General Properties of the BBB 4 страница

Thymic corpuscles are isolated masses of closely packed, concentrically arranged epithelioreticular cells.

Figure 37. Schematic diagram of the blood-thymus barrier

Blood thymic barrier

The blood thymic barrier present only in the cortex.

The blood vessels of the thymic cortex are impermeable to molecules that pass to the tissues spaces in most organs.

The components of the barrier, from lumen outward, are:

-capillary endothelium

-endothelial basal lamina

-thin perivascular connective tissue sheath containing many macrophages

-basal lamina of the epithelioreticular cells

-epithelioreticular cells sheath

Function of the blood thymic barrier

The blood thymic barrier forms a shield that prevents the contact between the high concentrations of antigens circulating in the blood and the developing immature lymphocytes in the thymic cortex.

Thymic function

The thymus is the site of the programming, differentiation and proliferation of T lymphocytes.

Within the thymus there is large-scale proliferation of lymphocytes and large-scale cell death, so that most of the newly formed lymphocytes die within a few days. The lymphocytes released by the thymus are the T lymphocytes.

The T lymphocytes survive for long periods and recirculate through lymphatic tissues.

The transformation of primitive or immature lymphocytes into T lymphocytes is promoted by a thymic humoral factor called thymosin.

The thymic epithelioreticular cells produce this factor.

Red bone marrow

Red bone marrow consists of developing blood cells in different stages of development and a network of reticular cells and fibers that serve as a supporting framework for the developing blood cells and blood vessels. Clusters of developing erythrocytes surround and receive iron from macrophages in groupings called erythroblastic islands.

As an individual growth the amount of red bone marrow does not increase in proportion to bone growth.

In later stages of growth and in the adult, when the rate of blood cell formation has diminished, the tissue in the medullary cavity consists mostly of fat cells; it is then called yellow marrow. Under appropriate stimuli; such as extreme blood loss, the yellow marrow can revert to red marrow. In the adult, red marrow is normally restricted to the spaces of spongy bone in a few locations such as the sternum and the iliac crest.

Spleen

The spleen is the largest lymphatic organ. It is located in the upper left quadrant of the abdominal cavity and has a rich blood supply.

The spleen has both morphologic and immunologic filtering functions. In addition to large numbers of lymphocytes, it contains specialized vascular spaces or channels, a meshwork of reticular cells and reticular fibers, and a rich supply of macrophages.

Figure 38. Schematic diagram and photomicrograph of splenic structure

These contents allow the spleen to monitor the blood immunologically, much as the macrophages of the lymph nodes monitor the lymph.

The substance of the spleen, other than the capsule and trabeculae, consists of splenic pulp. This, in turn, is divided into white pulp and red pulp, based on color seen in a fresh section.

The spleen is surrounded by a capsule of dense connective tissue from which trabeculae extend into the substance of the organ. The connective tissue of capsule and trabeculae contains myofibroblasts.

The spleen normally retains relatively little blood, but it has the capacity for contraction by means of the contractile cells in the capsule and trabeculae.

Splenic pulp

White pulp is the concentration of lymphatic tissue within the red pulp that surrounds portions of central arteries forming nodules along their lengths. Nodules consist of reticular mesh with spaces in mesh being filled with lymphocytes, monocytes, plasma cells and macrophages. The enlarged nodules in the white pulp are called splenic nodules or Malpighian corpuscles. Central artery is identifying characteristic.

Lymphocytes aggregated around the central artery constitute the periarterial lymphatic sheath.

The white pulp consists of germinal center and marginal zone.

The germinal center is a reaction center that forms in response to antigen exposure.

The marginal zone that the area that separates white pulp and red pulp.

Marginal zone surrounds white pulp nodules - contains few lymphocytes, but many

actively phagocytic macrophages with branching processes.

Marginal zone acts as a filter to pull foreign antigens out of blood so that

lymphocytes can react to them and be induced to participate in an immune

response.

