; they are the first line of defense in fighting infection. Mature neutrophils have a half-life of 2 to 3 days. During an acute inflammatory process (for example, infectious), neutrophils, reacting to chemotactic factors, leave the bloodstream and enter the tissues. Their goal is to phagocytize and destroy pathogenic factors. Microorganisms are destroyed when phagocytes produce lytic enzymes and reactive oxygen species (superoxide, hypochlorous acid) or trigger the release of the contents of the granules (defensins, proteases, bactericidal proteins that increase tissue permeability, lactoferrin and lysozyme). DNA and histones are also released and, together with granule contents such as elastase, form fibers in surrounding tissues, which can help kill bacteria and localize enzyme activity.
Basophils make up less than 5% of white blood cells and are similar to mast cells, although they belong to different cell lines. Both cells have high affinity receptors for IgE. When these cells encounter a certain antigen, this antigen crosslinks neighboring bivalent IgE molecules, which causes degranulation of the cells with the release of ready-made inflammatory mediators and the formation of new mediators (leukotrienes, prostaglandins, thromboxanes).
Mast cells are found in various tissues of the body. In mast cells of the mucous membranes, the granules contain tryptase and chondroitin sulfate, and if the cell is localized in the connective tissue, then its granules contain tryptase, chymase, and heparin. When these mediators are released, a protective acute inflammatory response is formed. Degranulation can be triggered by anaphylatoxin, complement fragments C3a and C5a.
Cytotoxic leukocytes
Cytotoxic leukocytes include:
- Natural killer cells.
- Lymphokine-activated killers.
Natural killer cells (NKC). Typical NK cells make up 5 to 15% of peripheral blood mononuclear cells. They have a round nucleus and granular cytoplasm. KNK induce apoptosis in infected and abnormal cells in different ways. As innate response cells, they lack antigen-specific receptors and immunological memory.
Typical NK cells are very important in the control of mutating cells, because they express both activating and inhibitory receptors. Activating EKK receptors recognize many target cell ligands (e.g. MHC class I chain A and chain B. Inhibitory NKK receptors recognize MHC class I molecules. NKK destroy their targets only in the absence of a strong inhibitory receptor signal. Presence of MHC class I molecules ( normally expressed on nucleated cells) on cells prevents their destruction, and the absence indicates that the cell is infected with some virus that inhibits MHC expression or that it has lost MHC expression because cancer has altered the cell. herpes infection and human papillomavirus (human papillomavirus).
NK cells also secrete some cytokines; they are the main source of IFN-γ. By secreting IFN-γ, NK cells can influence the acquired immune system by promoting the differentiation (differentiation) of type 1 helper cells (Tn1) and inhibiting type 2 helper cells (Tn2).
Lymphokine-activated killers (LAK). Some lymphocytes develop into very potent lymphokine-activated killers (LAKs), capable of killing a wide variety of tumor cells and abnormal lymphocytes (eg, those infected with certain viruses). These cells not only constitute a unique cellular subtype of lymphocytes, they are phenomenal. LAK progenitors are heterogeneous, but can initially be classified as EKK-like (most common) or T-lymphocyte-like cells.
Lymphocytes
The 2 most important types of lymphocytes are:
- B-lymphocytes that mature in the bone marrow.
- T-lymphocytes that mature in the thymus.
They do not differ in terms of morphology, but have different immune functions. They differ from each other by AG-specific surface receptors, molecules called clusters of differentiation (CDs), which are present or absent in a particular cell subtype. Over 300 CDs have been identified. Each lymphocyte recognizes a specific antigen through surface receptors.
B-lymphocytes. From 5 to 15% of blood lymphocytes are B-lymphocytes. They are also present in the spleen, lymph nodes on the mucous membrane of lymphoid tissues. B cells can present AG to T cells, but their primary function is to develop into plasma cells that produce and secrete antibodies (AT). Patients with B-cell immunodeficiencies (eg, X-linked agammaglobulinemia) are particularly susceptible to recurrent bacterial infections.
