Resultats sur diverses plaies cutanees d´un traitement ther- (2006) M echanical stretch induces clustering of ß1-integrins mal original a Royat order 2mg tizanidine otc. Body J (M arch 2008) Carbocrenotherapie pour les affec- Res 248(2):608–619 tions arteriolles purchase tizanidine american express. Irie H cheap tizanidine 2 mg otc, Tatsumi T, Takamiya M , Zen K, Takahashi T, Azuma 156(6):1149–1155 A, Tateishi K, Nomura T, Hayashi H, Nakajima N, Okigaki 34. J Drugs Dermatol 7(3):201–206 mobilisation of endothelial progenitor cells and activation of 35. Brandi C, D’Aniello C, Grimaldi L, Bosi B, Dei I, Lattarulo versus extrinsic skin aging. Springer, Berlin, pp 10–11 treatment of localised adiposities: clinical study and his- 37. Brandi C, D’Aniello C, Grimaldi L, Caiazzo E, Stanghellini topathological correlations. Aesthetic Plast Surg 25(3): E (2004) Carbon dioxide therapy: effects on skin irregularity 170–174 and its use as a complement to liposuction. Aesthetic Plast Surg and induces basic fbroblast growth factor and vascular 34(2):239–243 Emerging Technologies: 44 Chemical Peels Basil M. These effects lead technological advances, chemical peels represent a to an overall more favorable, remodeled dermal matrix more time-tested and cost-effective tool to use either with improved elastic and tensile properties. Chemical peels are agents that induce a controlled caustic injury to the epidermis and/ 44. As with any type of resurfacing modality, the aesthetic Indications for the application of chemical peels are surgeon must be familiar with basic skin anatomy and relatively similar to those presented for laser resurfacing the aesthetic facial subunits which are described in and include: photoaging, rhytids, actinic keratoses, pig- previous chapters. Chemical peels may be performed mentary dyschromias, postinfammatory hyperpigmen- within specifc facial subunits but are more commonly tation, superfcial scarring, and acne vulgaris. Once two or more unlike for laser resurfacing, certain peels can be useful facial subunits are treated, it is generally appropriate to for the treatment of active acne. The biological mecha- treat the entire face to avoid unwanted areas of demar- nisms accounting for skin enhancement after chemical cation. As with any type of intervention, a thorough treatment are similar to those described for laser resur- history and physical examination is central to the pre- facing and are extensively discussed in previous chap- operative assessment. Briefy, insult to the skin stimulates a wound infection, chemotherapy, radiation exposure, and previ- ous resurfacing treatments should be noted. No abso- lute contraindications exist for most peels (except for unrealistic patient expectations), although relative con- B. Hantash (*) traindications include connective tissue disorders, kel- Elixir Institute of Regenerative M edicine, 5941 Optical Court, Suite 218A2, San Jose, oid predisposition, and active herpetic infection. Antibiotics Skin type Skin color Tanning response and antiviral agents are commenced 1 and 2 days prior I W hite Always burns; never tans to the procedure, respectively. Superfcial or light peels exfoliate and refresh the skin at the level of the epidermis while medium-depth and deep peels penetrate to the papillary 44. M edications rec- tions set at 3–10% concentrations yield a slow ommended are similar to those prescribed for laser exfoliation process with repeat applications over a resurfacing and include ciprofoxacin, 500 mg twice period of several weeks. Higher strength concentra- per day for 7 days and valacyclovir, 500 mg twice per tions (i. Jessner’s • Cooling fan solution may be used as a mild, superfcial peel but is • Container with gauze soaked in iced water more commonly used as a preparatory peel immediately • Emollient (e. The disruption of the epidermis by Jessner’s keratolytic approach within 2–3 mm of the lid margin. As with laser • the patient is positioned at an incline with head ele- resurfacing, treatment should be feathered to approx- vated at 30–45° to prevent entry of peeling agents into imately 1–2 cm into the neck below the cheek and eyes. Cool saline- • the skin is thoroughly cleansed with acetone on soaked gauze is used to wipe off the peel. Glycolic acid peel skin’s outer surface and acts as a keratolytic of the treatments consist of weekly to monthly applications stratum corneum. Superfcial peels may be used • Each subunit is treated individually before moving in the neck whereas deeper peels are not recom- on to the next to avoid under- or overtreatment in mended in this area. Subunits may be marked out before be used for the treatment of facial acne, with or with- peel application or can be mentally noted. M ultiple applications of emphasis of working solution into deeper rhytids or such superfcial peels will eventually equal that of folds. The periocular region is usually addressed frst higher concentration and therefore are discouraged. Prophylactic