Innate immunity. What is it like: innate immunity

Acquired immunity( specific immunity) is the second phase of the protective reaction of our body. It is formed throughout a person’s life and is not transmitted to subsequent generations. Acquired immunity appeared during the evolution of lower vertebrates. It provides a more intense immune response and immunological memory, thanks to which each foreign microorganism is “remembered” by its unique antigens. Acquired immunity occurs due to adaptation immune system to foreign elements that enter the body. The formation of such immunity occurs, as a rule, during various infectious diseases or poisoning. However, not all diseases leave behind stable immunity. For example, after suffering from gonorrhea, the immunity is very short-lived and weak, for this reason the disease may reappear some time after the next contact with the infection. And some diseases, for example, chicken pox, leave behind a stable immunity, which makes repeated similar diseases impossible throughout life. The duration of immunity is determined by the immunogenicity of the microbe (the ability to cause an immune response). The more microorganisms the immune system encounters, the more large quantity various antibodies have been developed by the immune system to fight various diseases, the stronger a person’s acquired immunity. This is why children raised in sterile conditions get sick more often, although this seems illogical at first glance.

How does specific immunity work?

In order to repel a threat, the immune system must first recognize the intruder, then create an effective weapon against him, and, finally, store information about this intruder in memory in order to subsequently quickly and adequately respond to his repeated invasion. AND innate and acquired immunity, depend on the ability of the immune system to distinguish its own molecules from foreign ones, these two types of immunity overlap and largely complement each other. In immunology, self-molecules are understood as those components of the body that the human immune system can distinguish from foreign ones. Foreign molecules are molecules that are recognized by the immune system as foreign. During a nonspecific (innate) immune response, some microbes are destroyed and their parts are exposed on the surface of cells (for example, macrophages). In the second phase of the immune response, cells of the immune system (lymphocytes) recognize parts of microbes exposed on the membrane of other cells and launch a specific immune response as such. The specific (acquired) immune response can be of two types: cellular and humoral.

differences between innate and acquired immunity

Here are the main differences between innate and acquired immunity.
Human innate immunity:
The secondary response in terms of strength and duration of action is absolutely the same as in the primary response to the entry of an antigen into the body; the antigen is not remembered.
Acquired immunity person:
the secondary response develops faster and stronger than the primary one and has immunological memory, that is, the antigen is remembered.

The system and “warriors” of acquired immunity

The optimal functioning of the acquired immune system is determined by four key points:
1) functioning of the thymus and maturation of T-lymphocytes;
2) formation of antibodies;
3) synthesis of cytokines;
4) transfer factor.
The role of the thymus. The system of training immune cells can be compared to the education system, which has several stages: preschool education, primary and secondary school education, and higher education. If you follow this comparison, in the thymus immune cells receive preschool and primary school education. Because these lymphocytes mature in the thymus, they are called T lymphocytes. T lymphocytes include helper T cells, suppressor T cells, and cytotoxic T lymphocytes. The intensity of immune cell learning processes in the thymus is relatively low in childhood and gradually increases towards the onset of puberty. After puberty, the thymus begins to decrease in size and gradually loses its immunological activity throughout the rest of life. The process of loss of thymus function can be compared to a decrease in efficiency school education. A decrease in the number of prepared T lymphocytes due to aging of the thymus is considered one of the reasons for the development immunodeficiency states in the elderly.
Antibodies- these are protein molecules that are synthesized by B lymphocytes and are the main striking force of the immune system. Antibodies combine with antigens that are present on foreign cells. Antibodies have special form, corresponding to the shape of each antigen. By combining with the corresponding antigens, antibodies neutralize foreign elements. Antibodies also have another name - immunoglobulins. Most important classes antibodies are immunoglobulins A (IgA), IgG, IgE, IgM. Each class of immunoglobulins performs its own special function in the immune system.
Macrophages ("big eaters") are large immune cells that capture and then piece by piece destroy foreign, dead or damaged cells. In the event that the “engulfed” cell is infected or malignant, macrophages leave intact a number of its foreign components, which are then used as antigens to stimulate the formation of specific antibodies. Thus, macrophages act as antigen-presenting cells. It means that macrophages they specifically isolate antigens from the structure of a foreign cell in a form in which these antibodies can be easily recognized by T lymphocytes. After this, specific immune responses are triggered, as a result of which foreign or cancer cells are selectively destroyed. Memory cells (T- and B-cells) perform the function of storing immunological information that the body receives throughout life. It is precisely thanks to the preservation of information about the initial contact with a foreign cell that the immune response upon its repeated penetration is usually so effective that we do not even notice the fact reinfection.
Cytokines. In addition to the production of special cells, the immune system synthesizes a number of signaling molecules called cytokines. Cytokines play a very important role at all stages of the immune response. Some cytokines act as mediators of innate immune reactions, others control reactions specific immunity. Transfer factor is one of the most important cytokines.

Unique molecules of the immune system

These unique transfer factor molecules are large quantities are in the blood egg yolks, bovine colostrum. The American company 4life, having become interested in the possibilities of transfer factors and having conducted numerous studies in this area, began production of drugs called Transfer Factor. This drug is made from colostrum concentrate and chicken yolks. The fact is that it is the colostrum of all vertebrates that contains maximum amount unique molecules - transfer factors. Transfer factor is completely safe, both in quality prophylactic and as an adjunct to treatment. Transfer Factor is the best immunomodulator for children and is optimal for older people. Strengthening the immune system is very important question, which is best left to the best of the best. Immunomodulator Transfer Factor can be ordered on this website. You can also find many other interesting information on other pages of our site.

Good afternoon Let's continue the conversation about the uniqueness of our body.Its ability to biological processes and mechanisms is capable of reliably protecting itself from pathogenic bacteria.And the two main subsystems, innate and acquired immunity, in their symbiosis, are able to find harmful toxins, microbes and dead cells and successfully remove them, sterilizing our body.