Branched macrophages of this area are called dendritic cells.

Both B- and T-lymphocytes present in the white pulp: T-lymphocytes in sheath surrounding central artery, B-lymphocytes in lymphatic tissue of white pulp surrounding sheath (i.e. peripheral white pulp).

Red pulp contains large numbers of red blood cells that it filters and degrades. The red pulp consists of splenic sinuses separated by the splenic cords. The splenic cords consist of the loose meshwork of reticular cells and reticular fibers that contain large numbers of erythrocytes, macrophages, lymphocytes, plasma cells and granulocytes. Many of the macrophages are engaged in the phagocytosis of damaged red blood cells.

The iron from destroyed red blood cells is reutilized in the formation of new red blood cells. Present blood sinusoids are site of cellular exchange between spleen and circulatory system. Cells can enter or leave spleen through large spaces between endothelial cells lining sinusoids.

Blood circulation in the spleen

a. Arteries enter pulp via trabeculae.

b. Branches of arteries extend into white pulp forming the central arteries of the
white pulp.

c. These arteries are surrounded by a sheath of lymphocytes that form thickenings
along the length of the artery that are the white pulp lymph nodes.

d. Branches of central artery extend into white pulp.

e. Some of these leave white pulp and then loop back toward it emptying into
sinusoids that form part of marginal zone of loose lymphoid tissue that surrounds
white pulp.

f. Other branches of central arteries extend into red pulp to form the pulp arteries
that empty into various sinusoids of this tissue.

g. Blood from the sinusoids is collected into red pulp veins. These trabecular veins
combine to form the splenic vein that leaves the spleen through the hilum.

Functions of the spleen

The spleen functions in both the immune and hematopoietic system.

Immune system functions of the spleen include:

-proliferation of lymphocytes

-production of humoral antibodies

-removal of macromolecular antigen from the blood

Hematopoietic functions of the spleen include:

-formation of blood cells during fetal life

-removal and destruction of senile, damaged and abnormal red blood cells and platelets

-retrieval of the iron from red cell hemoglobin

-storage of blood, especially red blood cells, in some species

Proliferation of lymphocytes and differentiation of effector lymphocytes and plasma cells, as well as secretion of humoral antibodies, occur in the white pulp of the spleen.

The role of the red pulp is blood filtration, i.e. removal of abnormal or damaged blood cells and platelets from the circulating blood.

Lymph Nodes

There are 500-600 lymph nodes (lymph glands) in the body. A lymph node is round, ovoid or bean-shaped and varies in size from less than 1 mm to 2-3 cm. The nodes are located along the course of blood vessels. They have a depression on one side, the hilus. Blood vessels enter and leave the lymph node at the hilus, but lymphatic vessels enter at the periphery, and exit at the hilus. Lymph nodes may enlarge during infection or disease and then they are easily palpated.

Structure

- It is composed of stroma and parenchyma. In a section of a lymph node we can distinguish a peripherally situated cortex which lies under and close to the capsule, except the hilum. This cortex incompletely surrounds a centrally located medulla which is close to the capsule at the hilum.

A) The stroma:

1) The capsule:

The lymph node is enclosed inside a thick capsule which is surrounded by loose fatty C.T.

This capsule is composed of dense irregular C.T. formed of irregularly arranged collagenous fibers with fibroblasts, fibrocytes and blood vessels in between.

The capsule is penetrated at the cortex by the afferent lymphatics, and at the hilum by blood vessels, efferent lymphatics and nerves.

2) The C, T. septa:

From the inner surface of the capsule, septa arise. In the cortex of the node, the septa are thin, straight, non-branching and complete dividing the cortex of the node into compartments. In the medulla, these septa become irregular, branching and anastomosing and incomplete.

The septa (like the capsule) are composed of dense irregular C.T. formed of irregularly arranged collagenous fibers with fibroblasts, fibrocytes and blood vessels in-between.

