Control 1 Flashcards
(5 cards)
Changes in the thymus due to impaired immunogenesis (age-related and
accidental involution, a- hypo- and dysplasia, hyperplasia and thymomegaly),
their morphological characteristics and outcomes.
Thymus is the organ regulating the whole immune system. In disturbances
of immunogenesis usually the following processes and pathology are seen in the
thymus.
1. Accidental thymus transformation (involution), that is reduction in the
size and mass due to thymocytes migration to the peripheral immune organs and
blood as well as due to their partial decomposition and engulfment by
macrophages (this is called apoptosis).
According to T. Ivanovskaya (1976), accidental evolution has 5 stages.
Stage 1 – «holey clearing» – accumulation of lymphocytes around the
macrophages. It occurs in the cortex.
Stage 2 – transition of the lymphocytes from the cortex to the medullar
substance. The boundary between the layers is either poorly seen or not seen at all.
Stage 3 – «layer inversion», when the cortex layer looks light, and medullar
layer looks dark as a result of transition of lymphocytes from the cortex to the
medullar substance.
Stage 4 – Reduction in the lymphocyte amount in the both layers, reticular
stroma growth.
Stage 5 – collapse of the lobe of the thymus and sclerosis and lobe atrophy.
Accidental transformation more often occurs in the newborn suffering from
stress factors. The more powerful the stimulus, the more pronounced the degree of
involution. Accidental involution occurs in infections, intoxications, in children
born from sick mothers. The process is reversible. Elimination of pathological
agent results in thymus normalization.
2. Thymus hyperplasia (thymolymphatic state, thymomegaly). The weight
and the size of thymus are considerably increased. Microscopic examination
reveals a large number of immature lobules (zones are not distinct). The density of
the thymocytes is high. If this condition is accompanied by hypoplasia of adrenal
and sexual glands as well as narrowing of the aorta and arteries, this pathological
process is called «thymo-lymphatic state».
Sudden death syndrome (crib death) may occur in thymomegaly, it results
from insufficiency of T-lymphocytes of the cortex and, medullar substance of the
adrenal glands.
3. Thymus hypoplasia is characterized by absence of lobule division into
cortical and medullar substance, poor development of reticuloepithelial component
responsible for hormonal function, as well as lymphocyte component. As a rule thymus hypoplasia is typical for congenital immune deficiency.
4. Aplasia – total congenital lack of organ or its part.
5. Agenesis – congenital disorder which is characterized by absence of
thymus germ.
6. Dysplasia of thymus means morphological structure disorders: there is no
cortex and medulla in lobules, the boundary between lobules is poorly seen, etc.
Thymus hypoplasia, aplasia, agenesis and dysplasia are congenital
disturbances.
7. Thymus hyperplasia with lymphoid follicles.
Changes in peripheral lymphoid tissue due to impaired immunogenesis and
antigenic stimulation: morphological characteristics and outcomes.
In the bone marrow the first hyperplasia of B-lymphocytes is observed, and
then it becomes empty, as a result of increased transition of lymphocytes.
At antigen stimulation the morphologic processes developing in lymph
nodes and spleen of healthy person and sick man are similar. Nevertheless they
differ by the quantity of the involved in pathological process cells, as well as by
the character and grade of immune inflammatory reactions.
These changes are characterized by: macrophage reactions; hyperplasia of
B-lymphocytes with following transformation of them into plasma cells.
The number of plasma cells shows the intensity of immunogenesis and
corresponds to the level of antibodies production.
Lymph nodes are: hyperplastic, edematous; follicular centers are pale
(germinal centers are enlarged), contain numerous blasts and macrophages;
macrophage aggregations are seen; there are a lot of plasma cells and macrophages
in sinuses.
If cellular immune reaction develops in response to antigen the following
morphologic changes occur: proliferation of sensitized T-lymphocytes,
enlargement of T-dependent areas in lymph nodes (paracortical zones
Immediate and delayed hypersensitivity reactions: morphogenesis,
morphological characteristics, connection with inflammation, clinical value.
Hypersensitivity is defined as a state of exaggerated immune response to an
antigen. The lesions of hypersensitivity (immunologic tissue injury) are produced
due to interaction between antigen and product of the immune Hypersensitivity of immediate type. Immediate type of hypersensitivity is
further of three types – type I, II and III.
Immediate hypersensitivity reaction morphologically manifests by the
picture of acute immune inflammation which develops rapidly, alteration and
exudation stages prevail, and proliferation increases slowly. The vessels and connective tissues are involved first. Alteration manifests by mucoid, fibrinoid
swelling and fibrinoid necrosis. The exudate is either fibrinous or fibrino-
hemorrhagic. Acute immune inflammation is observed in some forms of leprosy
and syphilis. It is responsible for vascular reaction in lupus erythematosus,
glomerulonephritis, and nodular periarteritis.
Hypersensitivity of delayed type. Morphologically it manifests by chronic
immune inflammation characterized by lymphocyte-macrophage infiltration. When
the lymphocyte-macrophage infiltration accompanied by vascular plasmorrhagic
and degenerative processes is seen the conclusion of immune inflammation can be
made. The condition occurs in autoimmune diseases, tuberculosis, brucellosis,
dermatitis.
