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The null cells which Complementation: A mechanism whereby a hybrid cell have been committed to the T cell lineage migrate to the thy- develops the survival capacity of two separate parental cells mus to continue their differentiation purchase nootropil 800 mg chi infra treatment. It is related to macrophage colony- with required characteristics by complementation buy generic nootropil 800 mg line symptoms after miscarriage. Flt3-L is synthesized by bone the termination point in that cell line’s maturation pattern. They attack and destroy certain virus-infected refers to the perinuclear clear zone adjacent to the nucleus in cells. Immunologic memory is not involved, as previous contact with antigen is not necessary Hof. Fragmentins are serine esterases present in cytotoxic T cell and natural killer cell cytoplasmic granules. Granzymes induce target cell apoptosis after entering the ability to kill selected tumor cells and some virus-infected cytosol. Thus, they are Perforin/granzyme-mediated cytotoxicity is a means able to destroy antibody-coated nucleated cells. Following by a 51Cr release assay employing the K562 erythroleukemia the uptake of these molecules by the target cells, perforin cell line as a target. They are present in abundance in the liver and cells, but it is also found on some T and B cells. F3 target cell bearing antigenic determinants on its surface for which the Fab regions of the antibody molecule attached to the K cell are specifc, the lymphocyte-like K cell releases F3 lymphokines that destroy the target. This represents a type of immune effector function in which cells and antibody par- ticipate. They were described to have lymphocyte-like mor- phology but functional characteristics different from those of B and T cells. Molecules, Cells, and Tissues of the Immune Response 115 Fc receptor IgG K cell figure 2. Cytolysis is induced by insertion of perforin polymer in the target cell figure 2. Monocytes, which may differentiate into macrophages when Perforin is showered on the target cell membrane following they migrate into the tissues, make up 3 to 5% of leukocytes in release from the K cell. Macrophages that are tissue-bound may be found in the lung alveoli, as microglial cells in the central Macrophages (Figures 2. They are derived from cells in the skin, and as histiocytes in connective tissues, monocytes in the blood and are active in innate immunity as well as macrophages in lymph nodes and peritoneum. Macrophages Multiple substances are secreted by macrophages including act as professional antigen-presenting cells and effector complement components C1 through C5, factors B and D, cells in both humoral and cell-mediated immunity. They also produce cells have a powerful, although nonspecifc, role in immune monokines such as interleukin-1, acid hydrolase, proteases, defense. These intensely phagocytic cells contain lysosomes lipases, and numerous other substances. They are rial endotoxin can cause an activated macrophage to become frequently found in areas of epithelium, mesothelium, and “hyperactivated,” i. Macrophages have been referred to as adherent which possesses increased activity against pathogens and cells since they readily adhere to glass and plastic and may the ability to kill tumor cells. They have different names according to the tissue in which they are receptors for Fc and C3b on their surfaces, stain positively found, such as the microglia of the central nervous system, for nonspecifc esterase and peroxidase, and are Ia antigen the Kupffer cells of the liver, alveolar macro-phages of the positive when acting as accessory cells that present antigen to lung, and osteoclasts in the bone. Resting Macrophage An activated macrophage has been stimulated in some manner or by some substance to increase its functional eff- ciency with respect to phagocytosis, intracellular bactericidal activity, or lymphokine, i. A lymphokine- activated mononuclear phagocyte is double the size of rest- ing macrophages. Functional 116 Atlas of Immunology, Third Edition alterations include elevated metabolism and transport of and functioning in macrophages as a powerful microbicidal amino acids and glucose; increased enzymatic activity; an agent against ingested microorganisms. Its intracellular calcium ions, phagocytosis, pinocytosis; and the role in human host defense has