Sunday, April 11, 2010
chapter 45 notes
Hormones are chemical signals that are responsible for regulating body processes.
Blood transports hormones to the target tissues.
ENDOCRINE SYSTEM
The endocrine system consists of a collection of glands, cells and tissues that secrete hormones.
Its function is to regulate many aspects of metabolism, growth and reproduction.
Endocrine glands produce hormones and secrete them to the surrounding tissues and eventually into the capillaries.
Endocrinology is the study of endocrine gland function and hormonal effect on target tissues.
Exocrine glands release their secretions into ducts.
OVERLAP BETWEEN ENDOCRINE AND NERVOUS REGULATION
Some neurons secrete hormones (neurohormones) and are known as neurosecretory or neuroendocrine cells.
The regulation of several physiological processes involves structural and functional overlap between the endocrine and nervous systems.
Endocrine hormones regulate growth, development, fluid balance, metabolism and reproduction.
Hyposecretion: secretion lower than normal.
Hypersecretion: secretion higher than normal.
Homeostasis depends on the normal concentrations of hormones.
CONTROL PATHWAYS AND FEEDBACK LOOPS
Receptors or sensors throughout the body detect stimuli and send information to control center.
E. g. change in CO2 concentration in the blood.
The control center compares the signal to a “desired” value and sends out a signal to direct an effector to respond.
E.g. breathing centers in the pons and medulla oblongata; diaphragm and intercostal muscles receive a message to increase breathing.
Target cells have receptors that combine with a specific hormone. They are responsible for the specificity of the hormone. The receptors may be in or out of the cell.
Negative and positive feedback mechanisms control the amount of hormone and response needed.
Simple pathway: Stimulus → endocrine gland → hormone released into the blood → target
effector → response
Simple neurohormones pathway: Stimulus → sensory neuron → hypothalamus/pituitary → neurosecretory cell → hormone released into the blood → target effector → response
Simple neuroendocrine pathway: Stimulus → sensory neuron → hypothalamus/pituitary → neurosecretory cell → hormone released into the blood → endocrine gland → hormone into the blood → target effector → response
CHEMICAL SIGNALS TARGET CELL RECEPTORS
Hormones and other chemical signals bind to target cell receptors, initiating pathways that culminate in specific cell responses.
Review the mechanisms of chemical signaling, Chapter 11, p. 201.
HORMONE TYPES
Steroid hormones are synthesized from cholesterol, e.g. cortisol, progesterone, testosterone.
Amino acid derivatives called amines, e.g. thyroid, melatonin.
Peptide hormones are short chains of amino acids, e.g. secretin, ADH, oxytocin.
Modified fatty acids, e. g. prostaglandins.
Chemical signals produced by secretory cells either bind to a surface receptor or penetrates the cells and binds to a receptor inside the cell.
Receptor → transduction → response
Receptors for water-soluble hormones are embedded in the plasma membrane and project outward from the cell surface.
Intracellular receptors are found either in the cytoplasm or in the nucleus of the target cell.
Intracellular receptor proteins usually perform the entire transduction with the cell.
The chemical signal activates the receptor, which then directly triggers the cell's response.
The intracellular receptor activated by a hormone acts as a transcription factor.
The active factor, the receptor-hormone complex, activates or represses the transcription of a gene.
Epinephrine produces different responses in different target cells because the target cells have different transduction pathways.
PARACRINE SIGNALING
Local regulators affect neighboring target cells.
Some cells release hormones that act on nearby cells. This is called paracrine regulation.
Several types of chemical compounds function as local regulators; many are neurotransmitters.
Growth factors are peptides and proteins that stimulate cell reproduction and differentiation.
They must be present in the external environment for many cells to grow and develop normally.
GF may have several kinds of target cells and a variety of functions.
Cytokines are local regulators that play a role in the immune system.
Nitric oxide, NO, is a gas produced by many cells.
It is toxic and causes a fast reaction in cells before it is broken down.
It is secreted by neurons and functions as a neurotransmitter.
Secreted by leukocytes, kills bacteria and cancer cells in body fluids.
Released by endothelial cells, cause the blood vessels to relax and dilate.
Prostaglandins are modified fatty acids that have a wide range of activities.
Lungs, liver, digestive tract and reproductive organs release prostaglandins.
Affect cells in their immediate vicinity.
Mimic cyclic AMP and interact with other hormones that regulate many metabolic activities.
Some are involved in fever and inflammation.
Interleukins regulate immune responses.
VERTEBRATE ENDOCRINE SYSTEM
Tropic hormones affect other endocrine glands.
The hypothalamus and pituitary glands integrate many functions of the vertebrate endocrine system.
Table 45.1 summarizes the activity of major human hormones.
HYPOTHALAMUS
Part of the brain.
Links the endocrine system with the nervous system.
Most endocrine activity is controlled directly or indirectly by the hypothalamus.
Produces growth releasing and growth inhibiting hormones.
Anterior lobe of the pituitary is the target tissue.
Stimulates and inhibits secretion.
PITUITARY
At the base of the brain.
It has two regions that develop from different regions of the embryo and have different functions.
Posterior lobe of the pituitary or neurohypophysis.
The posterior pituitary gland is an extension of the hypothalamus.
Produces oxytosin.
Causes the uterus to contract during birth.
Causes the mammary glands to eject milk.
Produces antidiuretic hormone (ADH).
Causes the collecting ducts of the kidneys to reabsorb water.
Secretes growth-hormone-releasing hormone or GHRH and growth-hormone-inhibiting hormone or GHIH also called somatostatin.
Anterior lobe of the pituitary or adenohypophysis.
The anterior pituitary gland develops from a fold in the roof of the mouth of the embryo, which grows toward the brain and loses its connection with the mouth.
Tropic hormones stimulate other endocrine glands.
Thyroid-stimulating hormone (TSH) causes the thyroid to secrete hormones.
Adrenocorticotropic hormone (ACTH), a peptide, stimulates the secretion of hormones by adrenal cortex.
Gonadotropic hormones (follicle-stimulating hormone, FSH, luteinizing hormone, LH) stimulate gonad functions.
Nontropic hormones are peptide/protein hormones function in simple neuroendocrine pathways.
Prolactin is a protein that stimulates the mammary glands to produce milk.
Melanocyte-stimulating hormone (MSH), a peptide, regulates the activity of pigment containing cells in some vertebrates; in mammals probably acts as a feedback mechanism that targets the neurons of the hypothalamus.
Endorphins inhibit the perception of pain; increase the threshold of pain.
Nontropic and tropic effects:
Growth hormone (GH) stimulates linear body growth and tissue and organ growth by promoting protein synthesis.
A protein of about 200 amino acids.
Stimulates the uptake of AA from the blood and their incorporation into cellular proteins; increase in skeletal muscle mass.
Mobilizes fats from fat depots for transport to cells, increasing blood levels of fatty acids.
GH stimulates the liver to produce peptides called somatomedins including insulin-like growth factor, which stimulate bone and cartilage growth.
Secretion of GH is regulated by growth-hormone releasing hormone or GHRH and growth-hormone-inhibiting hormone or GHIH also called somatostatin. Both are released by the hypothalamus.
It has a diurnal cycle with the highest levels occurring during the night sleep; the total amount secrete peaks during adolescence and then decreases with age.
NONPITUITARY HORMONES
Nonpituitary hormones help regulate metabolism, homeostasis, development and behavior.
THYROID
In humans and other mammals, the thyroid is located at the base of the neck, on the ventral surface of the trachea.
Thyroxine (T4) and triiodothyronine (T3) contain iodine. They are derivatives of the amino acid tyrosine.
T4 is converted to T3 in many cases in target cells.
The receptor protein is located in the cell nucleus and has greater affinity for T3.
Stimulate general growth and development, and the metabolic rate in most tissues by stimulating enzymes involved in glucose oxidation.
T4 and T3 help maintain normal blood pressure, heart rate, muscle tone, digestion, normal hydration and secretory activity of the skin, and reproductive ability and lactation in females.
T3 induces or suppresses the synthesis of enzymes.
Hypothyroidism in childhood leads to cretinism, retarded mental and physical development.
Hypersecretion causes a fast use of nutrients, hunger, excessive sweat, high body temperature, nervousness, irritability and emotional instability.
These hormones require iodine. Lack of iodine causes goiter due to an over production of THS by the anterior pituitary.
The secretion of thyroid hormones is controlled by the hypothalamus through a negative feedback mechanism.
It affects every cell in the body except the adult brain, spleen, testes, uterus and the thyroid gland itself.
Goiter is a disease caused by hypothyroidism. In the absence of enough thyroid hormones, the hypothalamus continues to produce TSH, which leads to an increase in the size of the thyroid.
Produces calcitonin, which works antagonistically to the parathyroid hormone.
Lowers the blood calcium level by inhibiting calcium release form bones.
