The endocrine glands
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Some mechanisms have been developed in animals to enable the tissues and organs to function.
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The most primitive mechanism is paracrine secretion.
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The secretion from the cell to the intracellular area, with diffusion influences the function and movement of the target cell, which is at a limited distance
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These chemicals, show their effects very slowly with
simple diffusion.
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Their controls are rather difficult and their use is limited.
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This primitive humoral mechanism was then
supported by a nervous system, cells capable of responding to external stimuli.
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These cells can affect other cells with the help of long extensions (axons).
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In more advanced systems, the functions of the
nervous system related to behavior and rapid motor
events have developed and become quite affective
and complex.
The development of endocrine glands, with their secretions which are called hormones, supports these two complementary systems.
The response of internal and external stimuli in multicellular complex organisms.
Control and coordination of cell, tissue, organs and systems.
Protection of homeostasis is provided by the nervous system and endocrin system.
These two systems are called controller systems.
Endocrin system controls with special organic substances called hormones.
Ensures the body's adaptation to the external environment.
• Ensures the balance and continuity of the physical and chemical conditions of the
changing interior environment.
• Controls the construction and destruction events in cells.
• Regulates the functions of body organs.
• Regulates reproductive functions.
• Provides growth and development.
• Performs energy production, use and storage.
A receptor is a protein which binds to a specific molecule.
The molecule it binds is known as the ligand.
A ligand may be any molecule, from
inorganic minerals to organism-created
proteins, hormones, and neurotransmitters.
The ligand binds to the ligand-binding site on the receptor protein.
When this binding happens, the receptor undergoes a conformational change
This change is shape slightly alters the protein’s function.
From this, a number of things can happen.
The conformational change in the receptor can cause the receptor to become an
enzyme and actively combine or separate certain molecules.
The change can also cause a series of changes in related proteins, eventually transferring some sort of message to the cell.
This message could be a metabolic regulation message, or it could be a sensory signal.
The receptor has a certain capacity to hold onto the ligand, known as the binding affinity.
Once this attraction wears out, the receptor will release the ligand, undergo a change to the
original shape, and the message or signal will end.
The speed of this turnover depends on the strength of the affinity between receptor and ligand.
Other molecules can also attach to the ligand-binding site on a receptor.
These are called agonist molecules if they mimic the effect of the natural ligand.
Many drugs, are synthetic agonists to molecules like endorphins, which create feelings of satisfaction.
Still other molecules can act like antagonists, or molecules which block the ligand binding site on the receptor but do not allow the
receptor to undergo a conformation change.
This blocks a signal entirely.
Some receptor antagonists include drugs which are used to wean people off of heroin and alcohol dependency.
These act by making the use of the drug no longer pleasurable
• Hormones can be transported to long distances through the blood circulating in the body, thus affecting the target cells or organs.
• These chemicals effects are very slow and unrecognized; but they have a very strong influence.
• The endocrine glands are made of tubular protrusions made either inside or outside the epithelial sheath during embryonic development.
• These tube-like structures cut their association with the epithelium that they had formed in later developments.
• The secretory units of the endocrine glands are very rich in blood vessels.
• This close relationship between the secretory cells and the blood vessels plays an important role in entering of secretory products (hormones) to blood
Hormones can come into contact with all tissue cells while they are in the bloodstream; but only cells
carrying that hormone-specific receptor are affected.
The amounts of hormones are very small; but specific receptors in cells are very sensitive to hormones.
A well-developed endocrine gland is completely different from the exocrine gland; but sometimes there is very little structural difference.
For example, Langerhans islets, the endocrine
secretory unit of the pancreas, are dispersed in the exocrine part of the gland.
Pankreas Endokrin bez
Langerhans adacığı (Endokrin salgılama)
Seröz bez
(Ekzokrin salgılama)
Endokrin Bez (Pankreas,
Langerhans adacığı)
Similarly, the Leydig cells, which secrete male sex hormone endocrine to the testis, are also located in the interstitial tissue between the exocrine tubes of the organ.
Thus, in these mixed glands, some of the cells secrete their secretions into the canal system, while others secrete into the blood.
In the liver, the situation is more interesting.
The liver parenchyma cells secrete exocrine
secretion into the ducts, while other cells give
endocrine secretion to the blood, circulating in
the sinusoids.
