Lecture plan PURPOSE: to teach students an understanding of structural and functional organization immune system,
features of innate and adaptive
immunity.
1. The concept of immunology as a subject, basic
stages of its development.
2. .
3 Types of immunity: features of innate and
adaptive immunity.
4. Characteristics of cells involved in reactions
innate and adaptive immunity.
5. Structure of central and peripheral organs
immune system functions.
6. Lymphoid tissue: structure, function.
7. GSK.
8. Lymphocyte – structural and functional unit
immune system.
Cell population – cell types with the most
general properties
Subpopulation of cells - more specialized
homogeneous cells
Cytokines – soluble peptide mediators
immune system, necessary for its development,
functioning and interaction with others
systems of the body.
Immunocompetent cells (ICC) - cells
ensuring the performance of immune functions
systems
Immunology
- the science of immunity, whichstudies structure and function
body immune system
person as under normal conditions,
as well as in pathological
states.
Immunology studies:
The structure of the immune system and mechanismsdevelopment of immune reactions
Diseases of the immune system and its dysfunction
Conditions and patterns of development
immunopathological reactions and methods for them
corrections
Possibility of using reserves and
mechanisms of the immune system in the fight against
infectious, oncological, etc.
diseases
Immunological problems of transplantation
organs and tissues, reproduction
Main stages in the development of immunology
Pasteur L. (1886) - vaccines (prevention of infectious diseasesdiseases)
Bering E., Ehrlich P. (1890) - laid the foundation for humoral
immunity (discovery of antibodies)
Mechnikov I.I. (1901-1908) - theory of phagocytosis
Bordet J. (1899) – discovery of the complement system
Richet S., Portier P. (1902) - discovery of anaphylaxis
Pirke K. (1906) – the doctrine of allergies
Landsteiner K. (1926) – discovery of blood groups AB0 and Rh factor
Medovar (1940-1945) - the doctrine of immunological tolerance
Dosse J., Snell D. (1948) - laid the foundations of immunogenetics
Miller D., Klaman G., Davis, Royt (1960) - the doctrine of T- and B
immune systems
Dumond (1968-1969) – discovery of lymphokines
Koehler, Milstein (1975) - method for obtaining monoclonal
antibodies (hybridomas)
1980-2010 – development of diagnostic and treatment methods
immunopathology
Immunity
- a way to protect the body from living bodies andsubstances that carry genetic characteristics
foreign information (including
microorganisms, foreign cells,
tissue or genetically altered
own cells, including tumor cells)
Types of immunity
Innate immunity is hereditaryfixed defense system of multicellular organisms
organisms from pathogenic and non-pathogenic
microorganisms, as well as endogenous products
tissue destruction.
Acquired (adaptive) immunity is formed throughout life under the influence of
antigenic stimulation.
Innate and acquired immunity are
two interacting parts of the immune system
systems that ensure the development of the immune system
response to genetically foreign substances. Systemic immunity – at the level
the whole body
Local immunity -
additional level of protection
barrier fabrics ( skin And
mucous membranes)
Functional organization of the immune system
Innate immunity:- stereotyping
- non-specificity
(regulated by the pituitary-adrenal system)
Mechanisms:
anatomical and physiological barriers (skin,
mucous membranes)
humoral components (lysozyme, complement, INFα
and β, acute phase proteins, cytokines)
cellular factors (phagocytes, NK cells, platelets,
red blood cells, mast cells, endothelial cells)
Functional organization of the immune system
Acquired immunity:specificity
formation of immunological
memory during the immune response
Mechanisms:
humoral factors - immunoglobulins
(antibodies)
cellular factors – mature T-, B-lymphocytes
The immune system
- a set of specialized bodies,tissues and cells located in
different parts of the body, but
functioning as a single whole.
Peculiarities:
generalized throughout the body
constant recycling of lymphocytes
specificity
Physiological significance of the immune system
securityimmunological
individuality throughout life
immune recognition account with
involving components of congenital and
acquired immunity. antigenic
nature
endogenously arising
(cells,
changed
viruses,
xenobiotics,
tumor cells and
etc.)
or
exogenously
penetrating
V
organism
Properties of the immune system
Specificity - “one AG – one AT – one clonelymphocytes"
High degree of sensitivity - recognition
AG by immunocompetent cells (ICC) at the level
individual molecules
Immunological individuality “specificity of the immune response” - for everyone
the organism has its own characteristic, genetically
controlled type of immune response
Clonal principle of organization - ability
all cells within a single clone respond
only for one antigen
Immunological memory is the ability of the immune system
systems (memory cells) respond quickly and
intensively for re-entry of antigen
Properties of the immune system
Tolerance is a specific unresponsiveness tobody's own antigens
The ability to regenerate is a property of the immune system
systems to maintain lymphocyte homeostasis due to
replenishment of the pool and control of the population of memory cells
The phenomenon of “double recognition” of antigen by T lymphocytes - the ability to recognize foreign
antigens only in association with MHC molecules
Regulatory effect on other body systems
Structural and functional organization of the immune system
Structure of the immune system
Organs:central (thymus, red bone marrow)
peripheral (spleen, lymph nodes, liver,
lymphoid accumulations in different organs)
Cells:
lymphocytes, leukocytes (mon/mf, nf, ef, bf, dk),
mast cells, vascular endothelium, epithelium
Humoral factors:
antibodies, cytokines
ICC circulation pathways:
peripheral blood, lymph
Immune system organs
Features of the central organs of the immune system
Located in areas of the bodyprotected from external influences
(bone marrow - in the bone marrow cavities,
thymus in the chest cavity)
The bone marrow and thymus are the site
lymphocyte differentiation
In the central organs of the immune system
lymphoid tissue is in a peculiar
microenvironment (in bone marrow –
myeloid tissue, in the thymus - epithelial)
Features of peripheral organs of the immune system
Located on the paths of the possibleintroduction of foreign substances into the body
antigens
Consistently increasing their complexity
buildings depending on size and
duration of antigenic
impact.