Imagine a huge complex complex capable of self-learning, self-regulation, and self-reproduction. This is our defense system. From the very beginning of her life, she has been serving us constantly, without ceasing her work. Providing us with an individual biological program, which has the task of rejecting everything foreign, in any form of aggression and concentration.

If we talk about innate immunity at the level of evolution, it is quite ancient and focused on human physiology, factors and barriers outside. So our skin, secretory functions in the form of saliva, urine and others liquid discharge respond to virus attacks.

This list may include coughing, sneezing, vomiting, diarrhea, elevated temperature, hormonal background. These manifestations are nothing more than our body’s reaction to “strangers”. Immune cells Having not yet understood or recognized the foreignness of the invasion, they begin to actively react and destroy everyone who has encroached on their “native territory.” Cells are the first to enter the battle and begin to destroy various toxins, fungi, poisonous substances and viruses.

Any infection is regarded as an unambiguous and one-sided evil. But it’s worth saying what exactly infectious lesion can provide immunity useful action, no matter how strange it may sound.

It is at such moments that the complete mobilization of everyone occurs. protective forces the body and recognition of the aggressor begins. This serves as a kind of training and over time the body is instantly able to recognize the origin of more dangerous pathogenic microbes and sticks.

Innate immunity is a nonspecific defense system; at the first reaction in the form of inflammation, symptoms appear in the form of swelling and redness. This indicates an immediate flow of blood to the affected area, involvement begins blood cells in the process occurring in tissues.

Let's not talk about complex internal reactions in which leukocytes participate. Suffice it to say that redness from an insect bite or burn is just evidence of the work of the innate protective background.

Factors of two subsystems

The factors of innate and acquired immunity are very interconnected. They have common unicellular organisms, which are represented in the blood by white bodies (leukocytes). Phagocytes are the embodiment of innate defense. This includes eosinophils, mast cells, and natural killer cells.

Cells innate immunity, with the name dendritic, are called upon to come into contact with the environment from the outside, they are in skin, nasal cavity, pulmonary, as well as stomach and intestines. They have many processes, but they should not be confused with nerves.

This type of cell is a link between innate and acquired ways of fighting. They act through T cell antigen, which is the basic type of acquired immunity.

Many young and inexperienced mothers worry about early diseases children, in particular chicken pox. Is it possible to protect a child from infectious disease, and what guarantees can there be for this?

Only newborns can have innate immunity to chickenpox. In order not to provoke the disease in the future, it is necessary to support the fragile body with breastfeeding.

The supply of immunity that the baby received from the mother at birth is insufficient. With long-term and constant breastfeeding, the child receives required amount antibodies, which means it may be more protected from the virus.

Experts say that even if you create a child favorable conditions, innate protection can only be temporary.

Adults suffer from chickenpox much harder, and the picture of the disease is very unpleasant. If a person did not have this disease in childhood, he has every reason to be afraid of contracting a disease such as shingles. These are rashes on the skin in the intercostal space, accompanied by high fever.

Acquired immunity

This is a type that appeared as a result of evolutionary development. Acquired immunity, created during life, is more effective and has a memory that is able to identify a foreign microbe by the uniqueness of its antigens.

Cell receptors recognize pathogens of the acquired type of defense on cellular level, next to cells, in tissue structures and blood plasma. The main ones for this type of protection are B - cells and T - cells. They are born in the stem cell “productions” of the bone marrow, thymus, and are the basis of protective properties.

A mother's transfer of immunity to her child is an example of acquired passive immunity. This occurs during gestation, as well as during lactation. In the womb, this occurs in the third month of pregnancy through the placenta. While the newborn is not able to synthesize its own antibodies, it is supported by maternal inheritance.

Interestingly, acquired passive immunity can be transferred from person to person through the transfer of activated T lymphocytes. It's pretty a rare event, since people must have histocompatibility, that is, a match. But such donors are extremely rare to find. This can only happen through a bone marrow stem cell transplant.

Active immunity can appear after vaccination or in case of past illness. If the functions of innate immunity successfully cope with the disease, the acquired one calmly waits in the wings. Usually the command to attack is heat, weakness.

Remember, during a cold, when the mercury on the thermometer freezes at 37.5, we, as a rule, wait and give the body time to cope with the disease on its own. But as soon as the mercury column rises higher, measures should be taken. Helping the immune system can be used folk remedies or hot drink with lemon.

If you make a comparison between these types of subsystems, then it should be filled with clear content. This table clearly shows the differences.

Comparative characteristics of innate and adaptive immunity

Innate immunity

• A reaction of nonspecific properties.
• Maximum and instant reaction in a collision.
• Cellular and humoral links work.
• Has no immunological memory.
• All biological species have it.

Acquired immunity

• The reaction has a specific property and is tied to a specific antigen.
• There is a latent period between the infection attack and the response.
• The presence of humoral and cellular links.
• Has memory for certain types of antigens.
• Only a few creatures have it.

Only with a complete set, having congenital and acquired ways of combating infectious viruses, can a person cope with any disease. To do this, you need to remember the most important thing - to love yourself and your unique organism, be active and healthy image life and have a positive life position!

Immunity– this is immunity to genetically foreign agents (antigens), which include cells and substances of various origins, both coming from outside and those formed inside the body.

Antigens also include microbes that cause infectious diseases. Therefore, immunity can be considered as immunity to infectious diseases (immunity also includes immunity, for example, to transplanted organs and tissues).

Hereditary ( species), innate immunity is an immunity that is inherited, resulting in certain type(animals or humans) immune to microbes, causing disease in another species. This immunity is nonspecific (not directed at a specific type of microbe) and can be absolute or relative. The absolute does not change and is not lost, but the relative is lost when exposed to unfavorable factors.

Acquired immunity It is not inherited, but acquired by each organism during its lifetime. For example, after suffering from a disease (measles), a person becomes resistant to this disease (gains immunity to measles). A person can get sick with other diseases, i.e. acquired immunity is specific (directed towards a specific type of microbe).