The main endocrine glands found in mammals and in humans are:
Apart from these, there are some organs and tissues which have endocrine function.
Sample;
Renal renin and erythropoietin, Thymus gland thymopoietin, Gastric mucosa gastrin,
The intestinal mucus secretes secretin.
1 Pineal gland 2 Pituitary gland 3 Thyroid gland 4 Thymus 5 Adrenal
gland 6 Pancreas 7 Ovary (female)
8 Testis (male)
The thyroid gland is located at the front of the neck, in front of the thyroid cartilage, and is
shaped like a butterfly, with two wings connected by a central is thymus.
Thyroid tissue consists of follicles with stored
protein called colloid, containing thyroglobulin, a precursor to other thyroid hormones, which are manufactured within the colloid.
The thyroid hormones increase the rate of
cellular metabolism, and include thyroxine (T4) and triiodothyronine (T3).
Secretion is stimulated by the hormone TSH, secreted by the anterior pituitary.
When thyroid levels are high, there is
negative feedback that decreases the amount of TSH secreted.
Most T4 is converted to T3 (a more active form) in the target tissues.
Calcitonin, produced by the parafollicular cells of the thyroid gland in response to rising
blood calcium levels, depresses blood calcium levels by inhibiting bone matrix resorption
and enhancing calcium deposit in bone.
The parathyroid glands, of which there are 4-6, are found on the back of the thyroid glands,
and secrete parathyroid hormone (PTH), which causes an increase in blood calcium levels by targeting bone, the intestine, and the kidneys.
PTH is the antagonist of calcitonin.
PTH release is triggered by falling blood
calcium levels and is inhibited by rising blood calcium levels.
The adrenal glands are located above the kidneys in humans and in front of the
kidneys in other animals.
The adrenal glands produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol.
It controls the behaviour during crisis and emotional situations.
It stimulates the heart and its conducting tissues and metabolic processes.
The pancreas, located in the abdomen below and behind to the stomach, is both an
exocrine and an endocrine gland.
The alpha and beta cells are the endocrine cells in the pancreatic islets that release
insulin and glucagon and smaller amounts of other hormones into the blood.
Insulin and glucagon influence blood sugar levels.
Glucagon is released when blood glucose level is low, and stimulates the liver to
release glucose into the blood.
Insulin increases the rate of glucose uptake and metabolism by most body cells.
Somatostatin is released by Delta cells and act as an Inhibitor of GH, Insulin and
Glucagon.
The ovaries of the female, located in the pelvic cavity, release two main hormones.
Secretion of estrogens by the ovarian follicles begins at puberty under the influence of FSH.
Estrogens stimulate maturation of the female reproductive system and development of the secondary sexual characteristics.
Progesterone is released in response to high blood levels of Luteinizing hormone (LH).
It works with estrogens in establishing the menstrual cycle.
The testes of the male begin to produce testosterone at puberty in response to LH.
Testosterone promotes maturation of the male reproductive organs, development of secondary sex characteristics, and
production of sperm by the testes.
The pineal gland is located in the diencephalon of the brain.
It primarily releases melatonin, which
influences daily rhythms and may have an antigonadotropic effect in humans.
It may also influence the melanotropes and melanocytes located in the skin
Many body organs not normally considered
endocrine organs contain isolated cell clusters that secrete hormones.
Examples
include the heart (atrial natriuretic peptide);
gastrointestinal tract organs (gastrin, secretin, and others);
the placenta (hormones of pregnancy—estrogen, progesterone, and others);
the kidneys (erythropoietin and renin);
the thymus;
skin (cholecalciferol); and
adipose tissue (leptin and resistin).
Bağırsak enine kesidinde ekzokrin ve endokrin salgılama yapan hücreler. 1.Ekzokrin salgılama yapan Paneth hücreleri, büyük, kırmızı apikal granüllü, 2.Endokrin salgılama yapan Argentaffin
(enterokromafin) hücreler, küçük, kavuniçi-kırmızı, bazal granüllü.
Paneth h.
Argentaffin h.
