DEPARTMENT OF HISTOLOGY AND MEDICAL BIOLOGY OF
MEDICAL TREATMENT AND MEDICAL PROPHYLACTIC FACULTIES
The theme of lecture: " Organs of hematopoiesis and immunological protection
for students of a course of medical prophylactic, medical treatment departments
Tashkent 2012
Lecture: Organs of hematopoiesis and immunological protection.
The Plan:
1. Total morphofunctional characteristics of the blood.
2. Classification of blood.
3. Red bone marrow: development, structure and function.
4. The thymus gland: Development, structure and function. Age and accidental
involution thymus.
5. The development, structure, function, age-related features of lymph
of nodes.
6. The development, structure, function, age-sensitive spleen.
Bodies of hematopoiesis and immune defense - a set of supporting the
homeostasis of the blood and immune cells. These bodies serve two functions: 1)
make blood cells, 2) protect the body from external and internal antigens, ie,
provide immune protection.
Total morphofunctional characteristics.
Despite the considerable variety of hematopoietic organs and immune
defense have much in common - the sources of development, structure and
functions:
1. Channel development - all the organs of blood formation and immune
protection laid out the mesenchyme, the exception is the thymus gland - develop
from the epithelium of the 3-4th branchial pockets.
2. Commonality in the structure - the foundation of all of the blood and
immune defense of the reticular tissue. Exception - thymus: the basis of this body
is reticuloepithelial tissue.
3. abundantly supplied with blood, have hemocapillaries sinusoidal type
(diameter of 20 microns or more, between the endothelial cells have large cracks,
pores, basement membrane is not solid - sometimes absent; blood flows slowly).
It is known that the reticular tissue consists of cells (reticular cells in a small
number fibroblast-shaped cells, macrophages, mast and plasma cells, osteogenic
cells) and intercellular substance, represented by reticular fibers and amorphous
basic substance.
Reticulum in the organs of the immune defense has the following functions:
1. Creates a specific microenvironment that determines
direction of differentiation of mature blood cells.
2. Trophism mature blood cells.
3. Phagocytosis and disposal of dead blood cells by phagocytosis
reticular cells and macrophages.
4. Musculoskeletal and mechanical function - a supporting framework for
mature blood cells.
Classification. Bodies of hematopoiesis and immune defenses can be
divided into: 1) the central and peripheral.
The central are red bone marrow and thymus. Red bone marrow contains
stem cells that are formed by all blood cells except T lymphocytes. In the bone
marrow is the formation and differentiation of B lymphocytes. A differentiation of
T lymphocytes by the thymus. In the central organs of blood formation and
immune protection is antigen-presenting proliferation and differentiation of
lymphocytes.
Go to the peripheral organs are the lymph nodes, spleen, hemolymphatic
nodes and tonsils, lymphoid follicles (single and grouped) wall of the digestive
tube, the respiratory and urinary tract, appendix. They are here brought by
reproduction of the central organs of T-and B-lymphocytes and their specialization
under the influence of antigens (antigen-presenting proliferation and
differentiation) in the effector cells engaged in immune defense and cell memory.
In addition, here die blood cells have completed their life cycle.
Red bone marrow - the central organ of blood formation and immune
protection, which is as myelopoiesis and lymphocytopoesis.
Development. In the embryonic period is laid out in the mesenchyme second
month, a 4-month became the center of hematopoiesis.
Red bone marrow - the tissue semisolid consistency, dark-red color due to
the high content of red blood cells. He fills the spongy substance of flat and long
bones and in the adult is on average 4-5% of total body weight. A small amount of
bone marrow for research can be obtained by puncture of the sternum or the iliac
crest.
Stroma of the body of the reticular tissue, forming a microenvironment for
hematopoietic cells. At present, the items also include osteogenic
microenvironment, fat, adventitial, endothelial cells and macrophages. Stroma
richly imbued hemocapillar sinusoidal type. In the hinges of the reticulum are
islands or colonies of mature blood cells:
1. Erythroid cells in their islets, grouped around the colonies of
macrophages loaded with iron, derived from the dead in the spleen of old red blood
cells. Macrophages are a kind of "breadwinner" for erythroblasts, contribute to the
accumulation in the immediate vicinity of erythroblasts and erythrocytes are
entering into ropoetina, vitamins, and ferritin molecules. Macrophages
phagocytose islet core, pushed out when they are mature erythroblasts.