After a random rearrangement of the genes encoding lg, B-lymphocytes are able to recognize an almost infinite number of unique antigens. Gene rearrangement sequentially occurs during the development of B-lymphocytes in the red bone marrow. The process begins with a committed stem cell, goes through the pro-B and pre-B lymphocyte stages, and ends with an immature B-lymphocyte. If this immature B-lymphocyte interacts with AG, then inactivation (development of tolerance) or elimination (apoptosis) of this cell can occur. Immature B-lymphocytes that have not undergone inactivation or elimination may continue to develop into a mature young B-lymphocyte, leave the red bone marrow and move to peripheral lymphoid organs, where they may encounter AG. Their response to hypertension occurs in 2 stages:
- Primary immune response. When mature young B lymphocytes first encounter hypertension, these cells undergo blast transformation, clonal proliferation, and differentiation into memory cells that will respond to the same hypertension in the future, or into mature AT-producing plasma cells. There is a latency period of several days prior to AT production. Then only IgM is produced. Initially, only IgM is produced. After interaction with T-lymphocytes in B-lymphocytes, further rearrangement of the Ig genes can take place, which switches the synthesis to IgG, IgA or IgE.
- Secondary immune response (anamnestic, enhanced). When memory B cells and T helper cells re-encounter with the same AG. Memory B-cells rapidly proliferate, differentiate into mature plasma cells, rapidly synthesize and release large amounts of AT (mainly IgG, since T-lymphocytes induce a switch in the synthesis of this particular isotype) into the blood and other tissues, where AT can react with AG . Thus, after a second encounter with AH, the immune response is faster and more effective. T-lymphocytes.
There are 3 main types of T-lymphocytes:
- Helper.
- Regulatory.
- Cytotoxic.
More mature T lymphocytes express CD4 or CD8 as well as antigen-binding Ig-like receptors called T-cell receptors (TCRs). The genes encoding the TCR, like the immunoglobulin genes, are rearranged. As a result, a certain specificity and affinity are achieved upon contact with MHC molecules present on the APC membrane and associated with AG peptides. The number of specific connections in T-lymphocytes is almost infinite.
To activate the T-lymphocyte, the TCR binds either to the AG-MHC complex or to accessory molecules; otherwise, the T-lymphocyte will remain inactivated or die as a result of apoptosis. Some accessory molecules inhibit previously activated T-lymphocytes and thus complete the immune response. Polymorphism of the CTLA-4 gene is associated with some autoimmune pathologies.
T-helper (TH) cells are usually CD4, but may also be CD8. They differentiate from Tn0 cells into one of the following:
Each cell type secretes certain cytokines. There are various general patterns of cytokine production that define Tn-cell functional phenotypes. Th2 cells are capable of downregulating each other's functional activity to a certain level, which leads to the dominance of the Th1 or Th2 response.
The difference between different types of β-cells is clinically significant. For example, the Tn1 response is predominant in tuberculoid leprosy, while the Tn2 response is predominant in lepromatous leprosy. The Th1 response is characteristic of some autoimmune pathologies, and the Th2 response promotes IgG production and the development of allergic diseases, and also helps B cells secrete antibodies in some autoimmune pathologies (eg, Graves' disease, myasthenia gravis). Patients with immunodeficiency states are characterized by defective Tn 17 cells (eg, hyper IgE syndrome), such patients are most susceptible to infections caused by Candida albicans and Staphylococcus aureus.
Regulatory T cells. They mediate the suppression of immune responses and usually express the transcription factor Fox3. Professional cell subfamilies CD4 CD8 are involved in this process, they either secrete cytokines with immunosuppressive properties or suppress the immune response, the suppression mechanism is still poorly understood and requires direct contact between cells. Patients with functional mutations in Foxp3 develop autoimmune pathology, IPEX syndrome (immunodisregulation, polyendocrinopathy, enteropathy, X-linked).
Cytotoxic T(Tc) cells are usually CD8, but may also be CD4; they are necessary for the destruction of intracellular pathogens, in particular viruses.
Tc cells go through 3 stages of development:
- A progenitor cell that, upon appropriate stimulation, differentiates into a Tc cell.
- A differentiated effector cell capable of destroying targets.
- A memory cell at rest (no longer stimulated) but ready to perform an effector function after repeated stimulation with the original AG-MHC combination.
Fully activated Tc cells, like NK cells, are able to destroy the infected target cell by inducing apoptosis.
Tc cells can be:
- Isogenic: Produced in response to self (autologous) cells modified by viral infection or other foreign proteins.
- Allogeneic: Produced in response to cells expressing foreign MHC products (eg, in organ transplants where the donor MHC molecules differ from the recipient's MHC) Some Tc cells can recognize foreign MHC in a targeted manner (direct pathway); others may recognize foreign MHC fragments represented by the transplant recipient's own MHC molecules (indirect pathway).