Bone marrow
Functions:hematopoiesis of all types of blood cells
antigen-independent
differentiation and maturation B
- lymphocytes
Hematopoiesis scheme
Types of stem cells
1. Hematopoietic stem cells (HSCs) –located in the bone marrow
2. Mesenchymal (stromal) stems
cells (MSCs) – a population of pluripotent
bone marrow cells capable of
differentiation into osteogenic, chondrogenic,
adipogenic, myogenic and other cell lines.
3. Tissue-specific progenitor cells
(progenitor cells) –
poorly differentiated cells
located in various tissues and organs,
are responsible for updating the cell population.
Hematopoietic stem cell (HSC)
Stages of development of GSKMultipotent stem cell– proliferates and
differentiates into parent stems
cells for myelo- and lymphopoiesis
Progenitor stem cell - limited in
self-maintenance, intensively proliferates and
differentiates in 2 directions (lymphoid
and myeloid)
Progenitor cell - differentiates
into only one type of cell (lymphocytes,
neutrophils, monocytes, etc.)
Mature cells- T-, B-lymphocytes, monocytes, etc.
Features of GSK
(the main marker of HSC is CD 34)Poor differentiation
Self-sustaining ability
Moving through the bloodstream
Repopulation of hemo- and immunopoiesis after
radiation exposure or
chemotherapy
Thymus
Consists of lobulesmedulla.
each has a cortical
And
The parenchyma is represented by epithelial cells,
containing a secretory granule that secretes
“thymic hormonal factors.”
The medulla contains mature thymocytes, which
turn on
V
recycling
And
populate
peripheral organs immune system.
Functions:
maturation of thymocytes into mature T cells
secretion of thymic hormones
regulation of T cell function in others
lymphoid organs through
thymic hormones
Lymphoid tissue
- specialized fabric that providesconcentration of antigens, contact of cells with
antigens, transport of humoral substances.
Encapsulated – lymphoid organs
(thymus, spleen, The lymph nodes, liver)
Unencapsulated – lymphoid tissue
mucous membranes, associated with the gastrointestinal tract,
respiratory and genitourinary system
Lymphoid subsystem of the skin -
disseminated intraepithelial
lymphocytes, regional lymph nodes, vessels
lymphatic drainage
Lymphocytes are the structural and functional unit of the immune system
specificcontinuously generate
diversity of clones (1018 variants in T-
lymphocytes and 1016 variants in B-lymphocytes)
recirculation (between blood and lymph in
on average about 21 hours)
renewal of lymphocytes (at a speed of 106
cells per minute); among peripheral lymphocytes
blood 80% long-lived memory lymphocytes, 20%
naive lymphocytes formed in the bone marrow
and have not had contact with the antigen)
Literature:
1. Khaitov R.M. Immunology: textbook. Forstudents of medical universities. - M.: GEOTAR-Media,
2011.- 311 p.
2. Khaitov R.M. Immunology. Norm and
pathology: textbook. for students of medical universities and
Univ.- M.: Medicine, 2010.- 750 p.
3. Immunology: textbook / A.A. Yarilin.- M.:
GEOTAR-Media, 2010.- 752 p.
4. Kovalchuk L.V. Clinical immunology
and allergology with the basics of general
Immunology: textbook. – M.: GEOTARMEDIA, 2011.- 640 p.
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Text content of presentation slides: Central and peripheral hematopoietic organs and immune defense Author Ananyev N.V. GBPOU DZM "MK No. 1" 20016 Central organ of hematopoiesis - red bone marrow Central organ of immune defense - thymus Peripheral organs Spleen tonsils Lymph nodes Lymphoid follicles Red bone marrow In the embryo, it fills most bones, including tubular ones. In adults, it is found: in flat bones, in the vertebral bodies, in the epiphyses tubular bones. Red bone marrow Reticular tissue Hematopoietic elements Reticular tissue consists of: Cells Intercellular substance Reticular fibers Cells: 1. Reticular cells (fibroblast-like) 2. Macrophages 3. A small number of fat cells Hematopoietic elements – 1. All types of hematopoietic cells located on different levels differentiation 2. blood stem cells 3. mature blood cells Hematopoietic islets are groups of cells in the bone marrow. Red bone marrow I. ERYTHROPOIETIC ISLANDS: 1 - proerythroblast, 2-4 - erythroblasts: basophilic (2); polychromatophilic (3); oxyphilic (4); 5 - red blood cells. II. GRANULOCYTOPOIETIC ISLANDS (eosinophilic, basophilic, neutrophilic): 6 - promyelocyte, 7A-7B - myelocytes: eosinophilic (7A), basophilic (7B), neutrophilic (7B); 8A-8B - metamyelocytes: eosinophilic (8A) and basophilic (8B); 9 - band granulocyte (neutrophil); 10A-10B - segmented granulocytes: eosinophilic (10A) and neutrophilic (10B). III. Other hematopoietic cells: 11 - megakaryocyte; 12 - cells similar to small lymphocytes (cells of classes I - III and more mature cells of the monocyte and B-lymphocyte series). IV. Other components of red bone marrow: 13 - reticular cells(form stroma); 14 - adipocytes, 15 - macrophages; 16 - perforated sinusoidal capillaries. Features of blood supply - The bone marrow contains sinusoidal capillaries that do not allow immature blood cells to pass from the bone marrow into the blood. Mature cells enter the capillaries and the bloodstream. Functions Hematopoiesis is the formation of all blood cells. Differentiation of B lymphocytes, which then populate peripheral organs Thymus consists of stroma and parenchyma Stroma is loose fibrous connective tissue, which forms outer shell. Partitions extend from it into the gland and divide the gland into lobules. Parenchyma - consists of epithelial and lymphocytic structures. The thymus lobule has 3 parts: Subcapsular zone Cortical substance Medullary substance The thymic lobule has 3 parts Subcapsular zone Consists of branched epithelial cells that are connected to each other using