Gorbachev, unpublished observations). Anti-CD25 mAb treatment of mice receiving CYC202 nmr WT DC increased hapten-specific CD8+ T-cell activation, while blockade of CD4+CD25+ T-cell activity did not affect hapten-specific CD8+ T-cell activation in recipients of lpr DC. Finally, CD4+CD25+ T cells suppressed the activation of hapten-specific CD8+ T cells cultured with WT but not lpr DC, indicating that negative regulation of effector CD8+ T-cell activation was mediated through effects on Fas-expressing DC but not on Fas-expressing CD8+ T cells. Together these results indicate

that CD4+CD25+ T cells regulate the priming functions of hapten-presenting DC in CHS through Fas–FasL interactions. The ability of regulatory CD4+CD25+ Akt inhibitor T cells to express FasL and kill Fas-expressing target cells has been previously reported 19, 26, 27. This report is the first, to our knowledge, demonstrating the ability of these regulatory cells to restrict DC priming

functions in CD8+ T-cell-mediated immune responses through a Fas–FasL-dependent mechanism. Furthermore, CD4+CD25+ T cells suppress CD8+ T-cell-mediated CHS responses in a non-specific manner. CD4+CD25+ regulatory T cells activated by hapten sensitization restricted the ability of LC activated by subsequent sensitization with a non-related hapten to activate CD8+ T cells specific to the latter hapten. These results are consistent with studies demonstrating non-antigen-specific suppression of T-cell-mediated autoimmune gastritis and viral responses by CD4+CD25+ regulatory T cells 28, 29. The current report further supports the hypothesis that previously activated CD4+CD25+ regulatory T cells can exert non-specific suppressor functions 28. Collectively, these studies reveal the restriction of cutaneous DC priming functions in the skin-draining LN through Fas–FasL interactions as a mechanism employed by CD4+CD25+ T cells to regulate

effector CD8+ T-cell development and expansion during cutaneous immune responses. The findings may be also applicable to the understanding of immunoregulation of other T-cell-mediated immune responses. WT and lpr female mice on the C57BL/6 background were purchased from The Jackson Laboratory G protein-coupled receptor kinase (Bar Harbor, ME). All animal experiments were performed according to the National Institutes of Health Guides for the Care and Use of Laboratory Animals and all protocols were approved by the Institutional Animal Care Use Committee (IACUC) of The Cleveland Clinic. DNFB and FITC were purchased from Sigma (Sigma Chemical, St. Louis, MO). mAb for the capture and detection of IFN-γ in ELISPOT assays, PE-labeled and biotin-labeled hamster isotype control Ab, anti-CD11c, anti-Fas and anti-FasL mAb MFL3, and streptavidin-APC, streptavidin-PE and streptavidin-FITC were purchased from BD Bioscience (San Diego, CA). AlexaFluor 647-labeled mAb RMUL.

© 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Extension of the elbow is required to oppose gravity; however, activation of the triceps brachii is

frequently underestimated during the surgical planning for brachial plexus injuries. This report aims to describe a novel technique of distal nerve transfer designed RAD001 supplier for elbow extension reconstruction in patients sustaining a C5–C7 nerve root injury. We report a patient sustaining a brachial plexus injury with triceps palsy and preserved finger extension motion; after careful intraneural dissection of the radial nerve, a fascicle innervating the extensor digitorum communis muscle was sectioned, derouted and connected to a motor branch to the lateral head of the triceps. Eleven months after surgery, elbow extension strength scored MRC M4. No deficits on finger extension were observed. © 2011 Wiley Periodicals, Inc. Microsurgery, 2012. “
“Lipoprostaglandin E1 (lipo-PGE1) Carfilzomib cell line has been found accumulating in injured vascular regions. This study examined the localization of

lipo-PGE1 in the anastomotic region. The study was divided into three parts. First, we performed anastomosis of the rat femoral artery and vein (n = 17). Lipo-PGE1 labeled with 1,1′-dioctadecyl-1,3,3′,3′-tetramethyl-indocarbocyanine was infused intravenously. Hematoxylin-Eosin staining and fluorescence microscopic findings showed that lipo-PGE1 markedly accumulated at the anastomotic site when compared to the contralateral non anastomotic region. Then, we measured laser Doppler flow (LDF) of a lower leg before and after infusion of lipo-PGE1 (n = 7) and saline (n = 7). Increase of blood flow was maintained 1 hour after the infusion of lipo-PGE1 (144% ± 25.0%) when compared to saline infusion. Finally, we performed immunohistochemical and electron microscopic examinations