Antibodies
ATs function as an antigen receptor on the surface of B cells and are secreted by plasma cells in response to antigens. ATs recognize specific configurations on the surface of antigens (eg, proteins, polysaccharides, nucleic acids). AT and AG are exactly matched because their shapes and other surface properties (eg load) are complementary. The same AT molecule can cross-react with the corresponding antigen if their eptopes are sufficiently similar to the epitopes of the original antigen.
Structure. ATs are composed of 4 polypeptide chains (2 identical heavy chains and 2 identical light chains) linked by disulfide bonds to produce the Y configuration. Both the heavy and light chains have variable (V) and constant (C) regions.
V - Variable regions are located at the amino-terminal ends of the upper part of Y; they are called variable because they contain different amino acids, which determine the specificity of lg. Hypervariable regions contain idiotypic determinants to which certain natural (anti-idiotypic) ATs bind; this connection may help regulate the B-humoral response. B-lymphocytes can change the isotype of the heavy chain of the produced Ig, but retain the heavy chains of the V-region and the entire light chain, and therefore retain AG-specificity.
The C region consists of a relatively constant sequence of amino acids that is characteristic of each lg isotype.
The aminoterminal (variable) end of AT binds to AG and forms the AGAT complex. The AG-binding part of lg (Fab) consists of a light chain and a heavy fragment and includes the V-region of the lg molecule (mixed part).
Antibody classes. Antibodies are divided into 5 classes:
These classes differ in the type of heavy chain; There are also 2 types of light chains (K and A). All 5 lg classes have either k- or λ-light chains.
IgM is the first AT that is formed after encountering a new AG. It consists of 5 Y-molecules (10 heavy and 10 light chains) linked by a single bond. IgM circulates predominantly in the intravascular space; it binds to and agglutinates AG and can activate complement, which facilitates phagocytosis. IgM are isohemagglutinins and many antibodies to gram-negative microorganisms. The IgM monomer is an antigen receptor on the surface of B-lymphocytes. Patients with hyper-lgM syndrome have a defect in genes involved in turning on a particular class of antibodies (eg, genes encoding CD40 or CD154); therefore, IgA, IgM, and IgE levels are low or absent, and circulating IgM levels are often high.
IgG is the predominant lg isotype; it circulates in both intra- and extravascular spaces. IgG is the primary circulating Ig that appears after reimmunization (with a secondary immune response) and is the dominant isotype in commercial globulin products. IgG protects the body from bacteria, viruses, toxins, and is the only lg isotype that crosses the placental barrier. That is why this class of antibodies is important as a protector of newborns, but pathogenic IgG antibodies, if present in the body of a future mother, can provoke a serious pathological condition of the fetus.
There are 4 subclasses of IgG: IgG1, LgG2, lgG3, lgG4, numbered in descending order of serum IgG concentration. IgG subclasses differ mainly in their ability to activate complement; IgG1 and LgG3 are most effective, lgG2 is less effective and LgG4 is ineffective. IgG1 and IgG3 are effective mediators of antibody-mediated cellular cytotoxicity; lgG4 and lgG2 are less effective in this regard.
IgA is present on mucosal surfaces, in serum and in secretions (saliva, lacrimal fluid, secretions from the respiratory, gastrointestinal and urogenital tracts, colostrum), where it provides initial antibacterial and antiviral protection. The J-chain binds IgA into a dimer - a secretory IgA molecule is formed. Secretory IgA is synthesized by plasma cells in the subepithelial part of the mucous membrane of the gastrointestinal tract and respiratory tract. Selective IgA deficiency is relatively common, but of little clinical concern because there is cross-functionality between other classes of antibodies.
IgD is co-expressed with IgM on the surface of young B-lymphocytes. Whether these 2 classes have different functions, and if so, by how much, is still unclear. They may just be an example of molecular degradation. Serum IgD levels are very low and the function of circulating IgD is unknown.
Acute phase reactants
Acute phase reactants - plasma proteins, the level of which increases sharply or in some cases decreases during infectious processes or tissue damage. C-reactive protein and mannose-binding lectin (which fixes complement proteins and plays the role of opsonin) increase most significantly, α 1 -transport protein of acid glycoprotein and serum amyloid component of CPB and ESR are often measured; an increase in levels is a non-specific sign of infection or inflammation. Elevated fibrinogen is the main reason for the increase in ESR.