processes. Functions: participation in the differentiation and maturation of T-lymphocytes under the control of thymic hormones: thymosin, thymopoietin Cortical substance Formed by precursor cells of T-lymphocytes and T-lymphocytes located at different levels of differentiation and macrophages. The cortex is darker than the medulla. Functions: differentiation of T-lymphocytes. The medulla is formed by T-lymphocytes and macrophages and thymic bodies - layering. epithelial cells that have lost their oval-shaped processes. But there are significantly fewer of them than in the cortex, so it looks lighter when stained. Functions: unknown, perhaps some stages of differentiation of T-lymphocytes Features of blood supply: 1. The cortex and medulla are supplied with blood separately2. Blood from the cortex, without entering the medulla, immediately flows out of the thymus3. In the cortex there is a hematothymic barrier - a barrier between the parenchyma of the thymus and the blood of the capillaries of the cortex. The hematothymic barrier delays the flow of high-molecular substances from the capillaries into the thymus and allows thymocytes to differentiate in the absence of contact with foreign antigens. Involution of the thymus The thymus reaches its maximum development in childhood when the body’s immune system is intensively formed. IN old age its age-related involution occurs - a decrease in size and a decrease in functions. Under the influence of stress due to the effects of glucocorticoids (adrenal hormones), rapid involution occurs. Thymus cells die by apoptosis, the thymus shrinks, and its parenchyma is replaced by adipose tissue. Spleen The spleen consists of stroma and parenchyma. Stroma is loose fibrous connective tissue that forms the outer shell. Partitions - trabeculae - extend from it into the gland. Parenchyma - consists of pulp: red and white. The white pulp consists of lymphoid nodules. Lymphoid nodules of the spleen have a diameter of 0.3-0.5 mm. In the center of the nodule is an arteriole. The basis of the nodule is formed by reticular tissue, in the loops of which lymphocytes lie. There are 2 zones in the nodule: B-zone - the largest part, responsible for the differentiation of B-lymphocytes. T-zone - the smaller part - reproduction and differentiation of T-lymphocytes. Nodules have 3 stages of development: 1. Initial 2. Without a light center 3. With a light center - an indicator of high functional activity. Formed during antigenic stimulation. Lymph node with a light center It has 3 zones: 1. Reproduction center 2. Periarterial zone 3. Mantle or marginal layer Reproduction center Here are B-lymphocytes and their antigen-dependent differentiation occurs Periarterial zone Here are T-lymphocytes and their antigen-dependent differentiation occurs Mantle layer Here the interaction between T and B lymphocytes occurs, which is necessary for their differentiation. Red pulp Occupies most of the spleen. Consists of sinusoidal capillaries containing blood and reticular tissue. Functions of the spleen White pulp - antigen dependent differentiation of T and B lymphocytes. Red pulp – Death of old red blood cells. Death of old platelets. Blood depot – up to 1 liter. Final stages lymphocyte differentiation. Blood supply to the spleen Splenic artery – trabecular arteries – pulp arteries – central arteries (inside the nodule) – brush arteries (have sphincters) – ellipsoid arterioles – hemocapillaries. Blood supply to the spleen A minority of the hemocapillaries opens into the red pulp, the majority passes into the venous sinuses. A sinus is a cavity filled with blood. From the sinuses, blood can flow into the red pulp or into the venous capillaries. Blood supply to the spleen The venous sphincters contract - blood accumulates in the sinuses, they stretch. Arterial sphincters contract - shaped elements blood exits through pores in the walls of the sinuses into the red pulp. All sphincters are relaxed - blood from the sinuses flows into the veins, they empty. Blood supply to the spleen From the sinus, blood enters the pulp veins - trabecular veins - splenic vein - portal vein liver (portal). The lymph nodes
Epidemics of plague, cholera, smallpox, and influenza left a deep mark on the history of mankind. In the 14th century, a terrible epidemic of the “Black Death” swept through Europe, killing 15 million people. It was a plague that swept through all countries and killed 100 million people. She left an equally terrible mark behind. smallpox, called "black smallpox". The smallpox virus caused the death of 400 million people, and the survivors became permanently blind. 6 cholera epidemics have been registered, the last one in India and Bangladesh. The flu epidemic called “Spanish flu” has claimed the lives of hundreds of thousands of people over the years; there are known epidemics called “Asian”, “Hong Kong”, and today, “swine” flu.
Morbidity of the child population In the structure of the general morbidity of the child population over a number of years: in first place - diseases of the respiratory system; second place - occupied by diseases of the digestive system; in third place - diseases of the skin and subcutaneous tissue and diseases nervous system
Morbidity in children Statistical research recent years put diseases associated with decreased immunity in one of the first places in human pathology. Over the past 5 years, the level of general morbidity in children has increased by 12.9%. the largest increase was observed in the classes of diseases of the nervous system - by 48.1%, neoplasms - by 46.7%, pathologies of the circulatory system - by 43.7%, diseases of the musculoskeletal system - by 29.8%, endocrine system– by 26.6%.