3) Reticular C.T.:

From the inner surface of the capsule and both surfaces of the septa, a reticular C.T. stroma arises to fill the background of the organ and takes the arrangement of the parenchyma.

This stroma is formed of reticular fibers and dendritic reticular cells.

B) The Parenchyma:

The parenchyma of the lymph node is formed of lymphoid tissue which is differentiated into outer cortex and inner medulla.

1) The Cortex:

It is composed of cortical lymph follicles surrounded by lymph sinuses.

The cortical follicles:

Each cortical compartment is occupied by a lymph follicle which is composed mainly o f lymphocytes. Some macrophages and few plasma cells are also present. These cells are suspended in the reticular C.T. stroma.

The cortical follicles have germinal centers if they are activated.

Activated follicles (nodules) which contain germinal centres are termed "secondary nodules", whereas the resting nodules which lack germinal centers are termed "primary nodules".

The lymph sinuses of the cortex:

Each cortical follicle is surrounded by a group of lymph sinuses which are spaces present between the processes of the stromal dendritic reticular cells.

The sinuses are discontinuously lined by simple squamous endothelium.

The cortical sinuses are classified into three groups, namely;

-Subcapsular sinuses, under the capsule.

-Cortical sinuses, surrounding the follicle.

-Subcortical sinuses, present deep to the follicles.

The sinuses contain lymph which is received by the subcapsular sinuses from the afferent lymphatics. Lymph, then, passes into the cortical and subcortical sinuses.

2) The Medulla:

It is composed of medullary cords of lymphoid tissue surrounded by medullary

lymph sinuses.

Figure 39. schematic diagram and photomicrograph of the lymph node

The medullary cords:

They are branching and anastomosing cords of lymphoid tissue present in between the C.T. septa.

These cords are formed of lymphoid tissue which mainly contains plasma cells with some lymphocytes and macrophages all are suspended in the reticular C.T. stroma

The medullary lymph sinuses:

They are spaces present in between the processes of the stromal dendritic reticular cells. These spaces surround the medullary cords. The sinuses are discontinuously lined by simple squamous endothelium. The medullary sinuses receive lymph from the subcortical sinuses and transport it to the efferent lymphatics which get out of the node through its hilum.

Cells of the parenchyma of the lymph no de:

1) Lymphocytes:

They are more crowded in the cortical follicles.

The lymphocytes are generally of t he B-type, except in the deep part of the cortex (the para cortical zone) which contains only T-lymphocytes, so it is called; the thymus dependent zone.

2) Plasma cells:

They are more crowded in the medullary cords.

3) Macrophages:

They are more crowded around the lymph sinuses.

Function of the lymph node

1) Filtration of lymph:

About 99% of the antigens carried by the lymph from any organ or tissue are phagocytized by the macrophages present in the lymph node. Lymph arising from any tissue or organ in the body must pass through lymph nodes before getting back to the blood circulation.

Lymph gets into the lymph node through its afferent lymphatics. It percolates

through the subcapsular, cortical, subcortical and lastly the medullary lymph

sinuses. It gets out of the lymph node through its efferent lymphatics.

As lymph flows through the sinuses, 99% or more of the antigens and other debris

it carries are removed, by the phagocytic activity of macrophages that span the

sinuses.

2) Antibodies production:

Antigens carried to the lymph nodes, activate its B-lymphocytes to change into plasma cells which produce the specific antibodies.

About 1% of the antigens carried into the lymph node by the lymph pass through the cortical follicles. These antigens stimulate the B-lymphocytes to become active.

Activated B-lymphocytes proliferate in the germinal centres of the cortical follicles. Some of the daughter cells are preserved as memory cells. The other cells change to plasma cells which migrate to the medulla and secrete the specific antibodies. The antibodies pass with the lymph to the circulation. Memory cells leave the node with the lymph to the circulation. If they are stimulated again by the same antigen, they migrate to the surrounding CT. and change to plasma cells and secrete the antibodies.

