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This document contains Chapters 34 to 35 CHAPTER 34 CHEMICAL COORDINATION: ENDOCRINE SYSTEM CHAPTER OUTLINE 34.1. Mechanisms of Hormone Action (Figure 34.1) A. Overview 1. Along with the nervous system, the endocrine system controls the body’s activities; the endocrine system communicates through the use of chemical messengers called hormones. 2. Hormones are transported through the circulatory and lymphatic systems (although some may not enter general circulation) of the body to target cells that initiate a physiological response. 3. Endocrine Glands a. Endocrine glands are small, well-vascularized ductless glands with clustered cells. b. They have no ducts and they must secrete hormones into the blood. c. Endocrine glands capture raw materials from the bloodstream and secrete hormones into it. d. In contrast, exocrine glands secrete fluids through the ducts. 4. Some hormones function as neurotransmitters in the brain or as local tissue factors (parahormones). 5. Compared with nervous impulses, hormones are slower acting because the chemicals must reach the tissues and diffuse across membranes; however, hormonal responses in general are long lasting, for many minutes or days. Thus, endocrine control is superior if sustained effort is required for metabolism, growth or reproduction. 6. There is not a sharp distinction between nervous and endocrine systems; endocrine glands often receive nerve stimulation and hormones may act on the nervous system. 7. All hormones are low-level signals; a hormone rarely exceeds one billionth of a 1M concentration; some target cells respond to concentrations one thousandth less than this. 8. Some hormones such as growth hormone affect most, if not all cells. 9. The two kinds of receptors on target cells are membrane-bound receptors and nuclear receptors. B. Membrane-Bound Receptors and the Second Messenger Concept (Figure 34.2) 1. Many hormones are peptide hormones (often derivatives of amino acids) are too large to pass through cell membranes; consequently, they must bind to transmembrane proteins on the surface of target cells. 3. Hormones that bind to membrane-bound receptors are first messengers because they activate second messenger systems via cascades of kinase reactions within the cytoplasm. 4. A single hormone molecule may activate thousands of second messengers—the message is amplified. 5. Common second messengers include cyclic AMP, cyclic GMP, Ca++/calmodulin, inositol-triphosphate and diacylglycerol. 6. Cyclic AMP (cAMP) was discovered early and is known to mediate actions of many peptide hormones including parathyroid hormone, glucagon, ACTH, thyrotropic hormone, melanophore-stimulating hormone, vasopressin and epinephrine. 7. Recent evidence suggests that lipid-soluble hormones, such as estrogen, may also possess membrane-bound receptors that activate second messenger systems in the same way as peptide hormones, providing multiple and complex control of target cells. C. Nuclear Receptors 1. Steroid hormones (such as estrogen) are lipid-soluble and readily diffuse through cell membranes. 2. Nuclear receptors may be located in the cytoplasm or nucleus; the nucleus is their ultimate site of activity. 3. Gene regulatory proteins called hormone-receptor complexes, are activated or repressed by these hormones to activates or inhibits specific processes associated with gene transcription. 4. In contrast to peptide hormones that act indirectly through second messengers; steroids work directly with processes associated with gene expression. D. Cytoplasmic Receptors 1. Lipid-soluble hormones, such as estrogen, interact not only with nuclear receptors, but also with cytoplasmic receptors. 2. Cytoplasmic receptors may be membrane bound or free within the cytoplasm. 3. Activated hormone-receptor complexes interact with second messenger systems within the cytoplasm, or through a cascade of events in which activate factors enter the nucleus to stimulate or inhibit transcription processes. E. Control of Secretion Rates of Hormones (Figure 34.3) 1. The action of hormones is to not only activate, but regulate processes such as enzyme activity and cell metabolic rate, membrane permeability, cell proteins synthesis, or the release of other hormones.. 2. Release of a hormone into the blood depends on its rate of secretion and the rate it is inactivated. 3. Endocrine glands must receive information about the level of its own hormone in the plasma. 4. Many hormones are controlled by negative feedback systems between glands and target cells in which the signal (or output of the system) induces the control system to reduce levels of the initial signal. For example, the hypothalamus secretes CRH that stimulates the pituitary to release ACTH, which stimulates the adrenal gland to secrete cortisol; increases in blood ACTH inhibit release of CRH. 5. Other hormones are controlled by positive feedback systems in which the signal (or output of the system) induces the control system and causes an increase in the initial signal. In this way the initial signal becomes progressively amplified to produce an explosive event. For example, the posterior pituitary gland secretes the hormone oxytocin to control childbirth and ovulation. Positive feedback systems must have natural shutoff mechanisms. 34.2. Invertebrate Hormones (Figure 34.4) A. Overview 1. All invertebrates produce hormones, but there is less diversity in invertebrate endocrine function when compared to vetebrates. 2. Invertebrates like cnidarians, nematodes, and annelids possess endocrine cells, while endocrine glands appear in molluscs and arthropods. 3.Invertebrate hormones are often neuropeptides, steroids or terpenoids., and are responsible for regulating color changes, growth, reproduction, and internal homeostatic mechanisms. B. Neurosecretory Cells and Molting 1. In metazoans, a main source of hormones is neurosecretory cells, nerve cells that secrete hormones. 2. Neurosecretory hormones are placed directly in the circulation. 3. They link the nervous and endocrine systems. 4. Peptides and neuropeptides regulate many physiological processes in invertebrates. a. In crustaceans, cardioactive peptide increases heart rate, and the hyperglycaemic hormone family (CHH) in crustaceans and the adipokinetic hormone family in insects regulate metabolism of carbohydrates, fats, and amino acids. b. FMRF amide-related peptides regulate muscular tissues of the body, and digestive and reproductive processes in many invertebrates, as well as osmoregulatory processes in nematodes, annelids, molluscs and insects, and arterial hemolymph flow in crustaceans. 5. Two hormones control molting. a. Molting hormone, or ecdysone, is produced by the prothoracic gland. b. Juvenile hormone is produced by the corpora allata. c. Ecdysone is controlled by prothoracicotropic hormone (PTTH) produced in the brain and transported by axons to the corpora allata where it is stored. d. Ecdysone acts directly on chromosomes and favors development of adult structures. e. Juvenile hormone favors larval features and predominates at each larval stage. f. Juvenile hormone decreases at the final stage, allowing metamorphosis to the adult stage. g. Juvenile hormone appears to be important during diapause. h. It is also present in adult insects where it is involved in regulation of egg development. i. Analogs of juvenile hormone may be able to replace some insecticides by blocking development. 