and found that Lipo-PGE1 was incorporated in vascular smooth muscle cells of the anastomotic region. These findings suggest selective accumulation of the lipo-PGE1 in the vascular Protein tyrosine phosphatase anastomosis site and affect on the blood flow of repaired vessels. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“Distal fingertip replantation is associated with good functional and aesthetic results. Venous anastomosis is the most challenging procedure. For replantation with an artery anastomosis-only procedure (no venous anastomosis), some protocols have been designed to relieve venous congestion involve anticoagulation and the creation of wounds for persistent bleeding. This report presents the authors’ experience of fingertip survival after artery anastomosis-only replantation with no persistent external bleeding. Twelve Tamai zone I fingertip total amputation patients who underwent artery anastomosis-only replantations were recruited from February 2009 to June 2012. Nerve repair was performed if identified. The patients were not subjected to conventional external bleeding methods.

The authors thank Bertold Kastner

for kindly providing U1snRNP. A. K., D. H., J. L., and W. R. are supported by German Research Foundation grants KR2199/1-4, KR2199/3-1, SFB 455 and SFB 571. This work is part of the thesis of D. H. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. “
“Intravenous immunoglobulin (IVIg) therapy is widely used to treat a variety of autoimmune diseases including immunothrombocytopenia, Torin 1 clinical trial chronic inflammatory demyelinating polyneuropathy, and more recently autoimmune skin blistering diseases. Despite this well-documented clinical success, the precise molecular and cellular mechanisms underlying this immunomodulatory activity are discussed controversially. In particular, Z-VAD-FMK ic50 the clinically relevant therapeutic pathway of IVIg-mediated immune modulation has not been studied in detail. In the present study, we use four independent in vivo model systems of auto-Ab-mediated autoimmune disease to identify a common pathway explaining IVIg activity under therapeutic conditions in vivo. We show that irrespective of the in vivo model system, IVIg activity is strictly dependent on the presence of terminal sialic acid residues and

the inhibitory FcγRIIB under preventive as well as therapeutic treatment conditions. In contrast, specific ICAM3 grabbing nonintegrin related 1, previously demonstrated to be essential under preventative treatment conditions, showed a disease-specific impact on IVIg-mediated Tyrosine-protein kinase BLK resolution of established autoimmune disease. “
“Studies on the role of regulator of calcineurin 1 (RCAN1) in immunity are limited, but have demonstrated an involvement in T-lymphocyte function. Here, we expand these studies to macrophages and in vivo infection. The treatment of RAW and primary mouse macrophages

with lipopolysaccharide from Escherichia coli strongly induced RCAN1 isoform 4 (RCAN1-4), but not isoform 1. RCAN1-4 induction involved calcium, calcineurin, and reactive oxygen species. Subsequent analysis with whole bacteria including gram-negative E. coli and gram-positive Staphylococcus aureus revealed strong RCAN1-4 inductions by both, and where tested, dependence on calcium. Staphylococcus aureus cell wall components peptidoglycan and lipoteichoic acid also strongly induced RCAN1-4. In vivo, a significant induction in the proinflammatory cytokines monocyte chemotactic protein-1, interleukin-6, interferon-γ, and tumor necrosis factor-α was observed in knockout (KO) lung vs. wild-type (WT) mice 7 days after nasal infection with Fransicella tularensis. This induction was not accompanied by a significant increase in F. tularensis burden in the KO lung. Additionally, a modest increase in respiratory burst activity in KO vs. WT macrophages was observed.

