Immunopathological processes (pathological anatomy)

The immune system includes organs and tissues in which the maturation (differentiation) of T and B lymphocytes occurs. Primary and secondary organs of the immune system are distinguished.

I. Primary organs of the immune system

1. Thymus
2. Bone marrow
3. Squamous (stratified squamous) epithelium of integumentary tissues.

II. Secondary organs of the immune system

1. The lymph nodes
2. White pulp of the spleen
3. MALT structures
4. SALT structures
5. Optional lymphoid structures.

MALT structures

1. Tonsils of the Waldeer-Pirogov ring
2. Appendix of the cecum
3. Peyer's Plaques
4. Solitary follicles.

In the primary ( central ) organs , the first stage of lymphocyte differentiation takes place, before they interact with the antigen ( stage of antigen-independent differentiation ). In this case, T-lymphocytes mature in the thymus (after involution of the thymus, multilayered squamous epithelium take on its role), B-lymphocytes - in the red bone marrow.

Secondary ( peripheral ) organs provide the subsequent maturation of T- and B-lymphocytes after their interaction with antigens ( stage of antigen-dependent differentiation ). In the lymph nodes and in the lymphoid tissue of the spleen, both T and B lymphocytes are differentiated. In MALT structures and facultative lymphoid formations, mainly B-lymphocytes mature; in SALT-structures, mainly T-lymphocytes mature.

MALT-structures (MALT - an abbreviation from the English. Mucosa-associated lymphoid tissue ) - lymphoid tissue of the mucous membranes of the digestive tract, respiratory and genitourinary tracts, conjunctiva. MALT structures include (1) tonsils of the Waldeer – Pirogov ring , (2) the appendix of the cecum, (3) Peyer's patches, and (4) solitary follicles.

SALT structures (SALT - from the English. Skin-associated lymphoid tissue ) are small accumulations of immunocompetent cells around small vessels in the papillary and reticular layers of the dermis.

Facultative lymphoid formations are called lymphoid structures in the form of solitary follicles, which occur only during pathological processes in those organs where normal lymphoid tissue is absent. For example, lymphoid follicles form in the portal tracts of the liver in chronic viral hepatitis C, in the thyroid gland in autoimmune thyroiditis, or in the gastric mucosa in helicobacteriosis.

Thymus undergoes physiological atrophy ( age-related involution ). In this case, first of all, the volume of lymphoid tissue of the organ decreases. Age-related involution of the thymus begins from 5-7 years of age and basically ends by the puberty (puberty). Thymus parenchyma is replaced by white adipose tissue ( thymus lipomatosis ). However, small fragments of the active parenchyma persist throughout human life. The function of the thymus in the post-involutive period passes to the integumentary tissues lined with stratified squamous epithelium (skin, some mucous membranes, especially the mucous membrane of the oral cavity). A clear illustration of this is the change in immunity in Di George syndrome . The immunodeficiency state in this disease, due to congenital thymus hypoplasia, persists for the first five years of a child’s life. In subsequent years, if the patient does not die from manifestations of immunodeficiency, the function of the immune system is restored due to the fact that cells of multilayer squamous epithelium acquire the ability to produce thymic hormones and, therefore, attract T-lymphocyte precursors from the bone marrow, ensuring their maturation in integumentary tissues.

A variety of pathological processes can occur in the thymus: (1) inflammation (thymitis), (2) benign and malignant tumors, (3) malformations. However, the most important are (4) glucocorticoid-dependent lesions - incidental transformation and glucocorticoid-associated hyperplasia .

The effect of glucocorticoid hormones on lymphocytes

Glucocorticoids (hormones of the bundle zone of the adrenal cortex) are differentiating factors (i.e., factors promoting maturation) for all lymphocytes, including thymus lymphocytes.

1. Glucocorticoid hormones in normal concentration inhibit the multiplication (proliferation) of lymphocytes and contribute to their differentiation.