34.3. Vertebrate Endocrine Glands and Hormones A. Hormones of the Hypothalamus and Pituitary Gland (Figures 34.5–34.7) 1. Structure a. The pituitary gland, or hypophysis, is located within a depression of the floor of the cranium. b. The anterior pituitary is derived from the roof of the mouth. c. The posterior pituitary arises from the ventral portion of the brain, the hypothalamus, and is connected to it by a stalk, or infundibulum. d. The anterior pituitary’s only connection to the hypothalamus is a special portal circulatory system; therefore, the neurosecretory cells of the hypothalamus have a link to the anterior pituitary gland. 2. Hypothalamus and Neurosecretion a. The pituitary, controlled by the hypothalamus, influences most hormonal activities.. b. Neurosecretory cells in hypothalamus make releasing hormones and release inhibiting hormones. c. These neurohormones travel down nerve fibers to endings where they enter a capillary network. d. The pituitary portal system takes them directly to the anterior pituitary. e. The hypothalamic hormones stimulate or inhibit various anterior pituitary hormones. f. Some hormones have been isolated and characterized; others are tentative. 3. Anterior Pituitary (Table 34.1, Figure 34.6)) a. The anterior pituitary has an anterior lobe and an intermediate lobe (absent in humans). b. The anterior lobe produces six hormones and the intermediate produces one. c. Four hormones are tropic hormones that regulate other endocrine glands (Table 34.1). 1) Thyroid-stimulating hormone (TSH) stimulates production of thyroid gland hormones. 2) Follicle-stimulating hormone (FSH) promotes egg production or sperm production. 3) Luteinizing hormone (LH) induces ovulation and corpus luteum and sex steroid production. 4) Adenocorticotropic hormone (ACTH) increases production and secretion of steroid hormones from the adrenal cortex. d. Two hormones regulate other tissues directly. 1) Prolactin is a protein hormone that prepares mammary glands for lactation and milk production. It also is implicated in parental behavior of a wide variety of vertebrates, a mediator of the immune system, and a factor in formation of new blood vessels. 2) Growth hormone (GH or somatotropin) governs cell mitosis and metabolism and mRNA synthesis. It acts indirectly through a polypeptide hormone, insulin-like growth factor (IGF). 4. Intermediate lobe (Table 34.1) produces melanocyte-stimulating hormone (MSH) that promotes dispersion of pigment in cells in bony fishes, amphibians and nonavian reptiles. In birds and mammals, MSH is produced in the anterior pituitary and has unclear roles. 5. Posterior Pituitary (Table 34.1, Figure 34.7) a. Neuroscretory cells in hypothalamus form three hormones that are released through axons into capillaries of posterior lobe of the pituitary; posterior lobe therefore is not an endocrine gland, but a storage and release center. 1) Oxytocin, a fast-acting octapeptide a. Stimulates contraction of uterine muscle during birth; can be used to induce delivery. b. Triggers milk ejection by mammary glands in response to suckling. c. In some monogamous vole species is also involved in pair-bonding in both sexes. 2) Vasopressin or Antidiuretic Hormone (ADH), another fast-acting octapeptide a. Acts on collecting ducts of the kidney to increase water absorption. b. It increases blood pressure by constricting smooth muscles of arterioles. c. Vasopressin also acts centrally to increase thirst and drinking. 3) Vasotocin a. A widely distributed octapeptide and the parent hormone from which others evolved. b. Not found in mammals, but plays a water-conserving role in birds and nonavian reptiles. c. In amphibians it increases permeability of the skin and stimulates water reabsorption from the urinary bladder. B. Pineal Gland 1. In all vertebrates, the diencephalon gives rise to a sac-like pineal complex. 2. It lies just below the skull in a mid-line position. 3. In ectothermic vertebrates the pineal complex has glandular tissue and photoreceptors. 4. As a sensory organ, it is involved in pigments, responses and light-dark biological rhythms. 5. In lampreys, some amphibians, lizards and the tuatara it resembles a third eye in structure. 6. In birds and mammals, the pineal complex is entirely glandular and forms the pineal gland. 7. It produces melatonin in a cycle with exposure to light; production is highest at night. 8. In nonmammalian vertebrates, it maintains circadian rhythms and provides a biological clock. 9. In mammals, the suprachiasmatic nucleus of the hypothalamus is the primary circadian pacemaker. 10. In mammals with reproduction keyed to photoperiod, melatonin regulates gonadal activity. 11. Long-day breeders have reproduction suppressed during winter months. 12. Short-day breeders increase reproductive activity in the autumn. 13. Seasonal affective disorder, jet lag, shift-work, as well as psychiatric and metabolic disorders have been linked to circadian rhythms. C. Brain Neuropeptides 1. A growing list of hormone-like neuropeptides has been discovered in the central and peripheral nervous systems of both vertebrates and invertebrates. 2. Over 40 neuropeptides have been located using immunological techniques in mammals. 3. Many are both hormones carrying signals to gland cells, and neurotransmitters relaying nerve signals. 4. Both oxytocin and vasopressin occur in widespread sites in the brain. 5. Unrelated to its antidiuretic function, vasopressin can increase learning and memory. 6. Gastrin and CCK have been isolated in cerebral cortex and CCK functions in control of feeding. 7. Endorphins and Enkephalins a. These neuropeptides bind with opiate receptors and influence perception of pain and pleasure. b. They are also found in brain circuits that control blood pressure, body temperature, etc. c. They are derived from the same prohormones that give rise to ACTH and MSH. D. Prostaglandins and Cytokines 1. Prostaglandins a. Prostaglandins were discovered in seminal fluid in the 1930s. b. They are derived from long-chain unsaturated fatty acids. c. First thought to be produced only in the prostate, prostaglandins are in nearly all mammalian tissues. d. They have diverse actions in different tissues but have more effect on smooth muscle. e. They regulate vasodilation and vasoconstriction of blood vessels. f. They stimulate contraction of the uterine smooth muscle during childbirth. g. Overproduction of prostaglandins may contribute to dysmenorrhea. h. Prostaglandins also intensify pain in damaged tissues and mediate inflammation, and fever. 2. Cytokines a. Large group of hormones mediates communication between cells during the immune response. b. Cytokines affect the cells that secrete them, nearby cells, and distant target cells. c. One cytokine that activates some cells to divide may suppress division of other target cells. d. Cytokines are also involved in formation of blood. e. Adipokines, cytokines produced by adipose cells, apparently are important for regulating energy balance and obesity. E. Hormones of Metabolism 1. Thyroid Hormones (Figures 34.8–34.10) a. Hormones never initiate enzymatic processes but can alter their rate. b. The thyroid is a large endocrine gland located in the neck of vertebrates. c. The thyroid contains thousands of tiny sphere-like follicles that produce and store hormones. d. Calcitonin is also secreted by the thyroid gland in mammals. e. The thyroid concentrates iodine; it contains well over half the iodine in the body. f. The thyroid produces triiodothyronine (T3) with three iodine atoms and thyroxine (T4) with four. g. T4 is produced in greater amounts but T3 is the more physiologically active. h. T4 is considered a precursor to T3. i. Their most important actions are to promote normal growth and development of the nervous system and to stimulate metabolic rate. j. Undersecretion of thyroid hormones in fishes, birds and mammals dramatically impairs growth. k. Oversecretion of thyroid hormones causes premature development. l. Frogs and toads transform from tadpole to adult when the thyroid becomes active. m. In birds and mammals, thyroid hormones control oxygen consumption and heat production. n. The thyroid is critical in maintaining a normal level of metabolism in homeotherms. o. Thyroid hormones reduce efficiency of cellular oxidative phosphorylation to produce more heat. p. Therefore, many cold-adapted mammals eat more food in winter and more is converted to heat. q. Thyrotropic hormone from the anterior pituitary governs synthesis and release of these hormones. r. In turn, the hypothalamus controls TSH production with thyrotropin-releasing hormone (TRH). s. The TSH-TRH balance is a case of simple negative feedback between hypothalamus and pituitary. t. Goiter 1) Goiter is enlargement of the thyroid gland due to deficiency of iodine in food and water. 