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Nature sors order 200 mg acivir pills visa, generated in efficient bioreactors from the patient’s 2000;408:897–898 discount acivir pills 200mg with mastercard. Mayo eled by specific cytokines that direct the stem cells to Clin Health Lett 2000;18:1–3 cheap 200mg acivir pills fast delivery. Stem cell therapy and gene cells used to initiate the culture would be obtained from transfer for regeneration generic acivir pills 200 mg without prescription. Patients would receive an infusion whenever destroy migratory brain tumor cells while also providing a their T cell counts plummeted, protecting them against in- means of repairing tumor-associated damage? In addition to AIDS, hematotherapy holds promise for Spangrude GJ, Cooper DD. Paradigm shifts in stem-cell bi- several other diseases and conditions as well. They can exert potent antimicrobial matory response without compromising its antimicrobial effects, as well as release a variety of agents that can further efficiency. They do this by neutralizing inflammatory me- amplify and perpetuate the response. A variety of antiinflammatory agents control some of these undesirable effects. These agents are As discussed above, the innate and adaptive immune sys- designed to block some of the consequences of the inflam- tems work together in ways that obscure their differences. CHAPTER 11 Blood Components, Immunity, and Hemostasis 203 Tissue injury While characteristics of the innate and adaptive im- mune system differ, each system depends on elements of the other for optimal functioning. The initiation of re- Microbial invasion sponses by the innate system, as well as efficient phago- cytosis by neutrophils in the tissues, often depends on the presence of a small amount of specific antibody in Antibody binds to blood plasma. Antibody is generated by cells of the adap- microorganisms tive immune system in response to specific foreign mole- cules called antigens. In turn, the effective functioning of antibodies and other mediators of the adaptive immune Generation of bioactive peptides system depends on neutrophils and other effector agents usually associated with the innate immune system. Thus, the innate and the adaptive systems depend on highly Neutrophil adherence, evolved, interactive, defensive mechanisms to kill and re- and chemotaxis to move microbial intruders. This shows a possible route of inflammation initi- vating agent or antigen ated by tissue injury. The specificity of the recognition, effector, and mem- ory aspects of the adaptive immune system derives from the specificity of antibody molecules as well as that of Indeed, consideration of these two systems as distinct, in- receptors on T cells and B cells. The lymphocytes of the dividual entities is neither justified nor correct, owing to immune system are capable of recognizing and specifi- their extensive interdependence. They are described indi- cally responding to hundreds of thousands of potential vidually only as an aid to their presentation. In this respect, antigens, which may be presented, for example, as gly- it is important to define the characteristics that differenti- coproteins on the surface of bacteria, the coat protein of ate each system (Table 11. In general, responses of the viruses, microbial toxins, or membranes of infected cells. This initial recognition against a specific pathogen and is not amplified as a result induces proliferation of the responsive cell, a process of previous encounters with the pathogen. Clonal selection sponse, in contrast, is both specific and inducible; the re- amplifies the number of specific T cells or B cells (i. While all of the cells generated after a single clone has expanded are specific for the inducing antigen, they may Characteristics of the Innate and Adap- not all possess the same functional characteristics. For exam- ple, when B cells are activated, their progeny plasma cells Innate Adaptive are capable of generating antibodies. Other progeny in the Resistance Not improved by Improved by previous expanded clone may play an afferent recognition role and, repeat infection infection thereby, function as memory cells. The increased number Specificity Not directed toward Targeted response of these cells, which mimic the reactive specificity of the specific pathogen directed by specific original lymphocytes that responded to the antigen, accel- elements of immune erate responsiveness when the antigen is encountered system again. Memory cells thus account for one of the primary Soluble factors Lysozyme, complement, Antibodies tenets of immunity: Resistance is increased after initial ex- acute phase proteins, posure to the infectious agent. Long-term immunity to interferon, cytokines many viruses—such as influenza, measles, smallpox, and Cells Phagocytic leukocytes, T cells, B cells polio—can be induced by vaccination with a killed or mu- NK Cells tant form of the pathogen.