Stimulates calcium incorporation into the bone matrix.
Calcitonin activity is important in childhood when the skeleton grows quickly but is weak in adults.
PARATHYROID
These glands are embedded in the connective tissue surrounding the thyroid.
Secrete the parathyroid hormone (PTH) that regulates calcium level in the blood and tissue fluid.
Stimulate calcium release from bones. PTH stimulates the osteoclasts to decompose bone matrix.
Stimulates calcium reabsorption from the kidney, and conversion of vitamin D to its active form.
Vitamin D acts together with PTH and increases the absorption of calcium in the intestines. Vitamin D binds to receptors in the nuclei of target cells and regulates gene transcription.
It increases the concentration of Ca2+ in the blood and has an effect opposite to that of the thyroid hormone calcitonin.
Lack of PTH causes a drop of Ca2+ in the blood leading to convulsion of skeletal muscles.
ISLETS OF THE PANCREAS OR OF LANGERHANS.
The pancreas is considered a major endocrine gland but only 1 – 2% (by weight) of its cells secrete hormones. The rest of the cells are involved in the production of digestive enzymes.
About 1 million little clusters of cells scattered throughout the pancreas.
Alpha cells secrete glucagon (29-amino-acid polypeptide), which increases the concentration of glucose in the blood. Its major target is the liver.
Beta cells secrete insulin (51-amino-acid polypeptide), which lowers the concentration of glucose in the blood.
Insulin stimulates cells to take up glucose, inhibits the release of glucose from the liver, stimulates the deposit of fat in the adipose tissue, and inhibits the use of amino acids.
Glucose concentration regulates the secretion of glucagon and insulin.
The concentration of glucose is maintained in humans near 90mg/100mL of blood.
Insulin also inhibits the glycogen break down in the liver and inhibits the conversion of amino acids and glycerol from fats to sugar.
In general, insulin takes glucose out of the blood, causing it to be used in energy production or converted to other forms (glycogen and fats), and promotes protein synthesis and fat storage.
Diabetes mellitus is an endocrine disorder.
Type I diabetics do not produce enough insulin. The immune system or a virus destroys beta cells.
Type II diabetics produce enough insulin but the receptors on target cells cannot bind to it.
The adrenal glands are located above each kidney.
ADRENAL MEDULLA
Helps the body cope with stress, increases the heart rate, blood pressure, metabolic rate, reroutes blood, mobilize fats and increase glucose level in the blood, dilates bronchioles, decreases digestive system activity and urine output.
Secretes epinephrine (adrenaline) and norepinephrine. These hormones belong to a group of compounds called catecholamines, and derived from the amino acid tyrosine.
Their secretion is a response to stress.
Nervous system can increase their production.
ADRENAL CORTEX
Adrenal secretions do not initiate cellular and enzymatic activity but permit many biochemical reactions to proceed at optimal rates.
Secretes three hormones in significant amounts, but more than 30 steroids have been isolated.
The adrenal cortex responds to endocrine stimulus rather than the nervous system.
Hypothalamus → pituitary releases ACTH → adrenal cortex secretes corticosteroids.
Mineralocorticoids (aldosterone) maintain sodium and potassium balance by increasing sodium reabsorption and potassium excretion in the kidney tubules; increase in blood pressure and volume.
Glucocorticoids (cortisol) help the body adapt to stress, raise blood glucose level and mobilize fats and proteins for sugar production, and suppress the immune system.
Cortisone suppresses inflammation. Excessive amount of glucocorticoids suppresses the immune system.
DHEA (dehydroepiandrosterone) is converted in the tissues to testosterone.
Elevated levels of corticosteroids inhibit the secretion of ACTH.
There is evidence that corticosteroids help maintain homeostasis when the body experiences stress over an extended period of time.
A third group of corticosteroids are sex hormones, androgens and small amounts of estrogens. The physiological role of adrenal sex hormones is not well understood.
GONADS
Gonadal steroids regulate growth, development, reproductive cycles, and sexual behavior.
The gonads, testes and ovaries, produce androgens, estrogens and progestins.
Testes produce mainly testosterone, an androgen. It is responsible for secondary male characteristics.
Ovaries produce estrogens, the most important of which is estradiol. It is responsible for the secondary sexual characteristics of women.
The hypothalamus stimulates the anterior pituitary by releasing GnRH (gonadotropin releasing hormone).
The gonadotropin hormones LH and FSH, from the anterior pituitary control the synthesis of estrogens and androgens.
PINEAL GLAND
The pineal gland or body is located near the center of the mammalian brain. In other animals it is found closer to the surface of the brain.
Pineal body in the brain releases melatonin, a modified amino acid, which influences biological rhythms, sleep and the onset of sexual maturity.
Melatonin concentration increases at night and makes us drowsy.
Lowest levels occur during daylight hours around noon.
Depending on the species, the pineal body has connections from the eyes, and receives input about the intensity of light and length of the day
Melatonin secretion is a link between a biological clock daily or seasonal activity.
In some animals, mating behavior and gonadal size varies with the length of daylight and dark periods. Melatonin is involved in these effects.
An area of the hypothalamus called the suprachiasmatic nucleus (SCN) is rich in melatonin receptors and functions as a biological clock.
Changing melatonin concentration may also be a means by which the day-night cycles influence physiological processes that show rhythmic variations, such as body temperature, sleep, appetite, and hypothalamic activity in general.
Melatonin seems to decrease the activity of the SCN neurons. Bright light suppresses melatonin secretion.
There is still a lot to learn about this gland.
INVERTEBRATE HORMONES
Among insects, hormones are secreted mainly by neurons.
Hormones regulate regeneration in hydras, flatworms and annelids, molting and metamorphosis in insects, color changes in crustaceans, reproductive behavior and other activities.
In hydras, the hormone that stimulates growth and budding inhibits sexual reproduction.
Crustaceans have endocrine glands and neuroendocrine cells.
Molting, reproduction, heart rate and metabolism are influenced by hormones.
Pigment cells are located beneath the exoskeleton.
Pigment distribution is controlled by the neurosecretory cells.
Dispersed pigments cause color changes
Insect development is controlled by the interaction of various hormones.
Generally an environmental factor affects neuroendocrine cells in the brain.
Brain secretes BH hormone (brain hormone) that stimulates the prothoracic gland to produce MH, molting hormone or ecdysome, which stimulates growth and molting.
JH, juvenile hormone, maintains the larval stage and prevents metamorphosis.
When the JH decreases the larva develops into a pupa.
In the absence of JH, the pupa molts and becomes an adult.
The amount of JH decreases
chapter 44 notes
Excretion is the elimination of nitrogenous waste product of metabolism.
OSMOREGULATION
Osmoregulation controls the movement of solutes between tissues and their external environment.
This process also regulates water because water follows solutes by osmosis.
OSMOSIS
Diffusion is the movement of solutes from the region of higher concentration to the region of lower concentration.
Osmosis is the movement of water across a membrane from the area of higher concentration to area of lower concentration.
Osmolarity is the concentration of a substance expressed in moles per liter, mol/l.
The unit of osmolarity often used in physiology is milliosmoles per liter, mosm/L.
1 mosm/L = 10-3 M.
The osmolarity of the human blood is 300 mosm/L.
The osmolarity of seawater is 1000 mosm/L.
When two solutions separated by a selectively permeable membrane have the same osmolarity are said to be isoosmotic. The terms hyperosmotic and hypoosmotic are also used.
OSMOTIC CHALLENGES
The ability of animals to regulate their internal environment is called homeostasis.
A regulator is an animal that uses mechanisms of homeostasis to maintain an internal environment when the external environment fluctuates.
A conformer is an animal that allows the internal environment to fluctuate in agreement with the changes in the external environment. Conformers usually live in stable environments.
No organism is a perfect regulator or conformer. Organisms use a combination of mechanisms when faced with environmental changes.
Homeostasis requires a careful balance of materials and energy: gains versus losses.
Osmoconformers are isoosmotic to their surroundings.
Osmoregulators are animals that must control their internal osmolarity.
Stenohaline animals cannot tolerate substantial changes in external osmolarity.
Euryhaline animals can survive large fluctuations of external osmolarity.
Most organisms are stenohaline.
MARINE ANIMALS
Most marine invertebrates and hagfishes are osmotic conformers. Their body fluids vary with changes in the seawater.
The cells are hypoosmotic relative to the surrounding seawater.
Water tends to flow out of the gill cells.
The cells run the risk of plasmolysis, which is shriveling and dying.
Saltwater fish secrete large amounts of salt and drink lots of water.
Marine bony fish must replace lost fluid.
They lose water osmotically through their skin and gills.
Drink large amounts of water and take in salt.
Excrete excess salt through their gills
Excrete little urine in order to conserve water.