2) By striving to produce thyroid hormone, the gland grows much larger and swells the neck. 3) Goiter is prevented in the U.S. by adding iodine to salt; it still exists in mountainous regions. 2. Hormonal Regulation of Calcium Metabolism (Figures 34.11, 34.12) a. Human parathyroid glands occur in two pairs; they vary in number and position in other animals. b. Associated with the thyroid, they were discovered when removal of the “thyroid” caused death. c. In birds and mammals, removal of these glands causes blood calcium levels to drop. d. Continued decrease in calcium leads to excitability, muscle spasms, tetany and death. e. Parathyroid hormone (PTH) is essential to maintenance of calcium homeostasis. f. Although 98% of calcium is in bone, this living tissue is constantly being dissolved and rebuilt. g. Three hormones coordinate the absorption, storage, and excretion of calcium ions. h. If blood calcium decreases slightly, the parathyroids increase secretion of PTH. i. PTH stimulates osteoclasts to dissolve bone adjacent to these cells, releasing calcium and phosphate into the blood and returning calcium levels to normal. j. PTH also decreases the rate calcium is excreted by the kidney. k. PTH increases production of the hormone 1,25-dihydrovitamin D. l. Vitamin D 1) Vitamin D is a dietary requirement, but can also be synthesized in the skin by sunlight. 2) Vitamin D converts by a two-step oxidation to a hormonal form: 1,25-dihydroxyvitamin D. 3) Vitamin D deficiency causes rickets, a disease of low blood calcium and weak bones. m. Calcitonin 1) Calcitonin is secreted by C cells in the mammal thyroid gland and in the ultimobranchial gland of other vertebrates. 2) It is released in response to elevated levels of calcium in the blood. 3) It rapidly suppresses calcium withdrawal from bone, decreases intestinal absorption of calcium and increases excretion of calcium by the kidneys. 4) Calcitonin protects the body against a rise in blood calcium, just as PTH protects against loss. 5) However, removal of the thyroid (and therefore the C cells) does not affect homeostasis. 3. Hormones of the Adrenal Cortex (Figures 34.13, 34.14) a. The mammalian adrenal gland is a double gland composed of unrelated glandular tissue. b. The outer region is the adrenal cortex; the inner region is the adrenal medulla. c. In non-mammal vertebrates, the equivalent tissues are organized quite differently. d. 30 compounds have been isolated from adrenocortical tissue; only a few are steroid hormones. e. Many compounds are intermediates in the synthesis of hormones from cholesterol. f. Corticosteroid hormones are grouped into glucocorticoids and mineralocorticoids. g. Glucocorticoids 1) Cortisol and corticosterone are involved with food metabolism, inflammation and stress. 2) They promote synthesis of glucose from amino acids and fats by gluconeogenesis. 3) This increases glucose in the blood as a quick energy source for muscles and nerve tissues. 4) They also decrease the immune response and are used to treat inflammatory diseases. 5) ACTH controls synthesis and secretion; ACTH is controlled by corticotropin-releasing hormone (CRH) of the hypothalamus. 6) A negative feedback relationship exists between CRH, ACTH, and adrenal cortex. h. Mineralocorticoids 1) Mineralocorticoids are corticosteroids that regulate salt balance. 2) Aldosterone is the most important steroid in this group. 3) Aldosterone promotes tubular reabsorption of sodium and secretion of potassium in kidneys. 4) This helps many animals since sodium is often in short supply and potassium is in excess. 5) The salt-regulating action is controlled by the renin-angiotensin system and by blood levels. i. Adrenocortical tissue also produces androgens that act similar to testosterone. 4. Hormones of the Adrenal Medulla a. Adrenal medullary cells secrete epinephrine (adrenaline) and norepinephrine (noradrenaline). b. Adrenal medulla is embryologically the same tissue that gives rise to neurons of the autonomic nervous system and can be considered a very large sympathetic ganglion. c. Norepinephrine serves as a neurotransmitter at the endings of sympathetic nerve fibers. d. Release of epinephrine produces the same emergency responses as the sympathetic system. e. Activation of the adrenal medulla by the sympathetic nervous system prolongs the effects of sympathetic system activation. f. Both hormones moderate constriction of arterioles, mobilization of liver glycogen and fat stores, oxygen consumption, blood coagulation, and gastrointestinal tract. 5. Hormones from Islet Cells of the Pancreas (Figures 34.15, 34.16) a. The pancreas is both an exocrine and endocrine gland. b. Scattered among the exocrine portion are small islets of Langerhans. c. This endocrine portion only constitutes 1–2% of the total weight of the pancreas. d. In the islets of Langerhans, 1) Alpha cells produce glucagon a. Glucago is a hormone that induces the release of glucose from various storage areas into the blood stream. b. Induces metabolism of carbohydrate and fat reserves in the body. 2) Beta cells produce insulin and amylin a. Insulin is a hormone that induces the removal of glucose from the blood stream into tissues via various pathways. b. All body cells except neurons require insulin for entry of glucose into body cells. c. Without insulin, blood glucose levels rise to abnormal levels (hyperglycemia). d. Insulin deficiency also inhibits uptake of amino acids by skeletal muscle. e. Diabetes mellitus is a condition that results from improper regulation of blood glucose by insulin, and afflicts nearly 5% of humans. i. Earlier researchers had determined that removing the pancreas caused diabetes. ii. Banting and Best (1921) tied-off the pancreatic ducts of dogs, causing the exocrine portion to degenerate (Figure 34.16). f. Amylin is a hormone that appears to enhance the effect of insulin in the body. 3) Gamma cells produce pancreatic polypeptide (PP).. a. Pancreatic hormone (PP) is released after a meal and reduces appetite; it will probably become a focus in the fight against obesity. 4) Delta cells produce somatostatin. a. Somatostatin inhibits secretion of other pancreatic hormones. b. Somatostatin reduces the rate of gastric emptying. c. Somatostatic inhibits pancreatic exocrine secretion. 6. Growth Hormone and Metabolism a. Growth Hormone (GH) 1) GH is very important in young animals during growth and development. 2) It acts directly to increase bone length and density by cell division and protein synthesis. 3) GH releases fat from adipose tissue stores and glycogen from liver to support metabolism. 4) GH is diabetogenic; oversecretion leads to increased blood glucose, insulin insensitivity or diabetes. 5) If produced in excess, GH causes giantism; a deficiency in childhood leads to dwarfism. 6) GH also acts indirectly via stimulation of insulin-like growth factor (IGF) from the liver. 