Endokrin bir bez, Adrenal Bez (Düşük büyütme)
Adrenal bez korteksi, x33 (H-E). http://pathology.mc.duke.edu/ research/PTH225.html
Paratiroit bezi, H-E, x400
http://pathology.mc.duke.edu/ research/PTH225.html
Endokrin bir bez, Tiroit Bezi (H&E; x 400)
CLASSIFICATION OF HORMONES
It is extremely difficult to classify hormone-releasing glands histologically.
Because each contains different types of cells.
However, hormones containing amino acids, peptides, proteins, glycoproteins and steroids are classified in two ways:
A. According to chemical structures B. According to their mode of action
A.Hormones According to Chemical Constitutions
• They are separated in terms of molecular structures.
1. Amines (catecholamine hormones): such as dopamine, epinephrine and norepinephrine. The simplest hormones are ammonia group hormones.
2. Steroids
3. Polypeptides (peptide hormones: such as oxytocin, vasopressin, FSH, ACTH and angiotensin)
4. Proteins: The most complex ones are polypeptide
hormones and are important as evolutionary models.
Insulin, glucagon, thyroxine, adrenaline, noradrenaline, etc.
B.
Classification of Hormones according to their effect forms
Hormones have a very different mechanism of action.
Most important ones;
I. Kinetic effect hormones 2. Metabolic hormones
3. Morphogenetic hormones
I
1.
Kinetic effect hormones: These hormones may cause pigment migration, muscle contraction, glandular secretion etc.
e.g. Pinealin, MSH, Epinephrine etc.
Epinephrine and oxytocin present in this group are effective on muscle contraction.
It affects melatonin pigment dispersion.
The hormones secreted by the cells of the hypothalamus neurosecretion control hormone secretion from the anterior pituitary lobe.
2
. Metabolic hormones:
These hormones mainly changes the rate of metabolism and balance the reaction.
e.g. Insulin, Glucagon, PTH etc.
They control the balance of chemical
compounds in the tissues and the rate of chemical reactions.
For example, thyroxine regulates the respiratory rate of cells, insulin
carbohydrate metabolism, aldosterone
electrolyte balance.
3. Morphogenetic hormones:
These hormones are involved in growth and differentiation.
e.g. STH, LTH, FSH, Thyroid hor mones etc.
These are hormones that cause morphogenetic changes in the whole body or any organ of the living being.
The growth hormone controls the growth of the organism and the repair of the damaged region, thyroxine in metamorphosis organisms, the
identification of secondary sexual traits with estrogens and androgens.
THE STURUCTURE OF POLYPEPTIDE HORMONE SECRETING ENDOCRINE GLANDS
The fine structures of the endocrine gland cells, which
secrete the peptides and glycoprotein hormones, are very similar to the protein-secreting exocrine cells.
However, there is a significant difference in the degree of organelle development associated with protein synthesis.
GER is less congested in endocrine glands.
This is in agreement with the large variation in the volume of product.
While the exocrine part of the pancreas produces more than one liters of enzyme-rich digestive secretion per day, the
amount of protein released by a polypeptide or
glycoprotein-releasing endocrine gland is at the microgram level.
Beta cells in the Langerhans islets of the pancreas secrete protein-bound insulin hormone.
In the EM images of these types of cells, in the
cytoplasmic matrix less developed GER is seen and a large number of free ribosomes.
There is a small Golgi complex and a lot of granules surrounded by membranes 200-300 nm in diameter.
These granules are made in the Golgi complex as they are in the exocrine secretory glands.
They are found in the cytoplasm near the vessels of the cell.
In humans, insulin is present in the form of pleomorphic crystals within the secretory sac surrounded by the membrane.
Similar characteristics are observed in the following cell types, with very little difference in fine structure and
granule sizes;
◦ Glucagon-secreting alpha cells of the pancreas,
◦ Pituitary cells that secrete growth hormone (HGH),
◦ thyroid stimulating hormone (TSH),
◦ follicle stimulating hormone (FSH),
◦ adrenocorticotropic hormone (ACTH) and
◦ luteinized hormone (LH)
◦ C cells that secrete thyroidin calcitonin.
In all of these, secretions are synthesized in ribosomes, altered in the endoplasmic reticulum, concentrated in the Golgi complex, and stored in membrane-coated granules.
The thyroid gland, which enters the protein-releasing endocrine gland category, has a distinctive feature as it stores its product thyroglobulin outside the cell.
In a thyroid follicle, cubic cells are arranged in a single row around the gap in the center.
