RUSSIAN STATE UNIVERSITY OF PHYSICAL CULTURE, SPORT, YOUTH AND TOURISM (GTSOLIFK)
MOSCOW 2013
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IMMUNE SYSTEM The immune system is a collection of lymphoid organs, tissues and cells,
providing supervision over the constancy of the cellular and antigenic identity of the body. The central or primary organs of the immune system are the thymus gland, Bone marrow and fetal liver. They “train” cells, make them immunologically competent, and also regulate the body’s immunological reactivity. Peripheral or secondary organs of the immune system (lymph nodes, spleen, accumulation of lymphoid tissue in the intestine) perform an antibody-forming function and carry out a cellular immune response.
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Fig.1 Thymus gland (thymus).
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1.1. Lymphocytes are cells of the immune system, also called immunocytes, or
immunocompetent cells. They come from a pluripotent hematopoietic stem cell that appears in the gall sac of the human embryo at 2-3 weeks of development. Between 4 and 5 weeks of pregnancy, stem cells migrate to the embryonic liver, which becomes the largest hematopoietic organ during early pregnancy. Differentiation of lymphoid cells occurs in two ways directions: to perform the functions of cellular and humoral immunity. The maturation of lymphoid progenitor cells occurs under the influence of the microenvironment of the tissues into which they migrate.
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One group of lymphoid progenitor cells migrates to thymus gland- organ,
formed from the 3rd and 4th gill pouches in the 6-8th week of pregnancy. Lymphocytes mature under the influence epithelial cells cortical layer of the thymus and then migrate to its medulla. These cells, called thymocytes, thymus-dependent lymphocytes or T cells, migrate to the peripheral lymphoid tissue, where they are found starting at 12 weeks of pregnancy. T cells fill certain areas of the lymphoid organs: between the follicles in the depths of the cortical layer lymph nodes and in the periarterial zones of the spleen, consisting of lymphoid tissue. Making up 60-70% of the number of peripheral blood lymphocytes, T cells are mobile and constantly circulate from the blood into the lymphoid tissue and back into the blood through the thoracic lymphatic duct, where their content reaches 90%. This migration ensures interaction between lymphoid organs and sites of antigenic stimulation with the help of sensitized T cells. Mature T lymphocytes perform various functions: provide cellular immunity reactions, help in the formation of humoral immunity, enhance the function of B-lymphocytes, hematopoietic stem cells, regulate migration, proliferation, differentiation of hematopoietic cells, etc.
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1.2 A second population of lymphoid progenitor cells is responsible for humoral
immunity and antibody formation. In birds, these cells migrate to the bursa of Fabricius, an organ located in the cloaca, and mature there. No similar formation has been found in mammals. It is believed that in mammals these lymphoid progenitors mature in the bone marrow with possible differentiation in the liver and intestinal lymphoid tissue. These lymphocytes, which are known as bone marrow-dependent or bursa-dependent cells or B cells, migrate to peripheral lymphoid tissues. organs for final differentiation and are distributed in the centers of reproduction of follicles of the lymph nodes, spleen and intestinal lymphoid tissue. B cells are less labile than T cells and circulate from the blood into the lymphoid tissue much more slowly. The number of B lymphocytes is 15-20% of all lymphocytes circulating in the blood.
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As a result of antigenic stimulation, B cells turn into plasma cells that synthesize
antibodies or immunoglobulins; enhance the function of some T-lymphocytes, participate in the formation of the T-lymphocyte response. The population of B lymphocytes is heterogeneous, and they functional abilities are different.
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LYMPHOCYTE
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1.3 Macrophages are cells of the immune system that originate from bone marrow stem cells. IN
in peripheral blood they are represented by monocytes. Upon penetration into tissues, monocytes transform into macrophages. These cells make the first contact with the antigen, recognize its potential danger and transmit a signal to immunocompetent cells (lymphocytes). Macrophages participate in cooperative interactions between antigen and T and B cells in immune responses. In addition, they play the role of the main effector cells in inflammation, making up the majority of mononuclear cells in the infiltrates of delayed-type hypersensitivity. Among macrophages, there are regulatory cells - helpers and suppressors, which participate in the formation of the immune response.