oral antibiotic and antivirals are used Protocol involves facial nerve blocks, tumescent local anesthetic, starting 1 day preoperatively. The procedure is as follows: • After appropriate cleansing, marking, and position- b ing of the patient, 1–2 coats of Jessner’s solution are applied as an initial preparatory peel. This appear- ance is characterized by a uniform but not com- c pletely opaque white-coated frosting with slight permeating erythema. It is important to note the skin color changes from mild erythema initially to the light frost followed by a return to erythema (Fig. The return to erythema does not rep- resent under-treatment, and the peeling agent should not be applied further as excess treatment may induce scarring. W ound healing in the ensu- ing weeks may result in mild residual erythema that can be easily covered with make-up Fig. In the perioral region, application of peel is carried to 1–2 mm into the vermilion border to prevent obvious demarcation. The skin can be cleaned at least two below: times per day with a mild cleanser such as Cetaphil • the Baker–Gordon phenol peel is indicated for cleanser. Patients should have an adequate expectation severely photoaged skin but, as aforementioned, is of skin sloughing and signifcant erythema during the rarely used in treating the full face and will not be wound healing process after the peel treatment. Limited areas of application, to reepithelialize is 3–6 days for superfcial peels while however, such as the perioral region for deep perio- that associated with medium and deep peels is ral rhytids, represent contemporary applications for 7–10 days. The cleaning regimen is similar to that for characterized by a solid white frosting without laser resurfacing and includes the application of dilute penetrating erythema seen shortly after application acetic acid soaks (one tablespoon white vinegar in one of the peel. Following the soaks, the skin should be of treatment to help dilute and excrete absorbed pat dry with a soft towel and the Aquaphor emollient phenol. This technique is especially soaks may be discontinued; instead, Cetaphil cleanser useful for patients with darker skin types. Sun exposure should Similar to the fractional photothermolysis concept be minimized at least for the frst few weeks following in laser therapy, the limited application of 100% peel treatment. Suggested follow-up visits are on post- collagen formation within the scar depression to operative days 1, 7, 14, and 30 at the very least. A total of four to six applications spaced at 4- to 6-week intervals are generally required to achieve 44. As with standard peel- ing, Aquaphor ointment is applied to the treated As with laser resurfacing, potential complications fol- areas.
Once tolerance has developed order tizanidine 2 mg online, withdrawal of the drug for a seizures and in the other 11 patients there was no apparent efect cheap tizanidine 2mg without a prescription. Addition of acetazolamide resulted in complete disappearance of seizures in two cases of migrating focal seizures in infancy compli- cated with intractable epileptic apnoea  buy 2mg tizanidine with mastercard. Most of the reported side-ef- Catamenial seizures fects seem to be related to inhibition of carbonic anhydrase, with Body water content changes in the premenstrual phase. Acetazolamide Acetazolamide, like other sulphonamide drugs, may induce angle has a diuretic action which was thought to contribute to its antiep- closure glaucoma through a mechanism which is considered to in- ileptic efects, and this provided the rationale for using this drug in volve an idiosyncratic reaction in the uveal tissues, associated with women with catamenial seizures. However, as pointed out by Ansell expansion of the extracellular tissue of the ciliary body and choroid and Clarke , no signifcant diferences in total body water have . Immediate cessation of the ofending medication is required been observed between women with epilepsy and healthy controls in such cases. A 73-year-old man treated with 250 mg/day aceta- Although this mechanism of action has been questioned , exacerbation of seizures during menstruation was found to respond well and without side-efects to acetazolamide given at dosages of Table 28. In three women with catamenial Potentially life-threatening effects exacerbation of generalized tonic–clonic or absence seizures, Ansell Blood disorders: aplastic anaemia, agranulocytosis, and Clarke  reported that only increasingly higher doses of the thrombocytopenia drug could maintain seizure control. Tese authors also described Renal failure improvement for 3 months in two patients who were given aceta- Severe skin reactions zolamide just on the day before and the day of onset of menstrua- Other adverse effects tion; a prolonged follow-up, however, was not conducted in these Gastrointestinal symptoms: abdominal discomfort, nausea, women. Goetting  reported a case of post-anoxic myoclonus