Humoral factors of nonspecific protection of the internal environment. Humoral immunity Non-specific humoral factors that protect the body from microbes
Basically, these are substances of a protein nature that are in the blood plasma:
Scheme No. 2: Non-specific defense mechanisms: Humoral factors of the internal environment
Biological effects of complement activation:
1) Contraction of smooth muscles (C3a, C5a);
2) increase in vascular permeability (C3a, C4a, C5a);
3) degranulation of basophils (C3a, C5a);
4) platelet aggregation (C3a, C5a);
5) opsonization and phagocytosis (C3b);
6) activation of the kinin system (C2b);
7) MAC, lysis;
8) Chemotaxis (C5a)
Activation of the complement system leads to the lysis of foreign and virus-infected cells of the body. *
The foreign cell (left - classical complement activation pathway) is labeled (opsonized) by binding to immunoglobulins or (right - alternative complement pathway) specific membrane structures (e.g. lipopolysaccharides or membrane antigens induced by viruses) are made "noticeable" to the complement system. Product C3b combines both reaction routes. It splits C5 into C5a and C5b. Components C5b - C8 polymerize with C9 and form a tubular membrane attack complex (MAC), which passes through the membrane of the target cell and leads to the penetration of Ca 2+ into the cell (at high intracellular concentrations it is cytotoxic!), as well as Na + and H 2 O.
* Activation of the cascade of reactions of the complement system includes many more steps than are shown in the scheme. In particular, there are no various inhibitory factors that help control the overreaction in the coagulation and fibrinolytic systems.
Specific defense mechanisms of cellular homeostasis
Carried out by the immune system of the body and are the basis of immunity.
Tissues (including transplanted)Proteins and their compounds with lipids, polysaccharides
The immune system is a collection.
Humoral factors of nonspecific defense of the body include normal (natural) antibodies, lysozyme, properdin, beta-lysines (lysines), complement, interferon, virus inhibitors in the blood serum and a number of other substances that are constantly present in the body.
Antibodies (natural). In the blood of animals and humans that have never previously been ill and have not been immunized, substances are found that react with many antigens, but in low titers, not exceeding dilutions of 1:10 ... 1:40. These substances were called normal or natural antibodies. They are believed to result from natural immunization with various microorganisms.
L and o c and m. Lysosomal enzyme is present in tears, saliva, nasal mucus, secretion of mucous membranes, blood serum and extracts of organs and tissues, in milk; a lot of lysozyme in the protein of chicken eggs. Lysozyme is resistant to heat (inactivated by boiling), has the ability to lyse live and killed mostly gram-positive microorganisms.
The method for determining lysozyme is based on the ability of serum to act on a culture of micrococcus lysodecticus grown on oblique agar. Suspension of the daily culture is prepared according to the optical standard (10 IU) in physiological saline. The test serum is diluted sequentially with saline 10, 20, 40, 80 times, etc. An equal volume of microbial suspension is added to all test tubes. The tubes are shaken and placed in a thermostat for 3 hours at 37°C. Accounting for the reaction produced by the degree of clarification of the serum. The titer of lysozyme is the last dilution in which complete lysis of the microbial suspension occurs.
S ecretor n y and mm u n o g lo b l and N A. Constantly present in the contents of the secrets of the mucous membranes, mammary and salivary glands, in the intestinal tract; It has strong antimicrobial and antiviral properties.
Properdin (from Latin pro and perdere - prepare for destruction). Described in 1954 in the form of a polymer as a factor of nonspecific protection and cytolysin. It is present in normal blood serum in an amount up to 25 mcg / ml. It is a whey protein (beta-globulin) with a molecular weight
220,000. Properdin takes part in the destruction of microbial cells, the neutralization of viruses. Properdine acts as part of the properdine system: properdine complement and divalent magnesium ions. Native properdin plays a significant role in non-specific complement activation (alternative activation pathway).
L and z and n s. Serum proteins that have the ability to lyse (dissolve) some bacteria and red blood cells. In the blood serum of many animals, there are beta-lysins that cause lysis of the culture of hay bacillus, as well as many pathogenic microbes.
Laktoferrin. Non-heminic glycoprotein with iron-binding activity. Binds two atoms of ferric iron, competing with microbes, as a result of which the growth of microbes is suppressed. It is synthesized by polymorphonuclear leukocytes and grape cells of the glandular epithelium. It is a specific component of the secretion of glands - salivary, lacrimal, milk, respiratory, digestive and genitourinary tracts. Lactoferrin is a factor of local immunity that protects epithelial integument from microbes.