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Macrophages include blood monocytes, connective tissue histiocytes, endothelial cells
capillaries of hematopoietic organs, Kupffer cells of the liver, cells of the wall of the alveoli of the lung (pulmonary macrophages) and the wall of the peritoneum (peritoneal macrophages).
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Electron photography of macrophages
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Macrophage
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Fig.2. The immune system
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Immunity. Types of immunity.
- Throughout life, the human body is exposed to foreign microorganisms (viruses, bacteria, fungi, protozoa), chemical, physical and other factors that can lead to the development of diseases.
- The main tasks of all body systems are to find, recognize, remove or neutralize any foreign agent (either one that came from outside or one’s own, but which changed under the influence of some reason and became “alien”). To fight infections, protect against transformed, malignant tumor cells and to maintain homeostasis in the body there is a complex dynamic defense system. The main role in this system is played by immunological reactivity or immunity.
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Immunity is the body's ability to maintain constant internal environment, create
immunity to infectious and non-infectious agents (antigens) entering it, neutralizing and removing foreign agents and their breakdown products from the body. A series of molecular and cellular reactions that occur in the body after an antigen enters it constitutes an immune response, resulting in the formation of humoral and/or cellular immunity. The development of one or another type of immunity is determined by the properties of the antigen, the genetic and physiological capabilities of the responding organism.
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Humoral immunity is a molecular reaction that occurs in the body in response to exposure to
antigen. The induction of a humoral immune response is ensured by the interaction (cooperation) of three main types of cells: macrophages, T- and B-lymphocytes. Macrophages phagocytose the antigen and, after intracellular proteolysis, present its peptide fragments on their cell membrane to T helper cells. T-helpers cause activation of B-lymphocytes, which begin to proliferate, transform into blast cells, and then, through a series of successive mitoses, into plasma cells that synthesize antibodies specific to a given antigen. An important role in the initiation of these processes belongs to regulatory substances that are produced by immunocompetent cells.
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Activation of B cells by T helper cells for antibody production is not universal
for all antigens. This interaction develops only when T-dependent antigens enter the body. To induce an immune response by T-independent antigens (polysaccharides, protein aggregates of a regulatory structure), the participation of T-helper cells is not required. Depending on the inducing antigen, B1 and B2 subclasses of lymphocytes are distinguished. Plasma cells synthesize antibodies in the form of immunoglobulin molecules. Five classes of immunoglobulins have been identified in humans: A, M, G, D, E. In case of impaired immunity and development allergic diseases, especially autoimmune diseases, diagnostics are carried out for the presence and ratio of immunoglobulin classes.
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Cellular immunity. Cellular immunity is cellular reactions that occur in the body in
response to antigen exposure. T lymphocytes are also responsible for cellular immunity, also known as delayed-type hypersensitivity (DTH). The mechanism of interaction of T cells with antigen is still unclear, but these cells best recognize the antigen associated with cell membrane. Regardless of whether the information about antigens is transmitted by macrophages, B lymphocytes or some other cells, T lymphocytes begin to change. First, blast forms of T-cells are formed, then through a series of divisions - T-effectors that synthesize and secrete biologically active substances- lymphokines, or HRT mediators. The exact number of mediators and their molecular structure are still unknown. These substances are distinguished by biological activity. Under the influence of a factor that inhibits the migration of macrophages, these cells accumulate in areas of antigenic irritation.
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Macrophage activating factor significantly enhances phagocytosis and digestion
cell ability. There are also macrophages and leukocytes (neutrophils, basophils, eosinophils) that attract these cells to the site of antigenic irritation. In addition, lymphotoxin is synthesized, which can dissolve target cells. Another group of T-effectors, known as T-killers (killers), or K-cells, are represented by lymphocytes that have cytotoxicity, which they exhibit towards virus-infected and tumor cells. There is another mechanism of cytotoxicity, antibody-dependent cell-mediated cytotoxicity, in which antibodies recognize target cells and then effector cells respond to these antibodies. Null cells, monocytes, macrophages and lymphocytes called NK cells have this ability.