Immunity from lat. Immunities - liberation from something The immune system provides to the human body multi-stage protection against foreign invasions This is a specific protective reaction of the body, which is based on the ability to resist the action of living bodies and substances that differ from it in hereditarily foreign properties, to maintain its integrity and biological individuality. The main purpose of the immune system is to determine what is in the body and what is not someone else's. Your own must be left alone, and someone else’s must be destroyed, and as quickly as possible Immunity - ensures the functioning of the body as a single whole, consisting of one hundred trillion cells
Antigen - antibody All substances (microbes, viruses, dust particles, plant pollen, etc.) that enter the body from outside are usually called antigens. It is the influence of antigens that determines when they enter internal environment the body forms protein structures called antibodies. The main structural and functional unit of the immune system is the lymphocyte
Components of the human immune system 1. Central lymphoid organs: - thymus ( thymus); - Bone marrow; 2. Peripheral lymphoid organs: - lymph nodes - spleen - tonsils - lymphoid formations of the colon, vermiform appendix, lungs, 3. Immunocompetent cells: - lymphocytes; - monocytes; - polynuclear leukocytes; - white branched epidermocytes of the skin (Langerhans cells);
Nonspecific factors of the body's defense The first protective barrier Nonspecific mechanisms of immunity are general factors and protective devices of the body Protective barriers The first protective barrier impermeability healthy skin and mucous membranes (gastrointestinal tract, respiratory tract, genitals) impermeability of histohematological barriers the presence of bactericidal substances in biological fluids(saliva, tears, blood, cerebrospinal fluid) and other secrets of sebaceous and sweat glands have a bactericidal effect against many infections
Nonspecific factors of the body's defense The second protective barrier The second protective barrier is inflammatory reaction at the site of introduction of the microorganism. The leading role in this process belongs to phagocytosis (factor cellular immunity) Phagocytosis - is the absorption and enzymatic digestion of microbes or other particles by macro- and microphages, resulting in the liberation of the body from harmful foreign substances. Phagocytes are the largest cells of the human body, they perform important function nonspecific protection. Protects the body from any penetration into its internal environment. And this is its purpose, the phagocyte. The phagocyte reaction occurs in three stages: 1. Movement towards the target 2. Envelopment foreign body 3. Absorption and digestion (intracellular digestion)
Nonspecific body defense factors The third protective barrier operates when the infection spreads further. These are lymph nodes and blood (factors humoral immunity). Each of these factors of the three barriers and adaptations is directed against all microbes. Nonspecific protective factors neutralize even those substances that the body has not previously encountered
Specific mechanisms of immunity This is antibody formation in the lymph nodes, spleen, liver and bone marrow. Specific antibodies are produced by the body in response to the artificial introduction of an antigen or as a result of a natural encounter with a microorganism (infectious disease) Antigens are substances that carry a sign of foreignness (bacteria, proteins, viruses , toxins, cellular elements) Antigens are the pathogens themselves or their metabolic products (endotoxins) and bacterial breakdown products (exotoxins). Antibodies are proteins that can bind to antigens and neutralize them. They are strictly specific, i.e. act only against those microorganisms or toxins in response to the introduction of which they were developed.
Specific immunity It is divided into congenital and acquired. Innate immunity is inherent in a person from birth, inherited from parents. Immune substances from mother to fetus through the placenta. A special case of innate immunity can be considered the immunity received by a newborn with mother's milk Acquired immunity - occurs (acquired) during life and is divided into natural and artificial Natural acquired - occurs after suffering an infectious disease: after recovery, antibodies to the pathogen remain in the blood of this disease. Artificial - produced after special medical events and it can be active and passive
Artificial immunity Created by administering vaccines and serums Vaccines are preparations from microbial cells or their toxins, the use of which is called vaccination. 1-2 weeks after the introduction of vaccines, antibodies appear in the human body. Serums are often used to treat infectious patients and, less often, for prevention. infectious diseases
Vaccinal prophylaxis This is the main practical purpose of vaccines Modern vaccine preparations are divided into 5 groups: 1. Vaccines from live pathogens 2. Vaccines from killed microbes 3. Chemical vaccines 4. Toxoids 5. Associated, i.e. combined (for example, DTP - associated pertussis-diphtheria-tetanus vaccine)
Serums Serums are prepared from the blood of patients who have recovered from the disease. infectious disease people or by artificial infection of animals with microbes The main types of sera: 1. Antitoxic sera neutralize the poisons of microbes (antidiphtheria, antitetanus, etc.) 2. Antimicrobial sera inactivate bacterial cells and viruses, are used against a number of diseases, most often in the form of gamma globulins There are gamma-globulins globulins from human blood - against measles, polio, infectious hepatitis, etc. This safe drugs, because they do not contain pathogens. Immune serums contain ready-made antibodies and are effective from the first minutes after administration.
NATIONAL PREVENTIVE VACCINATION CALENDAR AgeName of vaccination 12 hours First vaccination hepatitis B 3-7 days Tuberculosis vaccination 1 month Second vaccination hepatitis B 3 months First vaccination diphtheria, whooping cough, tetanus, polio 4.5 months Second vaccination diphtheria, whooping cough, tetanus, polio 6 months Third vaccination diphtheria, whooping cough , tetanus, polio Third vaccination hepatitis B 12 months Vaccination measles, rubella, mumps
Critical periods in the formation of the immune system of children The first critical period is the neonatal period (up to 28 days of life) The second critical period is 3-6 months of life, due to the destruction of maternal antibodies in the child’s body The third critical period is 2-3 years of the child’s life The fourth critical period is 6-7 years Fifth critical period – adolescence(12-13 years old for girls; years old for boys)
Factors that reduce protective functions body Main factors: alcoholism and alcoholism drug addiction and addiction psycho-emotional stress physical inactivity sleep deficiency excess weight A person’s susceptibility to infection depends on: individual characteristics human features of constitution, metabolic state, nutritional status, vitamin supply, climatic factors and season of the year, pollution environment living conditions and human activities lifestyle
Increasing the child’s body’s defenses using general strengthening techniques: hardening, contrast air baths, dressing the baby appropriately for the weather, taking multivitamins, trying to limit contact with other children as much as possible during periods of seasonal outbreaks viral diseases(for example, during a flu epidemic, you should not take your child to Christmas trees and other public events) remedies traditional medicine, for example, garlic and onions When should you contact an immunologist? With frequent colds occurring with complications (ARVI, turning into bronchitis - inflammation of the bronchi, pneumonia - inflammation of the lungs or occurring against the background of ARVI purulent otitis– inflammation of the middle ear, etc.) In case of repeated infections, to which lifelong immunity must be developed ( chicken pox, rubella, measles, etc.). However, in such cases, it is necessary to take into account that if the baby has had these diseases before the age of 1 year, then immunity to them may not be stable and may not provide lifelong protection.