7. White Adipose Tissue as an Endocrine Organ a. In 1994, the ob gene was found to code for a hormone leptin produced in white fat cells. b. Many adipokines with autocrine, paracrine and endocrine functions have been described. c. Leptin regulates eating behavior and energy balance in the feedback system that informs the brain, particularly the hypothalamus and brain stem, of energy status in the body. d. Blood plasma levels of leptin are similar to insulin, another feedback signal. e. Adiponectin tends to lower blood glucose levels by increasing the effects of insulin on liver and skeletal muscle. f. Tumor necrosis factor-α (TNF- α) are secreted by adipose tissue and high levels are associated with obesity-related insulin insensitivity. Lecture Enrichment 1. The effect of estrogen and testosterone can be related to the broad shoulders, head and other features of a bull compared to the more-marbled meat and female-like development of a steer that develops without normal testosterone levels. 2. We tend to think of adaptations as being external morphological characteristics, but the biochemistry that shifts cells to more heat production is a biochemical adaptation vital to survival, just as the special digestive enzymes that allow an animal to eat a plant toxic to most others. 3. The history of Bayliss and Starling’s work as well as the classic experiments of Banting and Best are fundamental examples of research procedure and application. They provide students with background and insight on how pioneer experiments are performed, and also provide a foundation of understanding on the critical role animal research has played in solving both pure and medical research problems. Endocrinology is nearly 100% based on lab animal research and an instructor can provide additional examples, in both readings and lecture, from the history of physiology. Students who do not have an understanding of this extensive laboratory basis for endocrinology will be susceptible to claims being made that such work was not central or even necessary to this science. Commentary/Lesson Plan Background: Nearly all students’ experiences with hormones will center on the sex hormones, testosterone and estrogens. For rural students, the effects of these hormones are quite dramatically seen in the different structuring of bulls, cows, steers, etc. Women will be familiar with the action of estrogen creams for reducing hair growth and keeping the skin smooth. Misconceptions: Hormones and the endocrine system are closely associated with puberty and sex due to society’s allusion to hormones and adolescent development, etc.; it is therefore necessary to paint the full picture where sex hormones are a relatively minor although interesting small sample. The only other examples given in general biology textbooks are usually under- or over-secretion problems which likewise presents a “freakish” perspective; an instructor will have to work hard to normalize the vital role of endocrines. Because we speak of “estrogen” as if it was just one molecule, students may not recognize there are three common natural estrogen molecules in humans and a growing number of eco-estrogens in the environment. Due to dietary advertisements, “cholesterol” is often seen by the public as something that is always bad and something we can live without; this error can be addressed under coverage of steroid hormones. Schedule: HOUR 1 34.1. Hormones and Mechanisms of Hormone Action A. Overview B. Membrane-Bound Receptors and the Second Messenger Concept C. Nuclear Receptors D. Control of Secretion Rates of Hormones 34.2. Invertebrate Hormones A. Overview B. Neurosecretory Cells and Molting HOUR 2 34.3. Vertebrate Endocrine Glands and Hormones A. Hormones of the Hypothalamus and Pituitary Gland B. Pineal Gland C. Brain Neuropeptides D. Prostaglandins and Cytokines E. Hormones of Metabolism ADVANCED CLASS QUESTIONS: 1. An effect of thyroid hormones is the reduced efficiency of cellular phosphorylation. Why would evolution ever select for a less efficient metabolism? Answer: It's important to note that thyroid hormones typically have the opposite effect of increasing cellular metabolism and energy expenditure, rather than reducing efficiency. However, if we were to consider a hypothetical scenario where thyroid hormones lead to reduced efficiency of cellular phosphorylation, it might not seem immediately advantageous from an evolutionary perspective. Nonetheless, there could be certain contexts where such a trait could confer benefits, although these would likely be rare and highly specific. 1. Energy Conservation During Stress: In environments where resources are limited or where organisms face periods of scarcity or stress, reducing cellular phosphorylation efficiency could serve as a means of conserving energy. By dampening metabolic rates, organisms may be able to survive longer periods without food or during adverse environmental conditions. This strategy could enhance survival during times of famine or environmental stress, allowing individuals to better endure until conditions improve. 2. Life History Trade-Offs: Evolution often involves trade-offs between different traits, where improvements in one area come at the expense of others. In some cases, reducing metabolic efficiency may be a trade-off for other beneficial adaptations. For example, if diverting resources towards growth, reproduction, or other fitness-enhancing traits requires a reduction in metabolic efficiency, natural selection may favor this trade-off if the overall benefits outweigh the costs. 3. Environmental Fluctuations: In environments characterized by unpredictable fluctuations in resource availability or environmental conditions, phenotypic plasticity may confer advantages. Organisms with the ability to adjust their metabolic rates in response to changing environmental cues may be better equipped to survive and reproduce under variable conditions. Reduced metabolic efficiency could be one component of this adaptive plasticity, allowing organisms to modulate energy expenditure based on prevailing environmental conditions. 4. Maintenance of Homeostasis: In some cases, a temporary reduction in metabolic efficiency may serve as a mechanism for maintaining homeostasis or preventing cellular damage. For example, during periods of oxidative stress or exposure to toxins, slowing down metabolic processes could reduce the generation of reactive oxygen species and minimize cellular damage. In this context, a temporary decrease in metabolic efficiency could be a protective mechanism to preserve cellular integrity and ensure survival under adverse conditions. Overall, while it may seem counterintuitive for evolution to select for a less efficient metabolism, there could be specific circumstances where this trait provides adaptive advantages, such as energy conservation during stress, trade-offs with other fitness-enhancing traits, adaptation to fluctuating environments, or maintenance of cellular homeostasis. However, it's essential to recognize that such scenarios would likely be context-dependent and subject to complex interactions with other evolutionary pressures and environmental factors. 2. You notice your urine is milky colored. You add a drop of weak vinegar and it immediately clarifies. What is in your urine that makes it milky? What hormone imbalance(s) could cause this? Answer: The milky appearance of urine, which clears upon the addition of weak vinegar, suggests the presence of a substance that is soluble in acidic conditions but becomes insoluble and precipitates out in alkaline conditions. One possible explanation for this phenomenon is the presence of phosphates in the urine, which can form insoluble precipitates under alkaline conditions but dissolve in acidic conditions. Phosphate crystals in the urine can result from various factors, including dietary intake, metabolic disorders, or hormonal imbalances. Hormone imbalances that could contribute to the formation of phosphate crystals in the urine include: 1. Parathyroid Hormone (PTH) Imbalance: Parathyroid hormone, produced by the parathyroid glands, plays a crucial role in regulating calcium and phosphate levels in the blood and tissues. Abnormalities in PTH secretion or function, such as hyperparathyroidism (excessive PTH production) or hypoparathyroidism (insufficient PTH production), can disrupt calcium and phosphate balance, leading to the formation of phosphate crystals in the urine. 