3) Site of proliferation of lymphocytes:

Activated lymphocytes, arising from the non-capsulated lymphoid tissues, migrate through the blood vessels to the lymph nodes. The cells pass in-between the high endothelial cells of the post-capillary venules to the nodal parenchyma where they proliferate. Daughter cells get out of the node through the efferent lymphatics to be finally poured back, to the circulation.

Lymphatic tissue and the immune response

The lymphatic system is specialized form of connective tissue that consists of cells, tissues, and organs that monitor body surfaces and internal fluid compartments and react to the presence of potentially harmful antigenic substances.

Included in this system are thymus, spleen, lymph nodes, lymphatic nodules, and diffuse lymphatic tissue.

The several forms of lymphatic organs and tissue are often collectively referred to as the immune system.

Lymphatic vessels connect parts of the system to the blood vascular system.

Lymphocytes are the chief cellular constituent of lymphatic tissue.

Functionally, two types of lymphocytes are identified: T lymphocytes and B lymphocytes.

T lymphocytes or T cells, involved in cell-mediated immunity

B lymphocytes or B cells, involved in humoral immunity and the production of antibodies

The bone marrow and thymus have been identified as primary or central lymphaticorgans. Lymphocytes undergo their antigen independent proliferation and differentiation into immunocompetent cells in these organs.

Immunocompetent lymphocytes, together with plasma cells derived from B lymphocytes and with macrophages, organize around mesenchymal reticular cells and their reticular fibers to form the adult effector lymphatic tissues and organs, i. e. lymphatic nodules, lymph nodes, tonsils and spleen. It is in these secondary orperipheral lymphatic organs that T and B lymphocytes undergo antigen-dependent proliferation and differentiation into effector lymphocytes and memory cells.

Cells of the lymphatic system

B lymphocytes may differentiate into plasma cells that produce antibodies

or into memory cells.

B lymphocytes that have been activated by contact with antigen transform into immunoblasts (plasmoblasts) that proliferate and then differentiate into:

- plasma cells, which synthesize and secrete a specific antibody

- memory cells, which are able to respond more quickly to the next encounter with the same antigen

The specific antibody produced by the plasma cell binds to the stimulating antigen, forming an antigen-antibody complex.

These complexes are eliminated in a number of ways, including phagocytosis by macrophages and eosinophils.

The complexes may also activate a system of plasma proteins, the complement system, and cause one of the components, to bind to an antigenic bacterium and act as a ligand for its phagocytosis by macrophages.

Memory cells do not participate in the initial or primary response to a specific antigen. However, memory cells are programmed and ready to respond to the same antigen should it appear again. The response to the same antigen on second exposure is called the secondary response. It is more rapid and intense than the primary response, because of the presence of a population of specific memory B lymphocytes already programmed to respond to that antigen.

T lymphocytes

Immunocompetent T lymphocytes that have been activated by interaction with an antigen also transform into lymphoblasts that proliferate and differentiate into several types of effector.

Three types of T lymphocytes have been identified:

-Cytotoxic lymphocytes (CTL) or killer T cells, which serve as primary effector cells in cell-mediated immunity.

-Helper T lymphocytes (T_H cells) which assist B cells as well as other T cells in their response to antigens

-Suppressor T lymphocytes (T_S), which suppress the activity of B cells

The primary function of cytotoxic lymphocytes is to screen other cells for signs of viral infection or other signs of abnormality, such as development into cancer cells. The antigen receptors on the killer cells enable them to recognize viral or cancer-related peptides on the surface of cells and to kill the cells by causing them to lyse.

Helper T cells assist in the stimulation of B lymphocytes to produce antibodies. T_H cells have surface receptors that bind to a surface peptide complex on the membrane of macrophages or B cells that have “processed” an antigen. Thus, stimulates the helper T cells to become active, dividing and producing polypeptide hormones called interleukins that, in turn, stimulate B cells to divide and produce their antibodies.