Complement. A multicomponent system of proteins in blood serum and other body fluids that play an important role in maintaining immune homeostasis. It was first described by Buchner in 1889 under the name "alexin" - a thermolabile factor, in the presence of which microbes are lysed. The term "complement" was introduced by Erlich in 1895. Complement is not very stable. It was noted that specific antibodies in the presence of fresh blood serum can cause hemolysis of erythrocytes or lysis of a bacterial cell, but if the serum is heated at 56 ° C for 30 minutes before the reaction, then lysis will not occur. It turned out that hemolysis (lysis) occurs after calculation of the presence of complement in fresh serum.The greatest amount of complement is contained in the serum of the guinea pig.
The complement system consists of at least nine different serum proteins, designated C1 to C9. C1, in turn, has three subunits - Clq, Clr, Cls. The activated form of complement is indicated by a dash above (c).
There are two ways of activation (self-assembly) of the complement system - classical and alternative, differing in trigger mechanisms.
In the classical activation pathway, complement component C1 binds to immune complexes (antigen + antibody), which include successively subcomponents (Clq, Clr, Cls), C4, C2, and C3. The C4, C2, and C3 complex ensures the fixation of the activated C5 component of the complement on the cell membrane, and then they are switched on through a series of C6 and C7 reactions, which contribute to the fixation of C8 and C9. As a result, damage to the cell wall or lysis of the bacterial cell occurs.
In an alternative way of complement activation, the activators themselves are the viruses, bacteria, or exotoxins themselves. The alternative activation pathway does not involve components C1, C4 and C2. Activation begins from the C3 stage, which includes a group of proteins: P (properdin), B (proactivator), proactivator convertase C3, and inhibitors j and H. In the reaction, properdin stabilizes C3 and C5 convertases, therefore this activation pathway is also called the properdin system. The reaction begins with the addition of factor B to C3, as a result of a series of successive reactions, P (properdin) is inserted into the complex (C3 convertase), which acts as an enzyme on C3 and C5, "and the complement activation cascade begins with C6, C7, C8 and C9, resulting in damage to the cell wall or cell lysis.
Thus, the complement system serves as an effective defense mechanism of the body, which is activated as a result of immune responses or by direct contact with microbes or toxins. Let us note some biological functions of activated complement components: they participate in the regulation of the process of switching immunological reactions from cellular to humoral and vice versa; C4 bound to the cell promotes immune attachment; C3 and C4 enhance phagocytosis; C1 and C4, binding to the surface of the virus, block the receptors responsible for the introduction of the virus into the cell; C3a and C5a are identical to anaphylactoxins, they act on neutrophil granulocytes, the latter secrete lysosomal enzymes that destroy foreign antigens, provide directed migration of macrophages, cause smooth muscle contraction, and increase inflammation.
It has been established that macrophages synthesize C1, C2, C3, C4 and C5; hepatocytes - C3, Co, C8; liver parenchyma cells - C3, C5 and C9.
In terferon. Separated in 1957. English virologists A. Isaacs and I. Linderman. Interferon was originally considered as an antiviral protection factor. Later it turned out that this is a group of protein substances, the function of which is to ensure the genetic homeostasis of the cell. Bacteria, bacterial toxins, mitogens, etc. act as inducers of interferon formation, in addition to viruses. agents; (3-interferon, or fibroblastic, which is produced by fibroblasts treated with viruses or other agents. Both of these interferons are classified as type I. Immune interferon, or y-interferon, is produced by lymphocytes and macrophages activated by non-viral inducers.
Interferon takes part in the regulation of various mechanisms of the immune response: it enhances the cytotoxic effect of sensitized lymphocytes and K-cells, has an anti-proliferative and antitumor effect, etc. Interferon has specific tissue specificity, i.e., it is more active in the biological system in which it is produced, protects cells from viral infection only if it acts on them before contact with the virus.
The process of interaction of interferon with sensitive cells includes several stages: adsorption of interferon on cell receptors; induction of an antiviral state; development of viral resistance (filling of interferon-induced RNA and proteins); pronounced resistance to viral infection. Therefore, interferon does not directly interact with the virus, but prevents the penetration of the virus and inhibits the synthesis of viral proteins on cellular ribosomes during the replication of viral nucleic acids. Interferon also has radiation-protective properties.