been controversial. Cells possess elaborate systems to scav- the citric acid cycle and microbial enzymes that contain iron enge free radicals. When free radicals exceed the capacity of or sulfur atoms, and inhibits virus replication. Cell death induced by free radicals has characteristics of both apoptosis and necrosis. Superoxide dismutase is an enzyme that defends an organ- the most compelling observation that cell death resulting ism against oxygen-free radicals by catalyzing the interaction from free radicals is related to the apoptotic process is found of superoxide anions with hydrogen ions to yield hydrogen at the level of the mitochondria. An adherent cell is a cell such as a macrophage (mononu- the radical-induced cell death may involve the mitochon- clear phagocyte) that attaches to the wall of a culture fask, drial permeability transition pore. Bcl-2 has been observed thereby facilitating the separation of such cells from B and T to be located near the permeability transition pore in the lymphocytes which are not adherent. Given the rapidly expanding of an experimental animal develop into epithelioid cells. On the con- trary, epithelioid cells are able to divide, resulting in round, Reactive oxygen species are oxygen-derived radicals that small daughter cells which mature in 2 to 4 d, gaining struc- are generated in the mitochondria as oxygen is reduced tural and functional characteristics of young macrophages. These can be produced Material that is taken up by macrophages but cannot be fur- by phagocytic cells to kill pathogens, but are also involved ther processed prevents the conversion of epithelioid cells. Damage from these toxic species is prevented by the epithelioid cell is a particular type of cell characteristic antioxidants (ascorbic acid, vitamin E, uric acid, glutathione, of some types of granulomas such as in tuberculosis, sarcoido- etc. During oxidative stress, these cloudy, abundant eosinophilic cytoplasm; and an elongated and protective mechanisms are overwhelmed leading to mem- pale nucleus. By electron microscopy, the cell shows a few short brane damage, protein modifcations, and apoptosis. Mitochondria are generally elongated, the Golgi com- A stimulated macrophage is one that has been acti- plex is prominent, and lysosomal dense bodies are scattered vated in vivo or in vitro. Enzyme the term resident macrophage refers to a macrophage nor- generated principally in phagocytes by products of microbes mally present at a tissue location without being induced to or proinfammatory cytokines. Molecules, Cells, and Tissues of the Immune Response 117 Macrophage immunity: Cellular immunity. Giant cells form are membrane-bound are termed “pattern recognition recep- from some of these fused cells. Activated macrophages rophages of lymph node, spleen, and tonsil germinal centers, trap antigen, which may cause T cells to release lymphokines, as well as in the dome of the appendix. Granulomas appear in cases of Tingible body macrophages are phagocytic cells that tuberculosis and develop under the infuence of helper T cells engulf apoptotic B cells which are formed in large numbers that react against Mycobacterium tuberculosis. There may also be occa- Phagocytosis is the uptake of particulate material, such as sional neutrophils and eosinophils. Particle ligands unite with numer- is a delayed type of hypersensitivity reaction that persists as ous receptors on the surface of the phagocyte in a “zippering” a consequence of the continuous presence of foreign body or effect and cause polymerization of actin, invagination of the infection. This monocytes are strongly adherent cells and have a rate of is an important clearance mechanism for the removal and locomotion slower than that of neutrophils.