Lymphokines are soluble substances released by sensitized lymphocytes on contact with a specific antigen. Along with other functions, these substances stimulate the activity of monocytes and macrophages in the cell-mediated immune response.

In persons infected with AIDS-causing human immunodeficiency virus, the number of helper T cells is dramatically reduced.

Antigen presenting cells

Antigen presenting cells interact with helper T cells to facilitate immune responses.

The interaction between most antigens and the antibodies on the surface of B cells is insufficient to stimulate B cell growth, differentiation, and secretion of soluble antibody. For the lymphocytes to function effectively, antigens are processed and presented to them by antigen-presenting cells.

The group of antigen presenting cells includes:

-Langerhans cells of the epidermis

-Lymphatic dendritic cells

-Perisinusoidal macrophages (Kupffer cells) of the liver

-Tissue macrophages

Macrophages and the immune response

Macrophages are closely associated with lymphocytes in both types of immune response. Macrophages can process and present the antigen to the B cells or helper T cells and destroy the antigen after it has been processed by other cells of the immune system

Endocrine organs

Communication between cells is necessary to maintain homeostasis and coordinate growth and development.

The primary function of two major organ systems, the endocrine system and the nervous system is intercellular communication.

The endocrine system communicates through the release of hormones, secretory products of endocrine cells and organs that pass into the circulatory system for transport to target cells that possess receptors for the hormones.

Functionally, the endocrine system and the nervous system are closely interrelated and may overlap in function. The hypothalamus, a part of the brain, coordinates most endocrine functions of the body and serves as one of the major controlling centers of the autonomic nervous system. The hypophysis and the hypothalamus the portion of the brain to which the hypophysis is attached, are morphologically and functionally linked in the endocrine and neuroendocrine control of other endocrine glands. They are often called the “master organs” of the endocrine system.

Endocrine hormones include three classes of compounds.

1. Steroids are synthesized and secreted by cells of ovaries, testes and adrenal cortex.

2. Small peptides, proteins and glycoproteins are synthesized and secreted by the cells of the hypothalamus, hypophysis (pituitary), thyroid, parathyroid, pancreas and scattered endocrine cells of the gastrointestinal tract and lungs.

3. Amino acid analogues and derivatives, including the catecholamines are synthesized and secreted by many neurons as well as cells of the adrenal medulla.

Hypophysis (pituitary gland)

The hypophysis has two functional components:

-adenohypophysis (anterior pituitary) the glandular epithelial tissue

-neurohypophysis (posterior pituitary) the neural secretory tissue

The adenohypophysis consists of:

-pars distalis

-pars intermedia

-pars tuberalis

The neurohypophysis consists of:

-pars nervosa

-pars infundibulum

Adenohypophysis

The adenohypophysis is the master gland of the endocrine system, regulating other endocrine glands.

Pars distalis

Figure 40. Photomicrograph of the human pars distalis, Ac, acidophils; Bas, basophils; Ch, chromophobes

Descriptions of the cells within the pars distalis were based only on the staining properties of secretory granules within the cells.

Histologists identified three types of cells according to their staining reaction, such as, basophiles 10%, acidophils 40%, and chromophobes 50%.

Basophiles is divided into:

-the adrenocorticolipotropes (the most common basophiles) which produce adrenocorticotropic hormone (ACTH) and lipotropic hormone (LPH)

-the gonadotropes (small basophiles) which produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH)

-the thyrotropes (large basophiles) which produce thyroid-stimulating hormone (TSH)

Acidophils is divided into:

-the somatotropes (small acidophils) which produces somatotropin, a growth hormone (GH)

-the lactotropes (mammotropes) are variable and scattered acidophils that produces prolactin (PR) or lactogenic hormone (LTH) and undergo hypertrophy during lactation.

Chromophobes have undifferentiated cells and follicular cells.

The long branching processes of follicular cells form a supporting network for the other cells.