I n g i b i to r y. Nonspecific antiviral substances of a protein nature are present in normal native blood serum, secretions of the epithelium of the mucous membranes of the respiratory and digestive tracts, in extracts of organs and tissues. They have the ability to suppress the activity of viruses in the blood and fluids outside the sensitive cell. Inhibitors are subdivided into thermolabile (they lose their activity when the blood serum is heated to 60 ... 62 ° C for 1 hour) and thermostable (withstand heating up to 100 ° C). Inhibitors have universal virus-neutralizing and anti-hemagglutinating activity against many viruses.
Inhibitors of tissues, secretions and excretions of animals have been found to be active against many viruses: for example, secretory inhibitors of the respiratory tract have antihemagglutinating and virus-neutralizing activity.
Bactericidal activity of blood serum (BAS). Fresh human and animal blood serum has pronounced bacteriostatic properties against a number of pathogens of infectious diseases. The main components that inhibit the growth and development of microorganisms are normal antibodies, lysozyme, properdin, complement, monokines, leukins and other substances. Therefore, BAS is an integrated expression of the antimicrobial properties of humoral nonspecific defense factors. BAS depends on the state of health of animals, the conditions of their maintenance and feeding: with poor maintenance and feeding, serum activity is significantly reduced.
The definition of BAS is based on the ability of blood serum to inhibit the growth of microorganisms, which depends on the level of normal antibodies, properdin, complement, etc. The reaction is set at a temperature of 37 ° C with different dilutions of serum, into which a certain dose of microbes is added. Serum dilution allows you to establish not only its ability to inhibit the growth of microbes, but also the strength of the bactericidal action, which is expressed in units.
Protective and adaptive mechanisms. Stress also belongs to non-specific protective factors. Stress-causing factors were called stressors by G. Silje. According to Silje, stress is a special non-specific state of the body that occurs in response to the action of various damaging environmental factors (stressors). In addition to pathogenic microorganisms and their toxins, cold, hunger, heat, ionizing radiation, and other agents that have the ability to cause responses in the body can act as stressors. Adaptation syndrome can be general and local. It is caused by the action of the pituitary-adrenocortical system associated with the hypothalamic center. Under the influence of a stressor, the pituitary gland begins to intensively secrete andrenocorticotropic hormone (ACTH), which stimulates the functions of the adrenal glands, causing them to increase the release of an anti-inflammatory hormone such as cortisone, which reduces the protective-inflammatory reaction. If the effect of the stressor is too strong or prolonged, then in the process of adaptation, a disease occurs.
With the intensification of animal husbandry, the number of stress factors to which animals are exposed increases significantly. Therefore, the prevention of stressful effects that reduce the body's natural resistance and cause diseases is one of the most important tasks of the veterinary service.
Cellular reactivity
The development of the infectious process and the formation of immunity are completely dependent on the primary sensitivity of cells to the pathogen. Hereditary species immunity is an example of the lack of sensitivity of cells of one animal species to microorganisms that are pathogenic for others. The mechanism of this phenomenon is not well understood. It is known that cell reactivity changes with age and under the influence of various factors (physical, chemical, biological).
In addition to phagocytes, there are soluble non-specific substances in the blood that have a detrimental effect on microorganisms. These include complement, properdin, β-lysines, x-lysines, erythrin, leukins, plakins, lysozyme, etc.
Complement(from lat. complementum - addition) is a complex system of protein blood fractions that has the ability to lyse microorganisms and other foreign cells, such as red blood cells. There are several complement components: C 1, C 2, Cs, etc. Complement is destroyed at temperature 55 °C for 30 min. This property is called thermolability. It is also destroyed by shaking, under the influence of UV rays, etc. In addition to blood serum, complement is found in various body fluids and in inflammatory exudate, but is absent in the anterior chamber of the eye and cerebrospinal fluid.
properdin(from Latin properde - to prepare) - a group of components of normal blood serum that activates complement in the presence of magnesium ions. It is similar to enzymes and plays an important role in the body's resistance to infection. A decrease in the level of properdin in the blood serum indicates an insufficient activity of immune processes.
β-lysines- thermostable (resistant to temperature) substances of human blood serum, which have an antimicrobial effect, mainly against gram-positive bacteria. Destroyed at 63 ° C and under the action of UV rays.