First and the English medical literature and the world medical litera- second-trim ester diagnosis of fetal ocular defects and associated anomalies: report o f eight cases discount nootropil online mastercard symptoms of kidney stones. Axial growth of the fetal eye and prenatal + anophthalmia trusted nootropil 800 mg medications 1800, prenatal + microphthalmia, prenatal + evaluation of the hyaloid artery: in utero ultrasonographic study. A case report o f prcnatally holoprosencephaly and cyclopia with triploidy by transvaginal three- diagnosed ophthalm o-acrom elic syndrom e type W aardenburg. U ltrasound dom inant cataracts of the fetus: early detection by transvaginal O bstet G ynecol 2005;25:629-30. Л large retinoblastom a facial dcfccts, am niotic bands, adhesions and upper lim b deficiency. Congenital orbital cyst dctcctcd and m onitored by products o f conccption obtained by dilation an d evacuation. Prenatal detection of orbital trim ester diagnosis of cyclopia and holoprosencephaly. I Clin U ltrasound tom ography and m agnetic resonance im aging use during prcgnancy 1986;11:550-3. Philadelphia: trisom y 3p(3p23—> pter) an d m onosom y 7q(7q36— > qter) in a Lippincott W illiams & W ilkins, 2005. Prenatal diagnosis ofotocephaly proboscis in a fetus with norm al chrom osom e at 13 weeks o f gestation with m icrophthalm ia/anophthalm ia using ultrasound and magnetic by three-dim ensional transabdom inal sonography. C ongenital axial high m yopia detected by three-dim ensional ultrasound: a novel application of the reverse by prenatal ultrasound. Prenatal two- and three-dim ensional rhizomelic shortening and bilateral cataracts. Clinicopathological genital nasolacrim al duct cyst by ultrasonography: a case report. Traboulsi, and Ethylin Wang Jabs Syndromes with craniofacial malformations commonly be displaced or placed asymmetrically and there can be involve the orbits and arc sometimes associated with signifi hearing loss. It is beyond the scope of As the phenotypic expression of the craniosynostosis is this chapter to cover all the clinical details of the individual highly variable, the parents of an atfectcd child should syndromes and to include all syndromes with craniofacial always be examined for subtle abnormalities of cranial abnormalities. We will give a synopsis of the clinical features shape to rule out mild expression of the genetic condition. Craniosynostosis, or the premature fusion of one or more Molecular genetic testing is available and useful in olTering cranial sutures, occurs in approximately 1of 2,500 births and insights into the diagnosis, recurrence risk, prognosis, may lead to derangement of craniofacial development. Eighty-four children (and 61 relatives) had patho associated with abnormal development of any structure in logic genetic alterations (86% single-gene mutations and 14% the craniofacial region. More complex patterns of genetic syndromes have been described in which cranio plagiocephaly (asymmetric skull shape) are evident when synostosis is a feature. In syndromic cases, the most frequent synostosis is unilateral, or when there is a combination of concomitant anomalies involve the limbs, cars, and cardio sutures involved. The forehead may be prominent or receding, depend discs were pale or atrophic in 50% of Crouzon syndrome ing on the specific sutures involved. Disc swelling was and orbital involvement with hypertelorism, proptosis, stra present in 31% of Crouzon and 9. The midface is often depressed, which can lead to a with craniosynostotic syndromes looking for prevalence narrowed airway and respiratory difficulties. Causes of visual impairment included that occurs within and between the resulting syndromes. Risk factors for Jackson-Weiss syndrome cases are allelic and result from amblyopia were strabismus (43. In craniosynostotic syndromes,31 suggesting the effect of contrast, ocular findings in nonsyndromic craniosynostotic modifying genes elsewhere in the genome. These conditions have significant cephaly patients were studied, 7% had an exodeviation and variability in expression, and mild cases may go undiag 28% had astigmatism. Okajima and colleagues reported on nosed until the birth of an affected offspring with features three craniosynostosis patients with Ser35lCys mutation in characteristic of the individual clinical phenotype. Lateral palatal swell Initially described in 1 9 1 2 , this disorder involves cranio - ings are common. Other frequent anomalies noted in synostosis, midface hypoplasia, and ocular proptosis Kreiborgs study’7 included calcification of the stylohyoid (Fig. In a study by prompt consideration of other related craniosynostotic Kreiborg,37 advanced paternal age was associated with the syndromes. In addition, several cases of involving hypcrpigmentation and hyperkeratosis, is also germinal mosaicism have been reported. This feature is, how Ocular Features ever, quite variable and range from almost no sutural involvement to severe multisutural fusion and a cloverleaf There is significant orbital and