In addition, the disease is affecting younger children; two recent reports from a Finish and a European cohort fully support these preoccupying conclusions [8,9]. This trend is not only valid for autoimmune diabetes. RO4929097 mouse In fact, over the past

three decades, in industrialized countries the prevalence of allergic and autoimmune diseases has increased tremendously [10]. Over the same period of time there has been an obvious decrease in these countries of the incidence of many infections due to the improvement of hygiene standards and of medical care (use of antibiotics, vaccination campaigns and better socio-economic conditions). In northern European countries, in particular, rheumatic fever and hepatitis A are good examples to illustrate this tendency. Intestinal infections are another interesting example; their frequency has decreased significantly in developed countries, especially in young children, and it has been proved that there are major quantitative and qualitative differences in the intestinal flora in developed countries versus less-developed

environments; i.e. colonization with Gram-negative bacteria occurs later. Major parasitic infections such as plasmodia or schistosoma are mostly non-existent in developed countries, and even infestation with minor parasites such as Enterobius vermicularis (pinworms) has decreased significantly over the last 10–20 years LEE011 in vitro [11]. The working hypothesis proposing a causal link between the increasing incidence of allergic diseases and the decrease of infections was referred to as the ‘hygiene hypothesis’, coined by Strachan Ergoloid in 1989 [12], and has been extended to autoimmune diseases [10].

As formulated in its original inception, the hypothesis predicts that increased hygienic living conditions, the use of antibiotics and sterile food preparation will result in the continued segregation of the immune system from positive microbial exposure, thus favouring an increased susceptibility to immune-mediated disorders. The best direct evidence in support of the hygiene hypothesis has been collected from experimental animal models. In susceptible strains of mice or rats, spontaneous autoimmune diseases develop faster and with a higher incidence in animals bred in a specific pathogen-free environment compared to those bred in conventional facilities. This is true in NOD mice and in BB rats and in rats with collagen or adjuvant-induced arthritis [10]. Disease is prevented in NOD mice by infecting the young mice with bacteria, viruses or parasites (i.e. mycobacteria, lymphocytic choriomeningitis virus, murine hepatitis virus, lactate dehydrogenase virus, schistosoma, filariae) [10]. Similarly, infection of lupus-prone New Zealand black (NZB) mice or NZB–New Zealand white (NZB–NZW) F1 hybrid mice with lactate dehydrogenase virus or Plasmodium berghei prevents disease very effectively [10].

7:1) were studied. Mean age was CHIR-99021 purchase 63.8 ± 2.9 years. The most common clinical syndrome observed in our study was nephrotic syndrome (46%), followed by acute nephritic syndrome (28%), acute kidney

injury (18%) and RPGN (13%). Sixty three % patients had secondary cause identified predominantly among them were due to post infectious glomerular nephritis (PIGN) and vasculitis, (23% & 17%) respectively. 37% patients had primary glomerular diseases (TABLE 1), which consisted of membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, IgA nephropathy, membranoproliferative glomerulonephritis. In PIGN, 65% had complete recovery, 25% had persistent renal dysfunction and 10% developed ESRD. On univariate analysis, peak serum creatinine of more than 4 mg/dl at presentation, need for dialytic support and the presence of crescents in biopsy were found to have statistical

significance for poor outcomes. In multivariate analysis, only peak serum creatinine at presentation had statistical significance- p value 0.012 (95% confidence interval 0.044 to 0.03352). In patients with Vasculitis, the outcome was poor.15% died on initial admission, 30% became dialysis dependent, 30% had persistent renal dysfunction and only 5% made complete recovery. Conclusion: Sixty four percent of glomerular diseases were due to secondary causes, primary renal disease contributed to about 36%. The Fulvestrant most common cause of glomerulonephritis was post infectious glomerulonephritis (23%). Vasculitis was the second most common cause glomerulonephritis in our elderly population, comprising 17% patients. Membranous nephropathy was the most common cause of nephrotic syndrome in our study accounting for 46% of patients with nephrotic

syndrome. NOTO RIO1, KAMIURA NOZOMU1, ONO YUICHIRO2, TABATA SUMIE2, HARA SHIGEO3, YOKOI HIDEKI4, YOSHIMOTO AKIHIRO1, YANAGITA MOTOKO4 1Department of Clinical Nephrology, Kobe City Medical Center General Hospital, Hyogo, Japan; 2Department of Clinical Aprepitant Hematology, Kobe City Medical Center General Hospital, Hyogo, Japan; 3Department of Diagnostic Pathology, Kobe University Hospital, Hyogo, Japan; 4Department of Nephrology, Kyoto University Hospital, Kyoto, Japan Introduction: Proliferative glomerulonephritis with monoclonal IgG deposits (PGN-MID) is a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. PGN-MID associated with a hematological or lymphoproliferative malignancy is rare. Now we present the first case of a patient with PGN-MID leading to the diagnosis of multiple myeloma and subsequent successful treatment by dexamethasone and bortezomib (BD). Case: A 75-year-old male with a history of hypertension presented for evaluation of progressive leg edema and fatigue. His laboratory data involved nephrotic-level proteinuria, urine occult blood, low serum albumin, and moderate renal impairment.