The immune system provides: Protection of the body from foreign cells (germs, viruses, transplanted tissue, etc.) Recognition and destruction of its own old, defective or modified cells. Neutralization and elimination of genetically foreign high-molecular substances (proteins, polysaccharides, etc.)
Central authorities immunity: (thymus, bone marrow) ensure the development, maturation and differentiation of lymphocytes before they meet the antigen, that is, they prepare the lymphocytes to respond to the antigen. Peripheral organs of immunity: (spleen, lymph nodes, lymphoid accumulations of border tissues (tonsils, appendix, Peyer's patches) an immune response is formed.
Functions of the thymus Functions of the thymus: formation and differentiation of T-lymphocytes synthesis of thymic factors thymic hormones) regulation and differentiation somatic cells in the fetus - “growth factors”. The heyday of the thymus is 0-15 years of life. Early involution - years, aging - after 40. The highest production of T-lymphocytes persists up to 2 years. Thymic hypertrophy can be caused by triiodothyronine (T3), prolactin and growth hormone. Thymus hypotrophy - genetic disorders, environmental influences, starvation. Tumors of the thymus - thymomas.
Lymphoid accumulations of border tissues Tonsils reception of antigens, production of immunoglobulins Appendix reception of intestinal microflora antigens, formation of general immune reaction Peyer's patches immunological control of substances absorbed from the intestinal lumen, synthesis of antibodies, mainly Ig A
Antigens are substances that are recognized by lymphocyte receptors. When they enter the body, they cause specific immunological reactions: synthesis of antibodies, cellular immunity reactions, immunological tolerance, immunological memory. AG, causing allergies– allergens, tolerance – tolerogens, etc. Antigens
Humoral factors of immunity Antibodies (immunoglobulins) are glycoproteins formed by plasma cells and capable of specifically binding antigen. Cytokines are a group of protein compounds that provide intercellular signal transmission during the immune response.
Haptens Haptens (incomplete antigens) are low molecular weight substances that normal conditions do not ensure the development of an immune response (i.e., they do not have the property of immunogenicity), but can interact with pre-existing antibodies, exhibiting the property of specificity. Haptens include medications and the majority chemical substances. After binding to the proteins of the macroorganism, these substances acquire the ability to trigger an immune response, that is, they become immunogenic. As a result, antibodies are formed that can interact with the hapten.
Basic postulates of antigen recognition by lymphocytes Antigen-binding receptors against any antigens possible in nature pre-exist on the surface of lymphocytes. The antigen acts only as a factor in the selection of cell clones carrying receptors corresponding to its specificity. One lymphocyte contains a receptor of only one specificity. Lymphocytes capable of interacting with an antigen of one specific specificity form a clone and are descendants of one parent cell. Three main cell types are involved in antigen recognition: T lymphocytes, B lymphocytes, and antigen presenting cells. T lymphocytes do not recognize the antigen itself, but a molecular complex consisting of a foreign antigen and the organism’s own histocompatibility antigens. Triggering of the T-cell response is associated with a two-signal activation system
Antigen-presenting cells Must: form a complex of the antigenic peptide with HLA and carry costimulators on their surface, ensuring the passage of the second signal upon cell activation. Adapted to process specific antigens. The main human APCs are: Macrophages – represent bacterial antigens. Dendritic cells represent predominantly viral Ags. Langerhans cells, the precursors of dendritic cells in the skin, are antigens that penetrate the skin. B cells - present soluble protein antigens, primarily bacterial toxins. Approximately times more efficient at presenting very small amounts of soluble antigens to T cells than macrophages.
ORGANS OF THE IMMUNE SYSTEM ARE DIVIDED INTO CENTRAL AND PERIPHERAL. THE CENTRAL (PRIMARY) ORGANS OF THE IMMUNE SYSTEM INCLUDE THE BONE MARROW AND THE THYMUS. IN THE CENTRAL ORGANS OF THE IMMUNE SYSTEM MATURATION AND DIFFERENTIATION OF IMMUNE SYSTEM CELLS FROM STEM CELLS OCCUR. IN THE PERIPHERAL (SECONDARY) ORGANS THE MATURATION OF LYMPHOID CELLS OCCURS TO THE FINAL STAGE OF DIFFERENTIATION. THESE INCLUDE THE SLEEN, LYMPH NODES AND LYMPHOID TISSUE OF THE MUCOUS MEMBRANES.
CENTRAL ORGANS OF THE IMMUNE SYSTEM Bone marrow. All the formed elements of blood are formed here. Hematopoietic tissue is represented by cylindrical accumulations around arterioles. Forms cords that are separated from each other by venous sinuses. The latter flow into the central sinusoid. The cells in the cords are arranged in islands. Stem cells are localized mainly in the peripheral part of the bone marrow canal. As they mature, they move toward the center, where they penetrate the sinusoids and then enter the blood. Myeloid cells in the bone marrow account for 60-65% of cells. Lymphoid 10-15%. 60% of cells are immature cells. The rest are mature or newly entered into the bone marrow. Every day, about 200 million cells migrate from the bone marrow to the periphery, which is 50% of their total number. In the human bone marrow, intensive maturation of all types of cells occurs, except for T cells. The latter pass only initial stages differentiation (pro-T cells, then migrating to the thymus). Plasma cells are also found here, constituting up to 2% of the total number of cells, and producing antibodies.
