Blood cells capable of phagocytosis. What is phagocytosis An animal cell is capable of phagocytosis
Phagocytosis is the body's defense mechanism that engulfs solid particles. In the process of destruction of harmful substances, slags, toxins, and decomposition waste are removed. Active cells are able to detect foreign tissue inclusions. They begin to quickly attack the aggressor, splitting it into simple particles.
The essence of the phenomenon
Phagocytosis is a defense against pathogens. Domestic scientist Mechnikov I.I. conducted experiments to investigate the phenomenon. He introduced foreign inclusions into the body of sea stars and daphnia and recorded the results of observations.
The stages of phagocytosis were recorded through microscopic examination of marine life. Fungal spores were used as the pathogen. By placing them in the tissue of a starfish, the scientist noticed the movement of active cells. The moving particles attacked again and again until they completely covered the foreign body.
However, after exceeding the number of harmful components, the animal was unable to resist and died. Protective cells are given the name phagocytes, consisting of two Greek words: devour and cell.
Active Particle Defense Mechanism
Allocate the action of leukocytes and macrophages as a result of phagocytosis. These are not the only cells guarding the health of the body; in animals, oocytes, placental "guards", act as active particles.
The phenomenon of phagocytosis is carried out by two protective cells:
- Neutrophils are made in the bone marrow. They belong to granulocytic blood particles, the structure of which is distinguished by its granularity.
- Monocytes are a type of white blood cell derived from the bone marrow. Young phagocytes are highly mobile and carry out the structure of the main protective barrier.
Electoral defense
Phagocytosis is an active defense of the body, in which only pathogenic cells are destroyed, beneficial particles pass the barrier without complications. To analyze the state of human health, a quantitative assessment is used through laboratory blood tests. An increased concentration of leukocytes indicates the current inflammatory process.
Phagocytosis is a protective barrier against a huge number of pathogens:
- bacteria;
- viruses;
- blood clots;
- tumor cells;
- fungal spores;
- toxins and slag inclusions.
White blood cell counts change periodically, the correct conclusions are drawn after several general analyzes blood. So, in pregnant women, the amount is slightly overestimated, and this is a normal state of the body.
Low rates of phagocytosis are noted in long-term chronic diseases:
- tuberculosis;
- pyelonephritis;
- infections respiratory tract;
- rheumatism;
- atopic dermatitis.
The activity of phagocytes changes under the influence of certain substances:
- cholesterol;
- calcium salts;
- antibodies;
- histamine.
Avitominosis, the use of antibiotics, corticosteroids inhibit the protective mechanism. Phagocytosis acts as an assistant to immunity. Forced activation occurs in three ways:
- Classic - carried out according to the antigen-antibody principle. Activators are immunoglobulins IgG, IgM.
- Alternative - polysaccharides, viral particles, tumor cells are used.
- Lectin - a group of proteins that pass through the liver is used.
Particle destruction sequence
To understand the process of the protective mechanism, the stages of phagocytosis are defined:
- Chemotaxis is the period of penetration of a foreign particle into the human body. Characterized copious excretion a chemical reagent that serves as a signal for activity for macrophages, neutrophils, monocytes. Human immunity directly depends on the activity of protective cells. All awakened cells attack the area of foreign body penetration.
- Adhesion - recognition of a foreign body due to receptors by phagocytes.
- Preparatory process of defense cells for an attack.
- Absorption - particles gradually cover the foreign substance with their membrane.
- The formation of a phagosome is the completion of the environment of a foreign body with a membrane.
- Creation of a phagolysosome - digestive enzymes are released into the capsule.
- Killing is the killing of harmful particles.
- Removal of residues of particle splitting.
The stages of phagocytosis are considered by medicine to understand the internal processes of the development of any disease. The doctor is obliged to understand the basics of the phenomenon for the diagnosis of inflammation.
The protective role of mobile blood cells and tissues was first discovered by I. I. Mechnikov in 1883. He called these cells phagocytes and formulated the main provisions of the phagocytic theory of immunity. Phagocytosis- absorption by the phagocyte of large macromolecular complexes or corpuscles, bacteria. Phagocyte cells: neutrophils and monocytes/macrophages. Eosinophils can also phagocytose (most effective in anthelmintic immunity). The process of phagocytosis is enhanced by opsonins that envelop the object of phagocytosis. Monocytes make up 5-10%, and neutrophils 60-70% of blood leukocytes. Entering the tissue, monocytes form a population of tissue macrophages: Kupffer cells (or stellate reticuloendothelial cells of the liver), CNS microglia, osteoclasts of bone tissue, alveolar and interstitial macrophages).
The process of phagocytosis. Phagocytes move towards the object of phagocytosis, reacting to chemoattractants: microbial substances, activated complement components (C5a, C3a) and cytokines.
The plasmalemma of the phagocyte embraces bacteria or other corpuscles and its own damaged cells. Then the object of phagocytosis is surrounded by the plasmalemma and the membrane vesicle (phagosome) is immersed in the cytoplasm of the phagocyte. The phagosome membrane fuses with the lysosome and the phagocytosed microbe is destroyed, the pH acidifies to 4.5; lysosome enzymes are activated. The phagocytosed microbe is destroyed by the action of lysosome enzymes, cationic defensin proteins, cathepsin G, lysozyme, and other factors. During the oxidative (respiratory) explosion, toxic antimicrobial forms of oxygen are formed in the phagocyte - hydrogen peroxide H 2 O 2, superoxide O 2 - , hydroxyl radical OH - , singlet oxygen. In addition, nitric oxide and the NO - radical have an antimicrobial effect.
Macrophages perform a protective function even before interacting with other immunocompetent cells (nonspecific resistance). Macrophage activation occurs after the destruction of the phagocytized microbe, its processing (processing) and presentation (representation) of the antigen to T-lymphocytes. In the final stage of the immune response, T-lymphocytes secrete cytokines that activate macrophages (acquired immunity). Activated macrophages, together with antibodies and activated complement (C3b), perform more efficient phagocytosis (immune phagocytosis), destroying phagocytosed microbes.
Phagocytosis can be complete, ending with the death of the captured microbe, and incomplete, in which microbes do not die. An example of incomplete phagocytosis is the phagocytosis of gonococci, tubercle bacilli and leishmania.
All phagocytic cells of the body, according to I. I. Mechnikov, are divided into macrophages and microphages. Microphages include polymorphonuclear blood granulocytes: neutrophils, eosinophils and basophils. Macrophages of various body tissues ( connective tissue, liver, lungs, etc.), together with blood monocytes and their bone marrow precursors (promonocytes and monoblasts), are combined into a special system of mononuclear phagocytes (MPS). The SMF is phylogenetically older than the immune system. It is formed quite early in ontogeny and has certain age characteristics.
Microphages and macrophages have a common myeloid origin - from a pluripotent stem cell, which is a single precursor of granulo- and monocytopoiesis. The peripheral blood contains more granulocytes (from 60 to 70% of all blood leukocytes) than monocytes (from 1 to 6%). At the same time, the duration of circulation of monocytes in the blood is much longer (half-period 22 hours) than that of short-lived granulocytes (half-period 6.5 hours). Unlike blood granulocytes, which are mature cells, monocytes, leaving the bloodstream, in the appropriate microenvironment, mature into tissue macrophages. The extravascular pool of mononuclear phagocytes is tens of times greater than their number in the blood. The liver, spleen, and lungs are especially rich in them.
All phagocytic cells are characterized by a commonality of basic functions, similarity of structures and metabolic processes. The outer plasma membrane of all phagocytes is an actively functioning structure. It is characterized by pronounced folding and carries many specific receptors and antigenic markers that are constantly updated. Phagocytes are equipped with a highly developed lysosomal apparatus, which contains a rich arsenal of enzymes. The active participation of lysosomes in the functions of phagocytes is ensured by the ability of their membranes to fuse with the membranes of phagosomes or with the outer membrane. In the latter case, cell degranulation and concomitant secretion of lysosomal enzymes into the extracellular space occurs.