X-lysine- a thermostable substance isolated from the blood of patients with high fever. It has the ability to complement lyse bacteria, mainly gram-negative ones, without participation. Withstands heating up to 70-100 °C.
Erythrin isolated from animal erythrocytes. It has a bacteriostatic effect on diphtheria pathogens and some other microorganisms.
Leukins- bactericidal substances isolated from leukocytes. Thermostable, destroyed at 75-80 °C. They are found in the blood in very small amounts.
Plakins- substances similar to leukins isolated from platelets.
Lysozyme An enzyme that breaks down the membranes of microbial cells. It is found in tears, saliva, blood fluids. The rapid healing of wounds of the conjunctiva of the eye, mucous membranes of the oral cavity, nose is largely due to the presence of lysozyme.
The constituent components of urine, prostatic fluid, extracts of various tissues also have bactericidal properties. Normal serum contains a small amount of interferon.
SPECIFIC FACTORS OF PROTECTION OF THE ORGANISM (IMMUNE)
The components listed above do not exhaust the entire arsenal of humoral protection factors. Chief among them are specific antibodies - immunoglobulins, formed when foreign agents - antigens - are introduced into the body.
Compliment, lysozyme, interferon, properdin, C-reactive protein, normal antibodies, bactericidin are among the humoral factors that ensure the body's resistance.
Complement is a complex multifunctional system of blood serum proteins that is involved in such reactions as opsonization, stimulation of phagocytosis, cytolysis, neutralization of viruses, and induction of an immune response. There are 9 known complement fractions, designated C 1 - C 9, which are in the blood serum in an inactive state. Complement activation occurs under the action of the antigen-antibody complex and begins with the addition of C 1 1 to this complex. This requires the presence of Ca and Mq salts. The bactericidal activity of complement is manifested from the earliest stages of fetal life, however, during the neonatal period, complement activity is the lowest compared to other age periods.
Lysozyme is an enzyme from the group of glycosidases. Lysozyme was first described by Fletting in 1922. It is secreted constantly and is found in all organs and tissues. In the body of animals, lysozyme is found in the blood, lacrimal fluid, saliva, nasal mucosal secretions, gastric and duodenal juice, milk, amniotic fluid of fetuses. Leukocytes are especially rich in lysozyme. The ability to lysozymalize microorganisms is extremely high. It does not lose this property even at a dilution of 1: 1,000,000. Initially, it was believed that lysozyme is active only against gram-positive microorganisms, but it has now been established that it acts cytolytically with respect to gram-negative bacteria, penetrating through the cell wall damaged by it. bacteria to objects of hydrolysis.
Properdin (from lat. perdere - to destroy) is a globulin-type blood serum protein with bactericidal properties. In the presence of a compliment and magnesium ions, it exhibits a bactericidal effect against gram-positive and gram-negative microorganisms, and is also able to inactivate influenza and herpes viruses, and exhibits bactericidal activity against many pathogenic and opportunistic microorganisms. The level of properdin in the blood of animals reflects the state of their resistance, sensitivity to infectious diseases. A decrease in its content was revealed in irradiated animals with tuberculosis, with streptococcal infection.
C-reactive protein - like immunoglobulins, has the ability to initiate reactions of precipitation, agglutination, phagocytosis, complement fixation. In addition, C-reactive protein increases the mobility of leukocytes, which gives reason to talk about its participation in the formation of non-specific resistance of the body.
C-reactive protein is found in the blood serum during acute inflammatory processes, and it can serve as indicators of the activity of these processes. This protein is not detected in normal blood serum. It does not pass through the placenta.
Normal antibodies are almost always present in the blood serum and are constantly involved in nonspecific protection. They are formed in the body as a normal component of serum as a result of contact of the animal with a very large number of various environmental microorganisms or some dietary proteins.
Bactericidin is an enzyme that, unlike lysozyme, acts on intracellular substances.
Throughout the path of evolution, a person comes into contact with a huge number of pathogenic agents that threaten him. In order to resist them, two types of defensive reactions have formed: 1) natural or non-specific resistance, 2) specific protective factors or immunity (from lat.
Immunitas - free from anything).
Nonspecific resistance is due to various factors. The most important of these are: 1) physiological barriers, 2) cellular factors, 3) inflammation, 4) humoral factors.