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Fig. 3 Diagram of the immune response
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Ri.4. Immune response.
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TYPES OF IMMUNITY
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Species immunity is a hereditary characteristic of a certain species of animal. For example, cattle does not suffer from syphilis, gonorrhea, malaria and other diseases contagious to humans, horses do not suffer from canine distemper, etc.
Based on strength or durability, species immunity is divided into absolute and relative.
Absolute species immunity is the type of immunity that occurs in an animal from the moment of birth and is so strong that no influence external environment it cannot be weakened or destroyed (for example, no additional influences can cause polio when dogs and rabbits are infected with this virus). There is no doubt that in the process of evolution, absolute species immunity is formed as a result of the gradual hereditary consolidation of acquired immunity.
Relative species immunity is less durable, depending on the effects of the external environment on the animal. For example, birds in normal conditions immune to anthrax. However, if the body is weakened by cooling and fasting, they become ill with this disease.
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Acquired immunity is divided into:
- naturally acquired,
- artificially acquired.
Each of them, according to the method of occurrence, is divided into active and passive.
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Occurs after an infection. diseases
During the transition protective antibodies from the mother's blood through the placenta into the fetus' blood, also transmitted through mother's milk
Occurs after vaccination (vaccination)
Injecting a person with serum containing antibodies against microbes and their toxins. specific antibodies.
Scheme 1. ACQUIRED IMMUNITY.
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The mechanism of immunity to infectious diseases. The doctrine of phagocytosis. Pathogenic microbes
penetrate through the skin and mucous membranes into the lymph, blood, nervous tissue and other organ tissues. For most microbes, these “entry gates” are closed. When studying the mechanisms of the body's defense against infection, one has to deal with phenomena of varying biological specificity. Indeed, the body is protected from microbes both by the integumentary epithelium, the specificity of which is very relative, and by antibodies that are produced against a specific pathogen. Along with this, there are mechanisms whose specificity is relative (for example, phagocytosis), and various protective reflexes. The protective activity of tissues that prevents the penetration of microbes into the body is due to various mechanisms: mechanical removal of microbes from the skin and mucous membranes; removal of microbes using natural (tears, digestive juices, vaginal discharge) and pathological (exudate) body fluids; fixation of microbes in tissues and their destruction by phagocytes; destruction of microbes using specific antibodies; release of microbes and their poisons from the body.
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Phagocytosis (from the Greek fago - devour and citos - cell) is the process of absorption and
digestion of microbes and animal cells by various connective tissue cells - phagocytes. The creator of the doctrine of phagocytosis is the great Russian scientist - embryologist, zoologist and pathologist I.I. Mechnikov. He saw phagocytosis as the basis inflammatory reaction, expressing the protective properties of the body. Protective activity of phagocytes during infection I.I. Metchnikoff first demonstrated this using the example of infection of daphnia by a yeast fungus. Subsequently, he convincingly demonstrated the importance of phagocytosis as the main mechanism of immunity in various human infections. He proved the correctness of his theory by studying the phagocytosis of streptococci during erysipelas. In subsequent years, the phagocytotic mechanism of immunity was established for tuberculosis and other infections. This protection is carried out by: - polymorphic neutrophils - short-lived small cells with a large number of granules containing various bactericidal enzymes. They carry out phagocytosis of pus-forming bacteria; - macrophages (differentiated from blood monocytes) are long-lived cells that fight intracellular bacteria, viruses and protozoa. To enhance the process of phagocytosis in the blood plasma, there is a group of proteins that causes the release of inflammatory mediators from mast cells and basophils; cause vasodilation and increases capillary permeability. This group of proteins is called the complement system.
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Questions for self-test: 1. Define the concept of “immunity.” 2. Tell us about the immune system
system, its composition and functions. 3. What are humoral and cellular immunity? 4. How are the types of immunity classified? Name the subtypes of acquired immunity. 5. What are the features of antiviral immunity? 6. Describe the mechanism of immunity to infectious diseases. 7. Give brief description the main provisions of I. I. Mechnikov’s teaching on phagocytosis.