Phagocytes have three functions:
1 - protective, associated with cleaning the body of infectious agents, tissue decay products, etc .;
2 - representing, consisting in the presentation of antigenic epitopes on the phagocyte membrane;
3 - secretory, associated with the secretion of lysosomal enzymes and other biologically active substances- monokines, which play an important role in immunogenesis.
Fig 1. Macrophage functions.
In accordance with the listed functions, the following consecutive stages of phagocytosis are distinguished.
1. Chemotaxis - targeted movement of phagocytes in the direction of the chemical gradient of chemoattractants in the environment. The ability to chemotaxis is associated with the presence on the membrane of specific receptors for chemoattractants, which can be bacterial components, degradation products of body tissues, activated fractions of the complement system - C5a, C3a, lymphocyte products - lymphokines.
2. Adhesion (attachment) is also mediated by the corresponding receptors, but can proceed in accordance with the laws of nonspecific physicochemical interaction. Adhesion immediately precedes endocytosis (capture).
3. Endocytosis is the main physiological function of the so-called professional phagocytes. There are phagocytosis - in relation to particles with a diameter of at least 0.1 microns and pinocytosis - in relation to smaller particles and molecules. Phagocytic cells are able to capture inert particles of coal, carmine, latex by flowing around them with pseudopodia without the participation of specific receptors. At the same time, phagocytosis of many bacteria, yeast-like fungi of the genus Candida, and other microorganisms is mediated by special phagocyte mannose-fucose receptors that recognize the carbohydrate components of the surface structures of microorganisms. The most effective is phagocytosis, mediated by receptors, for the Fc-fragment of immunoglobulins and for the C3-fraction of complement. Such phagocytosis is called immune, since it proceeds with the participation of specific antibodies and an activated complement system that opsonize the microorganism. This makes the cell highly sensitive to capture by phagocytes and leads to subsequent intracellular death and degradation. As a result of endocytosis, a phagocytic vacuole is formed - phagosome. It should be emphasized that the endocytosis of microorganisms to a large extent depends on their pathogenicity. Only avirulent or low virulent bacteria (capsular strains of pneumococcus, strains of streptococcus lacking hyaluronic acid and M-protein) are directly phagocytosed. Most bacteria endowed with aggressiveness factors (staphylococcus-A-protein, Escherichia coli-expressed capsular antigen, Salmonella-Vi-antigen, etc.) are phagocytosed only after they are opsonized by complement or (and) antibodies.
The presenting, or representing, function of macrophages is to fix antigenic epitopes of microorganisms on the outer membrane. In this form, they are presented by macrophages for their specific recognition by cells. immune system- T-lymphocytes.
The secretory function consists in the secretion of biologically active substances - monokines by mononuclear phagocytes. These include substances that have a regulatory effect on the proliferation, differentiation and function of phagocytes, lymphocytes, fibroblasts and other cells. A special place among them is occupied by interleukin-1 (IL-1), which is secreted by macrophages. It activates many functions of T-lymphocytes, including the production of lymphokine - interleukin-2 (IL-2). IL-1 and IL-2 are cellular mediators involved in the regulation of immunogenesis and various forms of the immune response. At the same time, IL-1 has the properties of an endogenous pyrogen, since it induces fever by acting on the nuclei of the anterior hypothalamus. Macrophages produce and secrete such important regulatory factors as prostaglandins, leukotrienes, cyclic nucleotides with a wide range of biological activity.
Along with this, phagocytes synthesize and secrete a number of products with predominantly effector activity: antibacterial, antiviral, and cytotoxic. These include oxygen radicals (O 2 , H 2 O 2), complement components, lysozyme and other lysosomal enzymes, interferon. Due to these factors, phagocytes can kill bacteria not only in phagolysosomes, but also outside the cells, in the immediate microenvironment. These secretory products can also mediate the cytotoxic effect of phagocytes on various target cells in cell-mediated immune responses, for example, in delayed-type hypersensitivity reactions (DTH), in homograft rejection, and in antitumor immunity.
The considered functions of phagocytic cells ensure their active participation in maintaining the homeostasis of the body, in the processes of inflammation and regeneration, in nonspecific anti-infective protection, as well as in immunogenesis and reactions of specific cellular immunity (SIT). The early involvement of phagocytic cells (first, granulocytes, then macrophages) in response to any infection or any damage is explained by the fact that microorganisms, their components, tissue necrosis products, blood serum proteins, substances secreted by other cells, are chemoattractants for phagocytes. In the focus of inflammation, the functions of phagocytes are activated. Macrophages are replacing microphages. In those cases when the inflammatory reaction involving phagocytes is not enough to cleanse the body of pathogens, then the secretory products of macrophages ensure the involvement of lymphocytes and the induction of a specific immune response.
complement system. The complement system is a multicomponent self-assembling system of blood serum proteins that plays an important role in maintaining homeostasis. It is able to be activated in the process of self-assembly, i.e., sequential attachment to the resulting complex of individual proteins, which are called components, or complement fractions. There are nine such factions. They are produced by liver cells, mononuclear phagocytes and are contained in the blood serum in an inactive state. The process of complement activation can be triggered (initiated) in two different ways, called classical and alternative.
When complement is activated, the classic initiating factor is the antigen-antibody complex (immune complex). Moreover, antibodies of only two classes IgG and IgM in the composition of immune complexes can initiate complement activation due to the presence in the structure of their Fc fragments of sites that bind the C1 fraction of complement. When C1 is attached to the antigen-antibody complex, an enzyme (C1-esterase) is formed, under the action of which an enzymatically active complex (C4b, C2a), called C3-convertase, is formed. This enzyme cleaves C3 into C3 and C3b. When the C3b subfraction interacts with C4 and C2, a peptidase is formed that acts on C5. If the initiating immune complex is associated with the cell membrane, then the self-assembling complex C1, C4, C2, C3 ensures the fixation of the activated C5 fraction on it, and then C6 and C7. The last three components together contribute to the fixation of C8 and C9. At the same time, two sets of complement fractions - C5a, C6, C7, C8 and C9 - constitute the membrane attack complex, after which the cell is lysed after its attachment to the cell membrane due to irreversible damage to the structure of its membrane. In the event that complement activation along the classical pathway occurs with the participation of the erythrocyte-antierythrocyte Ig immune complex, erythrocyte hemolysis occurs; if the immune complex consists of a bacterium and an antibacterial Ig, bacterial lysis occurs (bacteriolysis).
Thus, during complement activation in the classical way, the key components are C1 and C3, the cleavage product of which C3b activates the terminal components of the membrane attack complex (C5 - C9).
There is a possibility of C3 activation with the formation of C3b with the participation of the alternative pathway C3 convertase, i.e. bypassing the first three components: C1, C4 and C2. A feature of the alternative pathway of complement activation is that initiation can occur without the participation of the antigen-antibody complex due to polysaccharides of bacterial origin - lipopolysaccharide (LPS) of the cell wall of gram-negative bacteria, surface structures of viruses, immune complexes, including IgA and IgE.
He conducted his research in Italy, on the coast of the Strait of Messina. The scientist was interested in whether individual multicellular organisms retained the ability to capture and digest food, as unicellular organisms, such as amoeba, do. Indeed, as a rule, in multicellular organisms, food is digested in the alimentary canal and ready-made nutrient solutions are absorbed. observed starfish larvae. They are transparent and their contents are clearly visible. These larvae do not have a circulating, but wandering larva throughout the larva. They captured particles of red carmine paint introduced into the larva. But if these absorb paint, then maybe they capture any foreign particles? Indeed, the rose thorns inserted into the larva turned out to be surrounded by carmine-colored ones.
They were able to capture and digest any foreign particles, including pathogenic microbes. called wandering phagocytes (from the Greek words phages - devourer and kytos - receptacle, here -). And the very process of capturing and digesting different particles by them is phagocytosis. Later he observed phagocytosis in crustaceans, frogs, turtles, lizards, as well as in mammals - guinea pigs, rabbits, rats and in humans.