Chondrichthyes accumulate and tolerate urea and their tissues are hypertonic to seawater.
Water diffuses into their body.
They maintain a high concentration of urea and trimethylamine oxide (TMAO), which protects proteins from damage by urea.
Concentration of body salts, urea, TMAO and other compounds is greater than 1,000 mosm/L and therefore slightly hyperosmotic to seawater. This decreases the water loss through the skin.
Water slowly enters the body of sharks and relatives.
Kidneys excrete large volume of urine.
Excess salt is excreted by the kidney and in some by the rectal gland.
FRESHWATER ANIMALS
In freshwater fish...
Freshwater is hypotonic to the cell.
They constantly gain water.
Ions tend to move out of the cell into the surrounding water.
Electrolytes lost must be replaced by eating and by active transport from the surrounding water.
The gill cells are hypertonic relative to the surrounding water; therefore, the cells gain water through osmosis.
Cells and tissues that are gaining water are under osmotic stress.
Freshwater fish excrete large amounts of water in the urine and do not drink water.
Some protists have contractile vacuoles that pump out excess water.
ANIMALS THAT LIVE IN TEMPORARY WATER
Some animals that live in temporary ponds or films of water around soil particles can lose almost all their body water and survive. This ability is called anhydrobiosis.
Tardigrades (water bears) contain 85% water in their body; in a dehydrated state they have less than 2% water in their bodies.
These animals can live in this desiccated state for years. The mechanism is not understood.
The disaccharide trehalose seems to protect the cells by replacing the water that is normally associated with membranes and proteins.
Anhydrobiosis is not well understood by scientists and research is being done in this area.
Land animals...
Land animals constantly lose water to the environment through evaporation.
Gas exchange occurs through the wet surfaces of the lung epithelium.
Sweating and panting in order to keep their body cool also loses water.
They have adaptations that minimize water loss, e. g. exoskeleton, shells, and keratinized dead skin cell layer.
TRANSPORT EPITHELIA
Water balance and waste disposal depend on transport epithelia.
Transport epithelia have the ability to move specific substances in controlled amounts in particular directions.
In most animals, transport epithelia are arranged into complex tubular networks with extensive surface areas.
The secretory cells of the transport epithelium actively secrete salts from the blood into the tubules.
NITROGENOUS WASTE
Principal metabolic wastes are water, carbon dioxide and nitrogenous wastes (ammonia. urea and uric acid).
Nitrogenous wastes are the products of deamination of amino acids and breakdown of nucleic acids.
Ammonia is highly toxic and it is usually converted to uric acid or urea.
Ammonia excretion is most common in aquatic species.
Ammonia is converted to ammonium, NH4+.
Ammonium ions are excreted through the gills.
In many invertebrates, ammonia is excreted across the whole body surface.
Urea is formed in the liver by combining ammonia and carbon dioxide.
Urea is soluble and less toxic than ammonia.
It requires less water than the same amount of ammonia.
Mammals, most adult amphibians and many marine fishes and turtles excrete urea.
The animal must spend energy to produce urea.
Uric acid is the product of nucleic acid and amino acid breakdown.
It is excreted in the form of a crystalline paste with little water loss.
It is relatively non-toxic.
Uric acid production requires more energy than urea production.
Birds, reptiles, land snails, and some insects secrete uric acid.
The kind of nitrogenous waste excreted depends on the animal’s evolutionary history and habitat.
Uric acid precipitates out of solution and can be stored inside the amniotic egg.
Soluble wastes can diffuse out of the shell-less egg of amphibians.
The amount of nitrogenous waste produced is coupled to the animal’s energy budget.
DIVERSE EXCRETORY SYSTEMS
1. Sponges and cnidarians use diffusion from cells to environment.
2. Protonephridia are found flatworms, nemerteans, rotifers, lancelets and some annelids.
Internal tubules with no openings.
Blind ends called flame bulbs have flame cells.
Fluid enters the lumen of the tubule through selectively permeable membranes of the folding tubule cells.
The beating of the cilia of the flame cells keep the fluid moving towards the nephridiopore.
Excrete through nephridiopores.
It functions mostly in osmoregulation; wastes diffuse through the skin or are excrete through the lining of the gastrovascular cavity.
In some parasitic worms that are isoosmotic to their environment, the protonephridia are used to expel wastes.
3. Metanephridia are found in most annelids, in mollusks.
Metanephridia are found in most annelids.
Each metanephridium is a tubule open at both ends.
The inner ends open into the coelom as a ciliated funnel called nephrostome, which collects fluid from the coelom.
The outer end is a nephridiopore.
As coelomic fluids pass through the tubule, needed material is reabsorbed.
The urine is much diluted and balances the uptake of water through the skin.
Metanephridia have an osmoregulatory and excretory function.
4. Malpighian tubules are found insects and spiders.
Insects and other terrestrial arthropods have Malpighian tubules.
Blind end tubules of the digestive tract that stretch into the hemocoel.
Their cells transfer wastes and salts from the hemolymph to the lumen of the tubule by diffusion and active transport. Water follows.
They empty into the intestine.
Water and some salts are reabsorbed in the rectum and almost dry nitrogenous wastes are eliminated with the feces.
MAMMALIAN URINARY SYSTEM
Kidney produces urine.
Ureter brings urine to the urinary bladder.
Urinary bladder stores urine temporarily.
Urethra leads the urine to the outside.
The outer region of the kidney is called the renal cortex and the inner region the renal medulla.
The renal medulla contains a number of cone-shaped structures called renal pyramids.
At the tip of each renal pyramid is a renal papilla into which the collecting ducts open.
The renal pelvis is a pyramidal chamber that collects and leads the urine to the ureter.
The nephron is the functional unit of the kidney.
KIDNEY STRUCTURE
The outer region of the kidney is called the renal cortex and the inner region the renal medulla.
The renal medulla contains a number of cone-shaped structures called renal pyramids.
At the tip of each renal pyramid is a renal papilla into which the collecting ducts open.
The renal pelvis is a pyramidal chamber that collects and leads the urine to the ureter.
The nephron is the functional unit of the kidney. It consists of a single long tubule and a ball of capillaries. The blind end of the tubule forms the Bowman's capsule, which surrounds the glomerulus.
The filtrate consists of water, salts, HCO3–, H+, urea, glucose, amino acids, some drugs and other foreign chemicals.
1. The filtrate passes from capillaries ® Bowman's capsule ® proximal convoluted tubule ® loop of Henle ® distal convoluted tubule ® collecting duct ® renal pelvis.
About 80% of the nephrons in human are cortical nephrons with a short loop, and 20% are juxtamedullary nephrons with a long loop of Henle.
Mammals and birds are the only animals with juxtamedullary nephrons. The nephrons of all other animals lack the loop of Henle.
The tubules of the nephron are lined with a transport epithelium whose function is to reabsorb water and solutes.
From 1,000 to 2,000 liters of blood flows through a pair of human kidneys each day.
Nearly all of the sugar, and other organic nutrients and most of the water is reabsorbed.
Only about 1.5 liter urine is discarded.
2. Blood circulates through the kidney in the following sequence:
Renal artery ® afferent arteriole ® capillaries of glomerulus ® efferent arteriole ®
peritubular capillaries ® vasa recta ® small veins ® renal veins.
3. Filtration, reabsorption and secretion produce urine.
Bowman's capsule
Filtration is not selective with regard to ions and small molecules.
Reabsorption is highly selective.
Some substances are actively secreted from the blood.
Hydrostatic pressure in glomerular capillaries is higher than in other capillaries. Efferent arteriole is smaller than the afferent arteriole.
The high pressure forces about 10% of the plasma out of the capillaries into Bowman's capsule.
Glomerular capillaries are highly permeable with numerous small pores (fenestration) present between the endothelial cells.
There is a large permeable surface provided by the highly coiled capillaries.
Glucose, amino acids, ions and urea pass through and become part of the filtrate.
Reabsorption is highly selective.
Proximal tubule
H+ and NH3 are filtered into the lumen of the Bowman's capsule and the proximal tubule.
NH3 neutralizes the acid and maintains a constant pH.
HCO3- is a blood buffer and about 90% is reabsorbed here through active transport.
Toxins and foreign substances also pass into the filtrate.
K+, glucose and amino acids are reabsorbed.
NaCl and water are reabsorbed. Na+ is actively transported from the filtrate into the interstitial fluid of the kidney; water follows by osmosis.
The osmolarity of the filtrate in the proximal tubule is about 300 mosm/L.
Descending limb of the loop of Henle
The transport epithelium in this section of the tubule is permeable to water but not to salts and small solutes.
The interstitial fluid in this area, the outer medulla, is hyperosmotic to the filtrate.
The osmolarity of the interstitial fluid gradually increases from the outer cortex to the inner medulla of the kidney.
As the filtrate descends, it loses water to the interstitial fluid and it becomes more concentrated.