Type I reaction: Immediate type in which on administration of antigens, the
reaction occurs immediately (within seconds to minutes). Immune response in this
type is mediated mainly by humoral antibodies.
Type II reaction: antibody-mediated cytotoxicity. In this type, antibody
reacts with a normal or altered cell-surface component, leading to subsequent
destruction or inactivation of the target cell.
Type III reaction: immune complex disease. In this type of reaction,
circulating antigen–antibody (immune) complexes (which normally are removed
by the reticuloendothelial system) are deposited in tissues, leading to complement
activation and further tissue injury. Immune complexes may also develop in situ
(i.e., antibodies are directed against antigens that are endogenous to the tissues or
have been planted there), thus triggering localized tissue damage.
Type IV reaction: cell-mediated hypersensitivity. Cell-mediated
hypersensitivity reactions do not require the presence of antibody and,
characteristically, are delayed anywhere from about 24 hours to 2 weeks. Three
interrelated mechanisms are recognized, all of which involve activated T-cells.
Two types of cells take part in this reaction. They are sensitized lymphocytes and
macrophages. Granulomatosis is the morphological manifestation of delayed
hypersensitivity reaction.
Reactions of transplantation immunity: kinds, morphological characteristics.
Reaction of transplant rejection resembles slow hypersensitivity reaction.
Transplant antigens induce the production of antibodies and sensitized
lymphocytes which infiltrate the transplant.
Microscopically, lymphohistiocyte infiltration is observed in the transplant.
Cellular infiltration causes the disturbance of blood circulation and edema; as a
result degenerations and necrosis of transplant develop. The neutrophils and
macrophages appear in the transplant. Enzymatic destruction of the transplant
begins which is followed by its rejection.
Autoimmunization and autoimmune diseases: etiology, mechanism of development, classification, morphological characteristics.
Immunologic tolerance and autoimmunity. An immune response generated
against self antigens is an aberrancy that implies the loss of immunologic ability to
distinguish self and alien antigens. The normal status of immunologi unresponsiveness to self antigens is termed tolerance. Tolerance probably
represents an active process involving continuous generation of cellular and
humoral inhibitory regulators. Loss of tolerance to self antigen is referred to as
autoimmunity. The mechanisms by which tolerance is generated and lost are
poorly understood. Theories of autoimmunity include:
1. Recognition of previously hidden (physiological isolation) or sequestered
antigen.
2. Diminution of suppressor T-cell function.
3. Increase in helper T-cell activity.
4. T-cell-independent polyclonal B-cell activation by complex antigens.
5. Modification of self antigens by drugs or microorganisms.
6. Cross-reactivity between autologous antigens and microbial antigens.
Autoimmune diseases are those occurring as a result of the reaction of
autoantibodies and sensitized lymphocytes against normal antigens of the own
tissue. The causes of autoimmune diseases are not clearly known. Chronic viral
infections, radiation and genetic factors may be responsible for them.
In the pathogenesis of autoimmune diseases the following factors are
distinguished:
• predisposing (HLA genes, hormonal background, genetically dependent
features of the target cells);
• initiating (viral and bacterial infections, exposure of immune system and
target organs to chemical and physical factors);
• contributing (dysfunction of immune system, T-lymphocyte suppressor
activity).
In the pathogenesis 2 mechanisms can be distinguished; therefore all the
autoimmune diseases can be divided into 2 groups.
Group 1. Organ specific diseases. They are characterized by disturbance of
physiological isolation of the organs and tissues due to absence of immune
tolerance. Lymphohistiocyte infiltration occurs in the tissues (like at delayed
hypersensitivity reaction). The main organ specific diseases are:
1. Endocrine glands:
Hashimoto’s (autoimmune) thyroiditis.
Graves’ disease.
Insulin-dependent diabetes mellitus.
Idiopathic Addison’s disease.
2. Alimentary tract:
Autoimmune atrophic gastritis in pernicious anemia.
Ulcerative colitis.
Crohn’s disease.
3. Blood cells:
Autoimmune hemolytic anemia.
Autoimmune thrombocytopenia.
4. Others Myasthenia gravis.
Autoimmune orchitis.
Autoimmune encephalomyelitis.
Goodpasture’s syndrome.
Primary biliary cirrhosis.
Chronic active hepatitis.
Membranous glomerulonephritis.
Autoimmune skin diseases.
Group 2. Organ non-specific diseases. Primary disturbances in the immune
system causing the loss of ability to distinguish «own» and «foreign» antigens,
they are:
Systemic lupus erythematosus.
Rheumatoid arthritis.
Scleroderma (Progressive systemic sclerosis).
Polymyositis-Dermatomyositis.
Polyarteritis nodosa (PAN).
Sjogren’s syndrome.
Reiter’s syndrome.
Mixed connective tissue disease.
The diseases with autoimmune disturbances. In these diseases antigenic
properties of the tissues are changed, that causes immune reaction development.
Autoimmunization is responsible not for the beginning but the progress of the
disease as autoimmune antibodies appear during the disease. It is observed in
glomerulonephritis, hepatitis, chronic gastritis, burn disease, rheumatism, liver
cirrhosis.
