Viral envelopes and their antigenic characteristics. Antigens of viruses
To characterize microorganisms, the generic, species, group and type specificity of antigens are distinguished. The most accurate differentiation is carried out using monoclonal antibodies (MAbs) that recognize only one antigenic determinant.
Possessing a complex chemical structure, the bacterial cell presents a whole complex of antigens. Flagella, capsule, cell wall, cytoplasmic membrane, ribosomes and other components of the cytoplasm, toxins, and enzymes have antigenic properties. The main types of bacterial antigens are:
Somatic or O-antigens (in gram-negative bacteria, specificity is determined by deoxysugars of LPS polysaccharides);
Flagellar or H-antigens (protein);
Surface or capsular K antigens.
Protective antigens are isolated that provide protection (protection) against relevant infections, which is used to create vaccines.
Any microorganism (bacteria, fungi, viruses) is a complex of antigens.
By specificity microbial antigens are divided into:
· cross-reacting (heteroantigens) are antigens common to antigens of human tissues and organs. They are present in many microorganisms and are considered an important virulence factor and a trigger for the development of autoimmune processes;
· group-specific - common among microorganisms of the same genus or family;
· species-specific - common to different strains of the same type of microorganisms;
· variant-specific (type-specific) - found in individual strains within a microorganism species. Based on the presence of certain variant-specific antigens, microorganisms within a species are divided into variants based on antigenic structure - serovars.
Based on localization, bacterial antigens are divided into:
cellular (associated with a cell),
extracellular (not associated with a cell).
Among the cellular antigens, the main ones are: somatic - O-antigen (glucido-lipoid-polypeptide complex), flagellar - H-antigen (protein), surface - capsular - K-antigen, Vi-antigen. Extracellular antigens are products secreted by bacteria into the external environment, including antigens of exotoxins, enzymes of aggression and defense, and others.
Antigens of viruses
There are several groups of antigens in the structure of the viral particle:
nuclear (or O moat)
· capsid (or shell)
· supercapsid.
On the surface of some viral particles there are special V-antigens - hemagglutinin and the enzyme neuraminidase.
Viral antigens differ in origin. Part of them - virus-specific. Information about their structure is mapped in nucleic acid virus. Other viral antigens are host cell components(carbohydrates, lipids), they are captured in the outer shell of the virus at its birth by budding.
The antigenic composition of the virion depends on the structure of the viral particle itself. Antigen specificity simply organized viruses are associated with ribo- and deoxyribonucleoproteins. These substances are highly soluble in water and are therefore designated as S-antigens (from the Latin Solution - solution). U complexly organized In viruses, part of the antigen is associated with the nucleocapsid, and the other is localized in the outer shell - the supercapsid. The antigens of many viruses are different high degree variability. This is due to the constant mutation process that the genetic apparatus of the viral particle undergoes. Examples include influenza virus and human immunodeficiency virus.
14. Histocompatibility antigens. N and the cytoplasmic membranes of almost all cells of the macroorganism are found histocompatibility antigens. Most of them belong to the system of the major histocompatibility complex, or MHC (abbreviation for Major histocompatibility complex).
By chemical nature, histocompatibility antigens are glycoproteins tightly bound to the cytoplasmic membrane of cells. Their individual fragments have structural homology with immunoglobulin molecules and therefore belong to a single superfamily.
There are two main classes of MHC molecules. It is conventionally accepted that MHC class I induces predominantly a cellular immune response, and MHC class II induces a humoral response.
MNS I class consists of two non-covalently linked polypeptide chains with different molecular weights: a heavy alpha chain and a light beta chain. The alpha chain has an extracellular region with a domain structure (alpha1, alpha2, alpha3 domains), transmembrane and cytoplasmic.
The beta chain is a beta 2 microglobulin that sticks to the alpha 3 domain after expression of the alpha chain on the cytoplasmic membrane of the cell.
For MNS I class characterized by a high rate of biosynthesis - the process is completed in 6 hours. This complex is expressed on the surface of almost all cells except erythrocytes and villous trophoblast cells. The density of MHC class I reaches 7000 molecules per cell, and they cover about 1% of its surface.
In humans, the MHC is designated as HLA(abbr. from the English. Human Leukocyte Antigen), since it is associated with leukocytes.
Currently, there are more than 200 different HLA class I variants in humans. They are encoded by genes mapped to three main subloci of chromosome 6 and are inherited and expressed independently: HLA-A, HLA-B, HLA-C. Locus A unites more than 60 variants, B-130, and C - about 40.
The main biological role of class I HLA is that they determine biological individuality (“biological passport”) and are “self” markers for immunocompetent cells. Infection of a cell with a virus or mutation changes the structure of HLA class I. The class I MHC molecule containing foreign or modified peptides has a structure atypical for a given organism and is a signal for the activation of T-killer cells (CD8 + - lymphocytes). Cells that differ in class I are destroyed as foreign.