Phagocytes are special. Digestion of captured particles is not necessary for them to feed, like amoebas and other unicellular organisms, but to protect the body. In starfish larvae, phagocytes wander throughout the body, while in higher animals and humans they circulate in the vessels. This is one of the types of white blood cells, or leukocytes - neutrophils. It is they who, attracted by the toxic substances of microbes, move to the site of infection (see). Having left the vessels, such leukocytes have outgrowths - pseudopodia, or pseudopodia, with the help of which they move in the same way as an amoeba and wandering starfish larvae. Such leukocytes capable of phagocytosis are called microphages.
However, not only constantly moving leukocytes, but also some sedentary ones can become phagocytes (now they are all combined into a single system of phagocytic mononuclear cells). Some of them rush to dangerous areas, for example, to the site of inflammation, while others remain in their usual places. Both of them are united by the ability to phagocytosis. These tissue (histocytes, monocytes, reticular and endothelial) are almost twice as large as microphages - their diameter is 12-20 microns. Therefore, they called them macrophages. Especially a lot of them in the spleen, liver, lymph nodes, bone marrow and in the walls of blood vessels.
Microphages and wandering macrophages themselves actively attack the “enemies”, while immobile macrophages wait for the “enemy” to swim past them in the current or lymph. Phagocytes “hunt” for microbes in the body. It happens that in an unequal struggle with them they are defeated. Pus is the accumulation of dead phagocytes. Other phagocytes will approach it and begin to deal with its elimination, as they do with all sorts of foreign particles.
Phagocytes are cleansed of constantly dying and are involved in various restructuring of the body. For example, during the transformation of a tadpole into a frog, when, along with other changes, the tail gradually disappears, whole hordes of phagocytes destroy the tadpole's tail.
How do particles get inside the phagocyte? It turns out that with the help of pseudopodia, which capture them, like an excavator bucket. Gradually, the pseudopodia lengthen and then close over the foreign body. Sometimes it seems to be pressed into the phagocyte.
He suggested that phagocytes should contain special substances that digest the microbes and other particles captured by them. Indeed, such particles were discovered 70 years after the discovery of phagocytosis. They contain capable of breaking down large organic molecules.
Now it has been found out that, in addition to phagocytosis, they are predominantly involved in the neutralization of foreign substances (see). But for the process of their production to begin, the participation of macrophages is necessary. They capture foreign
Cells capable of phagocytosis are:
Polymorphonuclear leukocytes (neutrophils, eosinophils, basophils)
Monocytes
Fixed macrophages (alveolar, peritoneal, Kupffer, dendritic cells, Langerhans
2. What type of immunity provides protection for mucous membranes that communicate with the external environment. and skin from penetration into the body of the pathogen: specific local immunity
3. The central organs of the immune system include:
Bone marrow
Bag of Fabricius and its counterpart in humans (Peyer's patches)
4. What cells produce antibodies:
A. T-lymphocyte
B. B-lymphocyte
B. Plasma cells
5. Haptens are:
Simple organic compounds with low molecular weight (peptides, disaccharides, Hc, lipids, etc.)
Cannot induce antibody formation
Able to specifically interact with those antibodies in the induction of which they participated (after attaching to the protein and turning into full-fledged antigens)
6. The penetration of the pathogen through the mucous membrane is prevented by immunoglobulins of the class:
BUT.IgA
B. SIGA
7. The function of adhesins in bacteria is performed by:cell wall structures (fimbriae, outer membrane proteins, LPS)
U Gr(-): associated with pili, capsule, capsule-like shell, outer membrane proteins
U Gr (+): teichoic and lipoteichoic acids of the cell wall
8. Delayed type hypersensitivity is caused by:
Sensitized cells-T-lymphocytes (lymphocytes that have undergone immunological "training" in the thymus)
9. Cells that carry out a specific immune response include:
T-lymphocytes
B-lymphocytes
Plasma cells
10. Components required for the agglutination reaction:
microbial cells, latex particles (agglutinogens)
saline
antibodies (agglutinins)
11. The components for setting up the precipitation reaction are:
A. Cell suspension
B. Antigen solution (hapten in saline)
B. Warm culture of microbial cells
G. Complement
E. Immune serum or test patient serum
12. What components are necessary for the complement fixation reaction:
Saline
complement
patient's blood serum
ram erythrocytes
hemolytic serum
13 Components required for the immune lysis reaction:
BUT .Live cell culture
B.killed cells
IN .Complement
G .Immune Serum
D. Saline solution
14. In a healthy person in the peripheral blood, the number of T-lymphocytes is:
B.40-70%
15. Drugs used for emergency prevention and treatment:
A. Vaccines
B. Serum
B. Immunoglobulins
16. The method of quantitative assessment of human peripheral blood T-lymphocytes is the reaction:
A. Phagocytosis
B. Complement binding
B. Spontaneous rosette formation with ram erythrocytes (E-ROS)
D. Rosette formation with mouse erythrocytes
D. Rosette formation with erythrocytes treated with antibodies and complement (EAC-ROK )
17. When mixing mouse erythrocytes with human peripheral blood lymphocytes, “E-rosettes” are formed with those cells that are:
A. B-lymphocytes
B. Undifferentiated lymphocytes
B. T-lymphocytes
18. To set up the reaction of latex - agglutination, you must use all of the following ingredients, with the exception of:
A. Patient's blood serum at a dilution of 1:25
B. Alcohol
31. If an infectious disease is transmitted to a person from a sick animal, it is called:
A. anthroponotic
B. zooanthroponic
32. The main properties and features of a complete antigen:
A. is a protein
B. is a low molecular weight polysaccharide
G. is a macromolecular compound
D. causes the formation of antibodies in the body
E. does not cause the formation of antibodies in the body
Z. insoluble in body fluids
I. is able to react with a specific antibody
K. is not able to react with a specific antibody
33. Non-specific resistance of a macroorganism includes all of the following factors, with the exception of:
A. phagocytes
B. gastric juice
B. antibodies
G. lysozyme
E. temperature response
G. mucous membranes
Z. lymph nodes
I. interferon
K. complement system
L. properdin
Z, toxoid
49. What bacteriological preparations are prepared from bacterial toxins:
Prevention. toxoids
Diagnostic toxin
50. What ingredients are needed to prepare a killed vaccine:
Highly virulent and highly immunogenic microorganism strain (whole killed bacterial cells)
Heating at t=56-58C for 1 hour
Addition of formalin
Phenol addition
Adding alcohol
Irradiation with ultraviolet rays
Sonication
! 51. Which of the following bacterial preparations are used to treat infectious diseases:
A. live vaccine
B. toxoid
B. immunoglobulin
D. antitoxic serum
D. diagnosticum
E. bacteriophage
J. allergen
Z. agglutinating serum
I. vaccine killed
K. precipitating serum
52. For what immune reactions are diagnosticums used:
Extended Vidal type agglutination reaction
Reactions of passive, or indirect hemagglutination (RNHA )
53. The duration of the protective action of immune sera introduced into the human body: 2-4 weeks
54. Ways of introducing the vaccine into the body:
intradermally
subcutaneously
intramuscularly
intranasally
orally (enterally)
through the mucous membranes of the respiratory tract using artificial aerosols of live or killed vaccines
55. Main properties of bacterial endotoxins:
BUT. are proteins(cell wall of Gr(-) bacteria)