Kalinin Andrey VyacheslavovichDoctor of Medical Sciences Professor of the Department of Preventive Medicine
and basics of health
The main task of the immune system
Formation of an immune response toentering the internal environment
foreign substances, that is, protection
organism at the cellular level.
1. Cellular immunity is carried out
direct contact of lymphocytes (main
cells of the immune system) with foreign
agents. This is how it develops
antitumor, antiviral
protection, transplant rejection reactions.
Mechanism of immune response
2. As a reaction to pathogensmicroorganisms, foreign cells and proteins
comes into force humoral immunity(from lat.
umor - moisture, liquid, related to liquid
internal environment of the body).
Humoral immunity plays a major role
in protecting the body from bacteria present in
extracellular space and in the blood.
It is based on the production of specific
proteins - antibodies that circulate throughout
bloodstream and fight against antigens -
foreign molecules.
Anatomy of the immune system
Central authorities immune system:Red bone marrow is where
Stem cells are “stored”. Depending
depending on the situation, stem cell
differentiates into immune cells -
lymphoid (B lymphocytes) or
myeloid series.
Thymus gland (thymus) - place
maturation of T lymphocytes. Bone marrow supplies precursor cells for various
populations of lymphocytes and macrophages, in
specific immune responses occur in it
reactions. It serves as the main source
serum immunoglobulins. The thymus gland (thymus) plays a leading role
role in the regulation of the T-lymphocyte population. Thymus
supplies lymphocytes in which for growth and
development of lymphoid organs and cellular
populations the embryo needs different tissues.
By differentiating, lymphocytes thanks to
release of humoral substances is obtained
antigenic markers.
The cortex is densely filled with lymphocytes,
which are influenced by thymic factors. IN
the medulla contains mature T-lymphocytes,
leaving the thymus gland and joining the
circulation as T-helpers, T-killers, T-suppressors.
Anatomy of the immune system
Peripheral organs immune system:spleen, tonsils, lymph nodes and
lymphatic formations of the intestines and others
organs that have maturation zones
immune cells.
Cells of the immune system - B and T lymphocytes,
monocytes, macrophages, neutro-, baso-,
eozonophils, mast cells, epithelial cells,
fibroblasts.
Biomolecules – immunoglobulins, mono- and
cytokines, antigens, receptors and others. The spleen is populated by lymphocytes in
late embryonic period after
birth. The white pulp contains
thymus-dependent and thymus-independent
zones that are populated by T- and Blymphocytes. Entering the body
antigens induce the formation
lymphoblasts in the thymus-dependent zone
spleen, and in the thymus-independent zone
proliferation of lymphocytes and
formation of plasma cells.
Immune system cells
Immunocompetent cellsthe human body are T- and B-lymphocytes.
Immune system cells
T lymphocytes arise in the embryonicthymus. In the postembryonic period after
maturation, T-lymphocytes settle in T-zones
peripheral lymphoid tissue. After
stimulation (activation) by a certain antigen
T lymphocytes transform into large
transformed T-lymphocytes, of which
then the T-cell executive arises.
T cells are involved in:
1) cellular immunity;
2) regulation of B-cell activity;
3) delayed (IV) type hypersensitivity.
Immune system cells
The following subpopulations of T lymphocytes are distinguished:1) T-helpers. Programmed to induce reproduction
and differentiation of other cell types. They induce
secretion of antibodies by B lymphocytes and stimulated by monocytes,
mast cells and T-killer precursors to participate in
cellular immune reactions. This subpopulation is activated
antigens associated with MHC class II gene products
– class II molecules, represented predominantly on
surfaces of B cells and macrophages;
2) suppressor T cells. Genetically programmed to
suppressor activity, respond predominantly to
products of MHC class I genes. They bind antigen and
secrete factors that inactivate T-helper cells;
3) T-killers. Recognize antigen in combination with their own
MHC class I molecules. They secrete cytotoxic
lymphokines.
Immune system cells
B lymphocytes are divided into two subpopulations: B1 and B2.B1 lymphocytes undergo primary differentiation
in Peyer's patches, then found on
surfaces of serous cavities. During the humoral
immune response can turn into
plasma cells that synthesize only IgM. For their
transformations do not always require T helper cells.