2. Vitamin D Imbalance: Vitamin D plays a role in calcium and phosphate homeostasis by promoting the absorption of these minerals from the intestines. Imbalances in vitamin D levels, such as vitamin D deficiency or excess, can affect calcium and phosphate metabolism, potentially leading to the excretion of phosphate crystals in the urine. 3. Thyroid Hormone Imbalance: Thyroid hormones, including thyroxine (T4) and triiodothyronine (T3), influence various metabolic processes in the body, including bone metabolism and mineral balance. Thyroid disorders, such as hyperthyroidism (excessive thyroid hormone production) or hypothyroidism (insufficient thyroid hormone production), can disrupt calcium and phosphate homeostasis, contributing to the formation of phosphate crystals in the urine. 4. Insulin Imbalance: Insulin, a hormone produced by the pancreas, regulates glucose metabolism and has indirect effects on calcium and phosphate metabolism. Insulin resistance or deficiency, as seen in conditions like diabetes mellitus, can affect various metabolic pathways, potentially leading to disturbances in calcium and phosphate balance and the formation of phosphate crystals in the urine. It's essential to consult a healthcare professional for proper evaluation and diagnosis if you notice unusual changes in urine appearance or suspect hormonal imbalances. Testing may include urine analysis, blood tests, and assessment of hormonal levels to identify the underlying cause and appropriate management. CHAPTER 35 IMMUNITY CHAPTER OUTLINE 35.1. Susceptibility and Resistance A. Immunity 1. The immune system is dispersed throughout an animal’s body, and is crucial to survival. 2. Immunity is important to all animals that must defend against invading foreign agents, and to parasitic animals that must overcome the defenses of their host. 3. Hosts are susceptible to parasites if they cannot eliminate them before they become established. 4. A host is resistant if its physiological status prevents establishment and survival of a parasite. 5. Susceptible and resistant states in the host are infective and noninfective states in the parasite. 6. Organisms may be more or less resistant than other to various parasites. 7. An animal demonstrates immunity if it possesses tissues capable of recognizing and protecting the animal against nonself invaders. 8. Innate immunity is a mechanism of defense that does not depend on prior exposure. 9. Acquired immunity is specific to a particular nonself material and requires time to develop. 10. In premunition, resistance is not complete and a host may recover but harbor some parasites. 35.2. Innate Defense Mechanisms A. Physical Barriers and Chemical Defenses- Animal surfaces are first barrier to invading organisms. 1. Soft outer surfaces are protected by mucus layer that lubricates the surface and dislodges particles. 2. Many cellular secretions contain a variety of antimicrobial substances; for example, normal human milk can kill some intestinal protozoa; antimicrobial elements in milk include lysozyme, defensins, IgA, interferons and leukocytes (Table 35.1). a.. The low pH of stomach and vagina, and hydrolytic enzymes of alimentary tract are protective. b. Mucus on membranes lining the digestive and respiratory tract contains parasiticidal substances. c. IgA is a class of antibodies that can cross cellular barriers easily. 1) It is found in mucus of intestinal epithelium, but also present in saliva and sweat. 2) It is secreted onto the surface of cells lining the alimentary canal; it is part of the animal’s acquired immune response. c. Lysozyme is an enzyme found in tears and it attacks the cell wall of many bacteria. d. Interferons are a family of low-molecular weight glycoproteins released in response to invasion by viruses and other stimuli. e. Tumor necrosis factor (TNF) is produced by macrophages, is a major mediator of inflammation, and in high concentration causes fever. 3. Fever is a common symptom of infection in animals and may help destabilize viruses and bacteria. 4. Most animals harbor harmless bacteria in their intestines; this may inhibit pathogenic microbes. 5. Resistance of mammals to the Schistosoma mansoni parasite is related to their macrophages. 6. Complement a. Complement is a series of enzymes activated in sequence as a host response to an invader. b. Activation of complement by the classical pathway depends on fixed antibodies. c. Complement activated by alternative pathway defends against invasion by bacteria and fungi. d. The first component is activated in the blood and binds to cell surfaces, initiating a cascade of activations resulting in cell lysis. e. Host cells are not lysed since regulatory proteins inactivate the first active component. f. The process of tagging pathogens for phagocytosis is called opsonization. g. Complement-like proteins called Teps (thioester-containing proteins) have been discovered in insects and appear to function similar to the alternate pathway of the complement system. 7. Antimicrobial Peptides a. Insects tend to be resistant to infection with many microbial pathogens. b. Hundreds of antimicrobial peptides have been described among many animals. c. They are not as specific as the acquired immune response of vertebrates. d. Release of the peptide is immediate in the presence of the foreign organism. e. Antimicrobial peptides in mammals are called defensins. Defensins may be chemotaxic to neutrophils, enhance the inflammatory responses or acquired immune responses. f. Peptide release begins when receptors on the cell’s surface recognize a microbial molecule. g. Many of these receptors are known as Toll proteins or Toll-like receptors (TLRs). h. At least nine TLRs have been detected in humans. B. Cellular Defenses: Phagocytosis (Table 35.2) 1. Phagocytes and Other Defense Cells a. Cells in an animal must recognize substances that do not belong; they must recognize nonself. b. Phagocytosis is used for recognition of nonself materials and as a means for removing aging cells and cellular debris in eukaryotes. c. Phagocytosis occurs additionally as a feeding mechanism in nearly all metazoa. d. Phagocytes engulf particles and combine the vacuoles with lysosomes of digestive enzymes. e. Lysosomes also contain enzymes that catalyze production of cytotoxic reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates (RNIs). 1) ROIs include the superoxide radical (O2 –), hydrogen peroxide (H2O2), singlet oxygen (1O2) and hydroxyl radical (OH–). 2) RNIs include nitric oxide (NO) and its oxidized forms, nitrite (NO2–) and nitrate (NO3–). 3) These intermediates are toxic to invasive microorganisms and parasites. f. Many invertebrates have specialized cells that engulf or wall off foreign material. g. Small particles are engulfed; large particles are encapsulated or walled off with melanin. h. Various phagocytes have been identified in various parts of the body (Table 35.2) 1) Macrophages are derived from monocytes, and phagocytize various foreign bodies via different mechanisms, and are found throughout the body. 2) Kupffer cells are found specifically in the sinusoids of the liver. 3) Microglial cells are found within the nervous system. 