Physiological barriers. Can be divided into external and internal barriers.
external barriers. Intact skin is impervious to the vast majority of infectious agents. Constant desquamation of the upper layers of the epithelium, the secrets of the sebaceous and sweat glands contribute to the removal of microorganisms from the surface of the skin. When the integrity of the skin is violated, for example, with burns, infection becomes the main problem. In addition to the fact that the skin serves as a mechanical barrier to bacteria, it contains a number of bactericidal substances (lactic and fatty acids, lysozyme, enzymes secreted by the sweat and sebaceous glands). Therefore, microorganisms that are not part of the normal microflora of the skin quickly disappear from its surface.
Mucous membranes are also a mechanical barrier to bacteria, but they are more permeable. Many pathogenic microorganisms can penetrate even through intact mucous membranes.
The mucus secreted by the walls of internal organs acts as a protective barrier that prevents bacteria from "attaching" to epithelial cells. Microbes and other foreign particles captured by the mucus are removed mechanically - due to the movement of the cilia of the epithelium, with coughing and sneezing.
Other mechanical factors contributing to the protection of the surface of the epithelium include the washing out effect of tears, saliva, and urine. Many fluids secreted by the body contain bactericidal components (hydrochloric acid in gastric juice, lactoperoxidase in breast milk, lysozyme in lacrimal fluid, saliva, nasal mucus, etc.).
The protective functions of the skin and mucous membranes are not limited to non-specific mechanisms. On the surface of the mucous membranes, in the secrets of the skin, mammary and other glands, there are secretory immunoglobulins that have bactericidal properties and activate local phagocytic cells. The skin and mucous membranes are actively involved in antigen-specific reactions of acquired immunity. They are considered independent components of the immune system.
One of the most important physiological barriers is the normal microflora of the human body, which inhibits the growth and reproduction of many potentially pathogenic microorganisms.
internal barriers. Internal barriers include the system of lymphatic vessels and lymph nodes. Microorganisms and other foreign particles that have penetrated the tissues are phagocytosed on the spot or delivered by phagocytes to the lymph nodes or other lymphatic formations, where an inflammatory process develops aimed at destroying the pathogen. If the local reaction is insufficient, the process extends to the following regional lymphoid formations, which represent a new barrier to the penetration of the pathogen.
There are functional histohematic barriers that prevent the penetration of pathogens from the blood into the brain, reproductive system, and eyes.
The membrane of each cell also serves as a barrier to the penetration of foreign particles and molecules into it.
Cellular factors. Among the cellular factors of nonspecific protection, the most important is phagocytosis - the absorption and digestion of foreign particles, incl. and microorganisms. Phagocytosis is carried out by two populations of cells:
I. microphages (polymorphonuclear neutrophils, basophils, eosinophils), 2. macrophages (blood monocytes, free and fixed macrophages of the spleen, lymph nodes, serous cavities, liver Kupffer cells, histiocytes).
In relation to microorganisms, phagocytosis can be complete when bacterial cells are completely digested by the phagocyte, or incomplete, which is typical for diseases such as meningitis, gonorrhea, tuberculosis, candidiasis, etc. In this case, pathogens remain viable inside phagocytes for a long time, and sometimes they breed in them.
In the body, there is a population of lymphocyte-like cells that have natural cytotoxicity with respect to “target” cells. They are called natural killers (NK).
Morphologically, NK are large granular lymphocytes, they do not have phagocytic activity. Among human blood lymphocytes, the content of EC is 2 - 12%.
Inflammation. When the microorganism is introduced into the tissue, an inflammatory process occurs. The resulting damage to tissue cells leads to the release of histamine, which increases the permeability of the vascular wall. The migration of macrophages increases, edema occurs. In the inflammatory focus, the temperature rises, acidosis develops. All this creates unfavorable conditions for bacteria and viruses.
Humoral protective factors. As the name itself indicates, humoral protective factors are found in body fluids (blood serum, breast milk, tears, saliva). These include: complement, lysozyme, beta-lysins, acute phase proteins, interferons, etc.
Complement is a complex complex of blood serum proteins (9 fractions), which, like the proteins of the blood coagulation system, form cascade systems of interaction.
The complement system has several biological functions: it enhances phagocytosis, causes bacterial lysis, and so on.
Lysozyme (muramidase) is an enzyme that cleaves glycosidic bonds in the peptidoglycan molecule, which is part of the bacterial cell wall. The content of peptidoglycan in gram-positive bacteria is higher than in gram-negative ones, therefore, lysozyme is more effective against gram-positive bacteria. Lysozyme is found in humans in lacrimal fluid, saliva, sputum, nasal mucus, etc.