T IMUS. C SPECIALIZES EXCLUSIVELY ON THE DEVELOPMENT OF T-LYMPHOCYTES. AND HAS AN EPITHELIAL FRAMEWORK IN WHICH T-LYMPHOCYTES DEVELOP. IMATURE T-LYMPHOCYTES THAT DEVELOP IN THE THYMUS ARE CALLED THYMOCYTES. MATURATING T-LYMPHOCYTES ARE TRANSIT CELLS THAT ENTER THE THYMUS IN THE FORM OF EARLY PREcursors FROM THE BONE MARROW (PR-T-CELLS) AND AFTER MATURATION, EMIGRATE TO THE PERIPHERAL DEPARTMENT OF THE IMMUNE SYSTEM. THREE MAIN EVENTS OCCURRING IN THE PROCESS OF T-CELL MATURATION IN THE THYMUS: 1. APPEARANCE OF ANTIGEN-RECOGNIZING T-CELL RECEPTORS IN MATURING THYMOCYTES. 2. DIFFERENTATION OF T-CELLS INTO SUB-POPULATIONS (CD4 AND CD8). 3. ABOUT SELECTION (SELECTION) OF T-LYMPHOCYTE CLONES CAPABLE OF RECOGNIZING ONLY ALIEN ANTIGENS PRESENTED TO T-CELLS BY MOLECULES OF THE MAIN HISTO COMPATIBILITY COMPLEX OF THEIR OWN ORGANISM. THE HUMAN TIMUS CONSISTS OF TWO LOBES. EACH OF THEM IS LIMITED BY A CAPSULE, FROM WHICH CONNECTIVE FABRIC SEPARATIONS GO INSIDE. THE SEPTIA DIVIDE THE PERIPHERAL PART OF THE ORGAN CORTEX INTO LOBES. THE INTERNAL PART OF THE ORGAN IS CALLED THE BRAIN.
P ROTYMOCYTES ENTER THE CORTICAL LAYER AND AS THEY MATURATE, THEY MOVE TO THE MEDIUM LAYER. FROM THE DEVELOPMENT OF THYMOCYTES INTO MATURE T-CELLS IS 20 DAYS. IMMATURE T-CELLS ENTER THE THYMUS WITHOUT HAVING T-CELL MARKERS ON THE MEMBRANE: CD3, CD4, CD8, T-CELL RECEPTOR. AT THE EARLY STAGES OF MATURATION, ALL OF THE ABOVE MARKERS APPEAR ON THEIR MEMBRANE, THEN THE CELLS MULTIPLY AND PASS TWO STAGES OF SELECTION. 1. POSITIVE SELECTION SELECTION FOR THE ABILITY TO RECOGNIZE OWN MOLECULES OF THE MAIN HISTO COMPATIBILITY COMPLEX WITH THE HELP OF THE T-CELL RECEPTOR. CELLS THAT ARE NOT ABLE TO RECOGNIZE THEIR OWN MOLECULES OF THE MAIN HISTO COMPATIBILITY COMPLEX DIE BY APOPTOSIS (PROGRAMMED CELL DEATH). THE SURVIVED THYMOCYTES LOSE ONE OF THE FOUR T-CELL MARKERS OR THE CD4 OR CD8 MOLECULE. AS A RESULT, THE SO-CALLED “DOUBLE POSITIVE” (CD4 CD8) THYMOCYTES BECOME SINGLE POSITIVE. ON THEIR MEMBRANE EITHER THE CD4 OR THE CD8 MOLECULE IS EXPRESSED. THEREFORE, THE DIFFERENCES ARE ESTABLISHED BETWEEN THE TWO MAIN POPULATIONS OF T CELLS: CYTOTOXIC CD8 CELLS AND HELPER CD4 CELLS. 2. NEGATIVE SELECTION SELECTION OF CELLS FOR THEIR ABILITY TO NOT RECOGNIZE THE ORGANISM’S OWN ANTIGENS. AT THIS STAGE, POTENTIAL AUTOREACTIVE CELLS ARE ELIMINATED, THAT IS, CELLS WHOSE RECEPTOR IS CAPABLE OF RECOGNIZING ANTIGENS OF THEIR OWN BODY. NEGATIVE SELECTION LAYS THE FOUNDATIONS FOR THE FORMATION OF TOLERANCE, THAT IS, THE IMMUNE SYSTEM’S IMMUNE RESPONSES TO ITS OWN ANTIGENS. AFTER TWO STAGES OF SELECTION, ONLY 2% OF THYMOCYTES SURVIVE. THE SURVIVED THYMOCYTES MIGRATE TO THE MEDUAL LAYER AND THEN LEAVE INTO THE BLOOD, TURNING INTO “NAIVE” T-LYMPHOCYTES.
P PERIPHERAL LYMPHOID ORGANS Scattered throughout the body. The main function of peripheral lymphoid organs is the activation of naive T- and B-lymphocytes with the subsequent formation of effector lymphocytes. There are encapsulated peripheral organs of the immune system (spleen and lymph nodes) and non-encapsulated lymphoid organs and tissues.
L LYMPHATIC NODES CONSTITUTE THE MAIN MASS OF ORGANIZED LYMPHOID TISSUE. THEY ARE REGIONALLY LOCATED AND ARE NAMED ACCORDING TO THE LOCATION (AXILLARY, INGUINAL, PAROTICAL, ETC.). L LYMPHATIC NODES PROTECT THE BODY FROM ANTIGENS THAT PENETRATE THROUGH THE SKIN AND MUCOUS MEMBRANES. H CARRONS ANTIGENS ARE TRANSPORTED TO THE REGIONAL LYMPH NODES THROUGH LYMPHATIC VESSELS, OR WITH THE HELP OF SPECIALIZED ANTIGEN PRESENTING CELLS, OR WITH THE FLOW OF FLUID. IN THE LYMPH NODES, ANTIGENS ARE PRESENTED TO NAIVE T-LYMPHOCYTES BY PROFESSIONAL ANTIGEN-PRESENTING CELLS. THE RESULT OF THE INTERACTION OF T-CELLS AND ANTIGEN-PRESENTING CELLS IS THE CONVERSION OF NAIVE T-LYMPHOCYTES INTO MATURE EFFECTOR CELLS CAPABLE OF PERFORMING PROTECTIVE FUNCTIONS. L LYMPH NODES HAVE A B-CELL CORTICAL AREA (CORTICAL ZONE), a T-CELL PARACORTICAL AREA (ZONE) AND A CENTRAL, MEDULLARY (BRAIN) ZONE FORMED BY CELL TRADES CONTAINING T-I B-LYMPHOCYTES, PLASMA CELLS AND MACROPHAGES. THE ORCAL AND PARACORTICAL AREAS ARE DIVIDED BY CONNECTIVE TISSUE TRABECULES INTO RADIAL SECTORS.