The current study suggests the possibility to manipulate NKT-cell activity in inflammatory disorders through intervention to the adenosine-A2AR pathway. “
“Human respiratory syncytial virus (hRSV) is the leading cause of respiratory illness in infants and young children around the globe. This pathogen, which was discovered in 1956, continues to cause a huge number of hospitalizations due to respiratory disease and it is considered a health and economic burden worldwide, especially in developing countries. The immune response elicited by hRSV infection leads to lung

and systemic inflammation, which results in lung damage but is not efficient at preventing viral replication. this website Indeed, natural hRSV infection induces a poor immune memory that allows recurrent infections. Here, we review the most recent knowledge about the lifecycle of hRSV, the immune response elicited GSK126 by this virus and the subsequent pathology induced in response to infection in the airways. Novel findings about the alterations that this virus causes in the central nervous system and potential therapies

and vaccines designed to treat or prevent hRSV infection are discussed. In 1956 Morris and co-workers isolated a cytopathogenic agent from a colony of chimpanzees at the Walter Reed Army Institute of Research, which presented a respiratory illness characterized by coughing, sneezing and mucopurulent nasal discharge.[1, 2] The infected animals showed inflammatory damage in the upper respiratory tract and this condition was rapidly spread to other members of the colony, suggesting the presence of a highly infectious pathogen.[1] Because the major sign of disease in the affected monkeys was coryza – or nasal inflammation – the pathogen was termed ‘chimpanzee coryza agent’. One

year later, Chanock and Finberg[3] reported the isolation of a similar agent from two throat swab samples of infants with severe respiratory illness. These viruses were identical to the ‘chimpanzee coryza agent’ reported by Morris, suggesting that this pathogen Carnitine palmitoyltransferase II could infect both chimpanzees and humans.[3] The unusual cytopathic effect caused by the virus on HEp-2 cells, characterized by the syncytia formation and giant cells in cultures, led to its current denomination as human respiratory syncytial virus (hRSV).[1] Human RSV is now the most important cause of acute lower respiratory tract infections (ALRTI) that include acute bronchitis, bronchiolitis, pneumonia and tracheitis in infants and young children worldwide.[4] Data from a recent meta-analysis showed that this pathogen causes up to 33·8 million ALRTI in children under 5 years of age each year, of which around 3·4 million of cases need hospital admission worldwide.[5] Further, hRSV infection causes the deaths of 66 000–199 000 children every year in developing countries.[5] For these reasons, hRSV is considered a global health burden.

The Trappin-2/Elafin and β-actin primer/MGB probe sets were obtained from Applied Biosystems assays-on-demand (ID nos Hs00160066_m1 and Selleck NSC 683864 4333762T, respectively). This primer-probe set recognizes both Trappin-2 and Elafin. PCR was conducted using the following cycle parameters: 12 min at 95° for one cycle, followed by 40 cycles of 20 seconds at 95° and

1 min at 60°. Analysis was conducted using the sequence detection software supplied with the ABI 7300. The software calculates the threshold cycle (Ct) for each reaction, which was used to quantify the amount of starting template in the reaction. The Ct values for each set of duplicate reactions were averaged for all subsequent calculations. A difference in Ct values (ΔCt) was calculated for each gene by taking the mean Ct of each gene of interest and subtracting the mean Ct for the housekeeping gene β-actin for

each cDNA sample. Assuming that each reaction functions at 100% PCR efficiency, a difference of one Ct represents a twofold difference. Relative expression levels were expressed as a fold-increase in mRNA expression and were calculated using the formula 2–ΔΔCt. The TZM indicator cell line (kindly provided by Dr Phalguni Gupta, University of Pittsburgh) is a HeLa selleck cell derivative that expresses high levels of CD4, CCR5 and CXCR4.51 The cells contain HIV long terminal repeat (LTR)-driven β-galactosidase and luciferase reporter cassettes that are activated by HIV tat expression. TZM cells were routinely subcultured every 3–4 days by trypsinization and were maintained in TZM media consisting of DMEM (Invitrogen Life Technologies) supplemented with 10% defined FBS (HyClone), 2 mm l-glutamine (Invitrogen Life Technologies) and 50 μg/ml