Acquired immunity can be active and passive.

Active immunity is developed when an antigen acts on the body. As a result, the body becomes able to independently produce specific antibodies or cells against this antigen. Antibodies can persist in the body for a long time, sometimes throughout life (for example, after measles).

Active immunity can be natural or artificial.

Natural active immunity is developed after exposure to infectious disease. (post-infectious).

Artificial active immunity is developed in response to the artificial introduction of microbial antigens (vaccines). (post-vaccination)

Passive immunity occurs in the body when ready-made antibodies or lymphocytes enter it (they are produced by another organism). Such immunity does not last long (15-20 days), because “foreign” antibodies are destroyed and excreted from the body.

Passive immunity can also be natural or artificial.

Natural passive immunity occurs when antibodies are transferred from mother to fetus through the placenta (placental).

Artificial passive immunity occurs after administration medicinal serums (medicines containing ready-made antibodies). This type of immunity is also called post-serum immunity.

Nonspecific factors of the body's defense. Cellular and humoral immunobiological factors and their characteristics. Functions of phagocytes and stages of phagocytosis. Completed and incomplete phagocytosis.

Of great importance in protecting the body from genetically foreign agents are nonspecific defense mechanisms or nonspecific mechanisms of resistance (resistance).

They can be divided into 3 groups of factors:

1) mechanical factors (skin, mucous membranes);

2) physical and chemical factors (enzymes gastrointestinal tract, pH of the environment);

3) immunobiological factors:

Cellular (phagocytosis with the participation of cells - phagocytes);

Humoral (blood protective substances: normal antibodies, complement, interferon, b-lysines, fibronectin, properdin, etc.).

Skin and mucous membranes are mechanical barriers that microbes cannot overcome. This is explained by the desquamation of the epidermis of the skin, the acidic reaction of sweat, the formation of lysozyme by the mucous membranes of the intestines, respiratory and genitourinary tracts - an enzyme that destroys the cell wall of bacteria and causes their death.

Phagocyto h is the absorption and digestion of antigenic substances, including microbes, by special blood cells (leukocytes) and some tissues called phagocytes. Phagocytes include microphages (neutrophils, basophils, eosinophils) and macrophages (blood monocytes and tissue macrophages). Phagocytosis was first described by the Russian scientist I.I. Mechnikov.

Phagocytosis can be complete or incomplete. Completed phagocytosis ends with complete digestion of the microbe. With incomplete phagocytosis, microbes are absorbed by phagocytes, but are not digested and can even multiply inside the phagocyte.

In the process of phagocytosis, several main stages:
1 - The rapprochement of the phagocyte with the object of phagocytosis.
2 - Recognition by the phagocyte of the object of absorption and adhesion to it.
3 - Absorption of an object by a phagocyte with the formation of a phagolysosome.
4 - Destruction of the object of phagocytosis.

Normal antibodies– these are antibodies that are constantly present in the blood and are not produced in response to the introduction of an antigen. They can react with different microbes. Such antibodies are present in the blood of people who have not been sick and have not been immunized.

Complement- This is a system of blood proteins that are able to bind to the antigen-antibody complex and destroy the antigen (microbial cell). The destruction of a microbial cell is lysis. If there are no antigen microbes in the body, then complement is in an inactive (scattered) state.

Interferons are blood proteins that have antiviral, antitumor and immunomodulatory effects. Their action is not associated with a direct effect on viruses and cells. They act inside the cell and, through the genome, inhibit virus reproduction or cell proliferation.

Arreactivity body cells also have great importance in antiviral immunity and is explained by the absence of receptors on the surface of cells in this type of organism that viruses could contact.

Natural killer cells (NK cells)– these are killer cells that destroy (“kill”) tumor cells and cells infected with viruses. This is a special population of lymphocyte-like cells - large granule-containing lymphocytes.

Factors nonspecific protection– more ancient protective factors that are inherited.

There are also types of immunity such as

Humoral – explained by the presence of protective substances (including antibodies) in the blood, lymph and other body fluids (“humors” – liquid);

Cellular - explained by the “work” of special cells ( immunocompetent cells);

Cellular-humoral – explained both by the action of antibodies and the “work” of cells;

Antimicrobial – directed against microbes;

Antitoxic – against microbial poisons (toxins);

Antimicrobial immunity can be sterile or non-sterile.

Related information.

MECHANISMS OF INNATE IMMUNITY

Innate immunity is the earliest protective mechanism both in evolutionary terms (it exists in almost all multicellular organisms) and in terms of response time, developing in the first hours and days after the penetration of foreign material into the body. internal environment, i.e. long before the adaptive immune response develops. A significant portion of pathogens are inactivated precisely innate mechanisms immunity, without bringing the process to the development of an immune response with the participation of lymphocytes. And only if the mechanisms of innate immunity cannot cope with pathogens penetrating the body, lymphocytes are included in the “game”. At the same time, the adaptive immune response is impossible without the involvement of innate immune mechanisms. In addition, innate immunity plays a major role in the removal of apoptotic and necrotic cells and the reconstruction of damaged organs. In the mechanisms of the body's innate defense, the most important role is played by primary receptors for pathogens, the complement system, phagocytosis, endogenous antibiotic peptides and protection factors against viruses - interferons. The functions of innate immunity are schematically presented in Fig. 3-1.

RECEPTORS FOR “ALIEN” RECOGNITION

Microorganisms are present on the surface repeating molecular carbohydrate and lipid structures, which in the vast majority of cases are absent on the cells of the host body. Special receptors that recognize this “pattern” on the surface of the pathogen - PRR (Pattern Recognition Receptors–PPP receptor) - allow innate immune cells to detect microbial cells. Depending on the location, soluble and membrane forms of PRR are distinguished.