As the maturation of erythroblasts are separated from the islands and after
removal of the nucleus pass through the wall of venous sinuses in the bloodstream.
2. Granulocytopoetical cells also form islands around sinusoidal
hemocapillar.
Ripe blood cells pass through the sinusoidal wall and are carried
hemocapillar bloodstream. Passage of cells through the vascular wall contributes to
the increased permeability of the sinusoidal hemocapillar, high hydrostatic
pressure in the reticular tissue of the organ. High hydrostatic pressure due to two
factors:
1. The blood cells multiply in the bone tissue limited confined space, the
volume of which can not be changed, and this leads to increased pressure.
2. The total diameter of the vessels bearing the diameter of the efferent
vessels, which also leads to increased pressure.
Under normal physiological conditions through the wall of the bone marrow
sinuses penetrate only mature blood cells. Myelocytes and erythroblasts into the
blood only in pathological states of the organism. The reasons for this selective
permeability walls of blood vessels are not clear, but the fact of penetration of
immature cells in the bloodstream is always a sure sign of disorder of bone marrow
hematopoiesis.
THYMUS
Thymus - the central body and lymphocytopoesis immunogenesis. Of bone
marrow T lymphocyte precursors in it is antigen-presenting differentiation into T
cells that carry the cellular immune response and humoral immunity.
Development. The thymus is laid at the beginning of the 2nd month of
embryonic development of the epithelium of 3-4-gill pockets as exocrine gland.
Later cord connecting the iron with the epithelium of gill pockets undergoes
regression. At the end of the 2nd month body populated by lymphocytes.
Structure. External body is covered with a connective tissue capsule, from
which diverge into walls of loose connective tissue and the body divided into
segments. The basis of the parenchyma of the thymus is reticuloepithelial tissue:
epithelial cells dendritic cell, connected to each other and form a looped processes
of a network in which the loops are lymphocytes (thymocytes). In the central part
of the lobules aging epithelial cells form a layered calf thymus or calf Hassall concentrically layered epithelial cells with vacuoles, granules and fibrillar keratin
filaments in the cytoplasm. The number and size of Hassall corpuscles increases
with age.
The function of epithelial stroma of the thymus:
1. Creates a specific microenvironment for maturing lymphocytes.
2. The synthesis of the hormone thymosin, required in the embryonic period
for the normal development of the bookmark and peripheral lymphoid organs, and
in the postnatal period for the regulation of function of peripheral lymphoid organs,
synthesis of insulin-like factor-like growth factor cells factor.
3. Trophic - food mature lymphocytes.
4. Musculoskeletal and mechanical function - supporting frame for
thymocytes.
In the epithelial reticular loops are lymphocytes (thymocytes), especially
numerous at the periphery of lobules, so this part of the segments darker and is
called the cortical substance. Center segments contains fewer lymphocytes, so that
part is lighter and is part of the brain slices.
Cortex contains T-lymphocytes in the subcapsular zone lymphoblasts precursors of T lymphocytes, migrated here from the bone marrow. They are under
the influence of thymic hormone secreted by epithelial cells proliferate. T cells
migrate to the cortex into the bloodstream, without going into the medulla. These
cells differ in the composition of receptors from T lymphocytes of the brain
substance. From the bloodstream, they enter the peripheral organs, which mature in
subclasses: the killers, helpers, suppressors. However, not all produced in the
thymus lymphocytes out of the circulatory bed, but only those who have been
trained and have acquired specific receptors for foreign antigens.
In the cortex of the thymus is the "training" T-lymphocytes, ie they acquire
the ability to recognize "his" or "strange." What is this teaching? In the thymus
produced lymphocytes strictly specific (having a strictly complementary receptors)
for all possible conceivable antigens, even against its own cells and tissues, but in
the process of "learning" all cells have receptors for their tissues are destroyed,
retained only those cells that are directed against foreign antigens . That is why in
the cortex, along with increased reproduction occurs and the mass death of
lymphocytes.