Progestins acivir pills 200mg visa, such as progesterone acivir pills 200 mg with mastercard, are involved in maintenance of preg- Steroid Hormones Are Derived From Cholesterol nancy and are produced by the ovaries and placenta buy generic acivir pills 200 mg. Steroids are lipid-soluble order 200mg acivir pills, hydrophobic molecules synthe- The calciferols, such as 1,25-dihydroxycholecalciferol, sized from cholesterol. They can be classified into six cate- are involved in the regulation of calcium homeostasis. An ex- dihydroxycholecalciferol is the hormonally active form of ample of each category is shown in Figure 31. Gluco- Polypeptide and Protein Hormones Are corticoids generally produce effects that are catabolic in Synthesized in Advance of Need and nature. Aldosterone, a primary example of a mineralocorti- Stored in Secretory Vesicles coid, is produced in cells of the outermost portion of the adrenal cortex. Aldosterone is primarily involved in regu- Steroid hormones are synthesized and secreted on demand, lating sodium and potassium balance by the kidneys and is but polypeptide hormones are typically stored prior to se- the principal mineralocorticoid in the body. Steroid hormone synthesis and secretion are dis- Cortisol (Aldehyde) (Hemiacetal) (a glucocorticoid) Aldosterone (a mineralocorticoid) Testosterone Estradiol (an androgen) (an estrogen) Progesterone (a progestin) 1,25 (OH)2 Cholecalciferol (a calciferol) FIGURE 31. Like other proteins In some disease states, large amounts of intact precursor destined for secretion, polypeptide hormones are synthe- molecules are found in the circulation. This situation may sized with a pre- or signal peptide at their amino terminal end be the result of endocrine cell hyperactivity or even un- that directs the growing peptide chain into the cisternae of controlled production of hormone precursor by nonen- the rough ER. Although precursors usually have rela- synthesized as part of an even larger precursor or prepro- tively low biological activity, if they are secreted in hormone. The prepeptide is cleaved off upon entry of the sufficiently high amounts, they may still produce biological preprohormone into the rough ER, to form the prohor- effects. As the prohormone is processed through the Golgi nized sign of neoplasia. In many cases, preprohormones may contain the se- gene may be expressed in different tissues, tissue-specific quences for several different biologically active molecules. In contrast, in other cells of the gastrointestinal (POMC) actually contains the sequences for several bio- (GI) tract in which proglucagon is also produced, the mole- logically active signal molecules. Propressophysin serves as cule is cleaved at three different positions such that gli- the precursor for the nonapeptide hormone arginine vaso- centin, glucagon-like peptide-1 (GLP-1), and glucagon-like pressin (AVP). The precursor for TRH contains five repeats peptide-2 (GLP-2) are produced (Fig. In general, two basic amino acid residues, either lys-arg Intracellular Movement of Secretory Vesicles and Exocy- or arg-arg, demarcate the point(s) at which the prohor- tosis. Upon insertion of the preprohormone into the cis- mone will be cleaved into its biologically active compo- ternae of the ER, the prepeptide or signal peptide is rapidly nents. Presumably, these two basic amino acids serve as cleaved from the amino terminal end of the molecule. The specific recognition sites for the trypsin-like endopepti- resulting prohormone is translocated to the Golgi appara- dases thought to be responsible for cleavage of the prohor- mones. Although somewhat rare, there are documented cases of inherited diseases in which a point mutation in- Proglucagon volving an amino acid residue at the cleavage site results in an inability to convert the prohormone into active hor- N-peptide Glucagon IP-1 GLP-1 IP-2 GLP-2 mone, resulting in a state of hormone deficiency. Partially Pancreatic Gastrointestinal alpha cells tract ACTH Glicentin γ-MSH α-MSH CLIP γ-LPH β-Endorphin Proopiomelanocortin N-peptide N-peptide Glucagon IP-1 (POMC) Glucagon GLP-1 AVP Neurophysin IP-2 Propressophysin IP-1 GLP-1 IP-2 GLP-2 GLP-2 FIGURE 31. In alpha cells of the pancreas (left), the major bioactive product formed from proglucagon is glucagon it- FIGURE 31. It is not currently known whether the other peptides are tive sizes of individual peptides are only ap- processed to produce biologically active molecules. MSH melanocyte-stimulating hormone; CLIP cells (right), proglucagon is cleaved to produce the four peptides corticotropin-like intermediate lobe peptide; LPH shown. Glicentin is the major glucagon-containing peptide in the lipotropin; AVP arginine vasopressin; TRH thyrotropin- intestine. IP-1, intervening peptide 1; IP-2, intervening peptide 2; releasing hormone. The product of the insulin gene is a peptide known beta cell insulin secretory capacity. As with other secretory peptides, the who are receiving exogenous insulin injections, the meas- prepeptide or signal peptide is cleaved off early in the urement of circulating insulin levels would not provide any biosynthetic process, yielding proinsulin.