Many acute phase reactants are produced in the liver. Together, they help limit tissue damage, increase the body's resistance to infection, promote tissue repair and stop inflammation.
Cytokines
Cytokines are polypeptides secreted by immune and other cells after their interaction with a specific antigen, endotoxin, and other cytokines. Major groups of cytokines include interferons:
- interferons;
- tumor necrosis factors (TNF-α, lymphotoxins-α, lymphotoxins-β);
- interleukins (IL);
- chemokines;
- transforming growth factors;
- hematopoietic colony stimulating factors (CSF).
Although a lymphocyte initiates cytokine secretion after interaction with a specific antigen, cytokines themselves are not antigen-specific.
Cytokines transmit signals through cell surface receptors. For example, the I/1-2 receptor consists of 3 chains: α, β and γ. Receptor affinity for IL-2 will be high if all 3 chains are expressed, moderate if only β and γ chains are expressed, and low if only α chain is expressed. Mutations or deletions of the chain form the basis of X-chained severe combined immunodeficiency.
Chemokines induce chemotaxis and leukocyte migration. There are 4 subfamilies that differ in the number of separating amino acids between the first two cysteine residues. Chemokine receptors (CCR5 on memory T-lymphocytes, monocytes/macrophages, dendritic cells; CXCR4 on other T-lymphocytes) are co-receptors for HIV (human immunodeficiency virus) entry into the cell.
human leukocyte antigens
The human leukocyte antigen (HLA) system is located on the 6th chromosome. This chromosome codes for cell surface molecules.
Class I MHC molecules are present on the surface of all nuclear cells as transmembrane glycoproteins; after these molecules are denatured and cleaved, they are taken up by platelets. A normal class I molecule consists of a heavy chain a linked to a p2 microglobulin molecule. The heavy chain consists of two linked peptide domains, an lg-like domain, a transmembrane region, and a cytoplasmic end. The heavy chain of the MHC class I molecule is encoded by the HLA-A, -B, or C-loci genes. Lymphocytes that respond to MHC class I molecules express CD8 molecules and perform effector functions, consisting in the ability to recognize any infected cells. Since any nucleated cell expresses class I MHC molecules, all infected cells are antigen-presenting for CD8 positive T lymphocytes (CD8 binds to the non-polymorphic region of the class I heavy chain). Some class I MHC genes encode non-classical MHC molecules, such as HLA-G and HLA-E (which present peptides to certain NK receptors).
Class II MHC molecules are usually present only on professional antigen-presenting cells, thymic epithelial cells, and activated (but not resting) T cells; most nucleated cells can be stimulated to express class II MHC molecules by interferon (IFN)-γ. Class I MHC molecules consist of two polypeptide (a and (3) chains; each peptide has a peptide-binding site, an lg-like site, and a transmembrane region with a cytoplasmic tail. Both polypeptide chains are encoded by the genes for the HLA-DP, -DQ, or -DR chromosome 6. Lyphocytes that respond to MHC class II molecules express CD4 and are often T-helper cells.
The MHC class III region encodes several molecules of importance in inflammation.
The individual antigens determined by serological typing encoded by the genes of the class I and II loci have standard designations. Alleles determined by DNA sequencing contain the name of the gene in the designation, followed by an asterisk, then numbers indicating the allele group (often corresponding to the serologically identified antigen encoded by this allele), then a colon and numbers denoting this allele. Sometimes the allele designation has additional digits after the colon to indicate allelic variants encoding identical proteins, and digits are added after the second colon to indicate polymorphisms in introns or in 5' or 3' untranslated regions.
MHC class I and II molecules are the most immunogenic antigens and are recognized during allogeneic transplant rejection. The strongest determinant is HLA-DR, followed by HLA-B and -A. Therefore, these three locus data are the most important in selecting a suitable (tissue-compatible) donor for a recipient.
Complement system
The complement system is a cascade of enzymes that facilitate the fight against the infectious process. This system links innate and adaptive immunity by:
- Increased antibody response (AT) and immunological memory.
- Leasing of foreign molecules.
- Removal of immune complexes. The components of the complement system perform many biological functions.
Activation of complement proteins: There are 3 pathways for complement activation:
- classical,
- lectin (mannose-binding lectin-MBL),
- alternative.
The components of the classical path are denoted by the letter C and a number indicating the order in which they are identified. The components of the alternative pathway are often referred to by letters (eg, factor B, factor D) or by a separate name (eg, properdin).