In structure and function MHC class II There are a number of fundamental differences. Firstly, they have a more complex structure. The complex is formed by two non-covalently linked polypeptide chains (alpha chain and beta chain) having a similar domain structure. The alpha chain has one globular region, and the beta chain has two. Both chains, as transmembrane peptides, consist of three sections - extracellular, transmembrane and cytoplasmic. Secondly, the “Björkman gap” in class II MHC is formed simultaneously by both chains. It accommodates a larger oligopeptide (12-25 amino acid residues), and the latter is completely “hidden” inside this gap and in this state is not detected by specific antibodies. Third, MHC class II includes a peptide taken up from the extracellular environment by endocytosis, rather than synthesized by the cell itself. Fourth, MHC class II is expressed on the surface of a limited number of cells: dendritic cells, B lymphocytes, T helper cells, activated macrophages, mast cells, epithelial and endothelial cells. The detection of MHC class II on atypical cells is currently regarded as immunopathology. Biosynthesis of MHC class II occurs in the endoplasmic reticulum, the resulting dimeric complex is then integrated into the cytoplasmic membrane. Before the peptide is included in it, the complex is stabilized by a chaperone (calnexin). MHC class II is expressed on the cell membrane within an hour after endocytosis of the antigen. In humans, the histocompatibility antigen is called HLA class II. According to available data, the human body is characterized by extremely high polymorphism of HLA class II, which is largely determined by the structural features of the beta chain. The complex includes products of three main loci: HLA DR, DQ, DP. At the same time, the DR locus unites about 300 allelic forms, DQ – about 400, and DP – about 500. The biological role of MHC class II is extremely large. In fact, this complex is involved in the induction of the acquired immune response. Fragments of the antigen molecule are expressed on the cytoplasmic membrane of a special group of cells, which is called antigen presenting cells (APCs)). This is an even narrower circle among cells capable of synthesizing MHC class II. The dendritic cell is considered the most active APC, followed by the B lymphocyte and macrophage. The structure of MHC class II with the peptide included in it in complex with co-factor molecules of CD antigens is perceived and analyzed by T helper cells (CD4+ lymphocytes). If a decision is made about the foreignness of a peptide included in the MHC class II, the T-helper begins the synthesis of the corresponding immunocytokines, and the mechanism of a specific immune response is activated. As a result, proliferation and final differentiation of antigen-specific lymphocyte clones and the formation of immune memory are activated. In addition to the histocompatibility antigens described above, class III MHC molecules have been identified. The locus containing the genes encoding them is wedged between class I and class II and separates them. MHC class III includes some components (C2, C4), heat shock proteins, tumor necrosis factors, etc.
There are the following types of bacterial antigens: group-specific (found in different species of the same genus or family); species-specific (found in different representatives of the same species); type-specific (determine serological variants - serovars).
Depending on the location in the bacterial cell, there are:
1) flagellar N-AGs, localized in the flagella of bacteria, its basis is the flagellin protein, which is thermolabile;
2) somatic O-AG is associated with the bacterial cell wall. It is based on LPS; it is used to distinguish serovariants of bacteria of the same species. It is heat-stable, does not collapse during prolonged boiling, and is chemically stable (withstands treatment with formaldehyde and ethanol);
3) capsular K-AGs are located on the surface of the cell wall. Based on sensitivity to heat, there are 3 types of K-AG: A, B, L. The greatest thermal stability is characteristic of type A, type B can withstand heating up to 60 0 C for 1 hour, type L quickly collapses at this temperature. On the surface of the causative agent of typhoid fever and other enterobacteria, which are highly virulent, one can detect a special version of the capsular antigen – Vi-antigen;
4) bacterial protein toxins, enzymes and some other proteins also have antigenic properties.
Virus antigens:
1) supercapsid AGs – superficial shell ones;
2) protein and glycoprotein antigens;
3) capsid - shell;
4) nucleoprotein (heart-shaped) antigens.
9.5. Antibodies and antibody formation: primary and secondary response. Assessment of immune status: main indicators and methods for their determination."
Antibodies - these are gamma globulins produced in response to the introduction of an antigen, capable of specifically binding to the antigen and participating in many immunological reactions. They consist of polypeptide chains: two heavy (H) chains and two light (L) chains. Heavy and light chains are linked together in pairs by disulfide bonds. There is also a disulfide bond between the heavy chains, the so-called “hinge” region, which is responsible for interaction with the first component of complement C1 and its activation along the classical pathway. There are 2 types of light chains (kappa and lambda), and 5 types of heavy chains (alpha, gamma, mu, epsilon and delta). The secondary structure of the polypeptide chains of the Ig molecule has a domain structure. This means that individual sections of the chain are folded into globules (domains). There are C-domains - with a constant structure of the polypeptide chain and V-domains (variable with a variable structure). The light and heavy chain variable domains together form a region that specifically binds to the antigen. This is the antigen-binding center of the Ig molecule, or parotope. Enzymatic hydrolysis of Ig produces three fragments. Two of them are capable of specifically binding to antigen and are called antigen-binding Fab fragments. The third fragment, capable of forming crystals, was named Fc. It is responsible for binding to receptors on the membrane of the cells of the macroorganism. Additional polypeptide chains are found in the structure of Ig molecules. Thus, the polymer molecules IgM and IgA contain a J-peptide, which ensures the conversion of polymer Ig into the secretory form. Secretory Ig molecules, unlike serum ones, have a special S-peptide called the secretory component. It ensures the transfer of the Ig molecule through the epithelial cell into the lumen of the organ and protects it in the secretion of the mucous membranes from enzymatic breakdown. Receptor Ig, which is localized on the cytoplasmic membrane of B lymphocytes, has an additional hydrophobic transmembrane M-peptide.