Thus, in the thymus of T lymphocyte precursors formed subpopulation of T
lymphocytes, which subsequently enter the peripheral lymphoid organs, ripen and
are functioning.
The cells of the cortex separated from the blood hematotymical barrier. The
composition of hematotymical barrier include:
endothelial cells hemocapillar to the basement membrane;
precapillar space with isolated lymphocytes, macrophages and intercellular
substance;
epithelioreticulocytes from their basement membrane. The barrier has a selective
permeability with respect to the antigen.
Medulla is lighter, because it contains fewer lymphocytes. Thymocytes in
this zone are recycled pool of T lymphocytes and can come in and out of the blood
flow through postcapillary venules.
In the middle of the medullary epithelial cells are layered (Hassall
corpuscles). They are formed by concentric layers of epithelioreticulocytes, the
cytoplasm contains large vacuoles, granules and bundles of keratin filaments. With
age, the number of cells Hassall zoom.
The blood supply of the thymus. Inside the body the arteries branch out in
interlobular and intralobular, which form the arched branches. They depart from
the blood capillaries, forming a dense network especially in the cortical zone. The
capillaries of the cortex are surrounded by a basement membrane and nereryvnoy
layer of epithelial cells, delimited precapillar space. Most of the cortical capillaries
passes directly into the subcapsular venules. A smaller part goes to the medulla and
on the border with the cortical substance passes into the postcapillary venules with
high endothelium. Through the endothelium can recycle lymphocytes. In the
medulla there is no barrier.
Thus, the outflow of blood from the cortex and medulla occurs
independently.
Age and accidental involution of the thymus.
After the birth weight of authority within the first 3 years of rapidly
increasing. In the period from 3 to 20 years there has been stabilized and his
weight is about 40 g. After 20 years, the reverse development (age involution) of
the thymus. This is accompanied by a decrease in lymphocytes amount cortex, the
replacement of fatty tissue, increase cell Hassall. Sometimes it does not undergo
thymic involution age (status timolimfatikus). This accompanied deficit of adrenal
glucocorticoids. These people differ in reduced resistance to infections and
intoxications. Particularly increased risk of disease tumors.
Accidental or temporary involution of the thymus. The cause of accidental
involution of the thymus may be excessively strong stimuli (trauma, infection,
intoxication, severe stress, etc.). Morphologically, the accidental involution is
accompanied by mass migration of lymphocytes from the thymus into the
bloodstream, the massive loss of lymphocytes in the thymus and phagocytosis of
dead cells by macrophages (phagocytosis, and sometimes normal, not dead
lymphocytes), epithelial growth of the thymus and foundations increased synthesis
of thymosin, erasing the boundaries between cortical and medullary part of the
lobules . Biological significance accidental thymus involution:
Dying cells are donor DNA, which is transported by macrophages in the
lesion and is used where proliferating cells authority.
Mass death of lymphocytes in the thymus is a manifestation of selection and
elimination of T lymphocytes with receptors against its own tissues in the lesion
focus and aims at preventing possible autoaggression.
Sprawl epithelialtissue basis of the thymus, increased synthesis of thymosin
and other hormone-like substances aimed at increasing the functional activity of
peripheral lymphoid organs, increased metabolic and regenerative processes in the
affected organ.
In contrast to age involution, thymic involution accidental process is
reversible.
The functional significance of the thymus in the process of hematopoiesis is
the formation of T-lymphocytes, as well as a selection of lymphocytes, the
regulation of proliferation and differentiation of hematopoietic peripheral organs
through secretes hormones thymosin. In addition, the thymus selects the blood and
other biologically active substances: insulin-like factor, which lowers blood sugar,
calcitonin like that reduces the concentration of calcium in the blood and the
growth factor.