Classic way. Activation of the classical pathway - an AT-dependent process that begins after the interaction of C1 with the AG-lgM or AG-lgG complex, or an AT-independent process when polyanions (heparin, protamine, DNA or RNA of apoptotic cells), gram-negative bacteria, or associated C- reactive protein react directly with C1. This pathway is regulated by the C1 inhibitor (C1-INM). Hereditary angioedema is associated with C1-INH genetic deficiency.
The lectin pathway (mannose-binding lectin) is an AT-independent process; it starts when MBL-whey protein binds to mannose, fructose.
The alternative pathway starts with the adherence of microbial cell surface components or lg to a small amount of C3. This pathway is regulated by properdin, factor H, a factor that accelerates necrosis.
These 3 pathways eventually converge when C3 convertase converts C3 to C3a and C3b. Cleavage of C3 can lead to the formation of the membrane attack complex (MAC), the cytotoxic component of the complement system. MAC is the cause of the lysis of foreign cells.
Complement deficient patients are often susceptible to recurrent bacterial infections, particularly in the absence of the C3 component. Defects C1 and C4 are associated with systemic lupus erythematosus.
Biological activity. The components of the complement system also perform other biological functions, which are realized by complement receptors (CR) on various cell types.
- CR1 (CD35) promotes phagocytosis and is involved in the clearance of immune complexes.
- CR2 (CD21) regulates the production of AT by B-lymphocytes and is the Epstein-Barr virus receptor.
- CR3 (CDllb/CD18), SR4 (CDllc/CD18) and Clq receptors play a role in phagocytosis.
- C3a, C5a and C4a (weakly) show anaphylactic activity. They cause mast cell degranulation leading to increased vascular permeability and smooth muscle contraction.
- C3b works as an opsonin by coating microorganisms and thereby enhancing their phagocytosis.
- C3d enhances AT production by B lymphocytes.
- C5a is a neutrophil chemotractant. It controls the activity of neutrophils and monocytes and can cause increased cell adhesion, degranulation and release of intracellular enzymes from granulocytes, production of toxic oxygen metabolites, and other actions associated with cellular metabolism.
The main cellular immune components include all blood leukocytes, which are the so-called immunocompetent cells. Mature leukocytes combine five populations of cells:
lymphocytes, monocytes, neutrophils, eosinophils and basophils. Immunocompetent cells can be found in almost any part of the body, but they are concentrated mainly in the places of their formation, primary and secondary lymphoid organs (Fig. 8.1). The primary site of formation of all these cells is the hematopoietic organ - red bone marrow, in the sinuses of which monocytes and all granulocytes (neutrophils, eosinophils, basophils) are formed and undergo a full cycle of differentiation. This is where the differentiation of lymphocytes begins. Leukocytes of all populations originate from a single bone marrow pluripotent hematopoietic stem cell whose pool is self-sustaining (Figure 8.2).
Various directions of stem cell differentiation are determined by their specific microenvironment in the foci of bone marrow hematopoiesis and the production of specific hematopoietic factors, including colony-stimulating factors, chalons, prostaglandins, and others. In addition to these factors, the control system for the formation and differentiation of immunocompetent cells in the bone marrow includes a group of all-organism regulatory substances, the most important of which are hormones and mediators of the nervous system.
Lymphocytes in the body are represented by two large subpopulations that differ in histogenesis and immune functions. This T-lymphocytes, providing cellular immunity, and B-lymphocytes, responsible for
wasp the existence of antibody formation, i.e., humoral immunity. If B-lymphocytes pass the entire cycle of differentiation to mature B-cells in the bone marrow, then T-lymphocytes at the stage of pre-T-lymphocytes migrate from it through the bloodstream to another primary lymphoid organ - the thymus, in which their differentiation ends with the formation of all cellular forms of mature T cells.
Fundamentally different from them is a special subpopulation of lymphocytes - normal (natural) killers(NK) and K-cells. NK are cytotoxic cells that destroy target cells (mainly tumor cells and cells infected with viruses) without prior immunization, i.e., in the absence of antibodies. K cells are capable of destroying target cells coated with small amounts of antibodies.
After maturation, immunocompetent cells enter the bloodstream, through which monocytes and granulocytes migrate to tissues, and lymphocytes are sent to secondary lymphoid organs, where the antigen-dependent phase of their differentiation occurs. The circulatory system is the main highway for the transport and recycling of immune components, including immunocompetent cells. In the blood, as a rule, no immunological reactions occur. The blood flow only delivers the cells to the place of their functioning.