Circulating (soluble) receptors for pathogens - serum proteins synthesized by the liver: lipopolysaccharide binding protein (LBP - Lipopolysaccharide Binding Protein), complement system component C1q and acute phase proteins MBL and C-reactive protein(SRB). They directly bind microbial products in body fluids and provide the possibility of their absorption by phagocytes, i.e. are opsonins. In addition, some of them activate the complement system.

Rice. 3-1. Functions of innate immunity. Legend: PAMP (PathogenAssociated Molecular Patterns)- molecular structures of microorganisms, HSP (Heat Shock Proteins)- proteins heat shock, TLR (Toll-Like Receptors), NLR (NOD-Like Receptors), RLR (RIG-Like Receptors)- cellular receptors

- SRB, binding phosphorylcholine to the cell walls of a number of bacteria and unicellular fungi, opsonizes them and activates the complement system along the classical pathway.

- MBL belongs to the collectin family. Having an affinity for mannose residues exposed on the surface of many microbial cells, MBL triggers the lectin pathway of complement activation.

- Lung surfactant proteins- SP-A And SP-D belong to the same molecular family of collectins as MBL. They are likely to be important in the opsonization (binding of antibodies to the cell wall of a microorganism) of the pulmonary pathogen - a unicellular fungus Pneumocystis carinii.

Membrane receptors. These receptors are located on both the outer and inner membrane structures of cells.

- TLR(Toll-Like Receptor- Toll-like receptor; those. similar to the Drosophila Toll receptor). Some of them directly bind pathogen products (mannose receptors of macrophages, TLRs of dendritic and other cells), others work in conjunction with other receptors: for example, the CD14 molecule on macrophages binds bacterial lipopolysaccharide (LPS) complexes with LBP, and TLR-4 interacts with CD14 and transmits the corresponding signal into the cell. A total of 13 have been described in mammals various options TLR (humans have only 10 so far).

Cytoplasmic receptors:

- NOD receptors(NOD1 and NOD2) are located in the cytosol and consist of three domains: the N-terminal CARD domain, the central NOD domain (NOD - Nucleotide Oligomerization Domain- nucleotide oligomerization domain) and the C-terminal LRR domain. The difference between these receptors is the number of CARD domains. The NOD1 and NOD2 receptors recognize muramyl peptides - substances formed after the enzymatic hydrolysis of peptidoglycan, which is part of cell wall all bacteria. NOD1 recognizes mesodiaminopimelic acid-terminated muramyl peptides (meso-DAPs), which are produced only from peptidoglycan of Gram-negative bacteria. NOD2 recognizes muramyl dipeptides (muramyl dipeptide and glycosylated muramyl dipeptide) with terminal D-isoglutamine or D-glutamic acid, resulting from peptidoglycan hydrolysis of both Gram-positive and Gram-negative bacteria. In addition, NOD2 has an affinity for L-lysine-terminated muramyl peptides, which are found only in Gram-positive bacteria.

- RIG-similarreceptors(RLR, RIG-Like Receptors): RIG-I (Retinoic acid-Inducible Gene I), MDA5 (Melanoma Differentiation-associated Antigen 5) and LGP2 (Laboratory of Genetics and Physiology 2).

All three receptors encoded by these genes have similar chemical structure and are localized in the cytosol. The RIG-I and MDA5 receptors recognize viral RNA. The role of the LGP2 protein is still unclear; perhaps it acts as a helicase, binding to double-stranded viral RNA, modifies it, which facilitates subsequent recognition using RIG-I. RIG-I recognizes single-stranded RNA with 5-triphosphate, as well as relatively short (<2000 пар оснований) двуспиральные РНК. MDA5 различает длинные (>2000 base pairs) double-stranded RNA. There are no such structures in the cytoplasm of a eukaryotic cell. The contribution of RIG-I and MDA5 to the recognition of specific viruses depends on whether these microorganisms produce the appropriate forms of RNA.

CONDUCTING SIGNALS FROM TOLL-LIKE RECEPTORS

All TLRs use the same circuitry to transmit the activation signal to the nucleus (Figure 3-2). After binding to a ligand, the receptor attracts one or more adapters (MyD88, TIRAP, TRAM, TRIF), which ensure signal transmission from the receptor to the serine-threonine kinase cascade. The latter cause activation of NF-kB transcription factors (Nuclear Factor of k-chain B-lymphocytes), AP-1 (Activator Protein 1), IRF3, IRF5 and IRF7 (Interferon Regulatory Factor), which translocate into the nucleus and induce the expression of target genes.

All adapters contain a TIR domain and bind to the TIR domains of TOLL-like receptors (Toll/Interleukin-1 Receptor, as well as the receptor for IL-1) through homophilic interaction. All known TOLL-like receptors, with the exception of TLR3, transmit signals through the MyD88 adapter (MyD88-dependent pathway). The binding of MyD88 to TLR1/2/6 and TLR4 occurs through the additional adapter TIRAP, which is not required in the case of TLR5, TLR7 and TLR9. The MyD88 adapter is not involved in signal transmission from TLR3; TRIF (MyD88-independent pathway) is used instead. TLR4 uses both MyD88-dependent and MyD88-independent signal transduction pathways. However, the binding of TLR4 to TRIF occurs through the additional adapter TRAM.

Rice. 3-2. Signaling pathways from Toll-like receptors (TLRs). TLR3, TLR7, TLR9 indicated in the figure are intracellular endosomal receptors; TLR4 and TLR5 are monomeric receptors embedded in the cytoplasmic membrane. Transmembrane dimers: TLR2 with TLR1 or TLR2 with TLR6. The type of ligand recognized by dimers depends on their composition

MyD88-dependent pathway. The MyD88 adapter consists of an N-terminal DD domain (Death Domain- death domain) and the C-terminal TIR domain associated with the receptor via homophilic TIR-TIR interaction. MyD88 recruits IRAK-4 kinases (Interleukin-1 Receptor-Associated Kinase-4) and IRAK-1 through interaction with their analogous DD domains. This is accompanied by their sequential phosphorylation and activation. IRAK-4 and IRAK-1 then dissociate from the receptor and bind to the adapter TRAF6, which in turn recruits the TAK1 kinase and ubiquitin ligase complex (not shown in Figure 3-2), resulting in TAK1 activation. TAK1 activates two groups of targets:

IκB kinase (IKK), consisting of the subunits IKKα, IKKβ and IKKγ. As a result, the transcription factor NF-kB is released from the IκB protein that inhibits it and is translocated into the cell nucleus;

A cascade of mitogen-activated protein kinases (MAP kinases) that promotes the activation of AP-1 group transcription factors. The composition of AP-1 varies and depends on the type of activating signal. Its main forms are c-Jun homodimers or c-Jun and c-Fos heterodimers.