B. consist of lipopolysaccharide complexes
? V. firmly associated with the body of the bacterium
G. are easily isolated from bacteria into the environment
D. thermostable
E. thermolabile
G. highly toxic
Z. moderately toxic
I. are able to pass into toxoid under the influence of formalin and temperature
K. causes the formation of antitoxins
56. The occurrence of an infectious disease depends on:
A. shaped bacteria
B. microorganism reactivity
B. ability to stain according to Gram
D. dose of infection
D. the degree of pathogenicity of the bacterium
E. entrance gate of infection
G. the state of the cardiovascular system of the microorganism
Z. environmental conditions (atmospheric pressure, humidity, solar radiation, temperature, etc.)
57. MHC antigens (major histocompatibility complex) are located on the membranes:
A. nucleated cells of different tissues of the microorganism (leukocytes, macrophages, histiocytes, etc.)
B. erythrocytes
B. only leukocytes
58. The ability of bacteria to secrete exotoxins is due to:
A. the shape of the bacterium
B. availability
tox
-gene
B. the ability to capsule formation
? 59. The main properties of pathogenic bacteria are:
A. the ability to cause an infectious process
B. ability to form spores
B. specificity of action on the macroorganism
G. thermal stability
D. virulence
E. ability to form toxins
G. invasiveness
Z. the ability to form sugars
I. capsulation ability
K. organotropism
60. Methods for assessing the immune status of a person are:
A. agglutination reaction
B. phagocytosis reaction
B. ring precipitation reaction
D. radial immunodiffusion according to Mancini
E. Immunofluorescence test with monoclonal antibodies to identify T-helpers and T-suppressors
E. complement fixation reaction
G. method of spontaneous rosette formation with ram erythrocytes (E-ROK)
61. Immunological tolerance is:
A. ability to produce antibodies
B. the ability to cause the proliferation of a particular clone of cells
B. lack of an immunological response to an antigen
62. Inactivated blood serum:
Serum subjected to heat treatment at 56°C for 30 min resulting in complement destruction
63. Cells that suppress the immune response and participate in the phenomenon of immunotolerance are:
A. T-helpers
B. erythrocytes
B. T-suppressor lymphocytes
D. lymphocytes T-effectors
E. lymphocytes T-killers
64. The functions of T-helper cells are:
Necessary for the transformation of B-lymphocytes into antibody-forming cells and memory cells
Recognize cells that have MHC class 2 antigens (macrophages, B-lymphocytes)
They regulate the immune response
65. Precipitation reaction mechanism:
A. formation of an immune complex on cells
B. toxin inactivation
B. formation of a visible complex when an antigen solution is added to the serum
D. Glow of the antigen-antibody complex in ultraviolet rays
66. The division of lymphocytes into T- and B-populations is due to:
A. the presence of certain receptors on the surface of cells
B. site of proliferation and differentiation of lymphocytes (bone marrow, thymus)
B. the ability to produce immunoglobulins
D. the presence of the HGA complex
D. ability to phagocytize antigen
67. Enzymes of aggression include:
Protease (breaks down antibodies)
Coagulase (clots blood plasma)
Hemolysin (destroys the membranes of red blood cells)
Fibrinolysin (dissolution of fibrin clot)
Lecithinase (acts on lecithin )
68. Immunoglobulins of the class pass through the placenta:
BUT .IgG
69. Protection against diphtheria, botulism, tetanus is determined by immunity:
A. local
B. antimicrobial
B. antitoxic
G. congenital
70. The reaction of indirect hemagglutination involves:
A. erythrocyte antigens are involved in the reaction
B. antigens adsorbed on erythrocytes participate in the reaction
B. receptors for pathogen adhesins are involved in the reaction
71. With sepsis:
A. blood is a mechanical carrier of the pathogen
B. pathogen multiplies in the blood
B. the pathogen enters the blood from purulent foci
72. Intradermal test to detect antitoxic immunity:
The Schick test with diphtheria toxin is positive if there are no antibodies in the body that can neutralize the toxin
73. The reaction of immunodiffusion according to Mancini refers to a reaction of the type:
A. agglutination reaction
B. lysis reaction
B. precipitation reaction
D. ELISA (enzymatic immunoassay)
E. phagocytosis reaction
J. RIF (immunofluorescence reaction )
74. Reinfection is:
A. a disease that developed after recovery from re-infection with the same pathogen
B. a disease that developed when infected with the same pathogen before recovery
B. return of clinical manifestations
75. Visible result positive reaction according to Mancini is:
A. formation of agglutinins
B. turbidity of the environment
B. cell dissolution
D. formation of precipitation rings in the gel
76. Human resistance to the causative agent of chicken cholera determines immunity:
A. acquired
B. active
B. passive
G. post-infectious
D. species
77. Immunity is preserved only in the presence of a pathogen:
A. active
B. passive
B. congenital
G. sterile
D. infectious
78. The reaction of latex agglutination cannot be used to:
A. identification of the causative agent of the disease
B. definition of classes of immunoglobulins
B. detection of antibodies
79. The reaction of rosette formation with sheep erythrocytes (E-ROK) is considered
positive if one lymphocyte adsorbs:
A. one ram erythrocyte
B. complement fraction
B. more than 2 sheep erythrocytes (more than 10)
D. bacterial antigen
? 80. Incomplete phagocytosis is observed in diseases:
A. syphilis
B. brucellosis
B. tuberculosis
G. dysentery
D. meningitis
E. leprosy
G. gonorrhea
Z. typhoid fever
I. cholera
K. anthrax
? 81. Specific and non-specific factors of humoral immunity are:
A. erythrocytes
B. white blood cells
B. lymphocytes
D. platelets
D. immunoglobulins
E. complement system
J. properdin
Z. albumin
I. leukins
K. lysins
L. erythrin
lysozyme
82. When ram erythrocytes are mixed with human peripheral blood lymphocytes, E-rosettes are formed only with those cells that are:
A. B-lymphocytes
B. undifferentiated
B. T-lymphocytes
83. Accounting for the results of the latex agglutination reaction is carried out in:
A. in milliliters
B. in millimeters
W. in grams
G. in the pros
84. Precipitation reactions include:
B. flocculation reaction (according to Korotyaev)
B. the phenomenon of Isaev Pfeifer
D. gel precipitation reaction
D. agglutination reaction
E. bacteriolysis reaction
G. hemolysis reaction
Z. Ascoli ring precipitation reaction
I. Mantoux reaction
K. reaction of radial immunodiffusion according to Mancini
? 85. The main features and properties of hapten:
A. is a protein
B. is a polysaccharide
B. is a lipid
G. has a colloidal structure
D. is a macromolecular compound
E. when introduced into the body causes the formation of antibodies
G. when introduced into the body does not cause the formation of antibodies
Z. soluble in body fluids
I. able to react with specific antibodies
K. unable to react with specific antibodies
86. Main signs and properties of antibodies:
A. are polysaccharides
B. are albumins
V. are immunoglobulins
G. are formed in response to the introduction of a full-fledged antigen into the body
D. are formed in the body in response to the introduction of hapten
E. are able to enter into interaction reactions with a full-fledged antigen
Zh. are able to enter into reactions of interaction with hapten
87. Necessary components for setting up an extended Gruber-type agglutination reaction:
A. patient's blood serum
B. saline
B. pure culture of bacteria
D. known immune serum, non-adsorbed
E. erythrocyte suspension
E. diagnosticum
G. complement
Z. known immune serum, adsorbed
I. monoreceptor serum
88. Signs of a positive Gruber reaction:
G.20-24h