Pars intermedia

The pars intermedium is in humans, a rudimentary region made up of cords and follicles of weakly basophilic cells that contain small secretory granules and chromophobic cells. The function of these cells is not known. In the basophilic cells are found small amount of melanocyte-stimulating hormone.

Pars tuberalis

The endocrine cells are arranged in short clusters or cords in association with the blood vessels. Nests of squamous cells and small follicles lined with cuboidal cells and scattered in the region. Some functional gonadotropes are present in this region.

Neurohypophysis

The neurohypophysis is a nerve tract whose terminals store and release secretory product from the hypothalamus.

The neurohypophysis contains pituicytes associated with the fenestrated capillaries. These cells are irregular in shape, with many branches, and resemble glial cells. Their nuclei are round or oval, and pigment granules are present in the cytoplasm.

The neurohypophysis consists of the pars nervosa and the infundibulum that connects it to the hypothalamus.

The pars nervosa contains nonmyelinated axons and nerve endings of approximately 100.000 neurosecretory neurons whose cell bodies lie in the supraoptic and paraventricular nuclei of the hypothalamus.

Dilatations of the axons are called Herring bodies. The membrane-bounded neurosecretory granules that aggregate to form the Herring bodies contain either oxytocin or vasopressin (antidiuretic hormone) (ADH).

Antidiuretic hormone (vasopressin) increases blood pressure by promoting the contraction of smooth muscle in small arteries and arterioles. ADH decreases urine volume by altering the permeability of kidney collecting tubules, decreases the rate of perspiration.

Oxytocin promotes contraction of smooth muscle of the uterus during copulation and parturition and myoepithelial cells of the breast.

The hypothalamus

The hypothalamus regulates hypophyseal function.

The hypothalamus has supraoptic and paraventricular nuclei. Antidiuretic hormone and vasopressin are secreted by these nucleuses.

The hypothalamus is the site of production of a number of neurosecretory proteins.

In addition to oxytocin and ADH, the hypothalamic neurons secrete proteins that promote and inhibit the secretion and release of adenohypophyseal hormones.

These other hypothalamic peptides also accumulate in nerve endings near the median eminence and infundibular stalk and are released into the first capillary bed of the hypophyseal portal system for transport to the pars distalis.

Hypothalamic regulatory peptides

-growth hormone releasing factor

-growth hormone inhibiting factor

-prolactin releasing factor

-prolactin inhibiting factor

-gonadotropin releasing factor

-corticotropin releasing factor

-thyrotropin releasing factor

Pineal gland

Figure 41. Photomicrograph of the human pineal gland

The pineal gland (pineal body) is now described as an endocrine or neuroendocrine gland but it is functions in humans are not clearly defined.

In humans, pineal activity, as indicated by changes in the plasma level of melatonin, rises during darkness and falls during light. Clinically, tumors that destroy the pineal gland are associated with precocious (early onset) puberty. Pineal gland function then influences seasonal sexual activity and circadian (24 hour) biorhythms. The pineal gland contains two basic types of parenchymal cells:

-pinealocytes and interstitial (glial) cells

Pinealocytes are the most common parenchymal cell in the pineal gland. They secrete 2 kinds of amines, serotonin and melatonin. They are arranged in clumps or cord within the lobules formed by connective tissue septa that extend into the gland from the pia matter that covers its surface. These cells have a large, deeply infolded nucleus with one or more prominent nucleoli and contain lipid droplets within their cytoplasm.

Pinealocytes show typical cytoplasmic organelles along with numerous, dense-cored, membrane-bounded granules in their elongated cytoplasmic processes. The expanded club- like endings of the processes are associated with the blood capillaries. This feature is strongly suggestive of neuroendocrine activity.

The interstitial (glial) cells comprise about 5% of the cells in the gland. They have staining and ultrastructural features that closely resemble those of astrocytes and are reminiscent of the pituicytes of the neurohypophysis.

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