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Many receptors—muscle spindles buy cheap acivir pills 200mg online, for exam- Seconds ple—show a combination of responses; on application of a stimulus buy acivir pills 200 mg mastercard, a rapidly adapting phasic response is followed by Adaptation purchase acivir pills 200mg. Both of these responses may be is often related to a decline in the generator po- graded by the intensity of the stimulus buy 200mg acivir pills with amex. A, The generator potential is maintained with- adapts, the sensory input to the CNS is reduced, and the out decline, and the action potential frequency remains constant. B, A slow decline in the generator potential is associated with slow adaptation. C, In a rapidly adapting receptor, the generator The phenomenon of adaptation is important in prevent- potential declines rapidly. When a change occurs, however, the phasic response will slow the rate of action potential production even though occur again, and the sensory input will become temporarily the generator potential may show no change. Rapidly adapting receptors are also im- dation refers to a gradual increase in threshold caused by portant in sensory systems that must sense the rate of prolonged nerve depolarization, resulting from the inacti- change of a stimulus, especially when its intensity can vary vation of sodium channels. Receptor adaptation can occur at several places in the transduction process. In some cases, the receptor’s sensitiv- The Perception of Sensory Information Involves ity is changed by the action of accessory structures, as in Encoding and Decoding the constriction of the pupil of the eye in the presence of bright light. This is an example of feedback-controlled After the acquisition of sensory stimuli, the process of per- adaptation; in the sensory cells of the eye, light-controlled ception involves the subsequent encoding and transmission of changes in the amounts of the visual pigments also can the sensory signal to the central nervous system. Further pro- change the basic sensitivity of the receptors and produce cessing or decoding yields biologically useful information. As mentioned above, adaptation of the genera- tor potential can produce adaptation of the overall sensory Encoding and Transmission of Sensory Information. Finally, the phenomenon of accommodation in Environmental stimuli that have been partially processed the impulse initiation region of the sensory nerve fiber can by a sensory receptor must be conveyed to the CNS in such 68 PART II NEUROPHYSIOLOGY a way that the complete range of the intensity of the stim- quence of locations along the nerve. The only information that can be conveyed by a single action potential is its presence or ab- Compression. Even when the receptor sensitivity is modi- potentials can convey large amounts of information, and fied by accessory structures and adaptation, the range of in- this is the system found in the sensory transmission process. At the This biological process can be explained by analogy to a left is a 100-fold range in the intensity of a stimulus. At the physical system such as that used for transmission of signals right is an intensity scale that results from events in the sen- in communications systems. An in- intensity; it increases less and less as the stimulus intensity put signal provided by some physical quantity (1) is con- increases. The frequency of the action potentials produced tinuously measured and converted into an electrical signal in the impulse initiation region is also not proportional to (2), analogous to the generator potential, whose amplitude the strength of the local excitatory currents; there is an up- is proportional to the input signal. This signal then controls per limit to the number of action potentials per second be- the frequency of a pulse generator (3), as in the impulse ini- cause of the refractory period of the nerve membrane. Like action poten- These factors are responsible for the process of compres- tials, these pulses are of a constant height and duration, and sion; changes in the intensity of a small stimulus cause a the amplitude information of the original input signal is greater change in action potential frequency than the same now contained in the intervals between the pulses. As sulting signals may be sent along a transmission line (anal- a result, the 100-fold variation in the stimulus is compressed ogous to a nerve pathway) to some distant point, where into a threefold range after the receptor has processed the they produce an electrical voltage (4) proportional to the stimulus. Some information is necessarily lost in this frequency of the arriving pulses. This voltage is a replica of process, but integrative processes in the CNS can restore the input voltage (2) and is not affected by changes in the the information or compensate for its absence. Physiologi- amplitude of the pulses as they travel along the transmis- cal evidence for compression is based on the observed non- sion line. Further processing can produce a graphic record linear (logarithmic or power function) relation between the (5) of the input data. In a biological system, these latter actual intensity of a stimulus and its perceived intensity. The en- coding processes in the receptors have already provided The Interpretation of Sensory Information. The interpre- the basis for this transfer by producing a series of action po- tation of encoded and transmitted information into a per- tentials related to the stimulus intensity. For instance, the in- is necessary for the transfer because of the nature of the terpretation of sensory input by the CNS depends on the conduction of action potentials. All information arriving els along a nerve fiber, it is sequentially recreated at a se- on the optic nerves is interpreted as light, even though the signal may have arisen as a result of pressure applied to the eyeball.