89. Necessary ingredients for setting up a detailed Vidal agglutination reaction:
Diagnosticum (suspension of killed bacteria)
The patient's blood serum
Saline
90. Antibodies that contribute to the enhancement of phagocytosis:
A. agglutinins
B. procytinins
B. opsonins
D. complement-fixing antibodies
D. homolysins
E. optitoxins
G. bacteriotropins
Z. lysine
91. Components of the ring precipitation reaction:
A. saline
B. precipitating serum
B. erythrocyte suspension
D. pure culture of bacteria
D. diagnosticum
E. complement
G. precipitinogen
Z. bacterial toxins
? 92. To detect agglutinins in the patient's blood serum, the following are used:
A. extended Gruber agglutination reaction
B. bacteriolysis reaction
B. extended Vidal agglutination reaction
G. precipitation reaction
D. reaction of passive hemagglutination with erythrocyte diagonosticum
E. Oriented glass agglutination reaction
93. Lysis reactions are:
A. precipitation reaction
B. Isaev-Pfeifer phenomenon
B. Mantoux reaction
D. Gruber agglutination reaction
D. hemolysis reaction
E. Vidal agglutination reaction
G. bacteriolysis reaction
Z. RSK reaction
94. Signs of a positive ring precipitation reaction:
A. turbidity of the liquid in the test tube
B. loss of bacterial motility
B. the appearance of a precipitate at the bottom of the test tube
D. the appearance of a clouding ring
D. formation of varnish blood
E. the appearance in the agar of white lines of turbidity ("uson")
95. Time of the final registration of the Grubber agglutination reaction:
G.20-24h
96. To set up a bacteriolysis reaction, you need:
B. distilled water
B. immune serum (antibodies )
D. saline
E. erythrocyte suspension
E. pure culture of bacteria
G. suspension of phagocytes
Z. complement
I. bacterial toxins
K. monoreceptor agglutinating serum
97. For the prevention of infectious diseases, the following are used:
A. live vaccine
B. immunoglobulin
V. diagnosticum
D. vaccine killed
D. allergen
E. antitoxic serum
G. bacteriophage
Z. toxoid
I. chemical vaccine
K. agglutinating serum
98. After an illness, the following type of immunity is developed:
A. species
B. acquired natural active
B. acquired artificial active
G. acquired natural passive
D. acquired artificial passive
99. After the introduction of immune serum, the following type of immunity is formed:
A. species
B. acquired natural active
B. acquired natural passive
G. acquired artificial active
D. acquired artificial passive
100. Time for the final recording of the results of the lysis reaction, put in a test tube:
B.15-20min
101. The number of phases of the complement fixation reaction (RCC):
B. two
G. four
D. more than ten
102. Signs of a positive hemolysis reaction:
A. erythrocyte precipitation
B. formation of varnish blood
B. agglutination of erythrocytes
D. the appearance of a clouding ring
E. turbidity of the liquid in the test tube
103. For passive immunization apply:
A. vaccine
B. antitoxic serum
V. diagnosticum
D. immunoglobulin
E. toxin
J. allergen
104. Ingredients needed for setting RSK are:
A. distilled water
B. saline
B. complement
D. patient's blood serum
D. antigen
E. bacterial toxins
G. ram erythrocytes
Z. toxoid
I. hemolytic serum
105. For the diagnosis of infectious diseases, the following are used:
A. vaccine
B. allergen
B. antitoxic serum
G. toxoid
D. bacteriophage
E. diagnosticum
G. agglutinating serum
Z. immunoglobulin
I. precipitating serum
K. toxin
106. Bacteriological preparations are prepared from microbial cells and their toxins:
A. toxoid
B. antitoxic immune serum
B. antimicrobial immune serum
G. vaccines
D. immunoglobulin
E. allergen
J. diagnosticum
Z. bacteriophage
107. Antitoxic sera are sera:
A. anticholera
B. antibotulinum
G. anti-measles
D. against gas gangrene
E. tetanus toxoid
G. antidiphtheria
K. against tick-borne encephalitis
108. Choose the correct sequence of the following stages of bacterial phagocytosis:
1A. approach of a phagocyte to a bacterium
2B. adsorption of bacteria on a phagocyte
3B. engulfment of a bacterium by a phagocyte
4G. phagosome formation
5D. fusion of phagosome with mesosome to form phagolysosome
6E. intracellular microbial inactivation
7G. enzymatic digestion of bacteria and removal of remaining elements
109. Choose the correct sequence of stages of interaction (intercellular cooperation) in the humoral immune response in case of introduction of thymus-independent antigen:
4A. Formation of clones of plasma cells producing antibodies
3B. Antigen recognition by B-lymphocyte
2G. Presentation of the disintegrated antigen on the macrophage surface
110. An antigen is a substance that has the following properties:
Immunogenicity (tolerogenicity), determined by foreignness
Specificity
111. The number of classes of immunoglobulins in humans: five
112. IgGin the blood serum of a healthy adult is from the total content of immunoglobulins: 75-80%
113. Electrophoresis of human blood serumIgmigrate to the zone:γ-globulins
Production of antibodies of different classes
115. The receptor for sheep erythrocytes is present on the membrane: T-lymphocyte
116. B-lymphocytes form rosettes with:
mouse erythrocytes treated with antibodies and complement
117. What factors should be taken into account when assessing the immune status:
The frequency of infectious diseases and the nature of their course
The severity of the temperature reaction
The presence of foci of chronic infection
Signs of allergization
118. "Null" lymphocytes and their number in the human body is:
lymphocytes that have not undergone differentiation, which are progenitor cells, their number is 10-20%
119. Immunity is:
The system of biological protection of the internal environment of a multicellular organism (maintaining homeostasis) from genetically alien substances of exogenous and endogenous nature
120. Antigens are:
Any substances contained in microorganisms and other cells or secreted by them, which carry signs of foreign information and, when introduced into the body, cause the development of specific immune reactions (all known antigens are of a colloidal nature) + proteins. polysaccharides, phospholipids. nucleic acids
121. Immunogenicity is:
Ability to induce an immune response
122. Haptens are:
Simple chemical compounds of small molecular weight (disaccharides, lipids, peptides, nucleic acids)
Incomplete antigens
Not immunogenic
Have a high level of specificity for immune response products
123. The main class of human immunoglobulins with cytophilicity and providing an immediate hypersensitivity reaction is: IgE
124. In the primary immune response, the synthesis of antibodies begins with a class of immunoglobulins:
125. In a secondary immune response, the synthesis of antibodies begins with a class of immunoglobulins:
126. The main cells of the human body that provide the pathochemical phase of the immediate hypersensitivity reaction, releasing histamine and other mediators, are:
Basophils and mast cells
127. Delayed-type hypersensitivity reactions involve:
T-helpers, T-suppressors, macrophages and memory cells
128. The maturation and accumulation of which cells of the peripheral blood of mammals never occur in the bone marrow:
T-lymphocytes
129. Find correspondence between the type of hypersensitivity and the implementation mechanism:
1.Anaphylactic reaction- the production of IgE antibodies upon initial contact with the allergen, antibodies are fixed on the surface of basophils and mast cells, when the allergen hits again, mediators-histamine, seratonin, etc. are released.
2. Cytotoxic reactions- IgG, IgM, IgA antibodies are involved, fixed on various cells, the AG-AT complex activates the complement system in the classical way, next. cell cytolysis.
3.Immune complex reactions- formation of IC (soluble antigen associated with an antibody + complement), complexes are fixed on immunocompetent cells, deposited in tissues.