anorexia, diarrhoea severely exacerbated premenstrually: 1000 mg acetazolamide given Dysgeusia intermittently during 5 days starting at the onset of each exacerba- Paraesthesia of hands, feet and circumoral region tion resulted in prompt and marked improvement. However, Ross Increased diuresis  observed no response to acetazolamide in 8 of the 25 menstru- Drowsiness, dizziness, fatigue ating females with epilepsy who reported having seizures related to Headache menstruation. Twenty women were identifed, and acetazolamide Angle closure glaucoma was given as an add-on therapy in all patients but one. The drug was 384 Chapter 28 zolamide because of oedema of the lower legs developed severe bone may also have been important in their pathogenesis. Symptoms of marrow depression which resulted in death afer 1 month of therapy metabolic acidosis develop slowly and are ofen difcult to diag- . The best-documented treatment is ed aplastic anaemia from spontaneous reporting in Sweden over 17 supplementation with sodium bicarbonate 56–70 mmol/day orally years. An 85-year-old man treated for congestive heart failure with ducing partial renal tubular acidosis, with resulting hypercalciuria 750 mg/day acetazolamide developed acute thrombocytopenia and hypocitraturia, both of which are recognized risk factors for . Tere are also a number of acute skin reactions attributed to etazolamide has been of special concern in patients treated for ep- acetazolamide, some of which can be severe, and, similar to oth- ilepsy  and glaucoma . The frequency of stone formation er sulphonamide derivatives, cases of Stevens–Johnson syndrome varies across studies. Cross-sensitivity to acetazolamide in patients 1 in 277)  and was absent altogether in 28 patients examined allergic to sulpha drugs can occur . However, 6 out of 14 (43%) young adults with juvenile myoclonic epilepsy Common non-idiosyncratic adverse effects  were reported to have developed renal calculi, without a clear Tese adverse efects are encountered mainly upon initiation of relationship with the administered dosage. Patients with glaucoma, perhaps ed a frequency as high as 12% in patients with glaucoma. Citrate because of their age, are less tolerant to the drug , whereas pa- supplementation and hydration may be efective in reducing stone tients with epilepsy tend to have fewer adverse efects . Acetazolamide may acceler- , 11% of patients reported the following adverse efects, in ate osteomalacia by diferent mechanisms, which include urinary descending order of frequency: drowsiness, anorexia, irritability, calcium and phosphate excretion and systemic acidosis . Mal- nausea, vomiting, enuresis, headache, thirst, dizziness and hyper- lette  described two acetazolamide-treated patients with os- ventilation. Tese efects have been reported in 8–30% of epilepsy teomalacia, but both patients were also receiving barbiturates. Transient distortion of post-menopausal women with glaucoma, long-term (more than 4 normal taste secondary to acetazolamide was ascribed to carbonat- years) use of carbonic anhydrase inhibitor therapy was associated ed and non-carbonated beverages and food, and was speculated to with a bone-sparing efect, as judged by spinal bone mineral density be caused by altered taste receptors secondary to inhibition of car- . Efects on the fetus and newborn infant Layton and Hallesy  reported that 36% of the ofspring of rats Other adverse effects fed with acetazolamide in their diet during pregnancy had a defect confned mainly to the right forepaw. The plasma levels achieved with Metabolic acidosis that diet were of the same order of magnitude as those recorded in pa- Acetazolamide may induce metabolic acidosis by inhibiting car- tients who receive 500–1500 mg acetazolamide. A similar efect was bonic anhydrase in the proximal tubular epithelium of the kidney, observed in mice and hamsters but not in monkeys . A human which leads to diuresis, excessive excretion of sodium and potassi- case of multiple congenital malformations (glaucoma, microphthal- um ions, and alkaline urine. Although the metabolic acidosis that mia and patent ductus arteriosus) has been described in a letter from is produced is mild, it can sometimes be symptomatic, especially in Lederle Laboratories in 1975, cited by Worsham et al. Although these symptoms are frequently associated with mild tween treatment for glaucoma throughout pregnancy with 500 mg metabolic acidosis, the central nervous system nature of these ad- acetazolamide and metabolic acidosis, hypocalcaemia and hypo- verse efects suggests that inhibition of brain carbonic anhydrase magnesaemia in a single preterm infant . Lombroso and For- Place in current therapy sythe  noted that in adults and children increasing dosage above 750 mg was rarely efective and that 500 mg/day was usually the Usefulness and limitations maximal useful dose in children less than 7 years of age. Monitoring Evidence on the efcacy of acetazolamide in epilepsy