Peripheral organs of blood formation and immune protection
In the peripheral organs of blood in a healthy adult is only
lymphocytopoesis. These include the lymph nodes, spleen, hematotymical nodes,
lymphoid accumulations (follicles) mucosa of the digestive, genitourinary,
respiratory system
Lymph nodes
Lymph nodes - located along the lymphatic vessels. It is round or oval
formation of the size of 0.5-1 cm, on the one hand have the impression, this place
is called the gate. Through the gate to the node consists of arteries and nerves,
veins and efferent come lymphatics. Options: in lymph nodes occurs antigenpresenting proliferation and differentiation of T and B lymphocytes in the effector
cells, the formation of memory cells; filtering and cleaning the lymph flows (the
role of a biological filter, flowing through the lymph nodes, the lymph is cleaned
of foreign particles and antigens) and enriched in lymphocytes;
A body of the deposit of lymph flowing.
Development. Lymph nodes in the embryonic period are laid at the end of 2
months from the mesenchyme along the lymphatic vessels. Of mesenchymal
stroma forms (capsule and trabeculae, partitions) and the foundation body - the
reticulum. As laid reticulum soon colonized hematopoietic cells from bone marrow
and thymus.
Structure. Lymph nodes are composed of stroma and parenchyma. Strom
presented a capsule of dense connective tissue and unformed off from the capsule
trabeculae, septa. The basis of the parenchyma of the reticular tissue, filled sinuses,
and bearing on its hinges lymphocytes.
In peripheral lymph nodes are distinguished, more dense cortex, central light
and medulla papocortical zone.
Clusters of lymphocytes in the cortex form lymph follicles in the medulla
and form a pulpy strands.
Lymph follicles are rounded education. Lymph nodules distinguish reactive
center (or center of reproduction), the mantle zone. The central part of the follicles
light due to the fact that it consists of larger cells with large pale nuclei: from
lymphoblasts, macrophages, dendritic cells. Lymphoblasts are usually in various
stages of division, resulting in this part of the nodule called germinal center or
center of the breeding season. With intoxication of the organism in the central part
of the follicle accumulation of phagocytic cells, indicating the high reactivity of the
described structures, so that part of the follicle is also called the jet center.
Lymphoid tissue between lymph nodules, and meat strands called zone. This
zone consists mainly of T lymphocytes, the DCO and postcapillary venules with
high endothelium, so it is a zone called the T-dependent zone. In parakortikalnoy
zone is T-cell proliferation and differentiation into effector cells. Postcapillary
place in the lymph node of circulating T and B lymphocytes.
Medulla is composed of anastomosing cords and sinuses of the brain. The
basis of the brain strands of reticulum, in which the loops are B-lymphocytes,
plasma cells and macrophages. Here is the maturation of plasma cells. Lymphoid
follicles and brain cords are in-dependent area of lymph nodes.
Space bounded by the capsule and trabeculae with one hand and knotted
cords and brain - on the other are called sinuses. They are a continuation of
bringing the lymphatic vessels.
There are the following sinuses:
1. Marginal sinus - between the capsule and lymph nodules.
2. Boundary continues in the intermediate sinuses or sinuses nodular - between
the trabeculae and lymphatic nodule.
3. Intermediate sinuses extend into the brain sinuses - between pulpy strands.
4. Cerebral sinuses at the gate going into the central sinus, from which the efferent
lymph imposed lymphatic vessels.
The wall of the sinus is lined by flat polygonal cells, which differ little from
the usual endothelium. Some authors call them shore reticulum. Lining of the
sinuses is not solid, the gap between the cells remain - fenestry, basement
membrane is absent, all of which facilitates entry into the lymph flowing over them
lymphocytes. Among the endothelial cells have a considerable number of
macrophages, which flows from the lymph phagocytose foreign particles and
microorganisms, recycle antigens and transmit B-lymphocytes, ie trigger
mechanism antigen-presenting lymphocytopoesis and humoral immunity.
Thus, the sine function as protective filters, which due to the presence of
phagocytic cells retained most of the fall in the lymph nodes antigens.
SPLEEN
Spleen - hemolymphatic body taking part in the elimination of moribund or
damaged red blood cells and platelets, and the organization of protective reactions
of antigens that have penetrated into the bloodstream and deposit in the blood.