2. With a deficiency of glucocorticoids ( chronic adrenal insufficiency ), enhanced proliferation of lymphocytes ( glucocorticoid-associated lymphoid tissue hyperplasia ) is noted, but their maturation does not occur. As a result of this, a large number of functionally defective lymphocytes are formed, therefore, an immunodeficiency state develops. Lymphoid organs (thymus, lymph nodes, tonsils, spleen, etc.) increase. A significant increase in thymus is indicated by the term thymomegaly ; an increase in all groups of lymph nodes is called generalized lymphadenopathy .

3. With a high concentration of glucocorticoids in the body, which is characteristic of chronic distress syndrome , lymphocytes are destroyed by apoptosis under the influence of these hormones (an excess of glucocorticoids activates the apoptosis program in lymphocytes). This reduces the number of lymphocytes and, consequently, the volume of lymphoid tissue. The decrease in the thymus is indicated by the term accidents (from lat. Accidentalis - random). This process was called “random” because its reasons were not clear. Chronic distress syndrome accompanies various serious diseases (malignant tumors, infectious diseases). Accidental transformation of the thymus contributes to the development of an immunodeficiency state, exacerbating the already severe course of the underlying disease.

Glucocorticoid-associated lymphoid hyperplasia

Depending on the period of ontogenesis of chronic adrenal insufficiency, two forms of glucocorticoid-associated hyperplasia of lymphoid tissue are distinguished: (1) congenital ( lymphatic-hypoplastic diathesis , status thymico-lymphaticus ) and (2) acquired . The congenital form develops in the prenatal period, acquired in postnatal ontogenesis.

In addition to dishormonal hyperplasia of lymphoid tissue, lymphatic-hypoplastic diathesis is characterized by malformations of the internal organs, especially the heart, in the form of hypoplasia. In such patients, in cases of significant tension of the protective-adaptive mechanisms (serious illness, trauma, surgical intervention, intense physical exertion), sudden death may occur. Its cause is a deficiency of glucocorticoid hormones in the body, as a result of which vascular collapse and shock develop.

Incidental Thymus Transformation

Widespread in the domestic pathological anatomy was the scheme of morphogenesis of accidental transformation proposed by T.E. Ivanovskaya. The first four stages of incidental transformation are reversible.

Stage 1 - moderate thymus hyperplasia in the acute phase of stress syndrome.

Stage 2 - focal delymphatization (death of lymphocytes) of the cortex of thymic lobules.

Stage 3 - total delimfatization of the cortex ( stage of inversion of the layers ). Thymus lymphocytes in the medulla quantitatively prevail over cortex thymocytes, and it becomes darker than cortical in tissue sections stained with hematoxylin and eosin (normal - on the contrary).

Stage 4 - total delymphatization of thymic lobules (both cortical and brain matter) and death of thymic epithelial cells ( stage of giant Gassal bodies ). At this stage, Gassalle's bodies, normally located only in the medulla, appear on the territory of the entire lobule, including in the cortex. There are many of them, they are of various sizes (polymorphism of Gassal bodies), some of the bodies are sharply enlarged (giant bodies). Gassal's bodies are mainly formed by detritus (destroyed epithelial cells), while normally they consist of keratinizing epithelial cells.

Stage 5 - irreversible atrophic changes in the thymus.

Allergy ( hypersensitivity reactions ) is a manifestation of an overly expressed immune response. An antigen that causes an allergy is called an allergen .

Classification of Allergy Forms

Allergic reactions are classified as follows:

I. The nature of the allergen

1. Allergy to external antigens
2. Autoallergy (host versus host reaction, GVHD)
3. The graft versus host reaction (GVHD).

II. Rate of change

1. Immediate allergy
2. Allergy of the delayed ( late ) type
3. Slow allergy .

Special types of delayed-type allergies:

1. Transplant immunity reactions ( transplant rejection reactions, host versus transplant reaction - RCPT)
2. Tuberculin type reactions
3. Contact hypersensitivity .

III. Allergy Development Mechanism (S. Sell, 1978)

1. Reagin ( IgE-dependent ) reactions [type I allergic reactions]
2. Humoral cytotoxic reactions [type II allergic reactions]
3. Immunocomplex reactions [type III allergic reactions]
4. Cellular cytotoxic reactions [type IV allergic reactions]
5. Allergic reactions of autoantibodies [allergic reactions of type V]
6. Granulomatous inflammation [type VI allergic reactions].