is restrict- plasma concentration has not been found to be generally helpful . In these studies, The starting dose should be 125 mg twice daily in children and conducted mostly in the 1950s, selection of patients, seizure type, 250 mg twice daily in adults, and it may be increased at weekly in- methods and duration of treatment, and defnition of response var- tervals. Before making the decision to increase the dosage, it should ied extensively, which makes it difcult to evaluate the value of the be considered whether tolerance has occurred to adverse efects and drug in seizure types and syndromes as currently classifed. Slow discontinuation over several weeks is recom- Most patients treated with acetazolamide had seizures unrespon- mended to prevent withdrawal seizures . Many studies defne acetazolamide Individuals at higher risk include older patients with compro- as an antiepileptic drug with a broad spectrum of action. Although mised renal function, who should be started out with a reduced some authors [23,29] failed to demonstrate its usefulness, efcacy dose to avoid acidosis . The best responses were reported in absence seizures Precautions and contraindications [19,24,30], but good results were also described in patients with Experience with acetazolamide shows that it is a relatively safe generalized tonic–clonic seizures [22,30,32,34], myoclonic seizures agent, and that it can be used for long periods without serious ad- [30,31,34] and focal seizures [30,31,32,33,36,65]. Because of rare cases of aplastic anaemia, agranulocy- that acetazolamide can be benefcial in a variety of seizure types, tosis and thrombocytopenia (Table 28. Acetazolamide can be helpful mainly as an add-on treatment haematology tests is unknown. Liver disease is a contraindication to the use of zymes makes acetazolamide valuable when drug interactions are a acetazolamide. The antiepileptic efect of acetazolamide develops prompt- origin from urine to the systemic circulation, potentially causing ly , and therefore the drug may be useful when a rapid onset of hepatic encephalopathy . Loss of seizure control has been reported When acetazolamide is given with carbamazepine, monitoring as early as several weeks afer instituting treatment or afer months of serum sodium may be indicated because both drugs may cause and years, and occasionally an increase in dosage has been required hyponatraemia , and carbamazepine levels should also be to maintain a sustained efect. Special attention to ensure appropriate hydration development of tolerance, acetazolamide has been proposed as ad- and to monitor for potential metabolic acidosis is required if aceta- junct intermittent therapy in the management of catamenial epi- zolamide is given in combination with topiramate, zonisamide or lepsy. However, controlled studies in women with catamenial sei- sulthiame, because these drugs inhibit carbonic anhydrase and may zures are required before acetazolamide can be recommended for cause lithiasis and acidosis (Table 28. Other antiepileptic drugs, particularly benzodiazepines, are also known to be subject to the Table 28. A comparison between the degree of tol- Elderly patients erance associated with acetazolamide and benzodiazepines has not been performed. Patients with concomitant disorders In this author’s opinion, acetazolamide has been too quickly Renal failure abandoned in favour of newer antiepileptic drugs without having Hepatic failure undergone adequate evaluation for its potential value.
Few patients have also had interstitial nephritis served predominantly in older patients (more commonly in fe- and exfoliative dermatitis buy tizanidine 2 mg with mastercard, nephrotic syndrome or a combination of males) cheap tizanidine 2 mg with mastercard, usually at serum carbamazepine concentrations within the nephropathy cheap tizanidine on line, haemolytic anaemia and thrombocytopenia. Overall, cardiac adverse efects in patients receiving therapeutic Adverse effects and quality of life studies doses of carbamazepine are relatively uncommon, and probably Gillham et al. In comparing 62 and myoclonic seizures and may even precipitate or aggravate these patients randomized to controlled-release carbamazepine with 63 seizure types. However, neither neuralgia, and it is also useful in other neuropathic pain syndromes. However, no formulations are as yet commercially available for par- Overdose enteral use. Sustained-release formulations are usually preferred Hundreds of patients with massive overdoses, fatalities included, to improve tolerability and can generally be used on a twice-daily have been reported and it has been estimated that over 6000 cases regimen. This aids in pre- conduction disorders, respiratory failure, seizures and coma . In children, iveness, hallucinations, choreiform movements, at concentrations treatment is ofen initiated with a daily dosage of no more than of 15–25 µg/mL (64–106 µmol/L); (iii) mild drowsiness, ataxia, at 5 