B2 lymphocytes undergo differentiation in the bone
brain, then in the red pulp of the spleen and lymph nodes.
Their transformation into plasma cells occurs with the participation of helper cells. Such plasma cells are capable of synthesizing
all human Ig classes.
Immune system cells
Memory B cells are long-lived B lymphocytes derived from mature B cells as a result of stimulation with antigenwith the participation of T-lymphocytes. When repeated
antigen stimulation of these cells
activated much more easily than the original ones
B cells. They provide (with the participation of T cells) the rapid synthesis of large
amount of antibodies upon repeated
penetration of antigen into the body.
Immune system cells
Macrophages are different from lymphocytes,but also play important role in the immune
answer. They can be:
1) antigen-processing cells when
the occurrence of a response;
2) phagocytes in the form of an executive
link
Specificity of the immune response
Depends:1. From the type of antigen (foreign substance) - its
properties, composition, molecular weight, dose,
duration of contact with the body.
2. From immunological reactivity, that is
state of the body. This is precisely the factor
which aims at various types of prevention
immunity (hardening, taking immunocorrectors,
vitamins).
3. From environmental conditions. They can both enhance
protective reaction of the body and prevent
normal functioning of the immune system.
Forms of immune response
The immune response is a chain of sequentialcomplex cooperative processes going on in
immune system in response to action
antigen in the body.
Forms of immune response
There are:1) primary immune response
(occurs at the first meeting with
antigen);
2) secondary immune response
(occurs when meeting again
antigen).
Immune response
Any immune response consists of two phases:1) inductive; presentation and
antigen recognition. A complex
cooperation of cells followed by
proliferation and differentiation;
2) productive; products are detected
immune response.
During the primary immune response, inductive
the phase can last a week, with secondary – up to
3 days due to memory cells.
Immune response
In the immune response, antigens that enter the bodyinteract with antigen presenting cells
(macrophages) that express antigenic
determinants on the cell surface and deliver
information about the antigen to peripheral organs
immune system, where T-helper cells are stimulated.
Further, the immune response is possible in the form of one of
three options:
1) cellular immune response;
2) humoral immune response;
3) immunological tolerance.
Cellular immune response
The cellular immune response is a function of T lymphocytes. Education takes placeeffector cells - T-killers, capable of
destroy cells that have an antigenic structure
by direct cytotoxicity and by synthesis
lymphokines that are involved in the processes
interactions of cells (macrophages, T cells, B cells) during the immune response. In regulation
The immune response involves two subtypes of T cells:
T-helpers enhance the immune response, T-suppressors have the opposite effect.
Humoral immune response
Humoral immunity is a functionB cells. T helper cells that received
antigenic information, transmit it to Blymphocytes. B lymphocytes form
clone of antibody-producing cells. At
this is where B cells transform
into plasma cells that secrete
immunoglobulins (antibodies), which
have specific activity against
invading antigen. The resulting antibodies enter into
interaction with antigen
formation of the AG – AT complex, which
triggers non-specific
defense mechanisms. These
complexes activate the system
complement. Interaction of the complex
AG – AT s mast cells leads to
degranulation and release of mediators
inflammation - histamine and serotonin.
Immunological tolerance
At a low dose of antigen it developsimmunological tolerance. Wherein
the antigen is recognized, but as a result
there is no cell production or
development of a humoral immune response.
Characteristics of the immune response
1) specificity (reactivity is directed onlyto a specific agent called
antigen);
2) potentiation (the ability to produce
enhanced response with constant admission to
organism of the same antigen);
3) immunological memory (ability
recognize and produce an enhanced response
against the same antigen when repeated
entering the body, even if the first and
subsequent hits occur through
long periods of time).
Types of immunities
Natural - it is purchased inas a result of an infectious
diseases (this active immunity) or
transmitted from mother to fetus during
pregnancy (passive immunity).
Species - when the organism is not susceptible
to some diseases of others
animals.
Types of immunities
Artificial - obtained byvaccine administration (active) or
serum (passive).