The nature of the allergen

Depending on the nature of the allergen, reactions to exoallergens, autoallergy, and the graft versus host reaction are distinguished.

1. Allergy to external antigens (exoallergens). Diseases that develop in this case are called exogenous allergoses (for example, allergic bronchial asthma, hay fever).

2. Autoallergy - an allergy to your own antigens ( autoantigens ). Diseases based on autoallergy are called autoimmune .

3. The reaction "graft versus host" (GVHD) - aggression of the immune factors contained in the graft against the organs and tissues of the recipient. GVHD often develops during bone marrow transplantation, is accompanied by damage to various organs and can lead to death of the patient. Three forms of GVHD are distinguished: (1) adult ( homologous disease ), (2) infant ( welt disease ), and (3) perinatal ( Omenn syndrome ).

The rate of development of an allergic reaction

According to the rate of development of changes, reactions of immediate, delayed and delayed types are distinguished.

1. An immediate type allergy (immediate type hypersensitivity reactions , ANT , GNT reactions ) usually develops within a few minutes. In this case, tissue changes are described by the term acute immune ( allergic ) inflammation .

2. Allergy of the delayed (late) type. Late type reactions form within 1-6 hours.

3. A delayed-type allergy (delayed-type hypersensitivity reactions , AZT , HRT reactions ) develops in no less than 24 hours. In this case, tissue changes are referred to as chronic immune ( allergic ) inflammation .

Special Delayed Allergy Options

Particular types of delayed-type allergies are transplant immunity reactions, tuberculin-type reactions, and contact hypersensitivity.

1. Transplant immunity reactions are also called transplant rejection reactions or the host versus transplant (RCPT) reaction. A microscopic examination reveals two types of changes in the graft: (1) a productive inflammatory reaction (lymphohistiocytic infiltrate) and (2) alternative changes in the graft cells until they die. The close contacts of the cells of the infiltrate and the cells of the transplanted tissue are characteristic.

2. Tuberculin type reactions develop with allergic skin tests , with which you can diagnose the severity of the immune response to a particular antigen (for example, samples with tuberculin , brucellin and other antigenic drugs).

3. Contact hypersensitivity - a delayed type reaction at the site of contact of the integumentary tissue (skin, mucous membrane) and the allergen. This form of allergy underlies diseases such as contact allergic dermatitis , contact allergic cheilitis and contact allergic stomatitis .

Allergic reaction development mechanism

According to S. Sell ( 1978 ), six types of allergic reactions are distinguished. Type VI reactions (granulomatous inflammation) are traditionally regarded as manifestations of productive inflammation.

1. Type I reactions ( reagin reactions , IgE-dependent reactions ) - allergic reactions that develop under the influence of IgE ( reagins ). In this case, mast cells (labrocytes, tissue basophils) are degranulated, causing (1) edema, (2) plethora of microvessels, and (3) bronchospasm. Necrosis usually does not develop. The presence of numerous eosinophilic granulocytes in the tissue is characteristic. There are two forms of reagin reactions - anaphylactic and atopic . Anaphylactic reaction ( anaphylactic shock ) under certain conditions can develop in every person. In contrast, atopy does not occur in all people, but only in predisposed individuals. Atopic reactions underlie diseases such as allergic forms of urticaria and Quincke's edema, pollinosis (allergic rhinosinusopathies), atopic (non-infectious-allergic) bronchial asthma, diffuse neurodermatitis, atopic diathesis (exudative-catarrhal diathesis).

2. Type II reactions ( humoral cytotoxic reactions ) - allergic reactions during which damage to target cells occurs under the influence of humoral immune factors (immunoglobulins). Typical examples of type II reactions are the interaction of “rheumatoid factor” (IgM to FC fragments of IgG with rheumatoid arthritis) and “lupus factor” (antinuclear antibodies in systemic lupus erythematosus) with body cells.