Beta-lysins are found in the blood serum of humans and many animal species, and their origin is associated with platelets. They have a detrimental effect primarily on gram-positive bacteria, in particular on anthracoid.
Acute phase proteins are the common name for some plasma proteins. Their content increases dramatically in response to infection or tissue damage. These proteins include: C-reactive protein, serum amyloid A, serum amyloid P, alpha1-antitrypsin, alpha2-macroglobulin, fibrinogen, etc.
Another group of acute phase proteins are proteins that bind iron - haptoglobin, hemopexin, transferrin - and thereby prevent the reproduction of microorganisms that need this element.
During infection, microbial waste products (such as endotoxins) stimulate the production of interleukin-1, which is an endogenous pyrogen. In addition, interleukin-1 acts on the liver, increasing the secretion of C-reactive protein to such an extent that its concentration in blood plasma can increase 1000 times. An important property of C-reactive protein is the ability to bind with the participation of calcium with some microorganisms, which activates the complement system and promotes phagocytosis.
Interferons (IF) are low molecular weight proteins produced by cells in response to the penetration of viruses. Then their immunoregulatory properties were revealed. There are three types of IF: alpha, beta, belonging to the first class, and interferon gamma, belonging to the second class.
Alpha-interferon, produced by leukocytes, has antiviral, antitumor and antiproliferative effects. Beta-IF, secreted by fibroblasts, has a predominantly antitumor and antiviral effect. Gamma-IF, a product of T-helpers and CD8+ T-lymphocytes, is called lymphocytic or immune. It has an immunomodulatory and weak antiviral effect.
The antiviral effect of IF is due to the ability to activate the synthesis of inhibitors and enzymes in cells that block the replication of viral DNA and RNA, which leads to suppression of virus reproduction. The mechanism of antiproliferative and antitumor action is similar. Gamma-IF is a polyfunctional immunomodulatory lymphokine that affects the growth, differentiation and activity of cells of different types. Interferons inhibit the reproduction of viruses. It has now been established that interferons also have antibacterial activity.
Thus, the humoral factors of nonspecific protection are quite diverse. In the body, they act in combination, providing a bactericidal and inhibitory effect on various microbes and viruses.
All of these protective factors are non-specific, since there is no specific response to the penetration of pathogenic microorganisms.
Specific or immune protective factors are a complex set of reactions that maintain the constancy of the internal environment of the body.
According to modern concepts, immunity can be defined "as a way to protect the body from living bodies and substances that bear signs of genetically alien information" (RV Petrov).
The concept of "living bodies and substances bearing signs of genetically alien information" or antigens may include proteins, polysaccharides, their complexes with lipids, and high-polymer preparations of nucleic acids. All living things consist of these substances, therefore, animal cells, elements of tissues and organs, biological fluids (blood, blood serum), microorganisms (bacteria, protozoa, fungi, viruses), exo- and endotoxins of bacteria, helminths, cancer cells and etc.
The immunological function is performed by a specialized system of cells of tissues and organs. This is the same independent system as, for example, the digestive or cardiovascular system. The immune system is a collection of all lymphoid organs and cells of the body.
The immune system consists of central and peripheral organs. The central organs include the thymus (thymus or thymus gland), the pouch of Fabricius in birds, the bone marrow, and possibly Peyer's patches.
The peripheral lymphoid organs include lymph nodes, spleen, appendix, tonsils, and blood.
The central figure of the immune system is the lymphocyte, it is also called the immunocompetent cell.
In humans, the immune system consists of two parts that cooperate with each other: the T-system and the B-system. The T-system carries out a cell-type immune response with the accumulation of sensitized lymphocytes. The B-system is responsible for the production of antibodies, i.e. for a humorous response. In mammals and humans, no organ has been found that would be a functional analogue of the bag of Fabricius in birds.
It is assumed that this role is performed by the aggregate of Peyer's patches of the small intestine. If the assumption that Peyer's patches are analogous to the bag of Fabricius is not confirmed, then these lymphoid formations will have to be attributed to peripheral lymphoid organs.
It is possible that in mammals there is no analogue of the Fabricius bag at all, and this role is performed by the bone marrow, which supplies stem cells for all hematopoietic lineages. Stem cells leave the bone marrow into the bloodstream, enter the thymus and other lymphoid organs, where they differentiate.