L LYMPH ENTERS THE NODE THROUGH SEVERAL AFFERENT LYMPHATIC VESSELS THROUGH THE SUBCAPSULAR ZONE COVERING THE CORTICAL AREA. AND FROM THE LYMPH NODE, LYMPH EXITS THROUGH A SINGLE OUTFERING (EFFERENT) LYMPHATIC VESSEL IN THE AREA OF THE SO-CALLED GATE. THROUGH THE GATE THROUGH THE CORRESPONDING VESSELS, BLOOD ENTERS AND OUTSIDE THE LYMPH NODE. IN THE CORTICAL REGION ARE LOCATED LYMPHOID FOLLICLES, CONTAINING MULTIPLICATION CENTERS, OR “GERMINAL CENTERS,” IN WHICH THE MATURATION OF B CELLS THAT ENCOUNTER THE ANTIGEN OCCURS.
THE PROCESS OF MATURATION IS CALLED AFFINE MATURATION. O N IS ACCOMPANIED BY SOMATIC HYPERMUTATIONS OF VARIABLE IMMUNOGLOBULIN GENES, OCCURING WITH A FREQUENCY 10 TIMES EXCEEDING THE FREQUENCY OF SPONTANEOUS MUTATIONS. C OMATIC HYPERMUTATIONS RESULT IN AN INCREASE IN THE AFFINITY OF ANTIBODIES WITH THE SUBSEQUENT REPRODUCTION AND CONVERSION OF B CELLS INTO PLASMA ANTIBODY PRODUCING CELLS. P PLASMIC CELLS ARE THE FINAL STAGE OF B-LYMPHOCYTE MATURATION. T-LYMPHOCYTES ARE LOCALIZED IN THE PARACORTICAL AREA. E E IS CALLED T-DEPENDENT. THE T-DEPENDENT AREA CONTAINS MANY T-CELLS AND CELLS WITH MULTIPLE PROGRESSES (DENDRITIC INTERDIGITAL CELLS). THESE CELLS ARE ANTIGEN-PRESENTING CELLS THAT ARRIVED INTO THE LYMPH NODE THROUGH THE AFFERENT LYMPHATIC VESSELS AFTER MEETING WITH A FOREIGN ANTIGEN AT THE PERIPHERY. NIVE T-LYMPHOCYTES, IN THEIR TURN, ENTER THE LYMPH NODES WITH THE LYMPH CURRENT AND THROUGH POST-CAPILLARY VENULES, HAVING AREAS OF THE SO-CALLED HIGH ENDOTHELIUM. IN THE T-CELL AREA, NAIVE T-LYMPHOCYTES ARE ACTIVATED WITH THE HELP OF ANTI-GEN-PRESENTING DENDRITIC CELLS. AND ACTIVATION RESULTS IN PROLIFERATION AND FORMATION OF CLONES OF EFFECTOR T-LYMPHOCYTES, WHICH ARE ALSO CALLED REINFORCED T-CELLS. THE LATTER ARE THE FINAL STAGE OF MATURATION AND DIFFERENTIATION OF T-LYMPHOCYTES. THEY LEAVE THE LYMPH NODES TO PERFORM EFFECTIVE FUNCTIONS FOR WHICH WERE PROGRAMMED BY ALL PREVIOUS DEVELOPMENT.
THE LENE IS A LARGE LYMPHOID ORGAN, DIFFERENT FROM THE LYMPH NODES BY THE PRESENCE OF A LARGE NUMBER OF RED CYTES. THE MAIN IMMUNOLOGICAL FUNCTION IS THE ACCUMULATION OF ANTIGENS BROUGHT WITH THE BLOOD AND THE ACTIVATION OF T- AND B-LYMPHOCYTES REACTING TO THE ANTIGEN BROUGHT BY THE BLOOD. THE SPLEN HAS TWO MAIN TYPES OF TISSUE: THE WHITE PULP AND THE RED PULP. THE WHITE PULP CONSISTS OF LYMPHOID TISSUE, WHICH FORMES PERIARTERIOLARY LYMPHOID COUPLINGS AROUND THE ARTERIOLES. THE CLUTCHES HAVE T- AND B-CELL AREAS. A T-DEPENDENT AREA OF THE CLUTCH, SIMILAR TO THE T-DEPENDENT AREA OF LYMPH NODES, DIRECTLY SURROUNDS THE ARTERIOLE. B-CELL FOLLICLES CONSTITUTE THE B-CELL REGION AND ARE LOCATED CLOSE TO THE EDGE OF THE MOUNT. THERE ARE REPRODUCTION CENTERS IN THE FOLLICLES, SIMILAR TO THE GERMINAL CENTERS OF LYMPH NODES. IN THE CENTERS OF REPRODUCTION, DENDRITIC CELLS AND MACROPHAGES ARE LOCALIZED, PRESENTING ANTIGEN TO B-CELLS WITH THE SUBSEQUENT CONVERSION OF THE LATTER INTO PLASMA CELLS. MATURATING PLASMA CELLS PASS THROUGH VASCULAR LINKERS INTO THE RED PULP. THE RED PULP IS A cellular network FORMED BY VENOUS SINUSOIDS, CELLULAR TRADS AND FILLED WITH ERYTHROCYTES, PLATELETS, MACROPHAGES, AND OTHER CELLS OF THE IMMUNE SYSTEM. THE RED PULP IS A SITE OF DEPOSITATION OF erythrocytes and platelets. THE APPILLARIES WITH WHICH END THE CENTRAL ARTERIOLES OF THE WHITE PULP OPEN FREELY IN BOTH THE WHITE PULP AND IN THE RED PULP TRADS. WHEN THE BLOOD LEAKS REACH THE HEAVY RED PULP, THEY ARE RESTAINED IN THEM. HERE MACROPHAGES RECOGNIZE AND PHAGOCYTE SURVIVED erythrocytes and platelets. PLASMIC CELLS, MOVED INTO THE WHITE PULP, CARRY OUT THE SYNTHESIS OF IMMUNOGLOBULINS. BLOOD CELLS NOT ABSORBED AND NOT DESTROYED BY PHAGOCYTES PASS THROUGH THE EPITHELIAL LINING OF VENOUS SINUSOIDS AND RETURN TO THE BLOOD STREAM TOGETHER WITH PROTEINS AND OTHER PLASMA COMPONENTS.