ocular involvement in skull. The most common cause of visual impairment was amblyopia (21% of patients), followed by optic atrophy (7%). Ametropia occurred in 77% of patients; 57% had hypcrmctropia of at least 2 diopters (D) and 20% had myopia of at least 0. Although exposure keratopathy was observed in 15% of patients, it was well managed, with no secondary reduction in visual acuity. This patient is status post craniectomy for coronal synostosis, which had caused increased intracranial pressure and syndrome. The proptosis may lead to exposure such as brachydactyly consistent with these short stature keratitis and, in extreme cases, spontaneous subluxation of syndromes, and they also have severe choanal atresia and the globe. Limon de Hiis condition is characterized by craniosynostosis, ocular Brown44 proposed that the superior oblique weakness is proptosis, and midface hypoplasia. In addition, a distinctive, due to the interplay of musculature around the foreshort symmetric “mitten-type” syndactyly of the hands and feet ened orbit. Others have proposed that the weakness of the makes this syndrome the most easily recognizable of the superior oblique muscles in Crouzon syndrome is of a acrocephalosyndactylies (Fig. Diamond and coworkers45reported absence report of this condition in 1906,ss large series of affected of various extraocular muscles in patients with Crouzon syn patients have been extensively reviewed by Cohen," and drome, leading to unusual patterns of strabismus. Visual loss and fashion, and at least 11 cases of familial inheritance have blindness are found in a smaller percentage ofcases. The palate is narrow and high-arched, often with a median furrow, giving the appearance of a Byzantine arch. The teeth are crowded because of the constricted dental arch, and malocclusion is common. Abnormalities of the hands and feet arc the true hall marks of the Apert syndrome. There is consistent syndactyly of the second, third, and fourth digits; the first and fifth arc involved to a variable degree. In addition to syndactyly, the digits exhibit a number of other abnormalities, including brachydactyly, and misshapen and/or fused bones.
An even more difﬁcult situation is rectovaginal or anovaginal ﬁstula associated with Crohn’s disease purchase nootropil 800mg overnight delivery in treatment 1-3. Two studies have Comparison with Other Surgeries for Fistula examined the use of dermal ﬂaps in this situation discount 800 mg nootropil with mastercard medications on nclex rn. They achieved an 85 % success rate over a period these studies have found no difference in recurrence rates of follow-up ranging from 10 months to 18 years. Ho and Ho did a randomized the majority of these patients had diverting ileostomies, and controlled trial comparing dermal ﬂap to “conventional the numbers of patients with dermal ﬂaps were too small to 114 C. Jensen evaluate whether the presence of an ileostomy contributed signiﬁcantly to healing in these patients. One healed after repeat functional results after repair for rectovaginal ﬁstula in Crohn’s dis- ﬂap, one healed after ﬁbrin injection, and one patient had a ease: a comparison of different techniques. Controlled, randomized trial of island ﬂap ano- patients had anal stenosis and four were reported to be plasty for treatment of trans-sphincteric ﬁstula-in-ano: early results. Anocutaneous advancement ﬂap closure of high dermal ﬂap in the treatment of anovaginal or rectovaginal anal ﬁstulas. Dermal island-ﬂap anoplasty for transsphincteric ﬁstula-in-ano: assessment of treatment failures. Sungurtekin U, Sungurtekin H, Kabay B, Tekin K, Aytekin F, Conclusion Erdem E, et al. Dermal ﬂaps are associated with sure: alternative method for treatment of complicated anal ﬁstulas. Effect of tobacco smoking on advancement ﬂap treat the patient with an anal ﬁstula. Fibrin glue as an adjunct to ﬂap repair of anal ﬁstulas: a randomized, controlled study. V-Y advancement the treatment of anal ﬁstulas and is associated with a good ﬂap for treatment of ﬁstula-in-ano. Success and failure after repair of rectovaginal ﬁstula sphincter muscles, but may still have deleterious effects in Crohn’s disease: analysis of prognostic factors. Treatment for horse- presence of other anorectal pathology, such as anal steno- shoe ﬁstulas-in-ano with primary closure of the internal ﬁstula opening: a clinical and manometric study. Island ﬂap