There are 5 classes of immunoglobulins in humans:
1) immunoglobulin class G is a monomer that includes 4 subclasses (IgG1, IgG2, IgG3, IgG4), which differ from each other in amino acid composition and antigenic properties, has 2 antigen-binding centers. It accounts for 70-80% of all serum Igs. Half-life 21 days. The main properties of IgG include: they play a fundamental role in humoral immunity in infectious diseases; penetrates the placenta and forms anti-infective immunity in newborns; capable of neutralizing bacterial exotoxins, fixing complement, and participating in the precipitation reaction. It is well detected in blood serum at the peak of the primary and secondary immune response. IgG4 is involved in the development of type 1 allergic reaction.
2) immunoglobulin class M- a pentamer that has 10 antigen-binding sites. Half-life 5 days. It accounts for about 5-10% of all serum Igs. It is formed at the beginning of the primary immune response, and is also the first to begin to be synthesized in the body of a newborn - it is determined already at the 20th week of intrauterine development. Properties: does not penetrate the placenta; appears in the fetus and participates in anti-infective protection; capable of agglutinating bacteria, neutralizing viruses, and activating complement; play an important role in eliminating pathogens from the bloodstream and activating phagocytosis; are formed in the early stages of the infectious process; are characterized by high activity in the reactions of agglutination, lysis and binding of endotoxins of gram-negative bacteria.
3) immunoglobulin class A – exists in serum and secretory forms. Serum Ig accounts for 10-15%, monomer, has 2 antigen-binding centers, half-life 6 days. Secretory Ig exists in polymeric form. Contained in milk, colostrum, saliva, lacrimal, bronchial, gastrointestinal secretions, bile, urine; participate in local immunity, prevent the attachment of bacteria to the mucosa, neutralize enterotoxin, activate phagocytosis and complement.
4) immunoglobulin class E- monomers, which account for 0.002%. The bulk of allergic antibodies - reagins - belong to this class. IgE levels increase significantly in people who suffer from allergies and are infected with helminths.
5) immunoglobulin class D – it is a monomer accounting for 0.2%. Plasma cells secreting IgD are localized mainly in the tonsils and adenoid tissue. Participates in the development of local immunity, has antiviral activity, in rare cases activates complement, participates in the differentiation of B cells, contributes to the development of an anti-idiotypic response, and participates in autoimmune processes.
The macroorganism acquires the ability to synthesize AT quite early. Already at the 13th week of the embryonic development period, B-lymphocytes appear that synthesize IgM, and at week 20 this Ig can be detected in the blood serum. The concentration of antibodies reaches a maximum during puberty and remains at high levels throughout the reproductive period. In old age, the antibody content decreases. An increase in the amount of Ig is observed in infectious diseases and autoimmune disorders; a decrease is noted in some tumors and immunodeficiency states. Antibody production in response to an antigenic stimulus has characteristic dynamics. There are latent, logarithmic, stationary and decreasing phases. During the latent phase, antibody production practically does not change and remains at the basal level. During the logarithmic phase, an intensive increase in the number of antigen-specific B lymphocytes is observed and an increase in the antibody titer occurs. In the stationary phase, the number of specific antibodies and the cells that synthesize them reaches a maximum and stabilizes. In the decline phase, a gradual decrease in antibody titers is observed. At initial contact with the antigen, a primary immune response develops. It is characterized by long latent (3-5 days) and logarithmic (7-15 days) phases. The first diagnostically significant antibody titers are recorded on the 10-14th day from the moment of immunization. The stationary phase lasts 15-30 days, and the decline phase lasts 1-6 months. As a result of the primary immune response, numerous clones of antigen-specific B lymphocytes are formed: antibody-producing cells and immunological memory B lymphocytes, and IgG and/or IgA (as well as IgE) accumulate in high titers in the internal environment of the macroorganism. Over time, the antibody response fades. Repeated contact of the immune system with the same antigen leads to the formation secondary immune response. The secondary response is characterized by a shortened latent phase (from several hours to 1-2 days). The logarithmic phase is characterized by more intense dynamics of growth and higher titers of specific antibodies. During a secondary immune response, the body immediately, overwhelmingly, synthesizes IgG. The characteristic dynamics of antibody production is due to the preparedness of the immune system to encounter the antigen again due to the formation of immunological memory.
The phenomenon of intense antibody formation upon repeated contact with an antigen is widely used for practical purposes, for example, in vaccine prophylaxis. To create and maintain immunity at a high protective level, vaccination schemes provide for the primary administration of an antigen to form immunological memory and subsequent revaccinations at various time intervals.