4) Langerhans cells (or dendritic cells) are found within the skin. 5) Neutrophils are a type of polymorphonuclear leukocyte (PMN, also known as a granulocyte) that also circulate throughout the body. 2. Other Innate Immune Defense Cells (Figures 35.1) 1) Mast cells in connective tissue and the dermis participate in inflammatory responses. 2) Natural Killer (NK) cells kill virus-infected cells and tumors by lysing them. C. Inflammation (Table 35.3) a. When tissues are damaged, they often chemical, like histamines, to both dilate blood capillaries and make them more permeable to leukocytes and macrophages. b. Blood plasma leads into the area, inducing swelling, and thereby isolating the area from foreign invaders. c. When macrophages destroy agents, they present remnants as antigens to T lymphcytes, thereby inducing an acquired immune response (see Acquired Immune Response in Vertebrates below). 35.3 Immunity in Invertebrates A. Grafts, Hemocytes and Genetic Factors 1. The principal test of invertebrate tissues to recognize nonself is use of grafted tissues from another individual of the same species (allograft) or another species (xenograft). 2. Most invertebrates reject xenografts and some allografts. (Table 35.1) 3. The simplest of Porifera and Cnidaria reject allografts and demonstrate individual identity. 4. Copepods and cockroaches reject tissues more quickly on second transplant, demonstrating short-term immunological memory. 5. Hemocytes function in phagocytosis and encapsulation. 6. Substances functioning as opsonins are known from annelids, insects, crustaceans and molluscs. 7. Bacterial infection in insects may stimulate production of general microbial proteins. 8. Susceptibility of snail hosts to trematode species depends on the genotype of the snail, and some hemocytes can confer resistance. 9. Memory and specificity of response have now been found in invertebrates. 35.4. Acquired Immune Response in Vertebrates (Table 35.2) A. Antigens and Antibodies 1. Nonself recognition produces resistance to specific foreign substances and repeat invaders. 2. A specific foreign substance called an antigen stimulates the immune response. 3. Antigens are various substances with molecular weights of over 3000 and are usually proteins. 4. Acquired immune response has two arenas, humoral and cellular. 5. Humoral immunity uses antibodies found on cell surfaces and dissolved in blood and lymph. 6. Cellular immunity is entirely associated with cell surfaces. B. Basis of Self and Nonself Recognition 1. Major Histocompatibility Complex a. Nonself recognition is very specific. b. Tissue transplanted from another individual soon dies as immunity is formed against it; additionally, unless the immune system is suppressed, tissue grafts are only successful when between nearly genetically identical animals. c. In vertebrates, this recognition is based upon a unique set of surface proteins found on the cell membrane. These proteins are coded by highly variable genes that are called the major histocompatibility complex (MHC). d. Class I MHC proteins occur on the surface of nearly all cells. e. Class II MHC proteins are only on certain cells participating in the immune responses. 2. Recognition Molecules a. MHC proteins are not themselves the molecules that recognize foreign substances. b. Antibodies and T-cell receptors are molecules that accomplish recognition. c. Each vertebrate individual has a huge variety of antibodies and T-cell receptors, each of which binds to one antigen. d. Antibodies (Figure 35.2) 1) Antibodies are proteins called immunoglobulins. 2) Antibodies are on the surface of B lymphocytes or secreted by plasma cells derived from B cells. 3) A basic antibody has two identical light chains and two identical heavy chains forming a Y-shape. 4) The amino acid sequence near the ends of the Y varies in both chains according to the antibody. 5) Each of the ends of the Y forms a cleft that is the antigen binding site. 6) The specificity of the molecule depends on this variable region, called Fab, for antigen-binding fragment. 7) The remainder of the antibody is the constant region, or Fc for crystallizable fragment. 8) In the “constant” region, light chains can be of two types and the heavy chains may be five types. 9) This forms classes of antibodies: IgM, IgG (gamma globulin), IgA, IgD and IgE. e. Functions of Antibody in Host Defense 1) A foreign antigen may become coated with antibody molecules as their Fab regions are bound to it. 2) Macrophages recognize projecting Fc regions and are stimulated to phagocytose the antigen-antibody complex. 3) Antibodies also may neutralize toxins secreted by an invader. 4) Binding of complement to antigen-antibody complexes facilitates clearance of harmful masses by phagocytic cells. 5) Antibody bound to the surface of an invading cell may trigger contact killing of the invader by host cells in antibody-dependent, cell-mediated cytotoxicity (ADCC). 6) T-cell Receptors a. T-cell receptors are transmembrane proteins on surfaces of T cells. b. T-cell receptors have a constant region and a variable region. c. The constant region extends to the cytoplasm and the variable region extends out to bind with specific antigens. d. T cells also bear other transmembrane proteins to serve as accessory or co-receptor molecules; these include CD4 and CD8. 7) Subsets of T Cells (Figure 35.4) a. Lymphocytes are activated when stimulated to move from the recognition phase to a phase where they proliferate and differentiate into cells that eliminate antigens. b. Subsets of T cells can be distinguished by characteristic proteins on their surface membranes. c. Variations in co-receptor proteins include CD4, CD4+, CD8 and CD8+. d. Some TH1 cells activate cell-mediated immunity and suppress humoral response. e. Other TH2 cells activate humoral response and suppress cell-mediated immunity. f. Cytotoxic T lymphocytes (CTLs) are CD8+ cells that kill target cells with certain antigens. g. A CTL binds to a target cell and secretes a protein causing pores to form in cell membranes. h. T-suppressor cells eventually suppress an immune response by inhibiting other T and B cell activity. i. T-memory cells provide antigen memory during future immune responses. 5. Cytokines (Table 35.3) a. Cells of immunity communicate with each other by cytokines. (Table 35.3) b. Cytokines produce effects on the cells that produce them, on nearby cells and on distant cells. c. Recently, several cytokines have been shown to possess antimicrobial activity. 6. Generation of a Humoral Response: TH2 Arm (Figures 35.4–35.6) a. When an antigen binds to a specific antibody on the surface of the appropriate B cell, it is usually not sufficient to activate the B cell to multiply. b. The B cell internalizes the antigen-antibody complex and then incorporate portions of antigen into their own cell surface bound in the MHC II protein. c. The portion of an antigen presented on the surface of the macrophage or other APC is the epitope. d. The specific T-cell receptor for the particular epitope recognizes the epitope bound to MHC II. e. Co-receptor CD4 helps bind the T-cell receptor to the epitope-MHC II complex. f. Activated TH2 cells secrete IL-4, IL-5 and IL-6 that activate the B cell that has the same epitope and class II MHC protein on its surface. g. If we measure the antibody titer soon after an antigen is injected, we detect none. h. Titer then rises rapidly as plasma cells secrete antibody. i. If we give another dose of antigen, there is no lag, and antibody titer rises quickly and higher. j. This secondary or anamnestic response occurs because activated B cells gave rise to long-lived memory cells. k. There are many more memory cells in the body than original B lymphocytes with antibody on its surface, and they rapidly multiply to produce additional plasma cells. l. Anamnestic response is the basis for protective vaccines. 