4.Cell mediated reactions– the antigen interacts with previously sensitized immune cells, these cells begin to produce mediators, causing inflammation (DTH)
130. Find correspondences between the complement activation pathway and the implementation mechanism:
1. Alternative path– due to polysaccharides, lipopolysaccharides of bacteria, viruses (AH without the participation of antibodies), the C3b component binds, with the help of the properdin protein, this complex activates the C5 component, then the formation of MAC => lysis of microbial cells
2. classic way- due to the Ag-At complex (complexes of IgM, IgG with antigens, binding of the C1 component, cleavage of the C2 and C4 components, formation of the C3 convertase, formation of the C5 component
3 .lectin pathway- due to mannan-binding lectin (MBL), protease activation, cleavage of C2-C4 components, classic variant. Ways
131. Antigen processing is:
The phenomenon of recognition of a foreign antigen by capturing, cleavage and binding of antigen peptides with molecules of the major histocompatibility complex class 2 and their presentation on the cell surface
? 132. Find correspondences between the properties of an antigen and the development of an immune response:
Specificity -
Immunogenicity -
133. Find correspondences between the type of lymphocytes, their number, properties and the way of their differentiation:
1. T-helpers, C D 4-lymphocytes - APC is activated, together with the MHC class 2 molecule, the division of the population into Tx1 and Tx2 (differ in interleukins), form memory cells, and Tx1 can turn into cytotoxic cells, differentiation in the thymus, 45-55%
2.C D 8 - lymphocytes - cytotoxic effect, activated by class 1 MHC molecule, can play the role of suppressor cells, form memory cells, destroy target cells ("lethal blow"), 22-24%
3.B-lymphocyte - differentiation in the bone marrow, the receptor receives only one receptor, after interaction with the antigen, it can go into the T-dependent path (due to IL-2 T-helper, the formation of memory cells and other classes of immunoglobulins) or T-independent (only IgM are formed) ,10-15%
134. The main role of cytokines:
Regulator of intercellular interactions (mediator)
135. Cells involved in antigen presentation to T-lymphocytes are:
Dendritic cells
Macrophages
Langerhans cells
B-lymphocytes
136. For the production of antibodies, B-lymphocytes receive help from:
T-helpers
137. T-lymphocytes recognize antigens that are presented in association with molecules:
Major histocompatibility complex on the surface of antigen-presenting cells)
138. Class antibodiesIgEproduced: at allergic reactions, plasma cells in bronchial and peritoneal lymph nodes, in the mucous membrane of the gastrointestinal tract
139. Phagocytic reaction is performed by:
neutrophils
eosinophils
basophils
macrophages
monocytes
140. Neutrophilic leukocytes have the following functions:
Capable of phagocytosis
Secreting a wide range of biologically active substances (IL-8 causes degranulation)
Associated with regulation of tissue metabolism and inflammatory cascade
141. In the thymus occurs: maturation and differentiation of T-lymphocytes
142. Major histocompatibility complex (MCHC) is responsible for:
A. are markers of the individuality of their body
B. are formed when cells of the body are damaged by some agents (infectious) and mark cells that must be destroyed by T-killers
V. participate in immunoregulation, present antigenic determinants on the membrane of macrophages and interact with T-helpers
143. The formation of antibodies occurs in: plasma cells
144. Class antibodiesIgGmay:
Pass through the placenta
Opsonization of corpuscular antigens
Binding and activation of complement along the classical pathway
Bacteriolysis and neutralization of toxigens
Agglutination and precipitation of antigens
145. Primary immunodeficiencies develop as a result of:
Defects in genes (such as mutations) that control the immune system
146. Cytokines include:
interleukins (1,2,3,4, etc.)
colony stimulating factors
interferons
tumor necrosis factors
macrophage inhibitory factor
147. Find correspondences between various cytokines and their main properties:
1. Hemopoietins- cell growth factors (ID provides growth stimulation, differentiation and activation of T-.B-lymphocytes,NK-cells, etc.) and colony-stimulating factors
2.Interferons- antiviral activity
3.Tumor necrosis factors- lyses some tumors, stimulates antibody formation and activity of mononuclear cells
4. Chemokines - attract leukocytes, monocytes, lymphocytes to the focus of inflammation
148. Cells synthesizing cytokines are:
activated T-lymphocytes
macrophages
thymic stromal cells
monocytes
mast cells
149. Alleghenes are:
1.full protein antigens:
food products (eggs, milk, nuts, shellfish); poisons of bees, wasps; hormones; animal sera; enzyme preparations (streptokinase, etc.); latex; house dust components (mites, fungi, etc.); pollen of grasses and trees; vaccine components
150. Find correspondences between the level of tests characterizing the immune status of a person and the main indicators of the immune system:
1st level- screening (leukocyte formula, determination of phagocytosis activity by the intensity of chemotaxis, determination of immunoglobulin classes, counting the number of B-lymphocytes in the blood, determination of the total number of lymphocytes and the percentage of mature T-lymphocytes)
2nd level - quantities. determination of T-helpers / inducers and T-killers / suppressors, determination of the expression of adhesion molecules on the surface membrane of neutrophils, assessment of the proliferative activity of lymphocytes for the main mitogens, determination of complement system proteins, determination of acute phase proteins, immunoglobulin subclasses, determination of the presence of autoantibodies, skin tests
151. Find the correspondence between the form of the infectious process and its characteristics:
Origin : exogenous- pathogenic agent comes from outside
endogenous- the cause of the infection is a representative of the conditionally pathogenic microflora of the macroorganism itself
autoinfection- when pathogens are introduced from one biotope of a macroorganism to another
According to the duration of the flow : acute, subacute and chronic (pathogen persists for a long time)
Distribution : focal (localized) and generalized (spread by lymphatic or hematogenous): bacteremia, sepsis and septicopyemia
By site of infection : community-acquired, nosocomial, natural-focal
152. Choose the correct sequence of periods in the development of an infectious disease:
1.incubation period
2. prodormal period
3.period expressed clinical symptoms(acute period)
4. period of convalescence (recovery) - possible bacteriocarrier
153. Find correspondences between the type of bacterial toxin and their properties:
1.cytotoxins- block protein synthesis at the subcellular level
2. membrane toxins– increase the permeability of surfaces. erythrocyte and leukocyte membranes
3.functional blockers- perversion of nerve impulse transmission, increased vascular permeability
4.exfoliatins and erythrogenins
154. Allergens contain:
155. Incubation period this: the time from the moment the microbe enters the body until the first signs of the disease appear, which is associated with reproduction, accumulation of microbes and toxin
PHAGOCYTOSIS (phagocytosis, Greek phagos devouring + kytos receptacle, here - cell + -osis) - the process of recognition, active capture and absorption of microorganisms, destroyed cells and foreign particles by specialized cells of the immune system.
The object of phagocytosis is microbes, foreign and altered own cells or their fragments, antigen-antibody complexes, etc. An integral part of phagocytosis is the directed movement - chemotaxis (see Taxis) - of phagocytes to the localization site of a foreign particle.
Determining the effectiveness of phagocytosis is carried out to assess the state of the immunobiological reactivity of the organism, as well as in various biomedical studies.
The phenomenon of phagocytosis as a biological universal reaction of unicellular, multicellular and higher organisms was discovered by I. I. Mechnikov, who in 1883 formulated the theory of phagocytosis. II Mechnikov considered phagocytosis as one of the forms of cell nutrition (starting with the simplest). In highly organized organisms, this form of nutrition is characteristic of special mesenchymal phagocyte cells that absorb and kill pathogenic microbes and thus perform a protective function. It was with the function of these cells that I. I. Mechnikov associated immunity to pathogens of infectious diseases. He described the phases of the phagocytic process and the state of activation of phagocytes, characterized by their new properties and enhanced ability to absorb and destroy bacteria. The key role of phagocytes was proved by him in immunity, inflammation, removal of damaged cells, regeneration, atrophy, and aging.
Phagocytes include granulocytes, mainly neutrophilic leukocytes (see), and mononuclear phagocytic cells (see System of mononuclear phagocytes), for example, monocytes, macrophages, etc. In the process of recognition of microbes, substances and particles by phagocytes, special components of blood serum play an important role , which are molecular mediators in the interaction of microbes with phagocytes and cause increased phagocytosis. These components are called opsonins (see), these include antibodies IgG1, IgG3, IgM, aggregated IgAl and IgA2 (see Immunoglobulins), and thermolabile complement subcomponents, mainly C3b (see Complement), as well as alpha-1 and beta -globulins, serum alpha-2-HS-glycoprotein. Indicate the opsonizing properties of the C-reactive protein (see), etc. IgG and IgM antibodies specifically bind to the antigens of the corresponding bacteria and through Fc receptors fix them to phagocyte receptors. Phagocytes can connect with the object of phagocytosis and non-specifically - through hydrophobic van der Waals bonds. Complement subcomponents arising from the classical or alternative pathway of its activation are sorbed on objects of phagocytosis, the attachment of which to the surface of the phagocyte is carried out through C3b and C4b receptors.
Opsonized and non-opsonized particles are also attached to phagocytes with the help of specific Fc receptors for IgE, glycoproteins and polysaccharides and nonspecific receptors for foreign substances. Most human neutrophils contain Fc receptors for aggregated IgGl and IgG3, and possibly for aggregated Ig A; monocytes are receptors for IgGl and IgG3. Complement receptors are highly affinity (have a high connection strength), they ensure the adherence of opsonized particles to non-activated macrophages, and only activated cells absorb such particles. On neutrophils, receptors for C3b-, C4b- and C5a-complement subcomponents were found, on macrophages - one receptor for C3b- and C4b-, the other for C3b- and C3c1-complement subcomponents. If the particle is opsonized by immunoglobulin and complement, binding to the phagocyte is carried out cooperatively through their specific receptors, which significantly activates its uptake. There are differences between the classes of receptors and the reactions of phagocytosis mediated by them. Phagocytosis of bacteria without opsonins is carried out by means of non-specific and specific for glycoproteins and polysaccharides receptors. Known phagocytosis of inert particles - silica, coal, etc.