The same phenomenon is used to obtain highly active therapeutic and diagnostic immune sera (hyperimmune). To do this, animals or donors are given multiple injections of antigen preparations according to a special scheme.
Immune status is the structural and functional state of an individual’s immune system, determined by a set of clinical and laboratory immunological indicators.
The immune status is influenced by the following factors: 1) climatic and geographical (temperature, humidity, solar radiation, day length); 2) social (food, living conditions, occupational hazards); 3) environmental (environmental pollution with radioactive substances, use of pesticides in agriculture); 4) the influence of diagnostic and therapeutic procedures, drug therapy; 5) stress.
Immune status can be determined by performing a set of laboratory tests, including assessment of the state of nonspecific resistance factors, humoral (B) and cellular (T) immunity. Assessment of immune status is carried out in the clinic during organ and tissue transplantation, autoimmune diseases, allergies, to monitor the effectiveness of treatment of diseases associated with a disorder of the immune system. Assessment of immune status is most often based on determining the following indicators:
1) general clinical examination (patient complaints, profession, examination);
2) the state of natural resistance factors (determine phagocytosis, complement, interferon status, colonization resistance);
3) humoral immunity (determination of immunoglobulins of class G, M, A, D, E in blood serum);
4) cellular immunity (assessed by the number of T-lymphocytes - rosette formation reaction, determination of the ratio of helpers and suppressors of T4 and T8 lymphocytes, which is normally approximately 2);
5) additional tests (determining the bactericidal properties of blood serum, titrating C3, C4 complement components, determining the content of C-reactive protein in blood serum, determining rheumatoid factors.
Virus antigens:
1) supercapsid antigens - surface shell;
2) protein and glycoprotein antigens;
3) capsid - shell;
4) nucleoprotein (core) antigens.
All viral antigens are T-dependent.
Under specificity of the viral antigen imply its ability to selectively react with antibodies or sensitized lymphocytes that are a response to the introduction of a given antigen.
Virion proteins vary from virus to virus type specificity and variability. Some of them have high variability, others are characterized by conservatism.
26. The main cells of the immune system: antigen-presenting cells (APC), T- and B-lymphocytes, their subpopulations (T-helpers 1, 2 (CD4+); T-killers (CD8+), B1 (CD5+), B2 (CD5-) , B-killers, immunological memory cells, etc.). Receptors (antigen-specific, Fc-, C3-, etc.) and CD markers.
The cells of the immune system include lymphocytes, macrophages and other antigen-presenting cells(A - cells, from the English accessory - auxiliary), as well as the so-called third population of cells(i.e. cells that do not have the main surface markers of T- and B-lymphocytes, A-cells).
According to their functional properties, all immunocompetent cells are divided into effector and regulatory. The interaction of cells in the immune response is carried out with the help of humoral mediators - cytokines. The main cells of the immune system are T and B lymphocytes.
Lymphocytes.
Lymphocytes have common morphological characteristics, but their functions, surface CD (from cluster differenciation) markers, and individual (clonal) origin are different.
Based on the presence of surface CD markers, lymphocytes are divided into functionally different populations and subpopulations, primarily into T-(thymus dependent that have undergone primary differentiation in the thymus) lymphocytes and IN -(bursa-dependent, matured in the bursa of Fabricius in birds or its analogues in mammals) lymphocytes.
T lymphocytes .
T lymphocytes recognize the antigen processed and presented on the surface of antigen-presenting (A) cells. They are responsible for cellular immunity, cell-type immune reactions. Distinct subpopulations help B lymphocytes respond to T-dependent antigens production of antibodies.
During differentiation, T lymphocytes acquire a specific set of membrane CD markers. T cells are divided into subpopulations according to their function and CD marker profile.
There are three main groups of T-lymphocytes: helpers (activators), effectors, regulators.
The first group is assistants ( activators) , which include T-helpers1, T-helpers2, inducers of T-helpers, inducers of T-suppressors.
1. T-helpers1 carry receptors CD4 (as well as T-helper2) and CD44, are responsible for maturation T-cytotoxic lymphocytes (T-killers), activate T-helpers2 and the cytotoxic function of macrophages, secrete IL-2, IL-3 and other cytokines.
2. T-helpers2 have common CD4 and specific CD28 receptors for helpers, ensure proliferation and differentiation of B lymphocytes into antibody-producing (plasma) cells, antibody synthesis, inhibit the function of T helper1, secrete IL-4, IL-5 and IL-6.
3. T-helper inducers carry CD29 and are responsible for the expression of HLA class 2 antigens on macrophages and other A cells.
4. Inducers of T-suppressors carry a CD45 specific receptor, are responsible for the secretion of IL-1 by macrophages, activation of the differentiation of T-suppressor precursors.
The second group is T-effectors.
5. T-cytotoxic lymphocytes (T-killers). They have a specific CD8 receptor and lyse target cells carrying foreign antigens or altered autoantigens (transplant, tumor, virus, etc.). CTLs recognize a foreign epitope of a viral or tumor antigen in complex with an HLA class 1 molecule in the plasma membrane of the target cell.
