The exact cause of lack of HDL-C protection in the learn more dialysis population is still obscure. Methods:  A total of 89 stable non-diabetic haemodialysis patients were recruited. Fasting serum biochemical parameters, complete blood counts and inflammatory markers were obtained before the mid-week

dialysis. Insulin resistance was assessed by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Results:  The mean age was 58.2 ± 13.1 years, 37 (41.6%) patients were male. The mean HDL-C level was 56.3 ± 17.1 mg/dL. By bivariate correlation analysis, a lower serum HDL-C level was related to higher body mass index (r = −0.425; P < 0.001), higher triglyceride (r = −0.479; P < 0.001) and higher HOMA-IR (r = −0.211; P < 0.05) levels. The serum HDL-C level was also inversely related to high-sensitivity C-reactive protein (hsCRP)

(r = −0.297; P = 0.005) and tumour necrosis factor-α (TNF-α) (r = −0.295; P = 0.005) and directly correlated with adiponectin (r = 0.560; P < 0.001). In multivariate linear regression analysis, HDL-C was found to be directly correlated with adiponectin (β-coefficient = 0.569; P < 0.001) and inversely correlated buy FK228 with TNF-α (β-coefficient = −0.292; P = 0.001). Conclusion:  A strong association between HDL-C, inflammatory surrogates, and insulin resistance in this non-diabetic, non-obese haemodialysis patient group is demonstrated. The HDL-C level is still a good parameter to screen high-risk patients. “
“Chronic kidney disease (CKD), and its associated cardiovascular events, is one of the major causes of morbidity and recurrent hospitalization in Asian Pacific region. The subtotal nephrectomy (STNx) model has remained the state-of-the-art prototype Molecular motor which closely mimics human CKD and cardiac-renal syndrome. In this article, we comprehensively outline the procedure and methodology required to develop the rat model 5/6 nephrectomy

and the associated procedures involved in assessing cardiac and renal functional outcomes. In addition, the expected functional outcomes from our own experience, and those of others, have been described. The STNx model in the rat is an established model of CKD and displays all the functional and structural hallmarks observed in the human condition. Lesser known are the cardiac effects of this model which make it ideal for studying cardiorenal syndrome. “
“Renal primary cilia are microscopic sensory organelles found on the apical surface of epithelial cells of the nephron and collecting duct. They are based upon a microtubular cytoskeleton, bounded by a specialized membrane, and contain an array of proteins that facilitate their assembly, maintenance and function. Cilium-based signalling is important for the control of epithelial differentiation and has been implicated in the pathogenesis of various cystic kidney diseases and in renal repair.

3a). In each case the ADCC responses targeted Vpu. ADCC responses to the 19 overlapping peptides comprising the Vpu peptide pool were measured and then responses were measured to three smaller pools of six or seven Vpu peptides (Fig. 3b). ADCC responses to individual Vpu peptides were then studied to identify the epitope (Figs 3c and 3d shows two separate subjects). A total of seven subjects in the LTSP cohort and no

subjects in the non-LTSP cohort had selleck chemical ADCC responses mapped within the RTV peptide pool (Table 2). Three epitopes within the Vpu pool were targeted by seven subjects, with six of these seven subjects targeting multiple Vpu peptides (an example of a subject targeting two Vpu epitopes is shown in Fig. 3d). We found that the three overlapping peptide epitopes identified (peptides 7–8: VVWTIVFIEYRKILRQRKI, see more peptides 10–12: ILRQRKIDRLIDRIRERAEDSGN and peptides 18–19: SALVEMGHHAPWDVDDL) in Vpu were targeted at higher frequencies by LTSP compared with subjects from the non-LTSP cohort. No responses to other peptides within Vpu were identified. The Vpu epitope VVWTIVFIEYRKILRQRKI

was targeted by five of the 65 subjects of the LTSP cohort and by no subjects in the non-LTSP cohort (P = 0·02, Table 2). The Vpu epitopes ILRQRKIDRLIDRIRERAEDSGN and SALVEMGHHAPWDVDDL were both targeted by four of the 65 subjects from the LTSP cohort and by no subjects in the non-LTSP cohort (P = 0·045). The ADCC responses to HIV are induced early during infection and several studies have shown that ADCC is associated with protection from SIV

disease in macaques,[4, 30] delayed progressive HIV infection in humans,[6, 8] protection from HIV-1 infection in intravenous drug users,[31] and lower genital HIV viral loads.[32] The specificities of ADCC responses associated with slower HIV-1 progression are unclear but of direct relevance as vaccine targets. In this study we investigated ADCC immune responses in HIV-infected subjects with LTSP. ADCC responses to multiple HIV peptide pools were significantly more common in LTSP subjects than in non-LTSP subjects. Specifically, we found that peptides spanning regulatory/accessory Nitroxoline proteins of HIV were targeted more frequently by LTSPs. Through a process of mapping ADCC epitopes, we found that three specific ADCC epitopes in Vpu were targeted in seven out of 65 individuals in the LTSP subjects and none of the non-LTSP subjects. Why would Vpu be targeted by ADCC and would this be relevant in HIV-infected cells? Vpu is a multifunctional protein that is expressed within the cell membrane and at least part of the protein may be accessible to ADCC antibodies.[33-37] It will be important in future studies to assess whether purified or monoclonal Vpu epitope-specific ADCC antibodies can recognize virus-infected cells.