ano- as other procedures for anal ﬁstula, surgeons should be plasty for treatment of transsphincteric ﬁstula-in-ano. Abcarian tested, either with direct probing or with injection of hydrogen Introduction peroxide or saline [2, 4, 5]. Several series report discharg- the main tenets in treating ﬁstula in ano are the amount of ing patients with a week of oral antibiotics [2, 4, 5]. As a stan- These considerations have led to the development of various dard, at our institution, setons are used to drain all infection sphincter sparing options throughout the years. This chapter prior to undertaking deﬁnitive surgical repair of the ﬁstula will focus on the ligation of intersphincteric ﬁstula tract and many of the other series do so as well. The operation is appropriate for and, in many cases, easier to dissect free from the surround- transsphincteric ﬁstulas with length sufﬁcient enough to per- ing tissues ensuring a successful ligation [3 , 6 ]. The ﬁbers of the internal and external sphincter lithotomy position, under either regional or general anesthe- are separated and the intersphincteric groove is entered. Some surgeons use lithotomy or prone jackknife position the ﬁstula tract is identiﬁed (Fig. Bowel prepara- lated, severed, and suture ligated at both ends and severed tion consists of two phospho soda enemas the day before after removal of the ﬁstula probe (Fig. Patients are administered only a single dose of ligature obliterates the internal opening. If the tract length appropriate peri-operative antibiotics intravenously, usually warrants, a portion of the tract may be excised, increasing the cefoxitin, or ciproﬂoxacin/metronidazole if the patient is distance between the two suture-ligated ends (Fig. At the end of the procedure, a dibucaine- the internal and external sphincter are reapproximated; coated piece of gelfoam is rolled and gently inserted into the the skin is closed loosely. The patients are not admitted for and left open to drain and heal secondarily (Fig. Results/Discussion We prefer to remove a portion of the tract if the length allows it . There was no reported incontinence Department of Surgery, University of Minnesota, 1055 Westgate Drive, Ste 190 , St. Reprinted with wound is closed loosely, and external opening of the tract is enlarged to permission [3 ]. Dissection of intersphincteric groove and identiﬁcation of ﬁbrotic Drawings courtesy of Russell K. These early reports sug- illustrates the desirable points of any novel sphincter sparing gested a healing rate of 57–82 % at 9–24 weeks follow-up, technique, i. In patients in whom endo- anal ultrasound revealed failure resulting in a simple ﬁstula, Failures the patients were successfully treated with application of silver nitrate or ﬁstulotomy. The series reports an over- categories: early (procedural failure) and late (recurrence). Including these patients in the overall randomized trials is hindered by the suitability of the healing percentage, they observed a 100 % healing rate. No Furthermore, the incontinence score after 6 months was “gold-standard” sphincter sparing technique exists [21 ]. Like other sphincter sparing later studies are minimal and on par with other sphincter techniques, the operation itself is very much dependent on sparing techniques. Subsequent studies have validated the success rates of the initial technique (see Table 16. Total series have varying healing rates; however, they are small anal sphincter saving technique for ﬁstula-in-ano; the ligation of series and none of them have been validated or duplicated. Ligation of intersphincteric Conclusion ﬁstula tract: early results of a pilot study. Does ligation ceric ﬁstula tract compared with advancement ﬂap for complex of the intersphincteric ﬁstula tract raise the bar in ﬁstula surgery? Fibrin glue treatment intersphincteric ﬁstula tract in low transsphincteric ﬁstulas: a new of complex anal ﬁstulas has low success rate. Outcomes with the use of bioprosthetic grafts to reinforce successful closure with anal ﬁstula plug in cryptoglandular ﬁstulas. Ligation of the intersphincteric improve the outcome of transanal advancement ﬂap repair for high ﬁstula tract: an effective new technique for complex ﬁstulas. Dis transsphincteric ﬁstulas by additional ligation of the intersphinc- Colon Rectum. Letter to the editor on “The management of ﬁstula-in- ligation of the intersphincteric ﬁstula tract procedure: the Western ano: a plea for randomized trials and standard reporting of a case Hospital experience.