The third group is T-cells-regulators. Represented by two main subpopulations.
6. T-suppressors are important in the regulation of immunity, providing suppression of the functions of T-helper 1 and 2, B-lymphocytes. They have receptors CD11, CD8. The group is functionally heterogeneous. Their activation occurs as a result of direct stimulation by antigen without significant participation of the major histocompatibility system.
7. T-consupressors. They do not have CD4, CD8, they have a receptor for a special leukine. They help suppress the functions of T-suppressors, develop resistance of T-helpers to the effect of T-suppressors.
B lymphocytes.
There are several subtypes of B lymphocytes. The main function of B cells is effector participation in humoral immune reactions, differentiation as a result of antigenic stimulation into plasma cells that produce antibodies. The formation of B cells in the fetus occurs in the liver, and subsequently in the bone marrow. The process of B cell maturation occurs in two stages - antigen - independent and antigen - dependent.
Antigen-independent phase. In the process of maturation, the B lymphocyte goes through the stage pre-B-lymphocyte- an actively proliferating cell having cytoplasmic H-chains of type C mu (i.e. IgM). Next stage- immature B lymphocyte characterized by the appearance of membrane (receptor) IgM on the surface. The final stage of antigen-independent differentiation is the formation mature B lymphocyte, which can have two membrane receptors with the same antigen specificity (isotype) - IgM and IgG. Mature B lymphocytes leave the bone marrow and populate the spleen, lymph nodes and other accumulations of lymphoid tissue, where their development is delayed until they meet “their” antigen, i.e. before antigen-dependent differentiation occurs.
Antigen-dependent differentiation involves the activation, proliferation, and differentiation of B cells into plasma cells and memory B cells. Activation occurs in various ways, which depends on the properties of antigens and the participation of other cells (macrophages, T-helpers). Most antigens that induce antibody synthesis require the participation of T cells to induce an immune response. thymus-dependent pntigens. Thymus-independent antigens(LPS, high molecular weight synthetic polymers) are able to stimulate the synthesis of antibodies without the help of T lymphocytes.
The B lymphocyte, using its immunoglobulin receptors, recognizes and binds the antigen. Simultaneously with the B cell, the antigen, presented by the macrophage, is recognized by the T helper (T helper 2), which is activated and begins to synthesize growth and differentiation factors. Activated by these factors, the B lymphocyte undergoes a series of divisions and simultaneously differentiates into plasma cells that produce antibodies.
The pathways of B cell activation and cell cooperation in the immune response to various antigens and with the participation of B cell populations with and without the Lyb5 antigen differ. Activation of B lymphocytes can be carried out:
T-dependent antigen with the participation of MHC class 2 T-helper proteins;
T-independent antigen containing mitogenic components;
Polyclonal activator (LPS);
Anti-mu immunoglobulins;
T-independent antigen that does not have a mitogenic component.
Cooperation of cells in the immune response.
In the formation of an immune response, all parts of the immune system are included systems-systems macrophages, T- and B-lymphocytes, complement, interferons and the major histocompatibility system.
Briefly, the following stages can be distinguished.
1. Uptake and processing of antigen by a macrophage.
2. Presentation of the processed antigen by the macrophage using the major histocompatibility system class 2 protein to T helper cells.
3. Antigen recognition by T-helpers and their activation.
4. Antigen recognition and activation of B lymphocytes.
5. Differentiation of B lymphocytes into plasma cells, synthesis of antibodies.
6. Interaction of antibodies with antigen, activation of complement systems and macrophages, interferons.
7. Presentation of foreign antigens to T-killers with the participation of MHC class 1 proteins, destruction of cells infected with foreign antigens by T-killers.
8. Induction of T- and B-cells of immune memory, capable of specifically recognizing the antigen and participating in the secondary immune response (antigen-stimulated lymphocytes).
Antibodies, immunoglobulin classes, structural and functional features. Active centers of immunoglobulins, their function. Partial antibodies, autoantibodies, lysines, opsonins, agglutinins, precipitins, antitoxins, etc.
In response to the introduction of an antigen, the immune system produces antibodies - proteins that can specifically bind to the antigen that caused their formation, and thus participate in immunological reactions. Antibodies to γ-globulins. In the body, γ-globulins are produced by special cells - plasma cells. γ-globulins that carry the functions of antibodies are called immunoglobulins and are designated by the symbol Ig. Therefore, antibodies are immunoglobulins, produced in response to the introduction of an antigen and capable of specifically interacting with the same antigen.
Functions. The primary function is the interaction of their active centers with their complementary antigen determinants. The secondary function is their ability to:
Bind an antigen in order to neutralize it and eliminate it from the body, i.e., take part in the formation of protection against the antigen;
Participate in the recognition of “foreign” antigen;
Ensure cooperation of immunocompetent cells (macrophages, T- and B-lymphocytes);
Participate in various forms of the immune response (phagocytosis, killer function, HNT, HRT, immunological tolerance, immunological memory).
Antibody structure. Immunoglobulin proteins are chemically classified as glycoproteins, as they consist of protein and sugars. Immunoglobulins according to their structure, antigenic and immunobiological properties are divided into five classes: IgM, IgG, IgA, IgE, IgD.