The osmolarity in the descending arm of the loop of Henle changes from 300 mosm/L at the beginning to 1,200 mosm/L at the tip of the loop.
Ascending limb of the loop of Henle
The filtrate reaches the tip of the loop deep into the inner medulla in the case of the juxtamedullary nephron, and then moves back to the cortex.
The transport epithelium of the ascending limb is permeable to salts but not water (in contrast with the descending limb).
The filtrate passes first through a thin section of the ascending limb and NaCl, which had become concentrated in the descending tube, now passes out by diffusion into the interstitial fluid.
This addition of salt contributes to the high osmolarity of the inner medulla.
In the following thick section of the tubule, NaCl is excreted into the medulla by active transport.
The filtrate passes out salts but no water, and becomes more diluted.
In the ascending arm, the osmolarity changes from 1,200 mosm/L to 100 mosm/L in the distal tubule.
Distal tubule
K+ and H+ are actively secreted into the filtrate.
NaCl and HCO3- are actively reabsorbed, and water diffuses out by osmosis.
The control secretion of H+ and reabsorption of HCO3- contribute to the pH regulation of the blood and interstitial fluids.
Osmolarity here is 100 mosm/L.
Collecting duct
The collecting duct brings the filtrate from the cortex to the inner medulla.
The filtrate is hypoosmotic to the interstitial fluid as it enters the collecting duct.
NaCl is actively reabsorbed here and determines how much salt is actually excreted in the urine.
The transport epithelium here is permeable to water and urea (in the inner medulla) but not to salt.
The filtrate becomes more concentrate as it loses more and more water to the hyperosmotic interstitial fluid of the medulla.
NaCl and urea are the major contributors to the high osmolarity of the interstitial fluid in the medulla.
By reabsorbing water, the urine becomes hyperosmotic to the general body fluids, but is isoosmotic to the interstitial fluid of the medulla.
In the inner medulla, the duct becomes permeable to urea; but most of the urea in the filtrate remains in the collecting tubule.
As the filtrate flows in the collecting duct passes interstitial fluid of increasing osmolarity, more water moves out of the duct by osmosis, thereby concentrating the solutes, including urea, that are left behind in the filtrate.
The high osmolarity of the interstitial fluid allows solutes to remain in the urine and be eliminated with minimal water loss.
In the collecting tubule, the osmolarity changes from an initial 100 moms/L to 1,200 mosm/L.
MAMMALIAN ADAPTATION TO CONSERVE WATER
The ability of the kidney to conserve water is a an adaptation to terrestrial life.
The nephron especially in the area of the loop of Henle uses energy in order to produce a region of high osmolarity in the outer and inner medulla of the kidney, which can then be used to extract water from the filtrate and urine in the collecting duct.
The principal solutes in this osmolarity gradient are NaCl, which is excreted by the loop of Henle, and urea, which leaks across the epithelium of the collecting duct in the inner medulla.
Summary of osmolarity change in the filtrate:
Bowman's capsule: 300 mosm/L
Proximal tubule: 300 mosm/L
Descending loop of Henle: 300 to 1,200 mosm/L.
Ascending loop of Henle: 1,200 to 100 mosm/L
Distal tubule: 100 mosm/L.
Collecting duct: 100 to 1,200 mosm/L.
Urine: 1,200 mosm/L
The process depends on the salt concentration in the interstitial fluid in the kidney medulla.
The interstitial fluid has higher salt concentration around the loop of Henle.
There is a counterflow of fluid through the two limbs of the loop of Henle.
Water is drawn by osmosis from the filtrate as it passes through the collecting ducts and it concentrates the filtrate.
As the filtrate flows in the collecting duct passes interstitial fluid of increasing osmolarity, more water moves out of the duct by osmosis, thereby concentrating the solutes, including urea, that are left behind in the filtrate.
Capillaries known as the vasa recta remove some of the water that diffuses from the filtrate into the interstitial fluid.
The vasa recta are extensions of the efferent arteriole that extend deeply into the medulla and then return fluid to the veins draining the kidney.
Urine is about 96% water, 2.5% urea, 1.5% salts and traces of other substances.
Urinalysis is the physical, chemical and microscopic examination of urine.
HORMONE REGULATION OF KIDNEY FUNCTIONS
Urine volume is regulated by the hormone ADH (antidiuretic hormone), which is produced by the hypothalamus, and stored and released by the posterior lobe of the pituitary gland in response to an increase in osmotic concentration of the blood, caused by dehydration.
An increase above the set point is 300 mosm/L releases ADH.
Low fluid intake decreases blood volume and increase osmotic pressure of blood.
ADH increases the permeability of collecting ducts to water, increasing reabsorption of water and decreasing water excretion.
An increase in fluid uptake decreases the osmolarity of the blood below 300 mosm/L.
Little ADH is released and the permeability to water of the distal tubule and collecting duct is reduced and more water is excrete.
A second regulatory mechanism involves the tissue called juxtaglomerular apparatus or JGA.
Renin-angiotensin-aldosterone system, RAAS.
Decrease in blood volume → decrease in blood pressure → cells of juxtaglomerular apparatus secrete renin → renin converts angiotensinogen in plasma to angiotensin → enzyme in lungs converts angiotensin to angiotensin II → blood vessels constrict and aldosterone is secreted by the adrenal gland→ aldosterone increases sodium and water reabsorption.
Angiotensin II causes an increase...
in blood pressure by constricting arterioles and decreasing blood flow to capillaries including those of the kidneys;
in blood volume by increasing the reabsorption in the proximal tubules of NaCl and water;
this results in a decrease of urine volume, and an increase in blood volume and pressure.
In stimulating the adrenal gland to produce aldosterone.
Aldosterone increases water and sodium reabsorption by distal and collecting ducts increasing blood volume and pressure.
Sodium is the most abundant extracellular ion.
It is produced by the adrenal gland as a reaction to a drop in blood pressure.
Decrease on blood pressure is caused by a decrease in blood volume due to dehydration.
The function of ADH and RAAS counter different osmoregulatory problems, even if both increase water reabsorption.
Injury and severe diarrhea will decrease blood volume and loss of electrolytes, but will not change the osmolarity of the blood. The RAAS will detect the loss of blood volume and will react but the ADH will not because the osmolarity remains the same.
Atrial natriuretic factor (ANF) is a peptide produced by the heart and increases sodium excretion and decreases blood pressure, and decreases the production of renin and ADH.
It works antagonistically to the renin-angiotensin system.
It is a response to an increase in blood volume and pressure.
KIDNEY ADAPTATIONS
The vertebrate kidney has evolved in different habitats.
Mammals have long loop of Henle to produce concentrated urine.
Birds have short loop of Henle but the main water conservation is the production of uric acid; birds will be too heavy to fly if they had a urinary bladder full of liquid.
Reptile have only cortical nephrons and produce urine that is isoosmotic to body fluids; the cloaca reabsorbs water and reptiles secrete uric acid.
Fresh water fish excrete large amounts of diluted urine because they are hyperosmotic to their environment; their kidneys reabsorb large amounts of salts.
Salt water bony fish are hypoosmotic to sea water; their kidneys secrete very little urine and large amounts of divalent ions Ca2+, Mg2+ and SO42ˉ; the monovalent Na+ and Clˉ and nitrogenous waste in the form of NH4+ through the gills.
Feedback mechanisms integrate the work of the nervous system and hormones in order to maintain homeostasis.
chapter 43 notes
They include bacteria, viruses, protozoans and fungi.
Immunology is the study of specific defense mechanisms.
Two major kinds of defense have evolved to counter the thread of infection.
Innate immunity: rapid response to a broad range of microbes.
Acquired immunity: slower response to specific microbes; it is also called adaptive immunity; it includes lymphocytes and antibodies.
There are specific defense mechanisms and nonspecific defense mechanisms also known as innate immune response.
INNATE IMMUNITY
It provides a wide range of defenses. These defenses are not specific for a type of pathogen.
External Defense Mechanisms
These mechanisms are nonspecific and include mechanical and chemical barriers.
Mechanical barriers include skin, hair, mucous.
Chemical barriers include sweat, sebum, tears, and stomach acid; lysozymes digest the cell wall of bacteria.
Intact skin is barrier that prevents pathogens from penetrating into the body.
Secretions from sweat and sebaceous glands give the skin a pH of 3 to 5, which is acidic enough to prevent colonization by many microbes.
Saliva, tears and mucus also kill bacteria.
Lysozymes are enzymes found in tears, sebum and tissues that attack the cell wall of bacteria.
Acid secretions and enzymes in the stomach kill most ingested pathogens.
Internal Cellular And Chemical Defenses.
Invading organisms are ingested and destroyed trough phagocytosis.
White blood cells or leukocytes are involved in this process.