The hypercalcemia is mediated

by extra-renal 1-alpha hydroxylation and is seen in other fungal infections in immunosuppressed patients. We suggest that PJP should be considered as a differential cause in unexplained PTH-independent hypercalcemia in renal transplant recipients even in the absence of respiratory symptoms. 288 INFECTIVE BURSITIS DUE TO MYCOPLASMA HOMINIS IN A SIMULTANEOUS PANCREAS KIDNEY TRANSPLANT RECIPIENT RS ELKHATIM1, CA MILTON1,3, DL GORDON2,3, JA BARBARA1,3, JY LI1,3 Department of 1Renal Medicine; 2Infectious Disease, Flinders Medical click here Centre and 3School of Medicine, Flinders University, Adelaide, South Australia, Australia Background: Mycoplasma hominis is a common inhabitant of the genitourinary tract and recognized as an opportunistic pathogen. We report a case learn more of infective bursitis due to M. hominis in a simultaneous pancreas kidney (SPK) transplant recipient. Case Report: A 39-year-old man with end stage renal failure secondary to diabetic nephropathy received SPK transplantation in November 2013. His post-transplant course was complicated by pancreatic graft loss due to arterial thrombosis.

Renal function has been stable (creatinine 76 μmol/L). Immunosuppressive therapy included tacrolimus, mycophenolate and prednisolone. Three weeks post-transplant, he developed a low grade fever, severe left hip pain and was unable to weight bear. The MRI showed an effusion in the trochanteric bursa with high T2 signal and oedema in the left gluteus and adductor muscles. The bursal fluid was aspirated and the culture grew M.

hominis. Muscle biopsy revealed no abnormality. He was treated with doxycycline which is planned for 6 months. He mobilized independently 4 weeks after treatment commenced. Conclusion: To the best of our knowledge, this is the first reported case of M. hominis causing bursitis in a transplant recipient. The combination of surgical manipulation of the urinary tract and immunosuppression places the renal transplant patient at high risk for GABA Receptor M. hominis infection. M. hominis lacks a cell wall, is not visualized on Gram stain and slow to grow in culture. Therefore, there is often a significant delay in diagnosis. It is important for clinicians to have high index of suspicion for atypical organisms whilst working up the cause of infection in immunosuppressed patients. The first choice antibiotic for M hominis is a tetracycline but the duration of therapy is not well established. 289 UNEXPLAINED NEPHROTIC-RANGE PROTEINURIA IN A CONSANGUINEOUS 2-YEAR-OLD BOY K BLAZE, T FORBES, C QUINLAN, A WALKER Royal Children’s Hospital, Melbourne, Victoria, Australia Background: We report a case of a consanguineous 26-month-old boy with a chromosome 2q35 deletion.

AFLP was a useful tool for identification to species-level and for the Ridaforolimus solubility dmso discrimination of inter- and intra-patient isolates. Scedosporium prolificans represents the most prevalent species in the respiratory tract of CF patients and immunocompromised patients in Northern-Spain, followed by Pseudallescheria boydii, P. apiosperma, and P. ellipsoidea. CF patients were exclusively colonised with either P. boydii or S. prolificans. Patients were colonised over years exclusively with isolates affiliated to one species, but some patients were colonised with multiple strains with different AFSP. The sum of those

co-colonising strains in one patient, may appear in vitro and in vivo as a multi-resistant S. prolificans isolate, as strains are morphologically identical and might therefore be regarded as only

one strain. A majority of Scedosporium strains (with exception of S. prolificans) were found susceptible for voriconazole and micafungin. Pseudallescheria/Scedosporium selleck products species are the second most frequently cultured filamentous fungi from the lungs of patients with cystic fibrosis (CF).1 Until 2005, only two clinically relevant species of Scedosporium were known: Scedosporium apiospermum (teleomorph: Pseudallescheria boydii) and S. prolificans. During the last 5 years, several sibling species have been introduced, 1–5 which has led to the subdivision of P. boydii into the following species: S. apiospermum (teleomorph P. apiosperma), S. aurantiacum, S. boydii (teleomorph: P. boydii), S. dehoogii, P. fusoidea, P. ellipsoidea, P. angusta, and P. minutispora. Pseudallescheria Sulfite dehydrogenase and Scedosporium infections are difficult to treat because of their therapy-refractory nature.6,7 Several infections by multi-drug resistant strains of Scedosporium species have been reported.8–11 Among these, S. prolificans is the most frequently encountered pathogen.12 Delayed diagnosis of the causative agent and ineffective antifungal therapy may have a negative impact on mortality rates of