Cells have abundant amounts of GER
The GER is composed of precursor proteins of the secretory product.
It is packaged as a secretion sac surrounded by a
membrane; but does not accumulate in the cytoplasm.
It goes directly to the apical surface and excretes its content into the follicle lumen with exocytosis.
STEROID - HORMONE SECRETING ENDOCRINE GLANDS
The steroid-hormone-expressing cells of the ovary, testis and adrenal glands resemble each other very finely.
These cells have a very different structure than protein and peptide-secreting cells.
Very small GER and relatively few free ribosomes.
The most characteristic features of these cells are that they have a very dense and very distinct SER network in their structure.
The Golgi complex around the nucleus is very large.
Since the hormones in the steroid structure are small molecules, they diffuse the cell membrane and affect the target cell metabolism.
The steroid hormones that enter the cell and bind to the receptors in the cell
Thus, genes in the DNA is affected and mRNA synthesis is initiated.
As a result, the synthesis of the desired
substance in the cell is stimulated by mRNAs and the production of the substance is carried out.
Depending on the species of the animal and the organ, the lipid particles t in the
cytoplasm may be many or in fewer numbers.
Mitochondria are numerous and vary in size.
These cells also contain lysosomes and peroxisomes, which can accumulate
lipochrome pigment.
In steroid-hormone-releasing cells cholesterol is stored.
Lipid particles, like triglycerides, contain
cholesterol.
In some species, cells that secrete steroid- hormones are dependent on blood
cholesterol, whereas in other species cells synthesize the majority of the cholesterol they use for hormone synthesis.
The enzymes responsible for cholesterol synthesis are mainly located in the SER
Hormone can’t stored in the cells
For this reason, a well-developed SER has the
enzymes necessary for the rapid synthesis of
steroid hormones
PACKAGING, STORING AND SECRETION OF HORMONES
Endocrine glands differ greatly in terms of the amount of hormone they store and the way they are stored.
The secretion granules of the endocrine
glands that secrete the steroid hormone are absent.
These glands can either store very little
amounth of hormones or never store them.
Most of the hormones are in vesicles
However, steroid hormones are not in vesicle , they are secreted in molecular form
In some endocrine glands that secrete
proteins, glycoproteins or polypeptide
hormones, the hormone synthesized in
GER surrounded by a membrane.
These vesicules come to the Golgi complex, proteins are modificated there.
◦ For example, carbohydrate is added.
Water is pulled out osmotically from the Golgi and condensed
◦ secretion vesicles are formed.
These vesicles, when necessary, combine with the
cell membrane to give the contents outside the cell or are stored in the cell for two to three weeks
Steroid hormones can dissolve in oil and diffuse out of the cell membrane.
Most of the hormones involved in the blood are inactive, bounded to the
proteins.
When it leaves the proteins, it becomes
active.
For example, vasopressin and oxytocin are stored in secretory granules in the nerve cells, together with the specific soluble protein called neuroficin.
The attachment of protein prevents them from diffusing out of the vesicles they are stored
Recent studies showed that microtubules
and microfilaments in the cytoplasm also
play a role in various stages of secretion
events.
In an experiment, colchicine inhibited the secretion of insulin from beta cells of the pancreas.
Colchicine and other alkaloids inhibit the polymerization of tubulin, which forms microtubules.
Similar observations have been made in the secretion of catecholamines from the adrenal medulla and thyroxine in the thyroid.
The thyroid cells store thyroglobulin in lumen
When a impulse for hormone secretion comes in, these colloidal particles are recovered by
macropinocytosis.
The cell with pseudopods picks up colloids and catches them.
This is done with the help of microfilaments.
The endocrine gland needs to be stimulated for secretion.
Stimulation occurs when another hormone or a
neurotransmitter reaches the endocrine cell surface.
Nerve stimulation leads to hormone release from the neuron.
Vasopressin is secreted in this way.
Calcium ions also interfere with hormone release.
◦ For example, stimulation of endocrine cell secretion increases calcium ion entry into the cell.
◦ Entry of calcium ions into the cell initiates exocytosis.
BLOOD and LYMPH
Despite histological and cytological variations, the most prominent feature of all of the endocrine
glands is that they are very rich in blood vessels.
Almost every cell has one or more thin-walled capillaries.