Besides the microcytase 800 mg nootropil visa medications like abilify, by Metchnikoff was the same substance Ehrlich signifcance of this temporal relationship with respect to called das Komplement buy cheap nootropil 800mg on line symptoms 9dpo. Metchnikoff’s term fxateur meant antigen administration, they observed what was necessary the same as Ehrlich’s Amboceptor. Thus, this represented to transfer the hypersensitivity passively, whether serum or the frst cellular theory of immunity which is quite different specifcally sensitized lymphoid cells. Dixon and associates developed an experimental Robert Koch, director of the Institute for Infectious Diseases model for serum sickness in the 1950s. As antigen, they in Berlin, discovered that an extract which he termed “old chose iodinated bovine serum albumin and injected it into tuberculin” was able to induce delayed hypersensitivity skin rabbits. They followed the elimination of the antigen in reactions in guinea pigs as well as in humans. Histological three phases, one of which was immune elimination, and studies of these local sites of reactivity in the skin revealed studied the development of experimentally induced path- accumulations of lymphocytes. Delayed skin reactivity was ological lesions in the vessels, kidneys, and joints of the found to be manifest within 24 h of the inoculation and to animals correlating with the immune complex content of reach maximum reactivity at about 48 h after injection. As a result of studies by these and numer- ous other investigators, immune complex disorders have Albert Calmette (1863–1933) (Figure 1. The In a popular book published in 1920, Bacillary Infection pathological alterations which they induce are governed by and Tuberculosis, he emphasized the necessity of separat- their molar ratios in the deposition sites. The Scripps Clinic and Research Foundation directed by Dixon became a center for immunology research. By applying modern techniques such as radiolabeling of serum pro- teins to a disease process which had been described almost half a century earlier, they were able to shed light on some of the more important basic mechanisms of immunologi- cally mediated human diseases. Other investigators have contributed much to our under- standing of alterations in complement during the course of disease processes. Frank James Dixon (1920–2008), American physician and researcher noted for his fundamental contributions to immu- nopathology that include the role of immune complexes in the production of disease. Dixon was the founding director of the Research Institute of Scripps Clinic, La Jolla, California. History of Immunology 33 Henry Sherwood Lawrence (1916–2004), American immu- nologist. A real breakthrough in cell-mediated immunity came with the demonstration that lymphocytes exposed to phytohe- magglutinin or other plant mitogens could be successfully cultured in vitro over extended periods of time. Besides the plant lectin’s hemagglutinat- ing property, it also had a mitogenic principle that induced blast transformation and division of lymphocytes in culture. With this wealth of new informa- tion, lymphocytes were demonstrated to release a variety of soluble mediator substances termed lymphokines. His famous text Microbiology (with Hiss), 1911, has been through two dozen editions since its frst John R. However, Rich and Lewis, in 1928, developed a than 10,000Da and was not preformed. They demon- ful transfer of reactivity to previously nonreactive animals strated that the inoculation of immunocompetent lymphoid by suspensions of lymphoid cells. Lawrence, in 1949, cells into an immunosuppressed host from whatever cause described transfer factor, which was an extract of leukocytes could lead to a reaction of the lymphoid cell graft against from tuberculin positive-reacting patients that was released the host on the basis of allogeneic differences between the upon freezing and thawing the cells, spinning down the cel- two. This graft-versus-host disease is very signifcant in bone lular debris and transferring the cell-free supernatant into marrow transplantation, or can occur following the adminis- tuberculin-negative individuals. Thus, a cell-free extract proved capable phocytes to a child with T-cell immunodefciency. The Koch phenomenon is