The result of activation of both cascades is the induction of the expression of antimicrobial factors and inflammatory mediators, including tumor necrosis factor alpha TNFa (TNFa), which, acting on cells in an autocrine manner, induces the expression of additional genes. In addition, AP-1 initiates the transcription of genes responsible for proliferation, differentiation and regulation of apoptosis.

MyD88-independent pathway. Signal transmission occurs through the TRIF or TRIF:TRAM adapter and leads to the activation of TBK1 kinase, which in turn activates the transcription factor IRF3. The latter induces the expression of type I interferons, which, like TNF-α in the MyDSS-dependent pathway, affect cells autocrinely and activate the expression of additional genes (interferon response genes). Activation of various signaling pathways upon TLR stimulation likely directs the innate immune system to fight a particular type of infection.

Comparative characteristics of innate and adaptive mechanisms of resistance are given in Table. 3-1.

There are subpopulations of lymphocytes with properties “intermediate” between those of non-clonotypic innate immune mechanisms and clonotypic lymphocytes with a wide variety of antigen receptors. They do not proliferate after antigen binding (i.e., clonal expansion does not occur), but the production of effector molecules is immediately induced in them. The response is not very specific and occurs faster than the “true lymphocytic” one; immune memory is not formed. These lymphocytes include:

Intraepithelial γδT lymphocytes with rearranged genes encoding TCRs of limited diversity bind ligands such as heat shock proteins, atypical nucleotides, phospholipids, MHC-IB;

B1 lymphocytes of the abdominal and pleural cavities have rearranged genes encoding BCRs of limited diversity that exhibit broad cross-reactivity with bacterial antigens.

NATURAL KILLERS

A special subpopulation of lymphocytes is natural killer cells (NK cells, natural killer cells). They differentiate from a common lymphoid progenitor cell and in vitro capable of spontaneously, i.e. without prior immunization, kill some tumors, as well as infected with viruses cells. NK cells are large granular lymphocytes that do not express lineage markers of T and B cells (CD3, CD19). In the circulating blood, normal killer cells make up about 15% of all mononuclear cells, and in tissues they are localized in the liver (the majority), the red pulp of the spleen, and mucous membranes (especially the reproductive organs).

Most NK cells contain azurophilic granules in the cytoplasm, where the cytotoxic proteins perforin, granzymes and granulysin are deposited.

The main functions of NK cells are the recognition and elimination of cells infected with microorganisms, altered as a result of malignant growth, or opsonized by IgG antibodies, as well as the synthesis of cytokines IFN, TNFa, GM-CSF, IL-8, IL-5. In vitro when cultured with IL-2, NK cells acquire a high level of cytolytic activity towards wide range targets, turning into so-called LAK cells.

General characteristics of NK cells are presented in Fig. 3-3. The main markers of NK cells are CD56 and CD16 (FcγRIII) molecules. CD16 is the receptor for the Fc portion of IgG. NK cells have receptors for IL-15, the growth factor of NK cells, as well as IL-21, a cytokine that enhances their activation and cytolytic activity. Adhesion molecules play an important role, ensuring contact with other cells and the intercellular matrix: VLA-5 promotes adhesion to fibronectin; CD11a/CD18 and CD11b/CD18 ensure attachment to endothelial molecules ICAM-1 and ICAM-2, respectively; VLA-4 - to the endothelial molecule VCAM-I; CD31, a homophilic interaction molecule, is responsible for diapedesis (exit through vascular wall into the surrounding tissue) NK cells through the epithelium; CD2, the sheep red blood cell receptor, is an adhesion molecule that

Rice. 3-3. General characteristics of NK cells. IL15R and IL21R are receptors for IL-15 and IL-21, respectively

interacts with LFA-3 (CD58) and initiates the interaction of NK cells with other lymphocytes. In addition to CD2, on NK cells person Some other T-lymphocyte markers are also detected, in particular CD7 and the CD8a homodimer, but not CD3 and TCR, which distinguishes them from NKT lymphocytes.

In terms of their effector functions, NK cells are close to T lymphocytes: they exhibit cytotoxic activity against target cells using the same perforin-granzyme mechanism as CTLs (see Fig. 1-4 and Fig. 6-4), and produce cytokines - IFNγ, TNF, GM-CSF, IL-5, IL-8.

The difference between natural killer cells and T lymphocytes is that they lack a TCR and recognize the antigen-

MHC in a different (not entirely clear) way. NK cells do not form immune memory cells.

On NK cells person there are receptors belonging to the KIR family (Killer-cell Immunoglobulin-like Receptors), capable of binding MHC-I molecules of their own cells. However, these receptors do not activate, but rather inhibit, the killer function of normal killer cells. In addition, NK cells have immunoreceptors such as FcyR and express the CD8 molecule, which has an affinity for

At the DNA level, KIR genes are not rearranged, but at the level of the primary transcript, alternative splicing occurs, which provides a certain diversity of variants of these receptors in each individual NK cell. Each normal killer cell expresses more than one KIR variant.

H.G. Ljunggren And K. Karre in 1990 they formulated a hypothesis "missing self"(“lack of self”), according to which NK cells recognize and kill cells of their body with reduced or impaired expression of MHC-I molecules. Since subnormal expression of MHC-I occurs in cells during pathological processes, e.g. viral infection, tumor degeneration, NK cells are able to kill virus-infected or degenerated cells of their own body. Hypothesis "missing self" shown schematically in Fig. 3-4.