Opsonins not only attach the object of phagocytosis to the surface of phagocytes, but also activate them, inducing signals coming from the plasma membrane, indirectly cause the activation of various humoral systems of the body, enhancing phagocytosis.
The process of absorption of an opsonized particle begins with the interaction of phagocyte receptors with opsonins localized on the surface of the particle. Subsequently, neighboring free phagocyte receptors interact with nearby free opsonins of the particle until all the opsonins covering the particle on the periphery are bound, and it is completely immersed in the cytoplasm of the phagocyte together with the surrounding area of the plasma membrane, forming a phagosome. The interaction of the particle with the plasma membrane of the phagocyte through the resulting opsonin-receptor complexes triggers a complex mechanism of phagocytosis, in which the main role belongs to the work of contractile proteins. The process of absorption begins with the formation of pseudopodia - stretching of the cytoplasm of the phagocyte in the direction of the particle. During the formation of pseudopodia, the unoriented actin filaments (filaments) located in it become parallel, which is accompanied by a transient change in the viscosity of the cytoplasm. The hypothesis of rigidity (gelatinization) is formulated - contraction of the cytoplasm, which changes its state and generates a mechanical force for the movement of the phagocyte, regulated by calcium ions. During gelatinization, actin filaments are cross-linked by an actin-binding protein, which turns the cytoplasm into a gel due to the formation of an actin lattice. This process is suppressed by a special calcium-dependent actin-regulatory protein - gelsolin, which is fiziol. actin gelatinization regulator. Further, myosin forms cross bridges with actin and the gel begins to contract, especially in the presence of magnesium ions, ATP and a cofactor, which is a kinase that phosphorylates the myosin heavy chain. At the point of contact between the plasma membrane and the particle, the rigidity of the cytoplasmic structures increases (gelatinization of a portion of the cytoplasm). The process is continuous; soluble actin-binding protein is constantly released from the plasma membrane and the membrane moves towards the particle. In the area of particle adhesion to the plasma membrane, the concentration of calcium ions increases, which “dissolve” the actin lattice, reduce the rigidity of the cytoplasm in this area, and it moves towards increased rigidity at the end of the pseudopodium, since myosin filaments pull the actin filaments in the direction of the region of greatest lattice stiffness.
In the process of phagocytosis, neutrophils consume energy stored in the form of ATP, formed as a result of the glycolysis reaction (see). In alveolar macrophages, energy for phagocytosis to a greater extent (perhaps mainly) is extracted from ATP formed in the process of oxidative phosphorylation (see Biological Oxidation). It has been established that the metabolic indicator in macrophages is not the absolute content of ATP, but the rate of renewal. The amount of ATP in phagocytic macrophages is partially maintained by phosphorylation of ADP by creatine phosphate (see Creatine), which is 3-5 times more abundant in macrophages than ATP, and consumption increases significantly during phagocytosis. Creatine phosphate in macrophages thus serves as the most important reserve and supplier of chemical energy for phagocytosis.
Phagocytosis is accompanied by a metabolic, or respiratory, burst, manifested by an increase in oxygen consumption and glucose oxidation through a hexose monophosphate shunt (see Carbohydrate metabolism). In this case, the main products of oxygen reduction are formed - superoxide anion and hydrogen peroxide due to the oxidation of nicotine adenine dinucleotides and nicotinamide adenine dinucleotide phosphates with the help of the corresponding NADH and NADPH oxidases; accumulating oxidized coenzymes cause an increase in the hexose monophosphate shunt due to their reduction with the help of glucose-6-phosphate-II 6-phosphogluconate dehydrogenases. Phagocytes have a complex system for destroying hydrogen peroxide. This system protects cell components from destruction and is represented by catalase, myeloperoxidase, glutathione peroxidase, reduced glutathione. The respiratory burst is accompanied by an increase in the metabolism of carbohydrates, lipids, RNA synthesis, an increase in the level of cyclic guanosine monophosphate, a decrease in protein synthesis and amino acid transport.
After completion of absorption of a particle the arisen phagosome and primary lysosomes (see), primary azurophilic and secondary specific granules of phagocytes mutually approach and merge, forming a phagolysosome. This process is accompanied by the disappearance of isolated granules in phagocytes. A large number of hydrolytic enzymes enter the phagosome from lysosomes. Phagocytosis is also associated with the secretion of a number of enzymes from phagocytes - (3-glucuronidase, N-acetyl-beta-glucosaminidase, acid and alkaline phosphatase, cathepsin, myeloperoxidase, lactoferrin, plasminogen activator. Such secretion is associated with activation of the hexose monophosphate shunt and lasts much longer than directly the process of phagocytosis.
After the penetration of bacteria into phagocytes, a complex microbicidal mechanism begins to function, represented by antimicrobial systems, both requiring oxygen and not dependent on it. The antimicrobial system that requires oxygen functions in two versions - with and without the participation of myeloperoxidase. The variant involving myeloperoxidase is highly active against bacteria, fungi, mycoplasmas, and viruses. The interaction of myeloperoxidase and hydrogen peroxide is accompanied by the formation of oxidizing agents, oxidation of halides and halogenation, which consists in iodination, chlorination, reservation of various bacterial components, which leads to the death of bacteria. In the described reactions, bactericidal ions of chlorine, iodine, chloramines, nitrites, bactericidal aldehydes, singlet oxygen are formed, which block many bacterial enzyme systems. The myeloperoxidase-independent variant of the microbial system of phagocytes causes the formation of intermediate forms of reduced oxygen toxic to microbes - superoxide anion, hydrogen peroxide, hydroxyl radical and singlet oxygen. The most active of them is hydrogen peroxide.
The antimicrobial system of phagocytosis, which does not depend on oxygen, includes: lysozyme (see), which breaks down the peptidoglycans of the cell walls of some gram-positive bacteria to disaccharides consisting of muramic acid and glucosamine; lactoferrin, which in its iron-unsaturated form has a microbostatic effect in phagosomes due to the binding of iron, which is a growth factor for a number of them; various cationic proteins. A certain bactericidal effect is also exerted by deep acidification forming in phagolysosomes up to pH 6.5-3.75.
Acidification also activates lysosomal hydrolases of primary lysosomes, which are inactive at slightly alkaline pH.
Microbicidal systems of phagocytes function in cooperation. They have different potency, but all together they have a mutually overlapping effect, therefore they have high reliability and efficiency even with defects in phagocytosis.
In violation of chemotaxis, phagocytosis of bacteria is suppressed, which contributes to the development and malignant course of a number of infectious diseases. Substances that induce chemotaxis are called chemoattractants and are divided into several groups: 1) products of specific, mainly immunological reactions, - C3-, C5a-subcomponents of complement, activated G567 complex, C3-convertase of the alternative pathway of complement activation, lymphokines (see Cell mediators immunity), lymphocyte transfer factor, cytophilic antibodies; 2) nonspecific endogenous chemo-attractants - products of damaged cells, kallikrein (see kinins), plasminogen activator, fibrinopeptide B, hydrolyzed or aggregated IgG, collagen, a- and P-casein of milk, cyclic adenosine monophosphate, etc .; 3) exogenous chemoattractants - bacterial protein fragments containing N-formylmethionine, peptides, lipids or lipoproteins released during the life of bacteria in the body.