7. Cell-Mediated Response: TH1 Arm a. Many immune responses involve little, if any, antibody and depend on cell action only. b. In cell-mediated immunity (CMI) the epitope of an antigen is presented by APCs, but the TH1 arm of the immune response is activated. c. In this case, APCs may be virally-infected cells, tumor cells or infected macrophages that have phagocytosed bacterial. d. TH1 cells recognize the epitope-MHCII complex and become activated to release IL-2, TNF and interferon- (INF-) e. IL-2 promotes the activity of activated B and T cells, and enhances the cytotoxic activity of natural killer cells. f. Natural killer cells proliferate and become lymphocyte-activated killer (LAK) cells. g. INF- is a major inducer of the non-specific response called inflammation. h. CMI shows a secondary response due to large numbers of memory T cells. 8. Acquired Immune Deficiency Syndrome (AIDS) a. Ability to mount an immune defense is disabled by infection with human immunodeficiency virus (HIV). b. The first case of AIDS was recognized in 1981, and the number of infected people continues to rise. c. In 2009, about 33 million people live with HIV, and 2.7 million were newly infected in 2007. d. Since TH cell populations are virtually destroyed by HIV, AIDS patients are plagued by microbes and parasites. e. HIV preferentially invades and destroys TH lymphocytes. f. Normally, these cells make up 60–80% of the T-cell population. g. The humoral immune response is destroyed and the cell-mediated response is compromised. h. If left untreated, AIDS is a terminal disease. i. There are effective, but costly, drugs that can slow the progression of the disease. 35.5. Blood Group Antigens A. ABO Blood Types 1. Different antigens naturally occur on the membranes of red blood cells. 2. The ABO blood group is best known. 3. Antigens A and B are inherited as codominant alleles of a single gene. 4. Type O blood is homozygous recessive and lacks A and B antigens. (Table 35.4) 5. Epitopes of A and B are present on the surfaces of many epithelial and endothelial cells. 6. Individuals with type B develop anti-A antibodies soon after birth, and the same is true in reverse. 7. Type AB has neither anti-A nor anti-B antibodies; type O has both anti-A and anti-A antibodies. 8. The antibodies may develop a response to A and B epitopes on intestinal microorganisms. 9. The ABO types are important in blood transfusions. B. Rh Factor 1. Karl Landsteiner discovered ABO blood types in 1900 and Rh blood type in 1940. 2. The “Rh” comes from rhesus monkeys, where the factor was first discovered. 3. About 85% of people have Rh factor and about 15% do not. 4. Rh factor is coded by a dominant allele at a single gene. 5. Rh positive blood presents antigen to an Rh negative person and can cause shock and death. 6. An Rh-negative mother who has an Rh-positive baby is immunized by the fetal blood during the first birth. 7. In subsequent pregnancies, anti-Rh antibodies on small IgG can cross the placenta and agglutinate the fetal blood of another Rh-positive baby. 8. ABO incompatibility is not as severe a problem because the antibodies of AB antigens are primarily larger IgM that do not cross the placenta. Lecture Enrichment 1. Immunology is a highly experimental science and careful elaboration of the methodology is necessary for students to understand the many complex concepts. 2. Immunology is a rapidly developing field and decade-old textbooks may contain incorrect information. This may also mean that students’ understanding of some concepts taught in high school may have to be updated or corrected. 3. Blood typing remains considerably high-interest to students who are interested in their blood type. While the genetics of blood type is clear cut and strictly Mendelian, there are very remote possibilities that a student’s parent could be a chimera and their blood type might not represent what would be indicated by a family blood type pedigree. 4. Additional examples of the use of animals in the early research into the immune system, and useful as readings or lecture examples, can be found in Robert Desowitz’s book The Thorn in the Starfish published by W. W. Norton, Inc. 5. Tracing the development of snake antivenin [from extraction of snake venom to inoculation of a horse, to build up of antibodies, to extraction of plasma and production of freeze-dried antivenin] can illustrate the function of the immune systems of both horse and human. This provides the discussing the basis for effectiveness of antivenins made specific to one snake species versus broad-spectrum, but less-effective antivenins. Commentary/Lesson Plan Background: Generally the instructors of this course will come from a generation that values the protection of vaccines against serious infectious diseases and has a perspective for the necessity of needle vaccinations, etc. The younger generation has grown up with most needlestick experiences at a young pre-memory age, and with little direct contact or appreciation of serious infectious diseases. International students may be able to relate a different perspective. All students experience brief mild infections that they overcome within a few days. More-and-more, they are aware of the continuous race with the highly variable influenza strains where each fall, the public health agencies attempt to build our active immunity against the three major strains arising the previous season. However, only graduate students are likely to possess a smallpox scar that was part of our heroic effort that drove this virus from existence in the wild. Recent research on AIDS has expanded students’ exposure to immunology in the press; terms such as “T cell” and “CD4” should be familiar although not necessarily understood. Misconceptions: The fact that there is a discrete and limited connection between mental and immunological states has led to exaggeration and hype in quasi-health journals and popular books asserting that immunity and defense against both infectious disease and other ailments is just a matter of having a good mental state. If class discussion extends to influenza, it will be important to distinguish influenza as strictly the respiratory infection [the “stomach flu” is a different enteric virus and not influenza]. Schedule: HOUR 1 35.1. Susceptibility and Resistance A. Immunity 35.2. Innate Defense Mechanisms A. Physical and Chemical Barriers B. Antimicrobial Peptides C. Cellular Defenses: Phagocytosis D. Phagocytes and Other Defense Cells HOUR 2 35.3. Immunity in Invertebrates A. Grafts, Hemocytes and Genetic Factors 35.4 Acquired Immune Response in Vertebrates A. Antigens and Antibodies B. Basis of Self and Nonself Recognition 35.5. Blood Group Antigens A. ABO Blood Types B. Rh Factor ADVANCED CLASS QUESTIONS: 1. Why does a human not suffer infections by corn rust fungi? What is the relationship between evolutionary phylogeny among host organisms and susceptibility to infection? Answer: Humans do not suffer infections by corn rust fungi because they lack the necessary biological compatibility for the fungi to infect human tissues. The relationship between evolutionary phylogeny among host organisms and susceptibility to infection is based on the co-evolutionary history between pathogens and their hosts, as well as the specific molecular interactions that determine host-pathogen compatibility. 1. Host Specificity: Pathogens, including fungi like corn rust fungi (Puccinia spp.), have evolved to infect specific host species or closely related taxa. This specificity is determined by the molecular interactions between pathogen surface molecules (e.g., fungal spore receptors) and host cell surface receptors. Humans lack the appropriate receptors and cellular machinery necessary for corn rust fungi to recognize and infect human cells. 