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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.)
The central organs of the immune system: (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 a 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: antibody synthesis, cellular immune 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 substances that under normal conditions do not provide the development of an immune response (i.e., do not have the property of immunogenicity), but can interact with pre-existing antibodies, exhibiting the property of specificity. Haptens include drugs and most 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.
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Main role in anti-infective protection, it is not immunity that plays a role, but various mechanisms of mechanical removal of microorganisms (clearance). In the respiratory organs, this is the production of surfactant and sputum, the movement of mucus due to the movements of the cilia of the ciliary epithelium, coughing and sneezing. In the intestines, this is peristalsis and the production of juices and mucus (diarrhea due to infection, etc.) On the skin, this is constant desquamation and renewal of the epithelium. The immune system turns on when the clearance mechanisms fail.
Slide 3
Ciliary epithelium
Slide 4
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Barrier functions of the skin
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Thus, in order to survive in the host’s body, the microbe must “fix” on the epithelial surface (immunologists and microbiologists call this adhesion, that is, gluing). The body must prevent adhesion using clearance mechanisms. If adhesion occurs, the microbe may try to penetrate deep into the tissue or into the bloodstream, where clearance mechanisms do not work. For these purposes, microbes produce enzymes that destroy host tissues. All pathogenic microorganisms differ from non-pathogenic microorganisms in their ability to produce such enzymes
Slide 7
If one or another clearance mechanism fails to cope with the infection, then the immune system joins in the fight.
Slide 8
Specific and nonspecific immune protection
Specific defense refers to specialized lymphocytes that can fight only one antigen. Nonspecific immune factors, such as phagocytes, natural killer cells and complement (special enzymes) can fight infection either independently or in cooperation with specific defense.
Slide 9
Slide 10
Complement system
Slide 11
The immune system consists of: immune cells, a number of humoral factors, immune organs (thymus, spleen, lymph nodes), as well as accumulations of lymphoid tissue (the most massively represented in the respiratory and digestive organs).
Slide 12
The immune organs communicate with each other and with body tissues through lymphatic vessels and the circulatory system.
Slide 13
There are four main types of pathological conditions of the immune system: 1. hypersensitivity reactions, manifested in the form of immune tissue damage; 2. autoimmune diseases, developing as a result immune reactions against one's own body; 3. immune deficiency syndromes resulting from congenital or acquired defects in the immune response; 4. amyloidosis.
Slide 14
HYPERSENSITIVITY REACTIONS Contact of the body with an antigen not only ensures the development of a protective immune response, but can also lead to reactions that damage tissue. Such hypersensitivity reactions (immune tissue damage) can be initiated by the interaction of an antigen with an antibody or cellular immune mechanisms. These reactions can be associated not only with exogenous, but also with endogenous antigens.
Slide 15
Hypersensitivity diseases are classified based on the immunological mechanisms that cause them. Classification There are four types of hypersensitivity reactions: Type I - the immune response is accompanied by the release of vasoactive and spasmogenic substances. Type II - antibodies are involved in cell damage, making them susceptible to phagocytosis or lysis. Type III - the interaction of antibodies with antigens leads to the formation of immune complexes that activate complement. Complement fractions attract neutrophils, which damage tissue; Type IV - a cellular immune response develops with the participation of sensitized lymphocytes.
Slide 16
Type I hypersensitivity reactions (immediate type, allergic type) can be local or systemic. A systemic reaction develops in response to intravenous administration antigen to which the host organism is previously sensitized and may have the character anaphylactic shock.Local reactions depend on the site of penetration of the antigen and have the character of limited swelling of the skin ( skin allergy, urticaria), nasal and conjunctival discharge ( allergic rhinitis, conjunctivitis), hay fever, bronchial asthma or allergic gastroenteritis (food allergy).