On the surface of phagocytes, specific receptors for chemoattractants - eicosatetraenoic acid, synthetic formyl methionyl peptides, C5a subcomponent of the complement were found. Apparently, the number of these receptors is not the same in different types of phagocytes, for example, circulating rabbit neutrophils bind chemotactic peptides 8 times weaker than peritoneal neutrophils. The reaction of the contractile system of the cell to the action of chemoattractants has been proven. Its orientation to the gradient of chemoattractants is due to the work of microtubules, which play the role of the cytoskeleton of the cell - they maintain the polarized shape of the cell extended to the gradient of chemoattractants. However, the direct movement of the phagocyte is carried out by a system of microfilaments. It is assumed that blood proteins - albumin and IgG are regulators of the locomotor function of phagocytes. The activation of phagocytes by chemoattractants is largely accompanied by the same changes that occur during phagocytosis - a metabolic explosion, secretion of enzymes from cells, etc. Cyclic nucleotides play a certain regulatory role: cyclic adenosine monophosphate suppresses, and cyclic guanosine monophosphate stimulates chemotaxis.
Methods and methodological approaches to the assessment of phagocytosis are diverse and depend on the specific objectives of the study. They make it possible to determine the efficiency of the processes of particle absorption, death and digestion of living microorganisms, and metabolic changes in phagocytes. Important data on phagocytosis can also be obtained from the study of chemotaxis and opsonization.
To assess phagocytosis, various microorganisms are used - staphylococci (see), Escherichia (see), Salmonella (see Salmonella), etc. Both live and killed microbes are used, but since live bacteria often secrete toxic products that suppress phagocytosis, it is better use the dead.
Phagocytosis is enhanced in the presence of serum that opsonizes bacteria. To enhance and standardize phagocytosis, preopsonization is used, that is, preliminary (before phagocytosis) treatment of the microbe with opsonins - specific antibodies - or fresh serum, in which microbes activate the complement system and adsorb the emerging complement subcomponents that facilitate phagocytosis. However, in experiments with live microbes, only those that are not killed by opsonizing serum are used. The rate of phagocytosis is analyzed by co-incubation of phagocytes and live bacteria. Samples are taken at different intervals, they are freed from phagocytes using differential centrifugation, and the supernatant is inoculated onto agar plates, which makes it possible to determine the decrease in the number of live bacteria in the process of phagocytosis. When working with fungi of the genus Candida, the drug is calculated in the Goryaev chamber, while determining the number of extracellularly located fungi.
To analyze phagocytosis by determining the percentage of phagocytes that have absorbed bacteria (Hamburger phagocytic index), or the average number of bacteria absorbed by one phagocyte (phagocytic Reig number), the rate of phagocytosis, particles of latex, starch, zymosan, carmine, coal, etc. are used. A method for studying phagocytosis is proposed. , in which droplets of paraffin oil containing a special dye and stabilized with protein are used. The absorbed material is determined spectrophotometrically (see Spectrophotometry). Particles or microbes labeled with radioactive isotopes are also used (see Labeled Compounds). The method is characterized by speed of execution, however, it does not allow to completely get rid of adhering bacteria, which overestimates the phagocytosis rates. Another option is to add labeled serum proteins to the medium with phagocytes and particles, which enter the phagosome during phagocytosis, which makes it possible to quantify the intensity of phagocytosis. Xenogenic intact or syngeneic damaged or opsonized erythrocytes are also used, analyzing their absorption visually or by the output of hemoglobin.
When studying the absorption of live bacteria, especially with the subsequent consideration of the number of killed bacteria, it is necessary to remove adhering microbes from the surface of phagocytes. To do this, various antibiotics are used that kill extracellular bacteria, but do not penetrate into phagocytes, special preparations (phenylbutazan), which interrupt phagocytosis and intracellular inactivation of microbes at certain points. A method has been developed to distinguish between adhering and absorbed dead fungi of the genus Candida by staining the preparation with trypan blue.
The death and digestion of the absorbed microbes is detected by incubating a suspension of phagocytes with microbes, subsequent washing of phagocytes of adherent microbial cells, counting live microbes remaining in phagocyte samples taken at different incubation periods. The number of live bacteria is determined by serial inoculation of phagocyte samples on Petri dishes with agar. The number of live fungi is counted in the phagocyte lysate after incubation by staining with methylene blue. Intracellular digestion of bacteria is also studied by including 3H-uridine in them. To do this, the culture of phagocytes that have absorbed bacteria is treated with actinomycin D, adding 3H-uridine to the medium. The label, being included in live intracellular bacteria, does not get into dead and phagocytes.
Analysis of the damaging effect of phagocytes on microbes can be carried out by the degree of staining of absorbed microbes with dyes or by staining with methylene blue phagolysosomes of phagocytes. The completion of phagocytosis is assessed by the ratio of the average number of killed microbes to living ones or the number of phagocytes with digested microbes to the total number of phagocytic phagocytes, as well as by the percentage of destroyed microbes from the number of phagocytized ones or by the average number of killed microbes per phagocyte. The severity of metabolic changes during phagocytosis is analyzed by oxygen consumption, chemiluminescence, glucose oxidation, iodination, etc.
Phagocytes play a key role in the formation of antimicrobial immunity (see Immunity), due to both specific and non-specific protective factors. Despite the fact that specific immunity is mediated by specific T cells, as well as specific antibodies that opsonize bacteria and enhance phagocytosis, elimination of pathogenic bacteria is carried out nonspecifically - by phagocytes activated by lymphokines of specific T lymphocytes. Activated phagocytes kill bacteria much more effectively, which was shown by II Mechnikov. Natural immunity to pathogens of infectious diseases is also mainly due to phagocytic cells. They also play a key role in the detoxification of bacterial toxins neutralized by antibodies.
Macrophages, processing the antigen and presenting it to lymphocytes, participating in intercellular cooperation, activation and suppression of lymphocyte proliferation, are a necessary link in the formation of immunological tolerance (see Immunological tolerance) and transplantation immunity (see Transplant immunity). Macrophages are involved in antitumor immunity (see Antitumor Immunity), providing a cytostatic and cytotoxic effect on tumor cells.
Damage to phagocytes by various immunosuppressors, blockers (see Immunity, Immunosuppressive substances), ionizing radiation (see) cause a sharp suppression of the body's antimicrobial resistance. When animals are exposed to high doses of ionizing radiation, phagocytic activity can practically disappear. Phagocytic activity in animals is normalized, as a rule, after the 20th day. In rabbits irradiated at a dose of 600 rad (6 Gy), it is restored only after 40 days. There is a correlation between the dose of ionizing radiation and the degree of suppression of phagocytosis. Doses of 10-75 rad (0.1 - 0.75 Gy) enhance phagocytosis of granulocytes, and 350-600 rad (3.5-6 Gy) sharply inhibit it, and the completeness of phagocytosis decreases, the mobility of phagocytes is suppressed 3-4 times , and their absolute number also decreases. The same regularities are characteristic of macrophages, the number and digestion capacity of which also sharply decrease under irradiation.
Diseases accompanied by primary (congenital) or secondary (acquired) defects in phagocytosis have been identified. These include the so-called chronic granulomatous disease that occurs in children in whose phagocytes, due to a defect in oxidases, the formation of peroxides and superperoxides and, consequently, the process of inactivation of microbes, is impaired. A reduced ability to kill bacteria has been found in people whose neutrophils synthesize an insufficient amount of myeloperoxidase, glucose-6-phosphate dehydrogenase, and pyruvate kinase. The slow death of microbes is found in patients with Chediak-Higashi syndrome (see Thrombocytopathies), in whose neutrophils the release of lysosomal enzymes into the phagosome is impaired due to a defect in the microtubule system. A disruption in the process of actin polymerization has been described, leading to a slowdown in the absorption of particles by neutrophils and their mobility. Patients with these phagocyte defects often suffer from severe bacterial and fungal infections.
Primary disorders of phagocytosis are also observed at the level of opsonins, for example, in congenital deficiency of the C3 and C5 complement components, which can lead to the development of recurrent infections affecting the lungs, bones, and skin.
Secondary defects in phagocytosis have been described in diseases of the connective tissue, kidneys, malnutrition, viral and recurrent bacterial infections.
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V. M. Zemskov.