2. Evolutionary Phylogeny: Evolutionary phylogeny plays a crucial role in determining host susceptibility to infection. Host organisms that are evolutionarily closely related to the natural hosts of a pathogen are more likely to share genetic and molecular similarities that facilitate infection. In the case of corn rust fungi, their natural hosts are plants in the genus Zea (corn), and they have co-evolved with these plant species over millions of years. Humans, being distant relatives in the evolutionary tree, do not share the necessary genetic and biochemical features for fungal infection. 3. Host-Pathogen Arms Race: The co-evolutionary arms race between hosts and pathogens drives the diversification of host defense mechanisms and pathogen virulence factors. Host organisms develop various defense strategies, such as physical barriers, immune responses, and biochemical defenses, to resist pathogen invasion. Conversely, pathogens evolve mechanisms to overcome host defenses and exploit host resources for their survival and proliferation. This co-evolutionary dynamic results in the specificity of host-pathogen interactions and determines the range of susceptible host species for a given pathogen. In summary, the lack of susceptibility of humans to corn rust fungi infection is primarily due to the absence of molecular compatibility between human cells and fungal spores, as well as the evolutionary divergence between humans and the natural hosts of the fungi. Evolutionary phylogeny influences host susceptibility to infection by shaping the genetic and biochemical characteristics that determine host-pathogen interactions. 2. Why would a short-lived insect have a simpler immune system and utilize a walling-off of bacteria (granuloma) rather than evolve an elaborate system as detailed as in mammals? Answer: Short-lived insects often have simpler immune systems and employ strategies such as walling-off bacteria (granuloma formation) rather than evolving elaborate immune systems like mammals for several reasons: 1. Life History Traits: Short-lived insects typically have rapid life cycles and may undergo multiple generations in a short period. As a result, there may be limited evolutionary pressure to invest in complex immune systems with long-term memory and elaborate defense mechanisms. Instead, these insects prioritize rapid development, reproduction, and survival in the face of immediate threats such as pathogens. 2. Resource Allocation: Evolutionary trade-offs dictate how organisms allocate limited resources (e.g., energy, nutrients) among competing physiological processes, including immunity. Short-lived insects may allocate resources predominantly towards growth, development, and reproduction, rather than investing extensively in immune defenses. Simplified immune systems allow for efficient resource allocation and maximize fitness under the prevailing ecological conditions. 3. Pathogen Exposure: Short-lived insects often inhabit dynamic environments with high pathogen diversity and variability. Rather than evolving species-specific immune recognition systems and elaborate immune responses like mammals, these insects may rely on broad-spectrum defense mechanisms, such as physical barriers (e.g., exoskeleton) and innate immune responses (e.g., antimicrobial peptides), to combat a wide range of pathogens encountered in their environment. 4. Selective Pressure: Short-lived insects may face strong selective pressure to evolve rapid and effective immune responses that can mitigate immediate threats posed by pathogens. Strategies such as granuloma formation allow insects to encapsulate and immobilize pathogens, preventing their spread and minimizing tissue damage. While this response may be simpler than the adaptive immune responses seen in mammals, it can provide effective short-term protection against infections. 5. Evolutionary History: The evolutionary history of insects has shaped the diversity of immune strategies observed across different taxa. Insects have evolved diverse immune mechanisms adapted to their specific ecological niches and life history traits. Short-lived insects have likely undergone selective pressures that favor rapid immune responses and effective pathogen clearance, leading to the emergence of simpler but efficient immune strategies like granuloma formation. In summary, the simpler immune systems and reliance on strategies like granuloma formation in short-lived insects reflect adaptations to their life history traits, resource limitations, pathogen exposure, selective pressures, and evolutionary history. These immune strategies allow insects to efficiently combat pathogens and maximize fitness within the constraints of their ecological niche and life cycle. 3. An Rh conflict is posed when the mother is Rh negative and the father is Rh positive. Why is there not also a problem when the reverse combination occurs? Answer: The Rh conflict, also known as Rh incompatibility or Rh disease, occurs when an Rh-negative mother is pregnant with an Rh-positive fetus. This situation can lead to complications in subsequent pregnancies if the mother's immune system produces antibodies against the Rh antigen present on the fetal red blood cells. However, when the reverse combination occurs (Rh-positive mother and Rh-negative father), Rh disease typically does not pose a problem for the following reasons: 1. Sensitization Process: The risk of Rh disease arises when fetal Rh-positive red blood cells enter the maternal bloodstream during childbirth or other events where there is potential mixing of fetal and maternal blood. In an Rh-negative mother carrying an Rh-negative fetus (regardless of the father's Rh status), there is no exposure to Rh-positive fetal red blood cells, and thus, there is no opportunity for maternal sensitization to occur. As a result, subsequent pregnancies are not at risk for Rh disease. 2. Immune Response: Rh disease occurs due to an immune response mounted by the mother against the Rh antigen on the fetal red blood cells, leading to the production of anti-Rh antibodies (IgG). In an Rh-negative mother carrying an Rh-positive fetus, fetal Rh-positive red blood cells may trigger the mother's immune system to produce anti-Rh antibodies, which can cross the placenta and attack fetal red blood cells in subsequent pregnancies. However, in an Rh-positive mother carrying an Rh-negative fetus, there is no antigenic mismatch between the mother and the fetus, and therefore, no immune response against fetal red blood cells occurs. 3. Antibody Formation: The formation of anti-Rh antibodies in an Rh-negative mother requires exposure to Rh-positive red blood cells, which occurs during pregnancy, childbirth, or other events where there is mixing of fetal and maternal blood. In the absence of such exposure, there is no stimulus for the mother's immune system to produce anti-Rh antibodies, and therefore, Rh disease does not develop in subsequent pregnancies with an Rh-negative fetus, regardless of the father's Rh status. In summary, Rh disease occurs when an Rh-negative mother is sensitized to the Rh antigen present on fetal Rh-positive red blood cells, leading to the production of anti-Rh antibodies that can harm subsequent Rh-positive fetuses. However, when the reverse combination occurs (Rh-positive mother and Rh-negative father), there is no antigenic mismatch between the mother and the fetus, and therefore, Rh disease does not pose a problem for subsequent pregnancies. Instructor Manual for Integrated Principles of Zoology Cleveland Hickman, Jr., Susan Keen, Allan Larson, David Eisenhour, Helen I'Anson, Larry Roberts 9780073524214