3. Type III reactions ( immunocomplex reactions ) - tissue damage that develops under the influence of an excess of circulating complete immune complexes. Complete immune complexes are formed by antigen, antibodies to it and complement proteins. The main manifestation of immunocomplex reactions is immunocomplex vasculitis . The capillaries of the renal glomeruli ( immunocomplex glomerulonephritis ) are most often involved in the process. For immunocomplex inflammation is characterized by a combination of alternative and exudative reactions. Alterative changes are manifested, as a rule, by fibrinoid necrosis of the walls of blood vessels and perivascular tissue. Typically, the formation of fibrinous and hemorrhagic exudate.

4. Type IV reactions ( cellular cytotoxic reactions ) - allergic reactions in which the destruction of target cells occurs under the influence of killer cells - cytotoxic T-lymphocytes and K-cells. Killer T-lymphocytes destroy only those cells to the surface antigens of which they are sensitized. K cells ("B-killer lymphocytes") destroy target cells coated with antibodies ( antibody-dependent cellular cytotoxicity ).

5. Type V reactions ( allergic reactions of autoantibodies ) - a change (loss or increase) in the activity of protein molecules under the influence of autoantibodies. For example, autoantibodies to insulin or to insulin receptors of cells inactivate (neutralize) them, which may lead to the development of diabetes mellitus. Autoantibodies to follicular thyroid cells, on the contrary, through special cytolemal receptors stimulate these cells and increase their production of thyroid hormones, which is the cause of thyrotoxicosis. Therefore, type V reactions can be divided into two options: (1) neutralization (inactivation) reactions and (2) body protein activity stimulation reactions.

Autoimmunization ( autoimmune response ) - an immune response to their own antigens. There are (1) physiological (not accompanied by tissue damage) and (2) pathological autoimmunization ( autoallergy ), in which damage occurs to those tissue structures against which the autoimmune response is directed. Significant damage to the tissue of any organ leads to the development of its functional insufficiency. So, with autoimmune thyroiditis , hypothyroidism forms (insufficiency of the production of thyroid hormones), with autoimmune agranulocytosis leukopenia develops due to the destruction of neutrophilic granulocytes in the course of the autoimmune response. Two types of autoimmune factors are distinguished: (1) factors of cellular autoimmunity (killer lymphocytes, primarily autosensitized T-killers) and (2) factors of a humoral autoimmune response ( autoantibodies ). The main role in the development of tissue damage is played by cellular autoimmune factors.

Mechanisms of pathological autoimmunization

Four main mechanisms play a role in the development of pathological autoimmunization: (1) modification of the normal autoantigen (change in the structure of autoantigen), (2) sequestration of autoantigen of tissue of the barrier organ (elements of the tissue of barrier organs beyond the histogenetic barrier when it is damaged), (3) antigenic mimicry (the similarity of epitopes of autoantigens and exoantigens, as a result of which the immune response to an external antigen is accompanied by a cross-reaction to a similar autoantigen) and (4) supra-cell deficiency Quarrel.

Autoimmune Diseases

Autoimmune diseases are diseases in which autoallergy is the main component of pathogenesis. Three groups of autoimmune diseases are distinguished: organ-specific, organ-specific and autoimmune diseases of the intermediate type. In autoimmune diseases, a lymphocytic or lymphoplasmacytic infiltrate is formed in the affected organ.

1. Organ-specific autoimmune diseases develop as a result of damage to the histohematological barriers and are characterized by a primary lesion of any one barrier organ (for example, thyroid gland with Hashimoto thyroiditis , thymus with autoimmune thymitis ).

2. Organ-specific autoimmune diseases are distinguished by the primary involvement of many organs in the process. Moreover, in some cases, an autoimmune lesion is formed in the connective tissues ( diffuse diseases of the connective tissues ), in others - in the walls of blood vessels ( systemic vasculitis ). Diffuse diseases of connective tissues include rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, polymyositis (dermatomyositis), ankylosing spondylitis (ankylosing spondylitis). Among systemic vasculitis , nodular polyarteritis (nodular periarteritis), nonspecific aortoarteritis of Takayasu, temporal arteritis of Horton, and Wegener's granulomatosis are most common. The leading mechanism for the development of pathological autoimmunization in these diseases is the inadequate function of suppressor cells.