Immunoglobulin class G. Isotype G makes up the bulk of Ig in blood serum. Easily passes through the placental barrier and provides humoral immunity to the newborn in the first 3-4 months of life. It is also capable of being secreted into the secretions of mucous membranes, including into milk by diffusion.
IgG ensures neutralization, opsonization and marking of the antigen, triggers complement-mediated cytolysis and antibody-dependent cell-mediated cytotoxicity.
Immunoglobulin class M. The largest molecule of all Igs.
Synthesized by precursors and mature B lymphocytes. It is formed at the beginning of the primary immune response, and is also the first to begin to be synthesized in the body of a newborn - it is determined already at the 20th week of intrauterine development. IgM ensures neutralization, opsonization and marking of the antigen, triggers complement-mediated cytolysis and antibody-dependent cell-mediated cytotoxicity.
Immunoglobulin class A. Exists in serum and secretory forms. About 60% of all IgA is contained in mucosal secretions.
The secretory form of IgA is the main factor in the specific humoral local immunity of the mucous membranes of the gastrointestinal tract, genitourinary system and respiratory tract. It prevents the adhesion of microbes on epithelial cells and the generalization of infection within the mucous membranes.
Immunoglobulin class E. Also called reagin. The content in blood serum is extremely low - approximately 0.00025 g/l. Does not bind complement. Does not pass through the placental barrier. It has a pronounced cytophilicity - tropism for mast cells and basophils. Participates in the development of immediate type hypersensitivity - type I reaction.
There are complete, or precipitating, antibodies , which, when interacting with an antigen, give visible immunological reactions (agglutination, precipitation, etc.), and incomplete, non-precipitating, or blocking antibodies, which do not give visible reactions when combined with an antigen.
By the nature of their action on microorganisms, antibodies can be antimicrobial, antitoxic, anticellular.Antimicrobial antibodies can glue microbes together - agglutinins, precipitate protein molecules or microbial particles - precipitins, dissolve bacteria - lysines, kill bacteria without noticeably changing their shape - bactericidal antibodies. Antibodies that enhance phagocytosis are called opsonins, or bacteriotropins. There are also virus-neutralizing antibodies and immobilizing antibodies that immobilize spirochetes. Antitoxic antibodies neutralize bacterial exotoxins. Anticellular antibodies are differentiated into hemagglutinins (glue red blood cells together), hemolysins (dissolve, lyse red blood cells) and cytotoxins (kill animal cells). Autoantibodies are produced by the body against its own proteins and cells of tissues and organs when the chemical structure of the latter changes or when antigens are released from destroyed organs and tissues.
Precipitins are antibodies that cause the formation of a fine sediment (precipitate) upon contact with a specific antigen.
The protective role of antibodies in acquired immunity: participation of antibodies in immediate hypersensitivity reactions (IHT), complement-dependent cytolysis, immune phagocytosis, antibody-dependent cellular cytotoxicity, etc.
Hypersensitivity reactions can be classified based on the immunological mechanisms that cause them.
In type I hypersensitivity reactions, the immune response is accompanied by the release of vasoactive and spasmogenic substances that act on blood vessels and smooth muscles, thus disrupting their functions.
In type II hypersensitivity reactions, humoral antibodies are directly involved in cell damage, making them susceptible to phagocytosis or lysis.
For type III hypersensitivity reactions (immune complex diseases) humoral antibodies bind antigens and activate complement. Complement fractions then attract neutrophils, which cause tissue damage.
In type IV hypersensitivity reactions, tissue damage occurs, which is caused by the pathogenic effect of sensitized lymphocytes.
In type II hypersensitivity reactions, antibodies appear in the body that are directed against antigens located on the surface of cells or other tissue components. Antigenic determinants can be associated with the cell membrane or represent an exogenous antigen adsorbed on the surface of cells. In any case, a hypersensitivity reaction occurs as a consequence of the binding of antibodies to normal or damaged antigens on the cell surface. Three antibody-dependent mechanisms for the development of this type of reaction have been described.
Complement-dependent reactions . There are two mechanisms by which antibody and complement can cause type II hypersensitivity reactions: direct lysis and opsonization. In the first case, an antibody (IgM or IgG) reacts with an antigen on the cell surface, causing activation of the complement system and activating the membrane attack complex, which disrupts the integrity of the membrane, “perforating” the lipid layer.
In the second case, cells are sensitized to phagocytosis by fixing an antibody or a C3 fragment of complement to the cell surface (opsonization). This type II hypersensitivity reaction most often affects blood cells (red blood cells, white blood cells and platelets), but antibodies can also be directed against extracellular structures, such as the glomerular basement membrane.
Antibody-mediated cellular dysfunction. In some cases, antibodies directed against receptors on the surface of cells disrupt their functioning without causing cell damage or inflammation. For example, in myasthenia gravis, antibodies react with acetylcholine receptors in the motor end plates of skeletal muscles, disrupting neuromuscular transmission and thus causing muscle weakness. On the contrary, when antibody-mediated stimulation cell functions, Graves' disease develops. In this disease, antibodies against thyroid-stimulating hormone receptors on the epithelial cells of the thyroid gland stimulate the cells, leading to hyperthyroidism. The same mechanism underlies the inactivation and neutralization reactions.