Slide 17
Hives
Slide 18
Type I hypersensitivity reactions go through two phases in their development - the initial response and the late one: - The initial response phase develops 5-30 minutes after contact with the allergen and is characterized by vasodilation, increased permeability, as well as spasm of smooth muscles or gland secretion. - Late the phase is observed after 2-8 hours without additional contact with the antigen, lasts several days and is characterized by intense tissue infiltration by eosinophils, neutrophils, basophils and monocytes, as well as damage to epithelial cells of the mucous membranes. The development of type I hypersensitivity is ensured by IgE antibodies formed in response to an allergen with the participation of T2 helper cells.
Slide 19
Type I hypersensitivity reaction underlies the development of anaphylactic shock. Systemic anaphylaxis occurs after the administration of heterologous proteins - antisera, hormones, enzymes, polysaccharides, and some drugs (for example, penicillin).
Slide 20
Type II hypersensitivity reactions (immediate hypersensitivity) is caused by IgG antibodies to exogenous antigens adsorbed on cells or the extracellular matrix. With such reactions, antibodies appear in the body directed against the cells of its own tissues. Antigenic determinants can be formed in cells as a result of disturbances at the gene level, leading to the synthesis of atypical proteins, or they represent an exogenous antigen adsorbed on the cell surface or extracellular matrix. In any case, a hypersensitivity reaction occurs as a consequence of the binding of antibodies to normal or damaged structures of the cell or extracellular matrix.
Slide 21
Type III hypersensitivity reactions (an immediate hypersensitivity reaction caused by the interaction of IgG antibodies and a soluble exogenous antigen) The development of such reactions is due to the presence of antigen-antibody complexes formed as a result of the binding of antigen to antibody in the bloodstream (circulating immune complexes) or outside the vessels on the surface or inside cellular (or extracellular) structures (immune complexes in situ).
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Circulating immune complexes (CICs) cause damage when they enter the wall of blood vessels or filtering structures (the tubular filter in the kidneys). There are two known types of immune complex damage, which are formed when an exogenous antigen (foreign protein, bacteria, virus) enters the body and when antibodies are formed against one’s own antigens. Diseases caused by the presence of immune complexes can be generalized, if these complexes form in the blood and settle in many organs, or associated with individual organs, such as the kidneys (glomerulonephritis), joints (arthritis) or small blood vessels skin.
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Kidney with glomerulonephritis
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Systemic immune complex disease One of its varieties is acute serum sickness, which occurs as a result of passive immunization resulting from repeated administration of large doses of foreign serum.
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Chronic serum sickness develops with prolonged contact with an antigen. Constant antigenemia is necessary for the development of chronic immune complex disease, since immune complexes most often settle in the vascular bed. For example, systemic lupus erythematosus is associated with long-term persistence of autoantigens. Often, despite the presence of characteristic morphological changes and other signs indicating the development of an immune complex disease, the antigen remains unknown. Such phenomena are typical for rheumatoid arthritis, periarteritis nodosa, membranous nephropathy and some vasculitis.
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Systemic lupus erythematosus
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Rheumatoid polyarthritis
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Systemic vasculitis
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Local immune complex disease (Arthus reaction) is expressed in local tissue necrosis resulting from acute immune complex vasculitis.
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Delayed-type hypersensitivity (DTH) consists of several stages: 1 - primary contact with the antigen ensures the accumulation of specific T helper cells; 2 - upon repeated administration of the same antigen, it is captured by regional macrophages, which act as antigen-presenting cells, removing fragments antigen on its surface; 3 - antigen-specific T helper cells interact with antigen on the surface of macrophages and secrete a number of cytokines; 4 - secreted cytokines ensure the formation of an inflammatory response, accompanied by the accumulation of monocytes/macrophages, the products of which destroy nearby host cells.
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When the antigen persists, macrophages are transformed into epithelioid cells surrounded by a shaft of lymphocytes - a granuloma is formed. This inflammation is characteristic of type IV hypersensitivity and is called granulomatous.
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Histological picture of granulomas
Sarcoidosis Tuberculosis
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AUTOIMMUNE DISEASESDisorders immunological tolerance lead to a peculiar immunological reaction to the body’s own antigens - autoimmune aggression and the formation of a state of autoimmunity. Normally, autoantibodies can be found in the blood serum or tissues of many healthy people, especially in older age group. These antibodies are formed after tissue damage and play a physiological role in removing its remains.