The structures between secretory cells and blood are:
A thin basal lamina around the endocrine cells, A narrow area around the vein,
Basal lamina of capillary endothelin,
Thin diaphragm cover of capillary pores.
In the majority of endocrine glands, hormones are completely given to the blood.
However, in some cases, lymphatic capillaries provide an alternative pathway for hormones to diffuse out of the endocrine gland into the body.
HORMONE INSULATION CONTROL It is done in two ways:
I) Negative feedback system 2) Neural control
Negative feedback system:
In this system, the secretion is very sensitive to the concentration of the substance (Ca and Na ion, water, hormone etc.)
When the concentration of the substance reaches a certain level, it stops the secretion of the
corresponding gland.
Less hormone released, the amount of the substance decreases.
Decrease in the concentration also stimulates the secretion of the hormone via positive feedback (positive feedback).
Neural control:
Some endocrine glands (the adrenal medulla) secrete their secretions after receiving nerve stimuli.
Other endocrine glands secrete
secretions of the hypothalamus-secreted
substances, such as the pituitary gland.
Paracrine signaling
Is a form of cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior of those cells.
Signaling molecules known as paracrine factors diffuse over a relatively short distance (local
action), as opposed to endocrine factors(hormones which travel considerably longer distances via the circulatory system)
Cells that produce paracrine factors secrete them into the extracellular environment.
Factors then travel to nearby cells in which the gradient of factor received determines the
outcome
Some cells are specialized for paracrine signalling.
For example, mast cells secrete histamine (a derivative of histidine amino acid).
The mast cells in the connective tissue scattered all over the body store histamine in theis large vesicules.
These cells secrete histamy very rapidly by
exocytosis, which will be effective in few milimeters area in injury, tissue injury, regional infection and some immunological reactions.
Histamine provides expansion and leakage in certain regions of the blood vessels.
This facilitates the passage of cells such as serum proteins ( antibodies) and phagocytic white blood cells to the troubled region.
Autocrine signaling
Is a form of cell signaling in which a cell
secretes a hormone or chemical messenger (called the autocrine agent) that binds to
autocrine receptors on that same cell, leading to changes in the cell.
This can be contrasted with paracrine
signaling, or classical endocrine signaling.
An example of an autocrine agent is the
cytokine interleukin-1 in monocytes.
When interleukin-1 is produced in
response to external stimuli, it can bind to cell-surface receptors on the same cell
that produced it.
Growth factors that have been
investigated in recent years and which can stimulate the mitogenic activity of many
cells, affect the secreted cells in autocrine
mechanism way.
Neuroepithelial Cells
DUYU EPİTELİ (NÖROEPİTEL)
Receptor cells located in the covering epithelium are specialized cells that take physical, chemical, mechanical and optical stimuli from the external environment and convert them into nerve
stimulation.
These specialized cells, also called neuroepithelial cells, they detect changes in their environment
and inform the nervous system.
It is an epithelium containing sensory cells that provide sensation of taste, sight, hearing,
temperature, pain and pressure.
Each of the smell receptors is a nerve cell.
Oval shaped taste cells are embedded in the lining of the epithelium.
There are up to 5-18 microvilli cells in the bud and support cells located between these cells.
The stimulu is taken by the dendrites of the nerve cells entering into these microvilli cells.
Sensations such as temperature and pain are taken through the dendrites of the nerve cells that extend into the epithelial tissue.
These structures, which enter the epithelial cell act as receptors.
Duyu epitelinde bulunan çeşitli reseptör hücreler. A.Koku reseptörü, B.Tat reseptörü, C.Deride sıcaklık ve ağrı duyularını alan reseptörler
Nöroepitel (Dil – Tat tomurcuğu)
Nöroepitel (Dil – Tat tomurcuğu)
Nöroepitel (Dil – Tat tomurcuğu)
N N
Larinksin üst kısmı, Çok tabakalı yassı epitel arasında tat tomurcuğu, nöroepitel
Tat tomurcuğunda nöroepitelin besin maddelerinden gelen uyarıyı alması ve beyne göndermesi olayı.
http://www.morphonix.com/software/education/science/brain/game/specimens/taste_bud.gif
Myoepithelial cell
Myoepithelial cells (sometimes referred to as
myoepithelium) are cells usually found in glandular epithelium as a thin layer above the basement
membrane but generally beneath the luminal cells.