1. Phagocytes destroy bacteria and other cells.
There are four types of white blood cells (leukocytes) that are phagocytes.
Neutrophils are the first phagocytes to arrive usually within an hour of injury.
Neutrophils make about 60%-70% of all white blood cells.
Damaged cells secrete chemical signals that attract neutrophils: chemotaxis.
Monocytes arrive next and become large macrophages.
Monocytes make about 5% of WBC.
Macrophages are long-lived cells.
Ingest the bacterium into a food vacuole that fuses with a lysosome which secrets superoxide ions, O2-, and nitric oxide, NO, both strong antimicrobial substances; hydrolytic enzymes digest the microbial components.
Macrophages are found in the lungs, liver, lymph nodes, kidney, brain, spleen, and connective tissues.
Both phagocytize pathogens, their products and dead and injured cells.
A neutrophil can phagocytize about 20 cells and a macrophage 100 cells before they become inactive and die.
Pus consists of dead phagocytic cell, fluid and proteins leaked out of capillaries.
Some bacteria are resistant to macrophage digestion.
Eosinophils make about 1.5%of all leukocytes.
They attack large parasitic invaders like blood flukes.
They discharge hydrolytic enzymes on the surface of the parasite.
They have limited phagocytic activity.
2. Antimicrobial proteins
Complement system proteins are regulatory proteins secreted by cells of the immune system.
There are about 30 of these serum proteins.
Two types of interferon provide innate defense against viral infection.
Some lymphocytes secrete a third type of interferon that activates microphages.
They are important signaling cells during immune responses and lead to the lysis of the viruses, yeast and bacteria, and enhance their phagocytosis by macrophages.
They are inactive until an infection occurs.
Defensins are secreted by activated macrophages.
Interferons are proteins produced by virus infected cells. They signal other cells to produce chemicals that inhibit viral replication.
3. Inflammation is a protective mechanism.
Damage to tissue by physical injury or by infection triggers the inflammatory response.
It is regulated by proteins in the plasma, by cytokines, and by substances called histamines released by platelets, by basophils (WBC), and by mast cells.
Blood flow increases bringing phagocytic cells to the site of infection. This is probably the most important element of inflammation.
Histamines released in response to injury cause vasodilation and make capillaries more permeable allowing antibodies to enter the tissues; postcapillary venules constrict.
Histamines are released by circulating leukocytes called basophils and by mast cells found in connective tissue.
Leukocytes and damaged cells release prostaglandins that increase blood flow to the injured area.
Chemokines secreted by flood vessel endothelial cells and monocytes attract phagocytes to the injured area.
Blood flow to the injured area brings clotting elements to initiate tissue repair, makes the skin feel warm, and may causes redness.
Edema (swelling) occurs.
Injured cells put out chemical signals that cause the release of leukocytes from the bone marrow.
4. Natural Killer Cells
Natural killer cells (NK) are large, granular lymphocytes that originate in the bone marrow.
Attack cancer cells, infected cells and pathogens including certain fungi.
Release proteins that destroy target cells by lysing the cells.
NK cells trigger apoptosis of infected cells.
5. Invertebrate Immune System
Invertebrates depend mostly on innate, non-specific mechanisms of defense.
Invertebrates apparently lack cells equivalent to lymphocytes responsible for specific immune response.
Insects defend themselves by mechanisms similar to those of vertebrates.
Hemocytes of insects ingest bacteria and damaged cells.
Invertebrates have a simple defense system. Their system is nonspecific.
Invertebrates in general do not have immunological memory.
Earthworms have immunological memory.
Echinoderms have coelomocytes that phagocytose foreign cells, and produce interleukins.
Cytokines have been found in some invertebrates.
ACQUIRED IMMUNITY - LYMPHOCYTES
Pathogens always come in contact with lymphocytes when they invade a vertebrate.
Phagocytes secrete cytokines that activate lymphocytes when they phagocytose microbes.
Pathogens have macromolecules on their cell surfaces that the body recognizes as foreign.
These foreign substances stimulate an immune response. They are called antigens.
Lymphocytes recognize and bind to a small portion of the antigen called the epitope.
An antigen that is a protein has a specific sequence of amino acids that makes up the epitope or antigenic determinant.
An antibody interacts with a small, accessible portion of the antigen, the epitope.
An epitope interacts with a specific antibody and is capable of inducing the production of the specific antibody.
These antigen determinants vary in number from 5 to more than 200 on a single antigen.
The shape of the epitope can be recognized by the antibody or a T cell receptor.
ANTIGEN RECOGNITION BY LYMPHOCYTES
Cells of the immune system include lymphocytes: T lymphocytes or T cells, B lymphocytes or B cells, natural killer (NK) cells and phagocytes.
These cells circulate throughout the body in the blood and lymph, and are concentrated in the spleen, lymph nodes and other lymphatic tissues.
T lymphocytes and B lymphocytes target specific invaders.
B cells and T cells recognize antigens by means of antigen-specific receptors embedded in their plasma membranes.
Each of these cells bears about 100,000 of these antigen receptors.
All the receptors on a single cell are identical, that is, they all recognize the same epitope.
Each lymphocyte displays specificity of a particular epitope on an antigen and defends against that antigen or a small set of closely related antigens.
B Cells Receptors For Antigens
A typical B-cell receptor or antibody is a Y-shaped molecule consisting of four polypeptide chains:
Two identical heavy chains and two identical light chains joined by disulfide bridges to form the Y-shaped molecule.
The transmembrane region of the tail portion anchors the receptor in the plasma membrane and a short portion penetrates into the cytoplasm.
The tips of the Y are the variable regions, V regions, of the heavy and light chains.
The tail of the Y shaped antibody is made of the constant or C regions of the heavy chains.
The interaction between the antigen-binding site and its corresponding antigen is stabilized by multiple noncovalent bonds between chemical groups on the respective molecules.
The receptor binds to molecules that are on the surface of the infectious agent.
They recognize intact antigens.
Antibodies have two main functions:
Combine with antigen and labels it for destruction.
Activates processes that destroy the antigen that binds to it.
Antibodies do not destroy the antigen. It labels the antigen for destruction.
Secreted antibodies are serum globular proteins also known as immunoglobulins, Ig.
T Cell Receptors For Antigens And The Role Of The MHC
T cell receptors consist of two polypeptide chains, α and β chains linked by disulfide bridge.
They have a straight shape, not a Y shape like the B-cell receptors.
The transmembrane region anchors the antibody to the plasma membrane.
The variable V regions at the other end of the antigen form a single antigen-binding site.
The remainder of the molecule is made up of the constant C region.
The T cell receptors bind with antigens like the B cell receptors.
T cell receptors are capable of recognizing small fragments of the antigen that are bound to normal cell-surface proteins called MHC molecules.
B cell receptors recognize intact antigens on the surface of the pathogen.
T cell receptors recognize fragments of antigens presented by the MHC complex.
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
The ability to distinguish self from non-self depends largely on a group of cell surface proteins known as MHC antigens.
These proteins are synthesized by a group of genes called the major histocompatibility complex, MHC.
The principal function of the MHC is to present antigens on the surface of cells recognition by T lymphocytes: cytotoxic T cell (Tc) and helper T cells (TH).
Class I MHC molecules and Class II MHC molecules mark body cells as "self".
It permits recognition of self, a biochemical "fingerprint".
The MHC antigens are a group of membrane glycoproteins that act as markers on the surface of the cells of the individual.
Glycoproteins are proteins with a sugar chain attached to it.
Antigen presentation:
When a cell is infected or a macrophage engulfs a pathogen, antigen protein fragments are combined with Class I or II MHC proteins and transported to the surface of the cell to be presented to a nearby T cell.
There are two sets of MHC genes that code for proteins.
Class I MHC molecules. Found on all nucleated cells. Distinguish self from non-self. Forms MHC-antigen complex with fragments of proteins made by the infecting microbe, usually a virus, on the surface of the cell surface. These MHC-antigen complexes are recognized by a subgroup of T cells called cytotoxic T cells.
Class II MHC molecules. Found on specialized antigen-presenting cells including macrophages, B cells, dendritic cells, activated T cells, spleen cells, lymph node cells, and the cells in the interior of the thymus. Class II MHC molecules form complexes with antigens from protein fragments of digested bacteria that have been digested after being taken in by phagocytosis. These complexes stimulate helper T cells to form interleukins and activate B cell. These phagocytic cells are called antigen-presenting cells.
The class II MHC antigens regulate the interaction between B cells, T cells and antigen-presenting cells.
An engulfed bacterium...
Macrophage engulfs bacterium.
Antigen forms complex with the class II MHC protein.
Macrophage displays MHC-antigen complex on its cell surface.
Helper T cells are activated when their receptors combine with the MHC-antigen complex.
An infected body cell...
Pathogen invades the body and infects cells.
Macrophage engulfs pathogen.