a delayed hypersensitivity reac- Transfer factor has been extensively studied biochemically, tion in the skin of a guinea pig after it has been infected with biologically and by other methods. Robert Koch described the 34 Atlas of Immunology, Third Edition phenomenon in 1891 following the injection of either living or dead M. He observed a severe necrotic reaction at the site of inoculation, which occasion- ally became generalized and induced death. This is a demonstration of cell- mediated immunity and is the basis for the tuberculin test. In 1942, Coons perfected immuno- fuorescence to demonstrate antigens and antibodies in cells. That same year, Landsteiner and Chase reported the transfer of delayed-type hypersensitivity with lymphoid cells but not with serum. The renewed interest in cellular and associates (1956) noted that antibody production did not immunology is reminiscent of the revolution brought about take place. This important discovery, which appeared in the by Virchow when he published his lectures on cellular pathol- journal Poultry Science, subsequently permitted the demon- ogy in 1858. Nevertheless, it is important for us to trace the stration that the immune system of the chicken is divisible main events relating cells of the lymphoid system to antibody into a thymic-dependent T-cell system and a bursa-dependent production and cell-mediated immunity. Glick correctly interpreted a laboratory Murphy, of the Rockefeller Institute for Medical Research, mistake to show the role of the bursa of Fabricius in the pro- wrote a monograph on the lymphocyte. In 1945, Harris and duction of antibody and the division of labor in lymphocyte associates discussed the role of the lymphocyte in antibody populations. Wolfe, University of Wisconsin, and Robert formation, and in 1948, Astrid Fagraeus (Figure 1. Good and his colleagues in Minneapolis and the bursa of Fabricius had been removed, Glick (Figure 1. Interestingly, William Hewson’s (1739–1774) early concepts on the thymus were remarkably correct. Miller demonstrated the role of the thymus in immu- T and B lymphocytes cooperate with one another in the pro- nity while in pursuit of Gross leukemia virus in neonatal duction of an immune response. Good and associates helped establish the role of the produced some of the frst evidence that T and B cells act thymus in the education of lymphocytes and made fundamen- synergistically in the humoral response. Various phenomena, tal contributions to understanding the ontogeny and phylog- such as the switch from forming one class of immunoglobu- eny of immunity. B cells stimulated by antigen in which no cell signal His insight that the lymphocytes recirculate via the thoracic was given continued to produce IgM antibody. Such antigens duct made radical changes in the understanding of the role of were referred to as thymic-independent antigens, and others lymphocytes. In 1966, Harris, Hummeler, and Harris clearly requiring T-cell participation as thymic-dependent antigens. Thus, immune regulation was considered investigator whose principal contribution to immunology was to depend in part upon a delicate balance between helper T the demonstration that lymphocytes recirculate via the tho- lymphocytes and these T-suppressor cells. Later advances in racic duct, which radically changed the understanding of the molecular biology cast some doubt on the suppressor con- role lymphocytes play in immune reactions. The Astrid Elsa Fagraeus-Wallbom (1913– ), Swedish inves- suppressor T cell was described as a subpopulation of lym- tigator noted for her doctoral thesis which provided the frst phocytes that diminish or suppress antibody formation by B clear evidence that immunoglobulins are made in plasma cells. The inability to confrm the pres- National Bacteriological Laboratory, and in 1965, professor of ence of receptor molecules on their surface has cast a cloud immunology at the Karolinska Institute in Stockholm. She also over the suppressor cell; however, functional suppressor-cell investigated cell membrane antigens and contributed to the effects are indisputable. Antibody Production in Relation to the Development of Plasma Cells, Stockholm, 1948. In 1975, Köhler and Milstein successfully fused splenic lym- phocytes from mice forming antibody with tumor cells to Milan Hasek (1925–1985), Czechoslovakian scientist whose produce what they called a hybridoma.