The influenza virus has two antigenic complexes:
· S antigen(soluble, from lat. solution– dissolve) is represented by nucleocapsid proteins, is type-specific, stable, non-infectious ( NP protein capable of fixing complement, therefore detected in RSC).
· V antigen(from lat. viral– viral) – strain-specific, consists of hemagglutinin and neuraminidase, located on spines, determines virulence (detected in RTGA).
Variability of viruses flu .
The internal structures of the virus are shielded from the action of the external environment and do not change. Variability is inherent in supercapsid antigens, and hemagglutinins and neuraminidase change independently of each other due to 2 genetic mechanisms - drift And shift.
Antigenic drift(from English drift– slow course) causes minor changes caused by a point mutation, mostly in the structure of hemagglutinin. This leads to the development of strain differences that do not go beyond the subtype. As a result of antigenic drift, epidemics(frequency – every 1-3 years).
Shift(from English shift-leap) is a complete replacement of a gene, which leads to the appearance of a new antigenic variant of the virus. It is believed that shift is the result of genetic recombination, i.e. exchange of genetic information between human and animal viruses entering the same cell, which leads to a change in subtype H or N (and sometimes both). This variability may lead to the emergence of new viral variants that can cause pandemic(frequency – every 10-20-40 years).
Influenza viruses B and C lack shift variability, therefore influenza B virus causes epidemics, A influenza C virus– sporadic diseases or small flashes.
Features of virus reproduction.
1. Adsorption on receptors sensitive cells containing sialic acid using hemagglutinins.
2. Penetration into the cell by receptor endocytosis, followed by fusion of the virus membranes with the wall of the cell vacuole and the formation of an endosome.
3. Deproteinization: the virus is first freed from the supercapsid, then from the capsid proteins.
4. Eclipse phase (NA replication and viral protein synthesis): viral RNA penetrates the cell cytoplasm, then into the nucleus, where the product necessary for transcription and translation is present. This is where RNA is synthesized. Capsid proteins NP, P1, P2, P3 and M are synthesized in the cytoplasm on ribosomes.
5. Nucleocapsid assembly occurs in the cytoplasm of the cell (RNA and viral proteins recognize each other and self-assemble).
6. Exit from the cell is carried out by budding or explosion (lysis), while a supercapsid is formed from the cytoplasmic membrane of the cell.
34-35. Features of pathogenesis and immunity in influenza. Laboratory diagnostics, epidemiology, specific prevention and therapy. Chemoprophylaxis of influenza.
Paramyxoviruses. Parainfluenza virus. Measles, mumps virus, respiratory syncytial virus. Their properties. Laboratory diagnostics. Immunity. Specific prevention.
Influenza is an acute respiratory disease characterized by damage to the mucous membranes of the upper respiratory tract, fever, symptoms of general intoxication, and disruption of the cardiovascular and nervous systems. Influenza is prone to epidemic and pandemic spread due to the high contagiousness and variability of the pathogen.
In 1933, W. Smith, K. Andrews and P. Laidlaw isolated a virus from patients with influenza, which was later named influenza virus type A. In 1940, influenza viruses type B were discovered, and in
1947 - type C. In Russia, the first influenza viruses were isolated in 1936 by A. A. Smorodintsev and classified as type A.
Taxonomy , classification. RNA viruses belong to the Orthomyxoviridae family (from the Greek orthos - correct, tukha - mucus). The family includes two genera: the genus Influenzavirus includes influenza viruses types A and B, the genus Influenza C is represented by influenza virus type C.
Morphology and chemical composition . Virions have a spherical shape with a diameter of 80-120 nm (Fig. 11.2, a), less often rod-shaped and filamentous; consist of a core and an outer lipoprotein shell. The core contains a single-stranded linear fragmented minus-strand RNA, a protein capsid, surrounded by an additional membrane - a layer of matrix protein. The nucleocapsid has a helical type of symmetry. On the surface of the supercapsid shell there are spikes of a glycoprotein nature, some of which are hemagglutinin, others are neuraminidase (Fig. 11.2, b).
Cultivation. For cultivation, chicken embryos, cell cultures, and sometimes laboratory animals are used.
Antigenic structure . Influenza viruses have internal and surface antigens. Internal heart-shaped antigens are type-specific, on the basis of which influenza viruses are divided into types A, B and C; surface antigens are represented by hemagglutinin (H) and neuraminidase (N). H is the main specific antigen that causes the formation of virus-neutralizing antibodies and ensures the adsorption of the virus on cells, including human or animal erythrocytes, resulting in their gluing (hemagglutination). N causes the formation of antibodies that partially neutralize viruses; Being an enzyme, N is involved in the release of viruses from the cell.