COMPLEMENT SYSTEM

Complement is a system of serum proteins and several cell membrane proteins that perform 3 important functions: opsonization of microorganisms for their further phagocytosis, initiation of vascular inflammatory reactions and perforation of membranes of bacterial and other cells. Complement components(Table 3-2, 3-3) are designated by the letters of the Latin alphabet C, B and D with the addition of an Arabic numeral (component number) and additional lowercase letters. The components of the classical pathway are designated by the Latin letter “C” and Arabic numerals (C1, C2 ... C9); for complement subcomponents and cleavage products, lowercase Latin letters are added to the corresponding designation (C1q, C3b, etc.). Activated components are marked with a line above the letter, inactivated components with the letter “i” (for example, iC3b).

Rice. 3-4. Hypothesis "missing self" (lack of one’s own). The figure shows three types of interaction between NK cells and targets. There are two types of recognition receptors on NK cells: activating and inhibitory. Inhibitory receptors distinguish MHC-I molecules and inhibit the signal from activating receptors, which, in turn, detect either MHC-I molecules (but with lower affinity than inhibitory receptors) or MHC-like molecules: a - the target cell does not express activation ligands, and lysis does not occur; b - the target cell expresses activation ligands, but does not express MHC-I. Such a cell undergoes lysis; c - target cells contain both MHC-I molecules and activation ligands. The outcome of the interaction depends on the balance of signals coming from activating and inhibitory NK cell receptors

Complement activation(Fig. 3-5). Normally, when the internal environment of the body is “sterile” and pathological decay of its own tissues does not occur, the level of activity of the complement system is low. When microbial products appear in the internal environment, the complement system is activated. It can occur through three pathways: alternative, classical and lectin.

- Alternative activation path. It is initiated directly by the surface molecules of microbial cells [factors of the alternative pathway are designated by letters: P (properdin), B and D].

Rice. 3-5. Activation of the complement system and formation of the membrane attack complex. For explanations, see the text and also the table. 3-2, 3-3. Activated components, according to international agreement, are underlined

◊ Of all the proteins of the complement system, C3 is the most abundant in blood serum - its normal concentration is 1.2 mg/ml. At the same time, there is always a small, but significant level spontaneous cleavage of C3 to form C3a and C3b. Component C3b is opsonin, i.e. it is capable of covalently binding both to the surface molecules of microorganisms and to receptors on phagocytes. In addition, “settled” on the cell surface, C3b binds factor B. This, in turn, becomes a substrate for serum serine protease - factor D, which splits it into fragments Ba and Bb. C3b and Bb form an active complex on the surface of the microorganism, stabilized by properdin (factor P).

◊ The C3b/Bb complex serves as a C3 convertase and significantly increases the level of C3 cleavage compared to spontaneous ones. In addition, after binding to C3, it cleaves C5 into fragments C5a and C5b. Small fragments C5a (the strongest) and C3a are complement anaphylatoxins, i.e. mediators of the inflammatory response. They create conditions for the migration of phagocytes to the site of inflammation and cause degranulation mast cells, contraction of smooth muscles. C5a also causes increased expression on CR1 and CR3 phagocytes.

◊ With C5b, the formation of a “membrane attack complex” begins, causing perforation of the membrane of microorganism cells and their lysis. First, the C5b/C6/C7 complex is formed and inserted into the cell membrane. One of the subunits of the C8 component, C8b, joins the complex and catalyzes the polymerization of 10-16 C9 molecules. This polymer forms a non-collapsing pore in the membrane with a diameter of about 10 nm. As a result, the cells become unable to maintain osmotic balance and lyse.

- Classical and lectin pathways are similar to each other and differ from the alternative mode of activation of C3. The main C3 convertase of the classical and lectin pathways is the C4b/C2a complex, in which C2a has protease activity, and C4b covalently binds to the surface of microbial cells. It is noteworthy that the C2 protein is homologous to factor B, even their genes are located nearby in the MHC-III locus.

◊ When activated via the lectin pathway, one of the acute phase proteins - MBL - interacts with mannose on the surface of microbial cells, and MBL-associated serine protease (MASP - Mannose-binding protein-Associated Serine Protease) catalyzes the activation cleavage of C4 and C2.

◊ The serine protease of the classical pathway is C1s, one of the subunits of the C1qr 2 s 2 complex. It is activated when at least 2 C1q subunits bind to the antigen-antibody complex. Thus, the classical pathway of complement activation links innate and adaptive immunity.

Complement component receptors. There are 5 types of receptors for complement components (CR - Complement Receptor) on various cells of the body.

CR1 is expressed on macrophages, neutrophils and erythrocytes. It binds C3b and C4b and, in the presence of other stimuli for phagocytosis (binding of antigen-antibody complexes through FcyR or when exposed to IFNu, a product of activated T-lymphocytes), has a permissive effect on phagocytes. CR1 of erythrocytes, through C4b and C3b, binds soluble immune complexes and delivers them to macrophages of the spleen and liver, thereby ensuring blood clearance of immune complexes. When this mechanism is disrupted, immune complexes precipitate - primarily in the basement membranes of the vessels of the glomeruli of the kidneys (CR1 is also present on the podocytes of the glomeruli of the kidneys), leading to the development of glomerulonephritis.

CR2 of B lymphocytes binds the degradation products of C3 - C3d and iC3b. This increases the susceptibility of the B lymphocyte to its antigen by 10,000-100,000 times. The same membrane molecule - CR2 - is used as its receptor by the Epstein-Barr virus, the causative agent of infectious mononucleosis.

CR3 and CR4 also bind iC3b, which, like the active form of C3b, serves as an opsonin. If CR3 is already bound to soluble polysaccharides such as beta-glucans, binding of iC3b to CR3 alone is sufficient to stimulate phagocytosis.