3. Most autoimmune diseases of the intermediate type are based on allergic reactions of autoantibodies (allergic reactions of type V).

Pseudo-autoimmune diseases

From autoimmune diseases, it is necessary to distinguish pseudo-autoimmune diseases (diseases with autoimmune disorders), in which the emerging autoimmune response is not a leading factor in pathogenesis. A typical pseudo-autoimmune disease is rheumatism , tissue damage in which is caused primarily by the action of aggression factors Streptococcus pyogenes , and pathological autoimmunization makes a less significant contribution to the development of the disease.

Immunodeficiency states ( immunodeficiencies ) are pathological changes characterized by an insufficient immune response. They are the background for the development of (1) infectious processes ( opportunistic infections ), (2) malignant tumors, and (3) some autoimmune diseases (with insufficient humoral and intact cellular immunity).

Primary Immunodeficiencies

Primary immunodeficiencies are hereditary and acquired in the prenatal period immunodeficiency states. These include (1) primary deficits of cellular immunity (e.g., DiGeorge syndrome - thymus hypoplasia), (2) primary deficits of humoral immunity (e.g., Bruton syndrome - complete absence of immunoglobulins), (3) primary combined deficits in which deficiency develops both cellular and humoral immunity (e.g. Louis Bar-ataxia-telangiectasia ), (4) primary defects of phagocytes and (5) deficiency of complement proteins .

Secondary Immunodeficiencies

Secondary immunodeficiencies are immunodeficiencies that develop in postnatal ontogenesis.

These include the following forms of immunodeficiency:

1. Immunodeficiency in chronic distress syndrome
2. Nosogenic immunodeficiencies
3. Iatrogenic immunodeficiencies
4. Age-related ( senile ) immunodeficiency
5. Alimentary immunodeficiencies
6. Physiological gravidar immunodeficiency .

1. Immunodeficiency in chronic distress. Long-term intense stress (chronic distress syndrome) is accompanied by an increase in the content of glucocorticoid hormones in the body, which in high concentrations have an immunosuppressive effect.

2. Nosogenic immunodeficiencies. Nosogenic (from the Greek. Nosos - disease) are immunodeficiencies, the development of which is associated with any serious illness. Most often, pronounced secondary immunodeficiency is formed with viral infections (for example, with HIV infection or measles), as well as with malignant neoplasms.

3. Iatrogenic immunodeficiencies. Iatrogenic (due to treatment) immunodeficiencies usually occur with the appointment of cytostatics and prolonged use of glucocorticoid hormone preparations ( drug immunodeficiency ). In some cases, immunodeficiency may be due to radiation therapy ( radiogenic immunodeficiency ), when significant amounts of tissue are exposed to radiation. Iatrogenic immunodeficiencies include postoperative immunodeficiency in patients who underwent surgery with massive surgical tissue trauma, and operated on under general anesthesia. The peak of postoperative immunodeficiency occurs 2-3 days after surgery. Postoperative immunodeficiency explains the increase in the incidence of opportunistic and hospital infections in this period, especially postoperative pneumonia.

4. Age-related immunodeficiency. Age-related immunodeficiency is due to the aging of the body.

5. Alimentary immunodeficiencies. Lack of protein , vitamins and trace elements in food lead to nutritional immunodeficiencies. Of the trace elements, zinc and cobalt are most important for the normal function of the immune system.

6. Physiological gravidar immunodeficiency. During pregnancy, under the influence of the placental hormone chorionic gonadotropin , a physiological immunodeficiency state occurs. Chorionic gonadotropin begins to be secreted by trophoblast cells from the 8th day of pregnancy. Immunodeficiency during pregnancy is necessary for the normal bearing of the fetus, since the fetal egg is foreign to the mother's body. In the pathological course of pregnancy, an immune response to the antigens of the ovum is formed and a rejection reaction develops. Acute rejection is manifested by spontaneous miscarriage (with gestational age up to 28 weeks) or premature birth (with gestational age more than 28 weeks). Prolonged rejection of the ovum is characterized by immunocomplex damage to internal organs, especially the kidneys, and is called gestosis , or late pregnancy toxicosis .

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