Granulocytes(neutrophils, eosinophils, basophils) after maturation in the bone marrow perform only an effector function, after a single performance of which they die. Monocytes after maturation in the bone marrow, they settle in the tissues, where the tissue macrophages formed from them also perform an effector function, but for a long period and repeatedly. Unlike all other cells, lymphocytes after maturation in the bone marrow (B-cells) or thymus (T-cells), they enter the secondary lymphoid organs (Fig. 8.3), where
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Rice. 8.1 Lymphomyeloid complex BM - bone marrow; KS - blood vessels; LTK - intestinal lymphoid tissue; LS - lymphatic vessels; LU - lymph nodes; SL - spleen; T - thymus gland (thymus). |
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Rice. 8.2 pluripotent hematopoietic stem cell and her descendants CTL - cytotoxic T-lymphocyte (T-killer). |
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their main function is reproduction in response to an antigenic stimulus with the appearance of short-lived specific effector cells and long-lived memory cells. "Immunological memory - the body's ability to respond to a second dose of an antigen with an immune response that is stronger and faster than the first immunization.
Secondary lymphoid organs scattered throughout the body to serve all tissues and surface areas. Secondary lymphoid organs include the spleen, lymph nodes, organ accumulations of lymphoid tissue in the mucous membranes - the appendix (appendix), Peyer's patches, tonsils and other formations of the pharyngeal lymphoid ring solitary (single). Lymphoid follicles of the walls of the intestine and vagina, as well as diffuse accumulations lymphoid cells in the subepithelial spaces of all mucous membranes of the body and newly formed foci of lymphoid tissue in the granulation tissue around chronic foci of inflammation.
In secondary lymphoid organs, T- and B-lymphocytes first come into contact with antigens foreign to the body. Such contact is carried out mainly in the lymphoid tissue, at the place of receipt of the antigen. Clones multiply after contact(from Greek klon - sprout, offspring)T- and B-cells specific to this antigen, and the differentiation of most of the cells of these clones into final effector short-lived (T-effectors from T-lymphocytes and plasma cells from B-lymphocytes). Some of the T- and B-lymphocytes of these antigen-specific clones multiply without turning into short-lived effector clones and turn into immunological memory cells. The latter partially migrate to other secondary lymphoid organs, as a result of which an increased level of lymphocytes appears in them, specific to the antigen, the attack of which the body has undergone at least once. This creates an immunological memory for a specific antigen throughout the immune system.
The flow of lymphocytes from the bloodstream to the secondary lymphoid organs is tightly controlled. A significant part of mature T- and B-lymphocytesclearly circulates in the bloodstream between the lymphoid organs (the so-called recirculating lymphocytes). Recirculation of lymphocytes is understood as the process of migration of lymphocytes from the blood to the organs of the immune system, peripheral tissues and back to the blood (Fig. 8.4). Only a small part of lymphocytes belongs to the non-recirculating pool.
The functional purpose of lymphocyte recycling is to carry out constant “immune surveillance” of body tissues by immunocompetent lymphocytes, to effectively detect foreign and altered self antigens, and to supply the organs of lymphocytopoiesis with information about the appearance of antigens in various tissues. Distinguish fast recycling (carried out within a few hours) and slow (lasts weeks). In the course of rapid recirculation, blood lymphocytes specifically bind to the wall of specialized vessels located in the lymphoid organs - postcapillary venules with high endothelium - and then migrate through these endothelial cells to the lymphoid tissue, then to the lymphatic vessels and return to the blood through the thoracic lymphatic duct. About 90% of the lymphocytes present in the lymph of the thoracic duct migrate in this way. With slow recirculation, blood lymphocytes migrate through postcapillary venules with a flat endothelium, characteristic of non-immune organs, into various peripheral tissues, then enter the lymphatic vessels, lymph nodes and through the lymph flow into the thoracic lymphatic duct again into the blood. Approximately 5-10% of the lymphocytes contained in the lymph of the thoracic duct recirculate in this way.
The specific binding of lymphocytes to the walls of postcapillary venules with high endothelium occurs due to the presence on the surface of endothelial cells of certain molecules and their corresponding receptors on T- and B-lymphocytes (Fig. 8.5). This mechanism provides selective accumulation in lymph nodes and other secondary lymphoid organs of certain populations of lymphocytes. Peyer's patches contain about 70% of B-lymphocytes and 10-20% of T-lymphocytes, while in the peripheral lymph nodes, on the contrary, about 70% of T- and 20% of B-cells. Many antigen-activated T- and B-lymphocytes leave the place where they were activated, and then, after circulating in the bloodstream, return to the same or close to them lymphoid organs. This pattern underlies local immunity organs and tissues. Among recirculating lymphocytes, more
migration speed is possessed by T-lymphocytes and immunological memory cells of both types.