C5aR consists of seven domains that penetrate the cell membrane. This structure is characteristic of receptors coupled to G proteins (proteins capable of binding guanine nucleotides, including GTP).

Protecting your own cells. The body's own cells are protected from the destructive effects of active complement thanks to the so-called regulatory proteins of the complement system.

C1 -inhibitor(C1inh) disrupts the bond of C1q to C1r2s2, thereby limiting the time during which C1s catalyzes the activation cleavage of C4 and C2. In addition, C1inh limits the spontaneous activation of C1 in the blood plasma. At genetic defect dinh develops hereditary angioedema. Its pathogenesis consists of chronically increased spontaneous activation of the complement system and excessive accumulation of anaphylactics (C3a and C5a), causing edema. The disease is treated with replacement therapy with the drug dinh.

- C4 -binding protein- C4BP (C4-Binding Protein) binds C4b, preventing the interaction of C4b and C2a.

- DAF(Decay-Accelerating Factor- degradation accelerating factor, CD55) inhibits convertases of the classical and alternative pathways of complement activation, blocking the formation of the membrane attack complex.

- Factor H(soluble) displaces factor B from the complex with C3b.

- Factor I(serum protease) cleaves C3b into C3dg and iC3b, and C4b into C4c and C4d.

- Membrane cofactor protein MCP(Membrane Cofactor Protein, CD46) binds C3b and C4b, making them available to factor I.

- Protectin(CD59). Binds to C5b678 and prevents subsequent binding and polymerization of C9, thereby blocking the formation of the membrane attack complex. With a hereditary defect in protectin or DAF, paroxysmal nocturnal hemoglobinuria develops. In such patients, episodic attacks of intravascular lysis of their own red blood cells by activated complement occur and hemoglobin is excreted by the kidneys.

PHAGOCYTOSIS

Phagocytosis- a special process of absorption by a cell of large macromolecular complexes or corpuscular structures. "Professional" phagocytes in mammals, there are two types of differentiated cells - neutrophils and macrophages, which mature in the bone marrow from HSCs and have a common intermediate progenitor cell. The term “phagocytosis” itself belongs to I.I. Mechnikov, who described the cells involved in phagocytosis (neutrophils and macrophages) and the main stages of the phagocytic process: chemotaxis, absorption, digestion.

Neutrophils make up a significant part of peripheral blood leukocytes - 60-70%, or 2.5-7.5x10 9 cells in 1 liter of blood. Neutrophils are formed in the bone marrow, being the main product of myeloid hematopoiesis. They are leaving Bone marrow at the penultimate stage of development - the rod form, or at the last - the segmented form. A mature neutrophil circulates for 8-10 hours and enters the tissue. The total lifespan of a neutrophil is

2-3 days. Normally, neutrophils do not leave the vessels in peripheral tissues, but they are the first to migrate (i.e., undergo extravasation) to the site of inflammation due to the rapid expression of adhesion molecules - VLA-4 (ligand on the endothelium - VCAM-1) and integrin CD11b/CD18 (ligand on endothelium - ICAM-1). Exclusive markers CD66a and CD66d (carcinoembryonic antigens) were identified on their outer membrane. Figure 3-6 shows the participation of neutrophils in phagocytosis (migration, engulfment, degranulation, intracellular killing, degradation, exocytosis and apoptosis) and the main processes occurring in these cells upon activation (by chemokines, cytokines and microbial substances, in particular PAMPs) - degranulation , education active forms oxygen and synthesis of cytokines and chemokines. Apoptosis of neurophils and their phagocytosis by macrophages can be considered as an important component inflammatory process, since their timely removal prevents the destructive action of their enzymes and various molecules on surrounding cells and tissues.

Rice. 3-6. The main processes occurring in neutrophils (NF) during their activation and phagocytosis

Monocytes and macrophages. Monocytes are an “intermediate form”; in the blood they constitute 5-10% of total number leukocytes. Their purpose is to become resident macrophages in tissues (Fig. 3-7). Macrophages are localized in certain areas of lymphoid tissue: medullary cords of lymph nodes, red and white pulp of the spleen. Monocyte-derived cells are present in almost all non-lymphoid organs: Kupffer cells in the liver, microglia nervous system, alveolar macrophages, Langerhans cells of the skin, osteoclasts, macrophages of the mucous membranes and serous cavities, interstitial tissue of the heart, pancreas, mesangial cells of the kidneys (not shown in the figure). Macrophages help maintain homeostasis by clearing the body of senescent and apoptotic cells and repairing tissue after infection and injury. Macrophages

Rice. 3-7. Heterogeneity of cells derived from monocytes. Tissue macrophages (TMCs) and dendritic cells (DCs) are derived from peripheral blood monocytes (MNs).

mucous membranes play a leading role in protecting the body. To implement this function, they have a set of recognition receptors, oxygen-dependent and oxygen-independent mechanisms for killing microorganisms. Macrophages of the alveolar and intestinal mucosa play a significant role in protecting the body from infection. The former “work” in a relatively opsonin-poor environment, so they express a large number of pattern recognition receptors, including scavenger receptors, mannose receptors, β-glucan-specific receptors, Dectin-1, etc. During a microbial infection, a large number of inflammatory monocytes additionally migrate to the site of microbial penetration , capable of differentiating into different cell lineages depending on the cytokine environment.

Everyone knows that the body has its own defense, a kind of “security service” - immunity. This topic is of interest to many today. Indeed, immunity is very important for human body- the more stable and stronger immunity, those better health. The work of the immune system is clearly coordinated, but with age and under the influence of adverse factors environment she is weakening. This leads to the development of various pathological processes. All mechanisms and properties of the immune system are studied by a special science - immunology.

Immunity is a word from Latin language, which means "liberation". Medicine explains immunity as the body’s ability to protect itself from many foreign agents - viruses, bacteria, helminths, various toxins, atypical (for example, cancer) cells, etc.