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There are three main signs of autoimmune diseases: - the presence of an autoimmune reaction; - the presence of clinical and experimental evidence that such a reaction is not secondary to tissue damage, but has a primary pathogenetic significance; - the absence of other specific causes of the disease.
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At the same time, there are conditions in which the action of autoantibodies is directed against one’s own organ or tissue, resulting in local tissue damage. For example, in Hashimoto's thyroiditis (Hashimoto's goiter), antibodies are absolutely specific for thyroid gland. In systemic lupus erythematosus, a variety of autoantibodies react with components nuclei of various cells, and in Goodpasture syndrome, antibodies against the basement membrane of the lungs and kidneys cause damage only in these organs. Obviously, autoimmunity implies a loss of self-tolerance. Immunological tolerance is a condition in which an immune response to a specific antigen does not develop.
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IMMUNE DEFICIENCY SYNDROMES Immunological deficiency (immunodeficiency) is a pathological condition caused by a deficiency of components, factors or parts of the immune system with inevitable violations of immune surveillance and/or immune response to a foreign antigen.
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All immunodeficiencies are divided into primary (almost always determined genetically) and secondary (associated with complications infectious diseases, metabolic disorders, side effects immunosuppression, radiation, chemotherapy for oncological diseases). Primary immunodeficiencies are a heterogeneous group of congenital, genetically determined diseases caused by impaired differentiation and maturation of T and B lymphocytes.
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According to WHO, there are more than 70 primary immunodeficiencies. Although most immunodeficiencies are quite rare, some (such as IgA deficiency) are quite common, especially in children.
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Acquired (secondary) immunodeficiencies If immunodeficiency becomes the main cause of the development of a persistent or often recurrent infectious or tumor process, we can talk about secondary immune deficiency syndrome (secondary immunodeficiency).
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Acquired immunodeficiency syndrome (AIDS)By the beginning of the 21st century. AIDS is registered in more than 165 countries around the world, and the largest number of people infected with the human immunodeficiency virus (HIV) is in Africa and Asia. Among adults, 5 risk groups have been identified: - homosexual and bisexual men make up the largest group (up to 60% of patients); - persons who inject drugs intravenously (up to 23%); - patients with hemophilia (1%); - recipients of blood and its components (2%); - heterosexual contacts of members of other high-risk groups, mainly drug addicts - (6%). In approximately 6% of cases, risk factors are not identified. About 2% of AIDS patients are children.
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EtiologyThe causative agent of AIDS is the human immunodeficiency virus, a retrovirus of the lentivirus family. There are two genetically different shapes virus: human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2, or HIV-1 and HIV-2). HIV-1 is the most common type, found in the USA, Europe, Central Africa, and HIV-2 - mainly in West Africa.
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PathogenesisThere are two main targets for HIV: the immune system and the central nervous system. The immunopathogenesis of AIDS is characterized by the development of deep immunosuppression, which is mainly associated with a pronounced decrease in the number of CD4 T cells. There is a lot of evidence that the CD4 molecule is actually a high-affinity receptor for HIV. This explains the selective tropism of the virus for CD4 T cells.
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The course of AIDS consists of three phases, reflecting the dynamics of interaction between the virus and the host: - the early acute phase, - the middle chronic phase, - and the final crisis phase.
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Acute phase. The initial response of the immunocompetent individual to the virus develops. This phase is characterized by a high level of virus production, viremia and widespread seeding of lymphoid tissue, but the infection is still controlled by the antiviral immune response. The chronic phase is a period of relative containment of the virus, when the immune system is intact, but there is weak replication of the virus, mainly in the lymphoid tissue. This phase can last several years. The final phase is characterized by a breakdown of the host's defense mechanisms and uncontrolled replication of the virus. The content of CD4 T cells decreases. After an unstable period, serious opportunistic infections, tumors appear, and the nervous system is affected.
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The number of CD4 lymphocytes and virus RNA copies in the patient’s blood from the moment of infection to terminal stage. CD4+ T lymphocyte count (cells/mm³) Number of viral RNA copies per ml. plasma