of primocin (Invivogen), and did not contain phenol red. TZM cells were seeded at 2 × 104 cells per well in a 96-well microtiter plate and allowed to adhere overnight at 37°. Varying doses of recombinant human Trappin-2/Elafin (Peprotech, Rocky Hill, NJ) were incubated with HIV-1 IIIB and BaL at a multiplicity of infection (MOI) of 1 for 1 hr at 37° in a final volume of 100 μl. Following incubation, the media was aspirated from TZM cells, and the virus plus Trappin-2/Elafin was added Rho to the cells along with 100 μl of TZM medium. Luciferase activity was measured after 48 hr at 37° with 5% CO2 in a humidified incubator. Briefly, the supernatants were aspirated and the cells were lysed using a Beta Glo luciferase assay substrate (Promega, Madis, WI). The light intensity of each well was measured using a luminometer. Uninfected cells were used to determine background luminescence. All infectivity assays were performed in quadruplicate. Other experiments were conducted in order to determine whether the inhibitory effects of Trappin-2/Elafin were at the cell-surface level, such as the blocking of a co-receptor.

In standard microarrays, the probes are attached to a solid surface by a covalent bond to a chemical matrix (via epoxy-silane, amino-silane, NVP-LDE225 lysine, polyacrylamide or others). DNA microarrays can be used to measure changes in gene expression levels to detect SNPs in genotyping or in resequencing mutant genomes [97]. The applicability of microarrays in genomics research has expanded with the evolution and maturation of the technology, but a major issue concerning these methods is still represented by complex data analysis and bioinformatics [98]. In fact, during the last few years, many bioinformatics approaches have been developed to

identify more clearly the genetic/genomic bases of complex and polygenic diseases. Traditionally, this objective has been reached by measuring expression levels of thousands of genes buy FK866 simultaneously and identifying, through different statistical algorithms (e.g. t-tests, non-parametric tests, Bayesian models), those genes expressed differentially among two or more different phenotypic conditions. However, it now well known that results obtained by these methodologies are, most of the time, over-optimistic and poorly reproducible. In addition, it has been demonstrated extensively

that pathway analysis rather than single gene evaluation has many advantages. In a recent paper, Abatangelo et al.[99] reviewed the main technical aspects of pathway analysis and provided practical advice to perform data analysis more efficiently. Therefore, it seems clear that, in future, researchers involved in pharmacogenomics studies

should combine all available methods (associative, U0126 supplier predictive) to obtain more reliable and reproducible results. However, considerable effort needs to be made to produce simple algorithms and statistical methods to identify easily genes expressed differentially or gene variants relevant to drug therapies. Nephrology researchers have begun to employ these innovative high-throughput procedures to identify the whole basal expression profile of normal or pathological human kidney [100], to select biomarkers predicting acute and chronic allograft outcomes [101,102] and to assess more clearly the intricate molecular pathways associated to the pathogenesis and onset of several immunological renal diseases [103,104]. On the contrary, only few reports to date have been published describing the multi-genetic influence on drug response in nephrology. Recently, our group, applying a classical pharmacogenomic approach, has identified a new potential therapeutic target responsible for MPA anti-fibrotic and anti-proteinuric effects. Microarray analysis has revealed that neutral endopeptidase (NEP), a gene encoding for an enzyme involved primarily in the degradation of angiotensin-II, was the most significant up-regulated gene in a cohort of stable renal transplant recipients 3 months after conversion from AZA to MPA.