Antigen forms complex with the class I MHC protein.
Macrophage displays MHC-antigen complex on its cell surface.
Helper T cells recognize the foreign antigen-MHC complex.
Each vertebrate species possesses numerous different alleles for each class I and class II MHC gene.
A group of closely linked polymorphic genes, e.g. multiple alleles for each locus; sometimes up to 200 alleles for one gene determine these glycoproteins.
They are located on chromosome 6 in humans.
Lymphocyte development.
T lymphocytes or T cells are responsible for cellular immunity.
Originate in the bone marrow.
In the thymus they become immunocompetent that is capable of immune response.
In the thymus they divide many times and some develop specific surface proteins with receptor sites. These cells are selected to divide: positive selection.
The T of T cells comes from “thymus”.
B cells are responsible for antibody-mediated immunity.
Produced in the bone marrow daily by the millions.
They mature in the bone marrow.
Carry specific glycoprotein receptor to bind to a specific antigen.
When a B cell comes into contact with an antigen that binds to its receptors, it clones identical cells, and produces plasma cells that manufacture antibodies.
Also produce memory B cells that continue to produce small amounts of antibody after an infection.
The B of B cells comes from “bursa of Fabricius” and organ unique to birds where the cells were first found. You may associate the B with “bone marrow”.
Lymphocyte diversity by gene rearrangement
The sequence of amino acids at the tip of the variable regions of the receptor determines the specificity of an antigen receptor.
During the early development of the B and T cells, genes are rearranged under the influence of enzymes called recombinases.
Maturing lymphocytes have genes that code for antigen receptor chains, V regions.
These genes consist of numerous coding gene segments that undergo random, permanent rearrangement, forming functional genes that can be expressed as receptor chains.
The V coding genes are separated by an intron from an exon that codes for the constant chain C.
Portions of the DNA between segment genes (V) are deleted and the new segments of DNA rejoined including the exon C.
The new gene is then transcribed and introns are removed during processing of the pre-mRNA.
Poly A and cap are added to the mRNA and processing is finished.
The mRNA is translated into variable and constant regions.
See Fig 43.11, page 906.
The rearrangement of genes occurs at random during maturation, and by chance a chain may end up being able to recognize a particular antigen.
Immune responses and immunological memory
Antigens cause the lymphocytes to form two clones of cells: effector cells and memory cells.
Antigen molecules bind to the antigen receptors of a B cell.
The selected B cell multiplies and gives rise to a clone of identical cells bearing receptors for the selecting antigen.
Some proliferating cells develop into short-lived plasma cells that secrete antibody specific for the antigen.
Other cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen.
Response caused by the first exposure to an antigen is called the primary immune response.
During the primary immune response, antibody-producing B cells called plasma cells and effector T cells multiply.
Exposure to the same antigen at a later time causes a more rapid and effective response called secondary immune response.
Antibodies produced in the secondary immune response are more numerous and have greater affinity for the antigen.
This is called immunological memory.
CELL-MEDIATED IMMUNITY
Cytotoxic T lymphocytes and macrophages are responsible for cell-mediated immunity.
Cytotoxic T cells destroy infected cells and cells altered in some way like cancer cells.
Cytotoxic T cells recognized antigens only when they are presented forming the MHD-antigen complex.
Cytokines are proteins and peptides that stimulate other lymphocytes.
Helper T Cells
When a helper T cell encounters and recognizes a class II MHC molecule-antigen complex on an antigen presenting cell, the helper T cell proliferates and differentiates into a clone of activated helper T cells and memory helper T cells.
Pathogen invades the body and infects cells.
Macrophage engulfs pathogen.
Antigen forms complex with the class II MHC protein.
Macrophage displays MHC-antigen complex on its cell surface.
CD4 proteins enhance the recognition of the MHC-antigen complex by helper T cells.
Helper T cells recognize the foreign antigen-MHC complex and secrete the cytokine IL-2.
Competent T cells are in turn activated, increase in size and divide mitotically.
Clones of competent T cells are produced.
Clones differentiate into memory T cells, cytotoxic T cells and other types of cells.
Cytotoxic T cells leave the lymph nodes and migrate to the area of infection.
Cytotoxic T cells
Cytotoxic T cells are the effectors of cell-mediated immunity.
They destroy pathogens, cancer and transplanted cells.
At the site of infection,
All nucleated cells have class I MHC proteins on its surface.
In infected cells, cancer cells and foreign cells, their proteins are broken down and carried by newly made class I MHC proteins to the surface of the cell.
The infected cell displays class I MHD-antigen complex on its surface.
Cytotoxic T cells recognize the displayed complex and binds to the infected cell with the help of CD8 proteins.
Cytotoxic T cells release proteins (lymphotoxins, perforins) in the site of infection and destroy pathogens by lysing.
Macrophages are attracted to the site to ingest pathogens.
MHC proteins have the ability to bind to different antigenic peptides displayed by the macrophage. Short peptides are flexible in solution and can adapt to the binding site of the MHC protein. Also, the MHC binding site is somewhat flexible and can accommodate a variety of peptides with not the exact homology.
B cells
B cells are responsible for antibody-mediated immunity, also called humoral immunity.
Antibody molecules serve as cell surface receptors that combine with antigens.
Only B cells bearing a matching receptor on its surface can bind a particular antigen.
Antigens that cause helper T cells produce cytokines and stimulate the production of memory cells and plasma cells, are known as T-dependent antigens. They can be produced only with help from a helper T cell.
Some polysaccharides and bacterial proteins can cause a B cell to proliferate into antibody-producing plasma cell without the intervention of helper T cells. These antigens are called T-independent antigens.
B cell must be activated.
Macrophage engulfs bacterium.
Antigen forms complex with the class II MHC protein.
Macrophage displays MHC-antigen complex on its cell surface.
Helper T cells are activated when their receptors combine with the MHC-antigen complex with the help of a CD4 protein.
Activated helper T cells secrete cytokines that activate B cells.
Independently B cells bind with complementary antigen and forms MHC-antigen complex on its own surface.
MHC-antigen complex stimulate B cells to divide and differentiate.
Cytokines also stimulate cytotoxic T cells to become active killers.
Activated B cells form many clones, some of which differentiate into plasma cells and some into memory B cells.
Plasma cells remain in the lymph nodes and secrete specific antibodies.
Antibodies are transported via lymph and blood to the infected region.
Antibodies form complexes with antigens on the surface of the pathogen.
Antibodies combine with antigens to forms specific complexes that stimulate phagocytosis, inactivate the pathogen, or activate the complement system.
Memory cells survive for a long time and continue to produce small amounts of antibody long after the infection has been overcome.
Memory cells when stimulated can produce clones of plasma cells.
Antibody classes
Antibodies are grouped into five classes of immunoglobulins or Ig based on the constant region of the heavy chains.
IgG and IgM defend the body against pathogens in the blood and stimulate macrophages and the complement system.
IgA is present in the mucus, saliva, tears and milk. It prevents pathogens from attaching to epithelial cells.
IgD found on B cells surface helps activate them following antigen binding. They are needed to initiate the differentiation of B cells into plasma and memory B cells.
IgE when bound to an antigen releases histamines responsible for many allergic reactions. It also prevents parasitic worms.
Antibodies combine with antigens to forms specific complexes that stimulate phagocytosis, inactivate the pathogen, or activate the complement system.
Antibodies may inactivate a pathogen, e.g. when the antibody attaches to a virus, the virus may lose its ability to attach to a host cell. This is called neutralization.
The antigen-antibody complex may stimulate phagocytic cells to ingest the pathogen. Antibodies enhance macrophage attachment to the microbes for phagocytosis. This is called opsonization.
Clumping of bacteria and viruses neutralizes and opsonizes the microbes for phagocytosis. This is called agglutination.
Antibodies can bind to soluble antigens and form immobile precipitates that can be disposed of by phagocytes. This is called precipitation.
The antigen-antibody complex allows complement system proteins to penetrate the pathogen's membrane and open a pore that causes the lysis of the pathogenic cell. These proteins form a membrane attack complex (MAC) that opens the pore. This is called complement fixation.
The classical pathway is triggered by antibodies bound to antigen and is part of the humoral response.
The alternative pathway is triggered by substances already present in the body and does not involve antibodies; it is part of the nonspecific defense system.
Microbes coated with antibodies and complement proteins tend to adhere to the wall of blood vessels, making them easy preys for phagocytes.
Opsonization, agglutination and precipitation enhance phagocytosis of the antigen-antibody complex.
Immunization
Constant evolution of pathogens causes different antigens that are no longer recognizable by memory cells and thus cause the disease again, e.g. cold, flu.
Types of immunity:
Active immunity is developed by exposure to antigens.
Naturally induced by an infection.
Artificially induced through a vaccine.