mg/kg body weight, which is gradually increased over 2–4 weeks concentrations of 11–15 µg/mL (46–64 µmol/L); and (iv) possibly to an initial target maintenance dosage of 10–20 mg/kg body weight mild ataxia, but otherwise normal neurological examination, with per day. Adults are usually started on 100–200 mg/day, to be in- concentrations <11 µg/mL (<46 µmol/L)]. Sudden and potential- creased to an initial target maintenance dosage of approximately ly catastrophic relapse to stages (i) to (iii) may occur unexpectedly 400 mg/day over 2–4 weeks [128,129]. In children, however, the In general, maintenance dosages afer dose optimization are in serum concentration of carbamazepine may not predict accurately the order of 5–30 mg/kg/day in children, while infants usually re- the severity of toxic manifestations. The majority of adults half-life may be prolonged and the carbamazepine-10,11-epoxide with newly diagnosed epilepsy who respond to carbamazepine concentration increased, sometimes at concentrations even higher monotherapy do so at low dosages (400–600 mg/day). When carbamazepine is combined with other drugs, dosage sis and haemodialysis should be avoided. Seizures should be treated may need to be adjusted to compensate for pharmacodynamic as with benzodiazepines. In the case of pharmacokinet- ic interactions, dose adjustment is facilitated by monitoring serum carbamazepine concentrations. Given that no other drug has been shown to be more of carbamazepine treatment in populations with a high prevalence efective, and in view of its usually good tolerability, carbamazepine of this allele. Other treatment alternatives are generally a preferred though the cost– beneft ratio of this test based on current evidence frst choice in the elderly, in whom carbamazepine appears to be is questionable. The eralized tonic–clonic seizures, and it could be regarded as one of the value of continued regular haematology and blood chemistry tests possible frst-line drugs for this indication. However, other drugs to identify rare idiosyncratic adverse efects is questionable, and 444 Chapter 32 repeated tests are not generally justifed unless there are clinical 13. Pharmacokinetic evaluation of sustained release formulations of antiep- 2–4 months afer initiation of treatment. Epilepsia diogram is also justifed before starting carbamazepine to identify 2007; 48: 1825–1832. Relative bioavailability of rectally admin- those few patients who may be at risk for cardiac adverse efects and istered carbamazepine suspension in humans. Serum concentra- Terapeutic monitoring of serum carbamazepine concentrations tion profle studies of tablets and suppositories of valproate and carbamazepine in is well established. A reference range of 4–12 µg/mL (17–51 µmol/L) healthy subjects and patients with epilepsy. Steady-state carbamazepine pharma- than to a predefned range of serum concentrations. However, it cokinetics following oral and stable-labeled intravenous administration in epilep- sy patients: efects of race and sex. This is ideally by determining bound and total drug concentrations following intravenously administered car- the trough (before morning dose) carbamazepine concentration at bamazepine in elderly and younger adult patients with epilepsy. Carbamazepine and a useful reference to determine whether subsequent possible chang- carbamazepine-10,11-epoxide concentration in human brain. Br J Clin Pharmacol es in clinical response are related to an alteration in serum drug 1977; 4: 535–540. Based on these considerations, a case can be made and its epoxide metabolite in man afer single and multiple doses. Eur J Clin Phar- for measuring the serum carbamazepine concentration a few weeks macol 1975; 8: 337–341. Autoinduction and steady- has been established, when seizure control is poor or deteriorated state pharmacokinetics of carbamazepine and its major metabolites. Br J Clin (also as a check for compliance), when dose-related adverse efects Pharmacol 1992; 33: 611–615. Interdosage fuctuations in plasma carbamazepine concentration de- are suspected or when drug–drug interactions or other conditions termine intermittent side efects. In general, there is little value in measuring the unbound drugs in paediatric patients. Phenytoin, carbamazepine, sulthiame, lam- serum carbamazepine concentration, and the total concentra- otrigine, vigabatrin, oxcarbazepine and felbamate. Serum carbamazepine concentrations in el- carbamazepine-10,11-epoxide metabolite is usually not justifed. Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy. Justus Liebig’s Annalen des Che- spective study of seizure control in relation to free and total plasma concentrations mie 1899; 305: 96–102. A common anticonvulsant binding site for phenytoin, carbamazepine, + blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and lamotrigine in neuronal Na channels. Relations between mechanisms of action and clinical Academy of Neurology and the American Epilepsy Society. The neurobiology of antiepileptic drugs for the treat- feeding in children of women taking antiepileptic drugs. An international multicenter randomized double-blind controlled trial of lamo- 41. Clinical signifcance of pharmacokinetic interactions between apy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for antiepileptic and psychotropic drugs. Antiepileptic drugs – best practice guide- monotherapy for epilepsy: a meta-analysis. Trigeminal neuralgia: its treatment with a new anticonvulsant drug (G- epine for the treatment of complex partial seizures and secondarily generalized 32883). A double-blind trial of gabapentin efcacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicen- monotherapy for newly diagnosed partial seizures. Carbamazepine in comparative trials: pharmacokinetic controlled-release carbamazepine in newly diagnosed epilepsy. Double-blind comparison of lamotrigine and carbamazepine: a multicentre, double-blind, cross-over study. Efcacy and tolerability of zonisamide versus phenobarbital, phenytoin, and primidone.
The principal cell type in the lymph is the small the initiation of immune responses buy tizanidine visa. Occasional red cells and eosinophils are pres- Nasopharyngeal-associated lymphoreticular tissue ent tizanidine 2mg low cost. The palatine tonsils usually contain 10 to 20 crypts buy genuine tizanidine line, that transports lymph, a tissue fuid derived from the blood. The deeper regions of It collects extracellular fuid from the periphery and chan- these crypts contain M cells that may take up encountered nels it via the thoracic duct to the blood circulation. The tonsils contain all major classes of antigen nodes at the intersection of the lymphatic vessels trap and presenting cells, including dendritic and Langerhans cells, retain antigens from the lymph. Situated at lymphatic ves- macrophages, class I positive B cells, and antigen-retain- sel intersections are lymph nodes, Peyer’s patches, and other ing follicular dendritic cells in B cell germinal centers. Lymphatics are vessels that transport the interstitial fuid called lymph to lymph nodes and away from them, direct- ing it to the thoracic duct from where it reenters the blood stream. Lymphatic vessels are thinly walled channels through which lymph and cells of the lymphatic system move through secondary lymphoid tissues such as lymph nodes, except for the spleen, to the thoracic duct which joins the blood circulation. An efferent lymphatic vessel is the channel through which lymph and lymphocytes exit a lymph node in transit to figure 2. Lymphoid nodules (or follicles) are aggregates of lymphoid cells present in the loose connective tissue supporting the A generative lymphoid organ is an organ in which lym- respiratory and digestive membranes. The principal in the spleen and may develop beneath any mucous mem- generative lymphoid organ for T cells is the thymus, and for brane as a result of antigenic stimulation. They may occur as isolated struc- Large pyroninophilic blast cells stain positively with methyl tures or may be confuent, such as in the tonsils, pharynx, green pyronin stain. In the tongue and pharynx, they form a areas of lymph nodes and other peripheral lymphoid tissues. In the terminal ileum, they form oblong patches termed Peyer’s the cortex is the outer or peripheral layer of an organ. Plasma cells in submucosal sites synthesize Hyperplasia: An increase in the cell number of an organ IgA, which is released in secretions. The interfollicular region refers to the tissue separating lym- phoid follicles situated in a group. Primary follicles Lymphoid patches are unencapsulated clusters of lymphoid contain B lymphocytes that are small and medium sized. They contain large B lymphocytes overlying single or aggregated lymphoid follicles that facili- in the germinal centers where tingible body macrophages tate transcytosis via the presence of M cells. Follicular center cells are B lymphocytes in germinal cen- An intraepithelial pocket is an invagination within the ters (secondary follicles). It enables interaction with antigens conveyed centers are usually present in the follicles. Lymphoid organs are organized lymphoid tissues in which numerous lymphocytes interact with nonlymphoid stroma. The thymus and bone marrow are the primary lymphoid organs where lymphocytes are formed. The term lymphoid is an adjective that describes tissues the medulla is the innermost or central region of an organ. Central lymphoid organs are requisite organs for the development of the lymphoid and, therefore, of the immune the medullary cord is a region of the lymph node medulla system. These include the thymus, bone marrow, and bursa composed of macrophages as well as plasma cells and lies of Fabricus (also termed primary lymphoid organs). Molecules, Cells, and Tissues of the Immune Response 141 the medullary sinuses are potential cavities in the lymph Postcapillary venules are relatively small blood vessels node medulla