The cells of the skin and mucous membranes, which create a mechanical barrier to the path of a foreign antigen, also take a direct part in the immune defense. As mechanical factors non-specific defense mechanisms we can consider desquamation (desquamation) of the cells of the surface layers of multilayered epithelium, the production of mucus covering the mucous membranes, the beating of cilia, which transports mucus along the surface of the epithelium (in the respiratory tract - mucociliary transport). Microbes are also removed from the surface of the epithelium by the flow of saliva, urine tears and other liquids.
TO humoral immune components include a wide variety of immunologically active molecules, from simple to very complex, which are produced by immunocompetent and other cells and are involved in protecting the body from foreign or defective ones. Among them, first of all, it is necessary to single out substances of a protein nature - immunoglobulins, cytokines, a system of complement components, acute phase proteins, interferon, and others. The immune components include enzyme inhibitors that suppress the enzymatic activity of bacteria, virus inhibitors, numerous low molecular weight substances that are mediators of immune responses (histamine, serotonin, prostaglandins, and others). Of great importance for the effective protection of the body are the saturation of tissues with oxygen, the pH of the environment, the presence of Ca 2+ and Mg2+ and other ions, trace elements, vitamins, etc.
8. 2. MECHANISMS OF NON-SPECIFIC (INNATURAL) IMMUNE
Non-specific (congenital) defense mechanisms are a combination of all physiological factors capable of a) preventing entry into the body or b) neutralizing and destroying foreign substances and particles that have penetrated into it or its own altered cells formed in it. These mechanisms do not have specificity with respect to the influencing agent.
In addition to the mechanical and chemical factors mentioned, there are several other ways to protect: phagocytosis(“eating” by cells), extracellular destruction of virus-infected and tumor cells with the help of cytotoxic factors (cellular cytotoxicity) and destruction of foreign cells with soluble bactericidal compounds.
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What is blood made of and how does the immune system function?Functions of the immune system
The main function of the immune system is to oversee the macromolecular and cellular stability of the body, to protect the body from everything foreign. The immune system, together with the nervous and endocrine systems, regulate and control all physiological reactions of the body, thereby ensuring the vital activity and viability of the body. Immunocompetent cells are an essential element of the inflammatory response and largely determine the nature and course of its course. An important function of immunocompetent cells is the control and regulation of tissue regeneration processes.
The immune system performs its main function through the development of specific (immune) reactions, which are based on the ability to recognize "own" and "alien" and the subsequent elimination of the foreign. Specific antibodies that appear as a result of an immune reaction form the basis of humoral immunity, and sensitized lymphocytes are the main carriers of cellular immunity.The immune system has the phenomenon of "immunological memory", which is characterized by the fact that repeated contact with the antigen causes an accelerated and enhanced development of the immune response, which provides more effective protection of the body compared to the primary immune response. This feature of the secondary immune response underlies the meaning of vaccination, which successfully protects against most infections. It should be noted that immune reactions do not always play only a protective role, they can be the cause of immunopathological processes in the body and cause a number of human somatic diseases.
Structure of the immune system
The human immune system is represented by a complex of lymphomyeloid organs and lymphoid tissue associated with the respiratory, digestive and genitourinary systems. The organs of the immune system include: bone marrow, thymus, spleen, lymph nodes. The immune system, in addition to these organs, also includes tonsils of the nasopharynx, lymphoid (Peyer's) patches of the intestine, numerous lymphoid nodules located in the mucous membranes of the gastrointestinal tract, respiratory tube, urogenital tract, diffuse lymphoid tissue, as well as lymphoid cells of the skin and interepithelial lymphocytes.
The main element of the immune system are lymphoid cells. The total number of lymphocytes in humans is 1012 cells. Macrophages are the second important element of the immune system. In addition to these cells, granulocytes are involved in the protective reactions of the body. Lymphoid cells and macrophages are united by the concept of immunocompetent cells.