These may be positive for alpha smooth muscle actin and can contract and expel the secretions of exocrine glands.
They are found in the sweat glands, mammary glands, lacrimal glands, and salivary glands.
Myoepithelial cells in these cases constitute the basal cell layer of an epithelium that harbors the epithelial progenitor.
In the case of wound healing, myoepithelial cells reactively proliferate.
MİYOEPİTEL (KASSI EPİTEL, KASSAL EPİTEL) HÜCRELER
Myoepithelial cells communicate with each other and secretory cells with nexus and desmosomes.
The cytoplasm contains actin, myosin and
tropomyosin microfilaments capable of contracting.
Presence of myoepithelial cells in a hyperplastic tissue proves the benignity of the gland and, when absent, indicates cancer.
Only rare cancers like adenoid cystic carcinomas contains myoepithelial cells as one of the malignant components.
Kassı epitel
Bez epiteli hücreleri
Kassı epitel hücreleri
Meme asinar bez hücreleri ve kassı epitel hücreleri,
http//: www.udel.edu/Biology/wags/histopage/empage/efr/efr3.gif
Ter bezi hücrelerini saran kassı epitel (miyoepitel) hücreleri Kassı epitel hücrelerinin
Sitoplazmik uzantıları
Kassı epitel hücrelerinin Çekirdekleri
RENOVATION AND REPAIR
In particular, the outer surface of the body and the epithelium that surrounds the
digestive tract are faced with mechanical and other physical effects.
Under physiological conditions, these tissue cells constantly die
This is most apparent in the cells on the
surface where keratinization takes place
Keratinization is a different kind of
differentiation that leads to the death and subsequent pouring of the cells on the
surface.
In the gastro-intestinal tract, cells are
continuously exfoliated from the tip of the villi.
On the other hand, degeneration of the epithelium in the respiratory tract, and in
particular in the majority of the glands, is very rare, and the cells there are long lived.
The physiological cell loss in the epithelium is in balance with a harmonious
regeneration.
Instead of keratinized cells that disappear from epithelium, the undifferentiated cells in the layers beneath the epithelium
multiply with mitosis, resulting in new cells.
These cells differentiate and keratinize as they move towards the surface of the
epithelium.
The simple squamous epithelium lining the stomach and intestine is renewed by the proliferation of undifferentiated cells in the neck or small bowel of Lieberkühn crypts.
The normal rate of replacement of cells by physiological loss and ingestion is so great that the epithelium that envelopes the
intestinal villi is completely renewed every
two or three days.
Epithelial cells are, in principle, immobilized.
However, in case of injury, they become flattened and thin to cover the large exposed regions of
connective tissue.
There is no mitotic activity at the beginning of this repair; but then the proliferation begins to appear on the edges of the wound.
Cell growth continues until the epithelial tissue reaches its normal thickness.
Epithelial cells can phagocytose cells like
macrophages in the areas of programmed cell death (apoptosis).
Other cells in Epithelium
Lymphocytes normally enter the epithelium from the connective tissue in some organs.
For example,
Lymphocytes are very common in the intestinal epithelium.
Peyer caches in the intestinal submucosa are places where lymphoid cells accumulate considerably.
The epithelial is frequently attacked by lymphocytes.
Lymphocytes entering into the tissue push the epithelial cells to the side, causing their shape to deteriorate.
Lymphocytes similarly enter the epithelium overlying the tonsils.
This is becouse of immunological defense of the organism against microorganisms which may
enter the body from the outside.
In some periods of the reproductive cycle of
rodents, to a certain extent in humans, several leukocytes migrate to a large number of vaginal epithelium.
BLOOD AND NERVE IN EPITHELIUM
As a rule, blood vessels do not enter the epithelium that lays the surface or gaps.
Nutrients in the blood vessels comes to underlying connective tissue and enter the epithelial cells
from the basal lamina and spaces between cells.
At the places where the epithelium is thick, the connective tissue at the bottom usually makes a
recess called the papilla approaching the surface to the epithelium.
These structures shorten the nutritional distance of surface epithelial cells.
Deri, çok tabakalı keratinleşmiş yassı epitel ve altta bağ dokusunun epitel içine girintileri