Of the spleen:
1. in the spleen is antigen-presenting proliferation and differentiation of T and B
lymphocytes and antibodies;
2. Depot.
3. Elimination of damaged, senescent red blood cells;
4. Supplier of iron for hemoglobin synthesis, globin - for bilirubin;
5. Cleaning the blood passes through the body of antigens;
6. In the embryonic period - myelopoiesis.
Development. At the beginning of the 2nd month of embryogenesis laid
mesenchyme. From the mesenchyme formed capsule, trabeculae, reticuloepithelial
base, smooth muscle cells. Of the visceral leaf splanchnotome formed peritoneal
cover body. In the future hematopoietic stem cells from the wall of the yolk sac
colonize the reticular tissue and on the 4th month of authority becomes, along with
the liver, blood center.
By the time of birth in the spleen myelopoiesis ceases, stored and amplified
limfotsitopoesis.
Structure. The spleen is composed of stroma and parenchyma. The stroma
is composed of fibro-elastic capsule with a small number of myocytes, the outside
covered with mesothelium, and extending from the capsule trabeculae.
In the parenchyma of the distinguished white and red pulp.
The white pulp is approximately 1 / 5 body and represented the lymph
nodules. Lymph nodules are accumulations of T-and B-lymphocytes, plasma cells
and macrophages. Unlike other nodules of lymphoid organs lymph nodule is
penetrated by the central artery of the spleen, situated eccentrically.
Lymph nodules isolated areas:
1. Periarterial zone - formed mainly of T lymphocytes and DCO (T-dependent
zone).
2. Breeding center - contains proliferating B lymphoblasts, plasma cells, and
differentiating a small number of macrophages (B-sensitive area).
3. Mantle zone - around periarterial zone and breeding center, and contains mainly
B-lymphocytes, and a small number of T-lymphocytes, plasma cells and
macrophages.
4. Marginal or marginal zone has a transitional area between the white and red
pulp, is the ratio of T-and B-lymphocytes = 1:1.
Red pulp - is the foundation of the body of the reticular tissue, permeated
sinusoidal vessels filled with blood counts, mainly erythrocytes. The abundance of
red blood cells in sinusoids attached to the red pulp red. The wall of the sinusoids
covered elongated endothelial cells, among them there are significant gaps.
Endothelial cells located on the discontinuous, interrupted basement membrane.
The presence of cracks in the wall of sinusoids gives the opportunity to enter red
blood cells from blood vessels into the surrounding reticular tissue. Macrophages
contained in large quantities as in the reticular tissue, and endothelial cells of
sinusoids phagocytose damaged, senescent red blood cells, so called the graveyard
of the spleen erythrocytes. Hemoglobin dead red blood cells by macrophages is
delivered to the liver (the protein portion - globin used in the synthesis of bile
pigment bilirubin) and red marrow (iron-containing pigment - heme is transferred
maturing erythroid cells). Another part of the macrophages is involved in cell
cooperation in humoral immunity.
Blood supply to the spleen. At the gate the spleen is the splenic artery, which
branches to trabecular artery. Of the trabecular artery leaves the pulp artery, which
enters into the white pulp and is called the central artery. The central artery coming
out of the knot, splits in the form of a brush on a few penicillar arterioles. The
distal end of the arterioles penicillar continues ellipsoid arterioles (equipped with a
clutch of reticular cells and fibers), which is divided into hemocapillar. Most of the
red pulp hemocapillar empties into the venous sinuses (closed circulation), but
neotorye can directly open the reticular tissue (open circulation). Closed circulation
- the way fast circulation and tissue oxygenation. Open circulation - more slowly,
providing contact with blood cells by macrophages.
Regeneration of the spleen - a very good, but the tactics of the surgeon in
case of damage usually determines the characteristics of the blood supply, which
makes very difficult to stop bleeding in parenchymal organ.
Literature
1. Histology (an introduction to pathology), edited by E.G. Ulumbekov,
Moscow, 1998
2. Histology - a textbook, ed. Afanasyev YI, Moscow, 2002
3. Histology - a textbook edited by Hem A., Cormack, D., 1983., Vol.4.