In the immune system, a T-link and a B-link or a T-system of immunity and a B-system of immunity are distinguished. The main cells of the T-system of immunity are T-lymphocytes, the main cells of the B-system of immunity are B-lymphocytes. The main structural formations of the T-system of immunity include the thymus, T-zones of the spleen and lymph nodes; B-systems of immunity - bone marrow, B-zones of the spleen (reproduction centers) and lymph nodes (cortical zone). The T-link of the immune system is responsible for cell-type reactions, the B-link of the immune system implements humoral-type reactions. The T-system controls and regulates the operation of the B-system. In turn, the B-system is able to influence the operation of the T-system.
Among the organs of the immune system, central organs and peripheral organs are distinguished. The central organs include the bone marrow and thymus, and the peripheral organs include the spleen and lymph nodes. B-lymphocytes develop from lymphoid stem cells in the bone marrow, and T-lymphocytes develop from lymphoid stem cells in the thymus. As they mature, T- and B-lymphocytes leave the bone marrow and thymus and populate peripheral lymphoid organs, settling in the T- and B-zones, respectively.
What is blood made of?
Blood consists of formed elements (or blood cells) and plasma. Plasma accounts for 55-60% of the total blood volume, blood cells account for 40-45%, respectively.
Plasma
Plasma is a slightly yellowish translucent liquid with a specific gravity of 1.020-1.028 (specific gravity of blood 1.054-1.066) and consists of water, organic compounds and inorganic salts. 90-92% water, 7-8% protein, 0.1% glucose and 0.9% salt.
blood cells
red blood cells
Red blood cells, or erythrocytes, are suspended in the blood plasma. The erythrocytes of many mammals and humans are biconcave discs that do not have nuclei. The diameter of human erythrocytes is 7-8 µ, and the thickness is 2-2.5 µ. The formation of red blood cells occurs in the red bone marrow, in the process of maturation, they lose their nuclei, and then enter the blood. The average lifespan of one erythrocyte is approximately 127 days, then the erythrocyte is destroyed (mainly in the spleen).
Hemoglobin
Hemoglobin molecules from old red blood cells in the spleen and liver are broken down, iron atoms are reused, and heme is broken down and excreted by the liver as bilirubin and other bile pigments. Nuclear erythrocytes can appear in the blood after large blood loss, as well as in violation of the normal functions of the red bone marrow tissue. In an adult man, 1 mm3 of blood contains about 5,400,000 erythrocytes, and in an adult woman - 4,500,000 - 5,000,000. Newborns have more erythrocytes - from 6 to 7 million in 1 mm3. Each red blood cell contains about 265 million molecules of hemoglobin, a red pigment that carries oxygen and carbon dioxide. It is estimated that about 2.5 million red blood cells are formed every second and the same number is destroyed. And since each erythrocyte contains 265 106 hemoglobin molecules, approximately 650 1012 molecules of the same hemoglobin are formed every second.
Hemoglobin consists of two parts: protein - globin and iron-containing - heme. In the capillaries of the lungs, oxygen diffuses from the plasma into the erythrocytes and combines with hemoglobin (Hb), forming oxyhemoglobin (HbO2): Hb+O2 « HbO2. In tissue capillaries, under conditions of low partial pressure of oxygen, the HbO2 complex decomposes. Hemoglobin combined with oxygen is called oxyhemoglobin, and hemoglobin that has given up oxygen is called reduced hemoglobin. A certain amount of CO2 is carried in the blood in the form of an unstable compound with hemoglobin - carboxyhemoglobin.
Leukocytes
Blood contains five types of white blood cells, or leukocytes, colorless cells containing a nucleus and cytoplasm. They are formed in the red bone marrow, lymph nodes and spleen. Leukocytes are devoid of hemoglobin and are capable of active amoeboid movement. There are fewer leukocytes than erythrocytes - on average, about 7,000 per 1 mm3, but their number varies from 5,000 to 9,000 (or 10,000) in different people and even in the same person at different times of the day: the least they are early in the morning, and most of all - in the afternoon. Leukocytes are divided into three groups: 1) granular leukocytes, or granulocytes (their cytoplasm contains granules), among them neutrophils, eosinophils and basophils are distinguished; 2) non-granular leukocytes, or agranulocytes, - lymphocytes; 3) monocytes.
platelets
There is another group of formed elements - these are platelets, or platelets - the smallest of all blood cells. They are formed in the bone marrow. Their number in 1 mm3 of blood ranges from 300,000 to 400,000. They play an important role in the beginning of the blood coagulation process. In most vertebrates