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These ganglia extend above and be- sympathetic innervation to the stomach cheap 200 mg acivir pills mastercard, liver discount acivir pills 200 mg on line, pancreas discount 200mg acivir pills fast delivery, low the thoracic and lumbar spinal levels 200mg acivir pills with amex, where pregan- gallbladder, small intestine, spleen, and kidneys. Pregan- glionic fibers emerge, to provide postganglionic sympa- glionic axons originate in the T5 to T12 spinal levels. The deficits of function occur ipsilateral to the le- • Brainstem lesions, such as produced by strokes, which sion and include: interrupt the tracts that descend to the sympathetic neu- • Partial constriction of the pupil as a result of loss of sym- rons in the spinal cord pathetic pupillodilator action • Upper thoracic nerve root lesions, such as those pro- • Drooping of the eyelid, termed ptosis, as a result of loss of duced by excessive traction on the arm or from infiltra- sympathetic activation of Müller’s muscle of the eyelid tion of the nerve roots by cancer spreading from the lung • Dryness of the face as a result of the lack of sympathetic • Cervical paravertebral ganglia lesions from accidental or activation of the facial sweat glands. Johann Horner, a 19th century Swiss ophthal- traveling in the carotid periarterial plexus. Note the named paravertebral and solid lines, postganglionic axons by dashed lines. CHAPTER 6 The Autonomic Nervous System 113 superior mesenteric ganglion innervates the small and large Preganglionic sympathetic axons Adrenal intestines. The inferior mesenteric ganglion innervates the lower colon and rectum, urinary bladder, and reproductive organs. Chromaffin Adrenal cell medulla The Sympathetic Division Can Produce Local Vesicles or Widespread Responses The sympathetic division exerts a continuous influence on the organs it innervates. This continuous level of control is called sympathetic tone, and it is accomplished by a per- Vein sistent, low rate of discharge of the sympathetic nerves. When the situation dictates, the rate of firing to a particular organ can be increased or decreased, such as an increased firing rate of the sympathetic neurons supplying the iris to produce pupillary dilation in dim light or a decreased firing rate and pupillary constriction during drowsiness. The number of postganglionic axons emerging from the Blood capillary paravertebral ganglia is greater than the number of pregan- glionic neurons that originate in the spinal cord. Preganglionic sympathetic axons ter- preganglionic neurons by 100:1 or more. When stimulated, the chromaffin cells release epinephrine into the circulation. Divergence enables the sympa- and fatty acids, and blood cells which participate in the thetic division to produce widespread responses of many clotting and immune responses. The Fight-or-Flight Response Is a Result The Adrenal Medulla Is a Mediator of Widespread Sympathetic Activation of Sympathetic Function This response is the classic example of the sympathetic In addition to divergence, the sympathetic division has a nervous system’s ability to produce widespread activation hormonal mechanism to activate target tissues endowed of its effectors; it is activated when an organism’s survival is with adrenergic receptors, including those innervated by in jeopardy and the animal may have to fight or flee. The hormone is the catecholamine components of the response result from the direct effects of epinephrine, which is secreted with much lesser amounts sympathetic activation, while the secretion of epinephrine of norepinephrine by the adrenal medulla during general- by the adrenal medulla also contributes. Sympathetic stimulation of the heart and blood vessels The adrenal medulla, a neuroendocrine gland, forms the results in a rise in blood pressure because of increased car- inner core of the adrenal gland situated on top of each kid- diac output and increased total peripheral resistance. Cells of the adrenal medulla are innervated by the There is also a redistribution of the blood flow so that the lesser splanchnic nerve, which contains preganglionic sym- muscles and heart receive more blood, while the splanch- pathetic axons originating in the lower thoracic spinal cord nic territory and the skin receive less. These axons pass through the paravertebral creased exchange of blood gases is met by acceleration of ganglia and the celiac ganglion without synapsing and ter- the respiratory rate and dilation of the bronchiolar tree. The chromaffin cells are modified ganglion cells proportion of mucus increases, permitting lubrication of that synthesize both epinephrine and norepinephrine in a the mouth despite increased ventilation. The potential de- ratio of about 8:1 and store them in secretory vesicles. Un- mand for an enhanced supply of metabolic substrates, like like neurons, these cells possess neither axons nor dendrites glucose and fatty acids, is met by the actions of the sym- but function as neuroendocrine cells that release hormone pathetic nerves and circulating epinephrine on hepato- directly into the bloodstream in response to preganglionic cytes and adipose cells. Lipol- Circulating epinephrine mimics the actions of sympa- ysis in fat cells converts stored triglycerides to free fatty thetic nerve stimulation but with greater efficacy because acids that enter the bloodstream. The sympathetic innervation of the 114 PART II NEUROPHYSIOLOGY skin vasculature can adjust blood flow and heat exchange Cranial Nerve VII. The parasympathetic presynaptic ax- by vasodilation to dissipate heat or by vasoconstriction to ons of the facial nerve arise from the superior salivatory protect blood volume. Presynaptic axons pass from tant structures that also can be activated to enhance heat the facial nerve into the greater superficial petrosal nerve loss. Sympathetic nerve stimulation of the sweat glands re- and synapse in the pterygopalatine ganglion.

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