Passive immunity is caused by the injection of antibodies produced by other organisms.
Naturally induced by the mother to the developing baby.
Artificially induced through injection of antibodies (gamma globulin).
Babies who are breastfed continue to receive immunoglobulins (IgA) in the milk.
Blood groups and blood transfusion
The ABO system is based on the antigens found on the surface of the RBC. See Ch. 14, table 14.2.
These "antigens" are polysaccharides that if placed in the system of another person will cause a devastating reaction; they are NOT antigens to the owner.
Type A has antigen A protein in the RBC plasma membrane; Type B has antigen B; Type AB has both antigens; and Type O has neither of the two antigens on its surface.
e. g. Type A blood will have antibodies against the B antigen. Type AB does not have antibodies against antigens A or B.
The Rh factor is an antigen that can cause problem if the mother is Rh negative and the fetus is Rh positive.
Late in pregnancy or during delivery the Rh-positive factor of the baby can cause the formation of Rh antibodies, anti-Rh-positive IgG, in the mother that will endanger the life of future Rh positive babies by destroying their RBC.
Grafts and organ transplants
Graft rejection is an immune response against transplanted tissue.
T cells are responsible for the destruction of the transplanted organ.
The transplanted tissue has MHC antigens that are different from those of the host that stimulate the immune response.
Certain part of the body accepts any foreign tissue, e.g. cornea.
Because of the difficulty of finding a good match to transplant tissues or organs, biologists are investigating techniques to transplant animal tissues and organs to humans. This procedure is called xenotransplantation.
Animals can be genetically engineered so that they do not produce antigens that stimulate the immune system of the host.
Abnormal immune functions
Allergic reactions
Hypersensitivity is an exaggerated immunological response to an antigen that is harmless.
Mild antigens called allergens cause allergic reactions.
It involves sensitization, activation of mast cells and allergic response.
It involves the production of IgE by plasma cells.
Hayfever reaction:
Exposure to pollen causes B cell to develop into plasma cells, which make pollen specific IgE antibodies.
IgE becomes attached to mast cells receptors.
When more pollen is inhaled, allergen pollen molecules attach to the IgE on the mast cells surface.
Mast cells then release histamine and serotonin, in a process called degranulation.
These chemicals cause vasodilation, increase permeability and inflammation.
Allergic asthma occurs when the IgE becomes attached to mast cells in the bronchioles of the lungs.
Chemical released by mast cells cause smooth muscles to contract and airways narrow making breathing difficult.
When the allergen reaction takes place in the skin, the person develops hives.
Systemic anaphylaxis is hypersensitivity to a drug like penicillin, compounds in food, insect sting or venom.
The reaction is widespread.
Massive amounts of histamine are released into the blood.
Extreme vasodilation and permeability follows causing a rapid drop in blood pressure, shock and death.
Antihistamine drugs (epinephrine) block the effect of histamines released by mast cells.
Autoimmune disease is a form of hypersensitivity when the body reacts against its own tissues.
E.g., Multiple sclerosis, insulin-dependent diabetes mellitus, rheumatoid arthritis, lupus and psoriasis.
During lymphocyte development complex mechanisms are developed so the WBC become self-tolerant and do not attack the tissues of their own body.
It is known that some lymphocytes capable of attacking self. There is a regulatory mechanism that prevents this from happening in healthy individuals. Failure to regulate these lymphocytes results in autoimmune diseases.
Primary immunodeficiency diseases result from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell mediated defenses.
An immunodeficiency that develops later in life following exposure to various chemical and biological agents is classified as an acquired or secondary immunodeficiency.
Stress can harm the immune system. Hormones secrete by the adrenal glands during stress affect the numbers of white blood cells and may prepress the immune system response.
Neurotransmitters released when the person is relaxed and happy may enhance immunity.
AIDS - ACQUIRED IMMUNE DEFICIENCY SYNDROME
It is cause by the retrovirus HIV, human immunodeficiency virus.
Retroviruses are RNA viruses that use RNA as a template to make DNA with the help of reverse transcriptase.
The DNA produced by the virus is inserted in the host DNA and exists as a provirus for the life of the infected cell. Because of its provirus existence, immune responses fail to eradicate the virus.
Frequent mutations at every viral replication compound the problem of eliminating the HIV.
HIV destroys helper T cells and macrophages by attaching to the CD4 molecules on the surface of the T lymphocyte.
There are some evidence of destruction of the lymph nodes.
The ability of suppress infection is impaired and the patient falls victim to infectious diseases and cancer.
AZT (acidothymidine) blocks the action of reverse transcriptase.
chapter 44 Outline: Osmoregulation and Excretion
Chapter 44 – Osmoregulation and Excretion
OSMOREGULATION: The regulation of solute and water concentrations in body fluids by organisms living in hyperosmotic, hypoosmotic, and terrestrial environments.
EXCRETION: The disposal of nitrogen-containing waste products of metabolism.
TRANSPORT EPITHELIUM: One or more layers of specialized epithelial cells that regulate solute movements.
NITROGENOUS WASTES: Simple nitrogen compounds produced by the metabolism of proteins, such as urea and uric acid.
AMMONIA: A small, very toxic molecule made up of three hydrogen atoms and one nitrogen atom; produced by nitrogen fixation and as a metabolic waste product of protein and nucleic acid metabolism.
UREA: A soluble nitrogenous waste excreted by mammals, most adult amphibians, and many marine fishes and turtles; produced in the liver by a metabolic cycle that combines ammonia with carbon dioxide.
URIC ACID: An insoluble precipitate of nitrogenous waste excreted by land snails, insects, birds, and some reptiles.
FILTRATION: In the vertebrate kidney, the extraction of water and small solutes, including metabolic wastes, from the blood by the nephrons.
FILTRATE: Fluid extracted by the excretory system from the blood or body cavity. The excretory system produces urine from the filtrate after extracting valuable solutes from it and concentrating it.
SELECTIVE REABSORPTION: The selective uptake of solutes from a filtrate of blood, coelomic fluid, or hemolymph in the excretory organs of animals.
SECRETION: (1) The discharge of molecules synthesized by a cell. (2) In the vertebrate kidney, the discharge of wastes from the blood into the filtrate from the nephron tubules.
EXCRETION: The disposal of nitrogen-containing waste products of metabolism.
Draw, label, and summarize the key functions of the excretory systems (Fig 44.9, p.929) : Most excretory systems produce a filtrate by pressure–filtering body fluids and then modify the filtrate′s contents. This diagram is modeled after the vertebrate excretory system.
Vertebrate / Mammalian (i.e. human) URINARY SYSTEM: the organs and passageways concerned with the production and excretion of urine, including the kidneys, ureters, urinary bladder and the urethra.
RENAL ARTERY: The blood vessel bringing blood to the kidney.
RENAL VEIN: The blood vessel draining the kidney.
URETER: A duct leading from the kidney to the urinary bladder.
URINARY BLADDER: The pouch where urine is stored prior to elimination.
URETHRA: A tube that releases urine from the body near the vagina in females and through the penis in males; also serves in males as the exit tube for the reproductive system.
RENAL CORTEX: The outer portion of the vertebrate kidney.
RENAL MEDULLA: The inner portion of the vertebrate kidney, beneath the renal cortex.
NEPHRON: The tubular excretory unit of the vertebrate kidney.
GLOMERULUS: A ball of capillaries surrounded by Bowman뭩 capsule in the nephron and serving as the site of filtration in the vertebrate kidney.
BOWMAN’S CAPSULE: A cup-shaped receptacle in the vertebrate kidney that is the initial, expanded segment of the nephron where filtrate enters from the blood.
PROXIMAL TUBULE: In the vertebrate kidney, the portion of a nephron immediately downstream from Bowman뭩 capsule that conveys and helps refine filtrate.
DESCENDING AND ASCENDING LIMB OF THE LOOP OF HENLE: The long hairpin turn, with a descending and ascending limb, of the renal tubule in the vertebrate kidney; functions in water and salt reabsorption.
DISTAL TUBULE: In the vertebrate kidney, the portion of a nephron that helps refine filtrate and empties it into a collecting duct.
COLLECTING DUCT: The location in the kidney where filtrate from renal tubules is collected; the filtrate is now called urine.
RENAL PELVIS: Funnel-shaped chamber that receives processed filtrate from the vertebrate kidney뭩 collecting ducts and is drained by the ureter.
CORTICAL NEPHRONS: Nephrons located almost entirely in the renal cortex. These nephrons have a reduced loop of Henle.
JUXTAMEDULLARY NEPHRONS: Nephrons with well-developed loops of Henle that extend deeply into the renal medulla.
AFFERENT ARTERIOLE: The blood vessel supplying a nephron.
EFFERENT ARTERIOLE: The blood vessel draining a nephron.
VASA RECTA: The capillary system that serves the loop of Henle.