Cells of the immune system (immunocytes) can be divided into three groups:
1) Immunocompetent cells capable of a specific response to the action of foreign antigens. This property is possessed exclusively by lymphocytes, which initially possess receptors for any antigen.
2) Antigen-presenting cells (APCs) are capable of differentiating self and foreign antigens and presenting the latter to immunocompetent cells.
3) Cells of antigen-nonspecific protection, which have the ability to distinguish their own antigens from foreign ones (primarily from microorganisms) and destroy foreign antigens using phagocytosis or cytotoxic effects.
1. Immunocompetent cells
Lymphocytes. The precursor of lymphocytes, as well as other cells of the immune system, is the pluripotent stem cell of the bone marrow. During the differentiation of stem cells, two main groups of lymphocytes are formed: T- and B-lymphocytes.
Morphologically, a lymphocyte is a spherical cell with a large nucleus and a narrow layer of basophilic cytoplasm. In the process of differentiation, large, medium and small lymphocytes are formed. The most mature small lymphocytes capable of amoeboid movements predominate in the lymph and peripheral blood. They constantly recirculate in the bloodstream, accumulate in lymphoid tissues, where they participate in immunological reactions.
T- and B-lymphocytes are not differentiated using light microscopy, but are clearly distinguished from each other in surface structures and functional activity. B-lymphocytes carry out a humoral immune response, T-lymphocytes - a cellular one, and also participate in the regulation of both forms of the immune response.
T-lymphocytes mature and differentiate in the thymus. They make up about 80% of all blood lymphocytes, lymph nodes, are found in all tissues of the body.
All T-lymphocytes have surface antigens CD2 and CD3. CD2 adhesion molecules cause the contact of T-lymphocytes with other cells. CD3 molecules are part of the lymphocyte receptors for antigens. There are several hundred of these molecules on the surface of each T-lymphocyte.
T-lymphocytes maturing in the thymus differentiate into two populations, the markers of which are the surface antigens CD4 and CD8.
CD4 make up more than half of all blood lymphocytes, they have the ability to stimulate other cells of the immune system (hence their name - T-helpers - from the English. Help - help).
The immunological functions of CD4+ lymphocytes begin with the presentation of an antigen by antigen-presenting cells (APCs). The receptors of CD4+ cells perceive the antigen only if the cell's own antigen (antigen of the major tissue compatibility complex of the second class) is simultaneously on the surface of the APC. This “double recognition” serves as an additional guarantee against the occurrence of an autoimmune process.
Tx after exposure to the antigen proliferate into two subpopulations: Tx1 and Tx2.
Th1s are mainly involved in cellular immune responses and inflammation. Th2 contribute to the formation of humoral immunity. During the proliferation of Th1 and Th2, some of them turn into immunological memory cells.
CD8+ lymphocytes are the main type of cells with cytotoxic activity. They make up 22 - 24% of all blood lymphocytes; their ratio with CD4+ cells is 1:1.9 – 1:2.4. The antigen-recognizing receptors of CD8+ lymphocytes perceive the antigen from the presenting cell in combination with the MHC class I antigen. MHC antigens of the second class are present only on the APC, and antigens of the first class on almost all cells, CD8+-lymphocytes can interact with any cells of the body. Since the main function of CD8+ cells is cytotoxicity, they play a leading role in antiviral, antitumor, and transplantation immunity.
CD8+ lymphocytes can play the role of suppressor cells, but recently it has been found that many types of cells can suppress the activity of immune system cells, so CD8+ cells are no longer called suppressors.
The cytotoxic effect of a CD8+ lymphocyte begins with the establishment of contact with the “target” cell and the entry of cytolysin proteins (perforins) into the cell membrane. As a result, holes with a diameter of 5–16 nm appear in the membrane of the “target” cell, through which enzymes (granzymes) penetrate. Granzymes and other lymphocyte enzymes inflict a lethal blow on the “target” cell, which leads to cell death due to a sharp rise in the intracellular Ca2+ level, activation of endonucleases, and destruction of cell DNA. The lymphocyte then retains the ability to attack other “target” cells.
Natural killers (NKs) are close to cytotoxic lymphocytes in their origin and functional activity, but they do not enter the thymus and are not subjected to differentiation and selection, do not participate in specific reactions of acquired immunity.
B-lymphocytes make up 10-15% of blood lymphocytes, 20-25% of lymph node cells. They provide the formation of antibodies and are involved in the presentation of the antigen to T-lymphocytes.