that receive lymph prior to its entering efferent lined with cuboidal epithelium through which blood circu- lymphatics. It is a frequent site of migration of lymphocytes and infam- Lymphadenitis is lymph node infammation often caused matory cells into tissues during infammation. Benign lymphadenopathy refers to lymph node enlarge- ment that is not associated with malignant neoplasms. Mantle zone refers to the rim of B lymphocytes that encir- Histologic types of benign lymphadenopathy include nod- cles lymphoid follicles. The function and role of mantle zone ular, granulomatous, sinusoidal, paracortical, diffuse or lymphocytes remain to be determined. Reticular cells are stroma or framework cells which, together with reticular fbers, constitute the lymphoid tissue Dermatopathic lymphadenitis is a benign lymph node framework of lymph nodes, spleen, and bone marrow. A draining lymph node collects fuid draining through lymphatic channels from an anatomical site of infection the frst event in an adaptive immune response when anti- before returning to the blood circulation. Lymphadenopathies are reactive processes This phase often occurs in secondary lymphoid tissues such in lymph nodes due to various exogenous and endogenous as lymph nodes or spleen where antigens and naïve lympho- stimulants. Lymphadenitis is reserved the pharyngeal tonsils are lymphoid follicles found in the for lymph node enlargement caused by microorganisms, roof and posterior wall of the nasopharynx. They are similar whereas lymphadenopathy applies to all other etiologies of to Peyer’s patches in the small intestine. Lymphadenopathies are divided follicles are rich in IgA-producing B cells that may be found into reactive lymphadenopathies, lymphadenopathies associ- in germinal centers. Secondary lymphoid organs are the structures that include In benign lymphadenopathy, there is variability of germinal the lymph nodes, spleen, gut-associated lymphoid tissues, center size, no invasion of the capsule or fat, mitotic activity and tonsils where T and B lymphocytes interact with antigen- confned to germinal centers, and localization in the cortex presenting accessory cells such as macro-phages, resulting in and nonhomogenous follicle distribution. Thymus-dependent areas are regions of peripheral lym- Secondary lymphoid tissues are tissues in which immune phoid tissues occupied by T lymphocytes. They include lymph nodes, spleen, include the paracortical areas of lymph nodes, the zone and mucosa-associated lymphoid tissues. Lymph nodes and between nodules and Peyer’s patches, and the center of splenic spleen are also often referred to as secondary lymphoid Malpighian corpuscles. Proof that these Peripheral lymphoid tissues: Refer to secondary lymphoid anatomical sites are thymus-dependent areas is provided by tissues. Antigen–antibody complexes adhere to the A primary follicle is a densely packed accumulation of rest- surfaces of follicular dendritic cells and are not generally ing mature B lymphocytes and macrophages and a network endocytosed but are associated with the formation of germi- of follicular dendritic cells from secondary lymphoid tissues, nal centers. They display antigens on their surface for 142 Atlas of Immunology, Third Edition C C C C C C C C C C C C C figure 2. C C B-cell recognition and participate in the activation and selec- tion of B cells expressing high-affnity membrane immuno- globulin during affnity maturation. It appears when surface Ig is expressed after few lymphocytes, and which reveal an onion-skin layering the pre-B cell stage and is lost during early stages of terminal of dendritic reticulum cells, vascular endothelial cells, and B cell differentiation to the fnal plasma cell stage. Germinal centers are sites of isotype switching, coded for by a gene found on chromosome 1 at band q32. The mantle the antigen functions as a receptor for the C3d complement zone (Figure 2. A ger- minal center is a site of intense B cell proliferation, selec- tion, maturation and death in secondary lymphoid tissue. Subscapular Germinal centers develop around follicular dendritic cell sinus networks when activated B cells migrate into lymphoid fol- Cortex licles. The mixed-cell population in the germinal center is Eﬀerent comprised of B lymphoblasts (both cleaved and transformed lymphatic lymphocytes), follicular dendritic cells, and numerous tin- Medulla Aﬀerent gible body-containing macrophages. Germinal centers seen lymphatics in various pathologic states include “burned out” germinal centers comprised of accumulations of pale histiocytes and Lymphoid follicle with scattered immunoblasts; “progressively transformed” cen- germinal center ters that show a “starry sky” pattern containing epithelioid (B cell zone) Paracortical zone histiocytes, dendritic reticulum cells, increased T lympho- (T cell zone) cytes, and mantle zone lymphocytes; and “regressively transformed” germinal centers that are relatively small, with figure 2.