A characteristic feature of influenza viruses, mainly type A, is the variability of the H and N antigens. Three varieties of H and two varieties of N are known. Depending on their combination, three subtypes of the human influenza A virus are distinguished: H1N1, H2N2, H3N2, respectively Al, A2, A3. Within the subtypes there are many antigenic variants that differ in the structure of the H- and N-antigens.
Variability of surface antigens is associated with the fragmentary structure of the RNA virus and can occur in the form of drift and shift. Drift is constantly occurring minor changes in the H- and N-antigens as a result of point mutations, leading to the emergence of new antigenic variants of the virus. Shift (jump) - rare significant changes in H- and N-antigens as a result of recombinations, leading to the emergence of new subtypes of the virus.
Compared to type A influenza viruses, the antigenic structure of type B influenza viruses changes only by drift, and type C does not have an N-antigen and is little variable.
Resistance . In the air, influenza viruses can remain infectious at room temperature for several hours; The higher the temperature and relative humidity, the faster the viruses are inactivated. Influenza pathogens are sensitive to UV rays, many disinfectants (formalin, ethyl alcohol, phenol, chloramine), fat solvents; in a liquid medium they are inactivated at a temperature of 50-60 ° C for several minutes. They can be stored for a long time frozen and in glycerin.
Animal susceptibility . Under natural conditions, influenza A viruses infect both humans and animals; viruses types B and C - only human. Among laboratory animals, African ferrets, Syrian hamsters, and white mice are sensitive to influenza viruses. The disease is characterized by damage to the lungs and often ends in the death of animals.
Epidemiology. Of all acute respiratory viral infections, influenza is the most widespread and severe disease. Pandemics and influenza epidemics affect up to 30-50% of the world's population or more, causing enormous damage to human health and the economies of countries. Thus, the Spanish flu pandemic, caused by the A (H1N1) virus in 1918-1920, affected about 1.5 billion people and claimed more than 20 million lives. People are highly susceptible to influenza. All age groups of the population are affected, mainly in the winter season.
The occurrence of pandemics and major epidemics is usually associated with the emergence of a new subtype of influenza A virus. Annual epidemic outbreaks are caused by new antigenic variants of one subtype. In recent years, influenza epidemics have been associated with the influenza A (H3N2) virus, although influenza A (H1N1) and B viruses continue to circulate among the population.
The source of influenza infection is a sick person with a clinically pronounced or asymptomatic form. The route of transmission is airborne droplets (when talking, coughing, sneezing).
Pathogenesis and clinical picture . Influenza viruses invade and reproduce in the epithelial cells of the mucous membrane of the upper respiratory tract, from where they enter the blood and spread throughout the body. The breakdown products of damaged cells and some viral proteins have a toxic effect on various organs and systems of the body.
Incubation period short - from several hours to 1-2 days. Influenza is characterized by an acute onset, high body temperature, general intoxication expressed in malaise, headache, pain in the eyeballs, and damage to the respiratory tract of varying severity. A febrile state with influenza without complications lasts no more than 5-6 days. The severity and outcome of the disease are often associated with complications caused by the influenza virus itself (influenza pneumonia, acute pulmonary edema) or opportunistic bacteria. The development of complications is facilitated by the inhibitory effect of influenza viruses on hematopoietic processes and the body's immune system.
Immunity. After an illness, stable type-, subtype- and variant-specific immunity is formed, which is provided by cellular and humoral protective factors. Antibodies of the IgA class are of great importance. Passive natural immunity persists in children up to 8-11 months of age.
Laboratory diagnostics . The material for detecting a virus or viral antigen is fingerprint smears from the mucous membrane of the nasal cavity, nasopharyngeal discharge, and in case of death - pieces of lung tissue or brain. Express diagnostics is based on identifying the viral antigen using RIF; a test system for ELISA has been developed. Chicken embryos are used to isolate viruses. Influenza viruses are indicated by performing a hemagglutination reaction. Isolated viruses are identified in stages: the type is determined using RSC, the subtype is determined by RTGA. Serodiagnosis is carried out using RSK, RTGA, RN in cell culture, gel precipitation reaction, ELISA.
Specific prevention and treatment . For specific prevention, live and inactivated vaccines from influenza A (H1N1), A (H3N2) and B viruses cultured in chicken embryos are used. There are three types of inactivated vaccines: virion (particle); cleaved, in which the structural components of the virion are separated using detergents; subunit, containing only hemagglutinin and neuraminidase. A vaccine of three influenza viruses is administered intranasally in one vaccination dose according to a special scheme. Vaccination is indicated for certain groups at high risk of infection.
A culture-inactivated vaccine is being tested. Development is underway to create a new generation of influenza vaccines: synthetic, genetically engineered. Unfortunately, in some years there is a rather low effectiveness of vaccination due to the high variability of influenza viruses.
For treatment and emergency prevention of influenza, chemotherapeutic antiviral drugs (rimantadine, virazole, arbidol, etc.), interferon drugs and immunomodulators (dibazole, levamisole, etc.) are used. In case of severe influenza, especially in children, the use of donor anti-influenza immunoglobulin, as well as drugs that are inhibitors of cellular proteases: gordox, contrical, aminocaproic acid, is indicated.