The protective function is performed by special antibodies, immunoglobulins. If there are enough antibodies, if they are “strong,” then the disease has no chance of developing.

The immune system is complex protective structure. It is well known that many organs take part in the fight against foreign agents. But there are only two main ones - red bone marrow, in which lymphocytes are born, and thymus(thymus), located in the upper part of the sternum. Immune cells appear in the lymph nodes and mature completely in the spleen. It also destroys old lymphocytes that have already done their job. The external defense of the body is, first of all, the skin, on which various pathogenic bacteria under the influence of special substances contained in sebum. Another barrier is the mucous membranes, impregnated lymphoid tissue and producing special fluids (tears, saliva), which also destroy infectious agents. Sebaceous and sweat glands, villi respiratory tract, eyelashes, etc. Phagocytes (leukocytes) constantly move through the blood and lymph and absorb pathogenic microflora. If there are a lot of leukocytes in the blood, then this is a signal that the disease is developing. When a person good blood circulation, good composition blood, this indicates that the immune system is fine. Immunity is divided into innate and acquired.

What is innate immunity

Already from the name it is clear that a person has innate immunity (also called nonspecific) from birth. Innate immunity is immunity to diseases that are characteristic of only one type of organism. For example, a person has innate immunity to canine distemper and will never get sick from it. And a dog will never get measles or cholera because it has an innate immunity to these diseases. Based on this, innate immunity can be called species immunity, since it is characteristic of a specific type of living organism.

Every person has innate immunity; it is transmitted from parents, i.e. fixed genetically. Therefore, it is often called hereditary immunity. Antibodies, which form the basis of a person's initial defenses when he is born, are transmitted from the mother. That's why it's very important play the right way intrauterine development and natural (breast) feeding of the child - only in this case good innate immunity is formed. The blood flow of a child in the womb is closely related to her circulatory system due to the placental barrier. Due to this barrier, the child receives oxygen, proteins, fats, carbohydrates, vitamins, hormones, etc. from the mother through the blood. necessary substances, including immune system factors. They protect the child. Therefore, when a child is born, he already has some immunity. As soon as the baby starts to feed mother's milk(and with the milk of the biological mother), the intake of these substances into the body continues. They are not destroyed in the stomach because gastric juice baby low acidity. Next, these substances of the immune system enter the intestines, from which they are absorbed into the blood, and then distributed by the blood throughout the body. It is this mechanism that provides innate immunity.

It has been noted that children who are fed mother's milk for the first 6 months practically do not get sick in the first year of life. The same children who were forced to stay artificial feeding from the first days of life, they often get sick both in the first year of life and thereafter. If the formation of natural defenses is disrupted, this can lead to an immunodeficiency state.

Factors of innate immunity

The mechanism of action of innate immunity is a combination of certain factors that create a line of defense for the human body from foreign agents. It consists of several protective barriers:

1. The primary barriers are the skin and mucous membranes; upon penetration of a foreign agent, an inflammatory process develops.
2. Lymph nodes - this defense fights the infectious agent before it enters the blood. If it is weakened, the infection enters the blood.
3. Blood – when an infection enters the blood, special blood elements come into play. If they are unable to contain the infection, then it enters the internal organs.

In addition, innate immunity also has humoral and cellular factors. Humoral factors are divided into specific and nonspecific. Specific include immunoglobulins, and non-specific include liquids that can destroy bacteria (blood serum, lysozyme, secretions different glands). TO cellular factors include those cells of the body that take part in protection against foreign agents - T- and B-lymphocytes, basophils, neutrophils, eosinophils, monocytes.

So, innate immunity has some characteristic features:

• does not change during life, determined genetically;
• inherited from generation to generation;
• is specific, i.e. both formed and fixed for each a separate type in the process of evolution;
• strictly defined antigens are recognized;
• resistance to certain antigens has a certain character;
• innate immunity always turns on at the moment when an antigen is introduced;
• the antigen is independently removed from the body;
• immune memory is not formed.

Acquired immunity

In addition to innate immunity, humans also have so-called acquired immunity.

It is formed throughout life and, unlike innate immunity, is not inherited. Acquired immunity begins to form during the first encounter with an antigen, triggering immune mechanisms, which remember this antigen and produce specific antibodies to this antigen. Thanks to this, the next time the body encounters the same antigen, the immune response occurs much faster and becomes more effective. In this case, the disease does not recur. For example, if a person has had measles, chickenpox or mumps once, then he will not get sick a second time. Unlike innate immunity, acquired immunity:

• not inherited;
• is formed throughout life, while changing the set of genes;
• individual for each person;
• recognizes any antigens;
• resistance to certain antigens is strictly individual;
• when the first contact occurs, immunity is activated, on average, from the 5th day;
• to remove the antigen, the help of the innate immune system is required;
• forms immune memory.

Acquired immunity can be either active or passive.

Active - is formed when a person has suffered from any disease or has been injected specific vaccine with weakened microorganisms or their antigens. As a result, lifelong, long-term or short-term immunity may develop. It depends on the properties of the pathogen. For example, from measles - lifelong, from abdominal type- long-term, and from influenza - short-term immunity. Active acquired immunity cannot be realized in case of immunodeficiency. For active acquired immunity to work, the immune system must be healthy. It is this type of immunity that forms immune memory.

Passive – is formed when ready-made antibodies are introduced into the body (for example, from a person who has been ill) or antibodies are transferred to the newborn with the mother’s colostrum. Acquired passive immunity develops instantly and is formed in conditions of immunodeficiency. However, compared to active immunity, acquired passive immunity has lower efficiency, does not form immune memory and has lower efficiency.

Innate and acquired immunity is a single defense system that must be constantly taken care of and constantly strengthened. Because good immunity- this is a pledge good health. It is necessary to take a comprehensive approach to strengthening the immune system. A person vitally needs a strong and healthy immunity, which will rid the body of invading foreign agents and will not allow various diseases to develop.