N ENCAPSULATED LYMPHOID TISSUE Most of the unencapsulated lymphoid tissue is located in the mucous membranes. In addition, non-encapsulated lymphoid tissue is localized in the skin and other tissues. Lymphoid tissue of the mucous membranes protects only the mucous surfaces. This distinguishes it from the lymph nodes, which protect against antigens that penetrate both the mucous membranes and the skin. The main effector mechanism of local immunity at the mucosal level is the production and transport of secretory antibodies IgA class directly onto the surface of the epithelium. Most often, foreign antigens enter the body through the mucous membranes. In this regard, antibodies of the IgA class are produced in the body in the greatest quantities relative to antibodies of other isotypes (up to 3 g per day). The lymphoid tissue of the mucous membranes includes: Lymphoid organs and formations associated with gastrointestinal tract(GALT gut-associated lymphoid tissues). Includes lymphoid organs of the peripharyngeal ring (tonsils, adenoids), appendix, Peyer's patches, intraepithelial lymphocytes of the intestinal mucosa. Lymphoid tissue associated with bronchi and bronchioles (BALT bronchial-associated lymphoid tissue), as well as intraepithelial lymphocytes of the mucous membrane of the respiratory tract. Lymphoid tissue of other mucous membranes (MALT mucosal associated lymphoid tissue), including as the main component the lymphoid tissue of the mucous membrane of the urogenital tract. Lymphoid tissue of the mucosa is most often localized in the basal plate of the mucous membranes (lamina propria) and in the submucosa. An example of mucosal lymphoid tissue is Peyer's patches, which are usually found in the lower part ileum. Each plaque is adjacent to a region of intestinal epithelium called follicle-associated epithelium. This area contains so-called M cells. Bacteria and other foreign antigens enter the subepithelial layer from the intestinal lumen through M cells. THE BASIC MASS OF LYMPHOCYTES IN PEYER'S PATCH ARE IN THE B-CELL FOLLICLE WITH A GERMAL CENTER IN THE MIDDLE. T-CELL ZONES SURROUND THE FOLLICLE CLOSE TO THE LAYER OF EPITHELIAL CELLS. THE MAIN FUNCTIONAL LOAD OF PEYER'S PATCHES IS THE ACTIVATION OF B-LYMPHOCYTES AND THEIR DIFFERENTIATION INTO PLASMA CYTES PRODUCING ANTIBODIES OF CLASSES I G A AND I G E. IN ADDITION TO THE ORGANIZED LYMPHOID TISSUE IN THE EPITHELIAL LAYER OF THE MUCOSA X AND IN LAMINA PROPRIA THERE ARE ALSO SINGLE DISSEMINATED T-LYMPHOCYTES. THEY CONTAIN BOTH ΑΒ T-CELL RECEPTOR AND ΓΔ T-CELL RECEPTOR. IN ADDITION TO LYMPHOID TISSUE OF MUCOSAL SURFACES, NON-ENCAPSULATED LYMPHOID TISSUE INCLUDES: SKIN-ASSOCIATED LYMPHOID TISSUE AND SKIN INTRAEPITHELIAL LYMPHOCYTES; LYMPH, TRANSPORTING FOREIGN ANTIGENS AND CELLS OF THE IMMUNE SYSTEM; PERIPHERAL BLOOD, UNITING ALL ORGANS AND TISSUE AND PERFORMING A TRANSPORT AND COMMUNICATION FUNCTION; CLUMPS OF LYMPHOID CELLS AND SINGLE LYMPHOID CELLS OF OTHER ORGANS AND TISSUE. AN EXAMPLE COULD BE LIVER LYMPHOCYTES. THE LIVER PERFORMES QUITE IMPORTANT IMMUNOLOGICAL FUNCTIONS, ALTHOUGH IT IS NOT CONSIDERED AN ORGAN OF THE IMMUNE SYSTEM FOR AN ADULT BODY. HOWEVER, ALMOST HALF OF THE TISSUE MACROPHAGES OF THE ORGANISM ARE LOCALIZED IN IT. THEY PHAGOCYTATE AND DISSOLVE IMMUNE COMPLEXES, WHICH BRING RED CELLS HERE ON THEIR SURFACE. IN ADDITION, IT IS ASSUMED THAT LYMPHOCYTES LOCALIZED IN THE LIVER AND IN THE INTESTINAL SUBMUCOSA HAVE SUPRESSOR FUNCTIONS AND PROVIDE CONSTANT MAINTENANCE OF IMMUNOLOGICAL TOLERANCE (UNRESPONDENCE) TO FOOD.