2A). Furthermore, animals were RNA Synthesis inhibitor immunized

with phOx emulsified in CFA and again a significant activation of BM eosinophils and an enhanced expression of cytokine mRNA were observed. Indeed, primary immunization with alum-precipitated phOx or injection of phOx emulsified in CFA equally activated eosinophils (Fig. 2B). These data show that the activation of eosinophils is independent of the type of adjuvant used for primary immunization. The specific effect of antigen on eosinophil activation and cytokine expression was even more pronounced when animals were boosted with soluble phOx. Six days after a secondary challenge with soluble antigen, a considerable increase in the level of IL-4, IL-6 and APRIL mRNA was seen, but only in animals which had previously been primed with antigen. No increase was seen in animals primed with alum alone or with PBS (Fig. 2A). Interestingly, even 60 days after antigenic boost, which is 4 months after priming the immune response with alum and antigen, eosinophils still showed enhanced levels of cytokine expression (Fig. 2A). Thus, antigen-dependent activation of the immune system leads to a stable production of mRNA for the plasma cell survival factors APRIL, IL-6, IL-10 and also TNF-α (Fig. 2C). Staining eosinophils with

APRIL and IL-6-specific antibodies showed that upon secondary immunization, BM eosinophils carry abundant APRIL and IL-6 protein in their granules (Fig. 2C). To investigate whether immunization with the T-cell-dependent antigen phOx affects the numbers of eosinophils in JNK signaling pathway inhibitors BM and spleen, animals were immunized with antigen, which had been for either precipitated

with alum or emulsified in CFA. In the first days after primary immunization, the percentage of CD11bintGr-1loSiglec-Fhi eosinophils increased in both BM and spleen (Fig. 3A). Maximal frequencies of eosinophils were found in the BM 6 days after immunization, whereas in the spleen the highest values were observed only on day 12 (Fig. 3B). In the BM, elevated levels of eosinophils were observed even 60 days after primary immunization. In contrast, the frequency of eosinophils in spleen declined with time after primary immunization to nearly baseline levels (Fig. 3B). Boosting animals with soluble antigen induced a further increase in the frequency of eosinophils in spleen and BM (Fig. 3B). In both, animals primed with phOx-CSA/alum or phOx-CSA/CFA, the number of eosinophils found in the BM 6 days after secondary immunization was even higher than after primary immunization (Fig. 3B). After secondary challenge with antigen, the rise in the number of eosinophils was only transient. Indeed, 12 days after the secondary boost eosinophil numbers were back down to the level present before the injection of soluble antigen (Figs. 3 and 4).

The function of circulating IgD has been debated for some time, but it was recently shown to bind to an unknown receptor on basophils, and cross-linking of IgD on the basophil surface leads to the production of inflammatory anti-microbial products and IL-4 (17). IL-4 from basophils was also recently shown to be crucial in the initiation and maintenance of TH2 responses

(18–20). Therefore, it is tempting Opaganib price to speculate that hookworm suppresses the IgD response in infected individuals to suppress the development of a potentially host-protective TH2 response. All data on humoral responses to hookworms in humans have come from blood serum studies. However,

in the context of a parasite that resides in the gut lumen, such as hookworm, the mucosal and faecal antibody titres may be important in immunity. A recent study in the hamster model of Ancylostoma ceylanicum infection showed detectable levels of CH5424802 concentration parasite-specific IgA in the faeces of multiply infected hamsters, associated with resistance to re-challenge (21). Further studies in human hookworm-endemic populations are needed to see whether the mucosal IgA response is important in resistance, as this may have implications for vaccine design. Studies on the cytokines produced in hookworm infections show variable results: experimental and endemic (chronic) infections result in different cytokine profiles, indicating that repeated infection in endemic areas may induce a qualitatively and quantitatively different response (5,22). However, differences in techniques used may also have a role here: many studies use whole blood culture rather than PBMC purified cultures, which can result in lower concentrations of some cytokines (23), possibly leading to levels falling below the limits of detection. In addition, some groups have stimulated cell cultures with antigens derived from the dog hookworm,

A. caninum, rather than antigens from human hookworms because of the difficulty in obtaining the latter (24–26). Gastrointestinal parasitic infections PJ34 HCl have been long regarded to induce polarized TH2 responses, with production of IL-4, IL-5, IL-13 and IgE, which are necessary for their expulsion (27). TH2 responses have been shown to be somewhat effective against controlling hookworm infections, with elevated IL-5 positively correlating with resistance to reinfection after drug cure in humans (28). In recent years, evidence has mounted that the immune response to hookworms may not be as simple as a polarized TH2 response. As mentioned previously, immune responses differ between experimental primary infection and responses in presumably multiply exposed endemic populations.