Describe/explain the COUNTERCURRENT MULTIPLIER SYSTEM (a picture might help!): A countercurrent system in which energy is expended in active transport to facilitate exchange of materials and create concentration gradients. For example, the loop of Henle actively transports NaCl from the filtrate in the upper part of the ascending limb of the loop, making the urine-concentrating function of the kidney more effective.
ANTIDIURETIC HORMONE (ADH): A hormone produced in the hypothalamus and released from the posterior pituitary. It promotes water rentention by the kidneys as part of an elaborate feedback scheme that helps regulate the osmolarity of the blood.
ALDOSTERONE: An adrenal hormone that acts on the distal tubules of the kidney to stimulate the reabsorption of sodium (Na+) and the passive flow of water from the filtrate.
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS): A part of a complex feedback circuit that normally partners with antidiuretic hormone in osmoregulation.
chapter 43 Outline: The Immune System
PATHOGEN: A disease-causing agent.
INNATE IMMUNITY: The kind of defense that is mediated by phagocytic cells, antimicrobial proteins, the inflammatory response, and natural killer (NK) cells. It is present before exposure to pathogens and is effective from the time of birth.
ACQUIRED/ADAPTIVE IMMUNITY: The kind of defense that is mediated by B lymphocytes (B cells) and T lymphocytes (T cells). It exhibits specificity, memory, and self-nonself recognition. Also called adoptive immunity.
LYMPHOCYTES: A type of white blood cell that mediates acquired immunity. Lymphocytes that complete their development in the bone marrow are called B cells, and those that mature in the thymus are called T cells.
ANTIBODIES: A protein secreted by plasma cells (differentiated B cells) that binds to a particular antigen and marks it for elimination; also called immunoglobulin. All antibody molecules have the same Y-shaped structure and in their monomer form consist of two identical heavy chains and two identical light chains joined by disulfide bridges.
INNATE IMMUNITY: The kind of defense that is mediated by phagocytic cells, antimicrobial proteins, the inflammatory response, and natural killer (NK) cells. It is present before exposure to pathogens and is effective from the time of birth.
External Defenses (1st line): A break in the skin.
SKIN: The skin is the body's outer covering. It protects us against heat and light, injury, and infection. It regulates body temperature and stores water, fat, and vitamin D. Weighing about 6 pounds, the skin is the body's largest organ. It is made up of two main layers; the outer epidermis and the inner dermis.
MUCOUS: Smooth moist epithelium that lines the digestive tract and air tubes leading to the lungs.
OIL & SWEAT GLANDS: give the skin a pH ranging from 3 to 5, which is acidic enough to prevent colonization by many microbes. (Bacteria that normally inhabit the skin are adapted to its acidic, relatively dry environment.)
LYSOZYMES: An enzyme in sweat, tears, and saliva that attacks bacterial cell walls.
Internal Cellular & Chemical Defenses:
PHAGOCYTOSIS: A type of endocytosis involving large, particulate substances, accomplished mainly by macrophages, neutrophils, and dendritic cells.
PHAGOCYTIC LEUCOCYTES (WBCs): A white blood cell; typically functions in immunity, such as phagocytosis or antibody production.
COMPLEMENT SYSTEM: yet another example of how life is protein dependant! A group of about 30 blood proteins that may amplify the inflammatory response, enhance phagocytosis, or directly lyse pathogens. The complement system is activated in a cascade initiated by surface antigens on microorganisms or by antigen-antibody complexes.
INTERFERONS: A protein that has antiviral or immune regulatory functions. Interferon ? and interferon-??, secreted by virus-infected cells, help nearby cells resist viral infection; interferon-??, secreted by T cells, helps activate macrophages.
DEFENSINS:
INFLAMMATORY RESPONSE: A localized innate immune defense triggered by physical injury or infection of tissue in which changes to nearby small blood vessels enhance the infiltration of white blood cells, antimicrobial proteins, and clotting elements that aid in tissue repair and destruction of invading pathogens; may also involve systemic effects such as fever and increased production of white blood cells.
ACQUIRED/ADAPTIVE IMMUNITY: acquired immunity is immunological memory—the ability to respond more quickly to a particular invader or foreign tissue the second time it is encountered.
CYTOKINES: Any of a group of proteins secreted by a number of cell types, including macrophages and helper T cells, that regulate the function of lymphocytes and other cells of the immune system.
ANTIGEN: A macromolecule that elicits an immune response by lymphocytes.
EPITOPE: A small, accessible region of an antigen to which an antigen receptor or antibody binds; also called an antigenic determinant.
LYMPHOCYTES: A type of white blood cell that mediates acquired immunity. Lymphocytes that complete their development in the bone marrow are called B cells, and those that mature in the thymus are called T cells.
B CELLS: what are they, what do they do, how did they get their name? A type of lymphocyte that develops to maturity in the bone marrow. After encountering antigen, B cells differentiate into antibody-secreting plasma cells, the effector cells of humoral immunity.
T CELLS: what are they, what do they do, how did they get their name? A type of lymphocyte, including the helper T cells and cytotoxic T cells, that develops to maturity in the thymus. After encountering antigen, T cells are responsible for cell-mediated immunity.
ANTIGEN RECEPTORS: what are they and how do they differ between B & T cells The general term for a surface protein, located on B cells and T cells, that binds to antigens, initiating acquired immune responses. The antigen receptors on B cells are called B cell receptors (or membrane immunoglobulins), and the antigen receptors on T cells are called T cell receptors.
ANTIGEN PRESENTATION: The process by which an MHC molecule binds to a fragment of an intracellular protein antigen and carries it to the cell surface, where it is displayed and can be recognized by a T cell.
ANTIGEN-PRESENTING CELLS [MACROPHAGES]: A cell that ingests bacteria and viruses and destroys them, generating peptide fragments that are bound by class II MHC molecules and subsequently displayed on the cell surface to helper T cells. Macrophages, dendritic cells, and B cells are the primary antigen-presenting cells.
Clonal Selection of Lymphocytes: also see figure 43.12
MEMORY CELLS: One of a clone of long-lived lymphocytes, formed during the primary immune response, that remains in a lymphoid organ until activated by exposure to the same antigen that triggered its formation. Activated memory cells mount the secondary immune response.
CLONAL SELECTION: The process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific for the antigen. The selected lymphocytes proliferate and differentiate into a clone of effector cells and a clone of memory cells specific for the stimulating antigen. Clonal selection accounts for the specificity and memory of acquired immune responses.
PRIMARY IMMUNE RESPONSE: The initial acquired immune response to an antigen, which appears after a lag of about 10 to 17 days.
PLASMA CELLS: The antibody-secreting effector cell of humoral immunity; arises from antigen-stimulated B cells.
SECONDARY IMMUNE RESPONSE: The acquired immune response elicited on second or subsequent exposures to a particular antigen. The secondary immune response is more rapid, of greater magnitude, and of longer duration than the primary immune response.
HUMORAL IMMUNE RESPONSE: The branch of acquired immunity that involves the activation of B cells and that leads to the production of antibodies, which defend against bacteria and viruses in body fluids.
CELL-MEDIATED IMMUNE RESPONSE: The branch of acquired immunity that involves the activation of cytotoxic T cells, which defend against infected cells, cancer cells, and transplanted cells.
HELPER T CELL: A type of T cell that, when activated, secretes cytokines that promote the response of B cells (humoral response) and cytotonic T cells (cell-mediated response) to antigens.
MONOCLONAL ANTIBODIES: Any of a preparation of antibodies that have been produced by a single clone of cultured cells and thus are all specific for the same epitope.
ACTIVE IMMUNITY: Long-lasting immunity conferred by the action of a person뭩 B cells and T cells and the resulting B and T memory cells specific for a pathogn. Active immunity can develop as a result of natural infection or immunization.
IMMUNIZATION (VACCINATION) = ARTIFICIAL IMMUNITY: acquired (active or passive) immunity produced by deliberate exposure to an antigen, as in vaccination.
PASSIVE IMMUNITY: Short-term immunity conferred by the administration of ready-made antibodies or the transfer of maternal antibodies to a fetus or nursing infant; lasts only a few weeks or months because the immune system has not been stimulated by antigens.
NATURAL IMMUNITY: immunity due to infection.
ANAPHYLACTIC SHOCK: An acute, whole-body, life-threatening, allergic response.
IMMUNODEFICIENCIES: Immunodeficiency disorders are a group of disorders in which part of the immune system is missing or defective. Therefore, the body's ability to fight infections is impaired. As a result, the person with an immunodeficiency disorder will have frequent infections that are generally more severe and last longer than usual.
AUTOIMMUNE DISEASES: An immunological disorder in which the immune system turns against self.
HUMAN IMMUNODEFICIENCY VIRUS (HIV): The infectious agent that causes AIDS. HIV is a retrovirus.