patients suffering from systemic Scedosporium infections.13,14 Since the segregation of these sibling species, no comprehensive studies on species-specific antifungal susceptibilities and clinical epidemiology have been published. The aim of this study was to provide antifungal susceptibility patterns of isolates identified according to the taxonomy proposed by Gilgado et al.2–5 Strains were identified using AFLP analysis. Moreover, this study provides qualitative molecular epidemiology data on Northern Spanish patients colonised or infected with Scedosporium strains. In total, 60 clinical isolates from 21 patients isolated at the University Hospital Miguel Servet, located in Zaragoza (Northern-East Spain) were included in this study. The University Hospital has an adherence of more than 500 000 persons.

These three peptides were mixed and used for the peptide GDC-0973 purchase antigens of the N-terminal region. We also synthesized three peptides corresponding to the sequences of the three extracellular loops of human-M3R, the sequences of which were FTTYIIMNRWALGNLACDLW for the first extracellular loop, KRTVPPGECFIQFLSEPTITFGTAI for the second and VLVNTFCDSCIPKTFWNLGY for the third (Sigma-Aldrich Japan).

As a control peptide, we synthesized a peptide corresponding to the sequences of the third extracellular loop of human-M5 muscarinic acetylcholine receptor (M5R), the sequences of which were STFCDKCVPVTLWH (Sigma-Aldrich Japan). As a negative peptide, we also synthesized a 25-mer peptide whose sequence was SGSGSGSGSGSGSGSGSGSGSGSGS (Sigma-Aldrich Japan). Peptide solution (100 µl/well at 10 µg/ml) in 0·1 M Na2CO3 buffer, pH 9·6, was adsorbed onto a Nunc-Immuno

plate (Nalge Nunc International, Rochester, NY, USA) overnight at 4°C, and blocked with 5% bovine serum albumin (NSA) (Wako Pure Chemical Industries, Osaka, Japan) in phosphate-buffered saline (PBS) for 1 h at click here 37°C. For the dose-dependent curve, serum from anti-M3R antibodies positive SS and from HC were diluted at 1:25, 1:50, 1:100, 1:200, 1:400, 1:800 and 1:1600 in blocking buffer, and incubated for 2 h at 37°C. Serum to be examined at 1:50 dilution in blocking buffer was also incubated for 2 h at 37°C. The plates were then washed six times with 0·05% Tween20 in PBS, and 100 µl of solution of alkaline phosphatase-conjugated goat anti-human IgG (Fc; American Qualex, San Clemente, CA, USA) diluted 1:1000 in PBS was added for 1 h at room temperature. After nine washes, 100 µl Astemizole of p-nitrophenyl phosphate (Sigma) solution was added at a final concentration

of 1 mg/ml as alkaline phosphatase substrate. Plates were incubated for 30 min at room temperature in the dark, and the absorbance at 405 nm was measured by plate spectrophotometry. Measurements were performed in triplicate and standardized between experiments by using the absorbance value of the positive control. We assessed salivary secretion by the gum test. In this test, the volume of saliva is measured after chewing gum for 10 min. Histopathological findings of the labial salivary glands were classified according to Greenspan grading [7]. Total RNA was extracted from HSG cells and cDNA was synthesized by cDNA synthesis kit (Fermentas International, Burlington, Ontario, Canada). Polymerase chain reaction (PCR) was performed with cDNA using the human-M3R-specific primers [2]. The human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was amplified to assess the cDNA yield. For immunofluorescent analysis, HSG cells were precultured in two-well chamber slides for 48 h.

Because in most mouse strains worm burdens are so stable for so long during primary infections, there was little to dissect immunologically with the available tools in the 1970s and so attention turned to secondary responses. Once reliable protocols for inducing acquired immunity had been devised, it was possible then to explore the components of the host immune responses to re-infection, and initially, antibody-mediated AG 14699 mechanisms were technically the easiest to investigate. Already by the mid-1970s, it was known that infection with H. p. bakeri elicited a marked IgG1 immunoglobulin response [39-42], much of which was not specific to parasite antigens [40], and these two observations

prompted the idea that the IgG1 may be acting as a blocking antibody enabling adult worms to survive rather than being detrimental to their survival [42]. Another idea Selleck BTK inhibitor at the time was that the elevated levels of IgG1 would also shorten the half-life of IgG1 and other immunoglobulin classes in infected animals through increased catabolic activity [43]. Despite several

reported attempts at transferring immunity to H. p. bakeri by serum from immune animals, most experimenters had failed to obtain satisfactory reductions in worm burdens in passively immunized animals [44-46]. The data published by Behnke and Parish [47] in the first volume of Parasite Immunology, however, showed for the first time high levels of transferred resistance, in some cases up to 86% reduction in parasite burdens, but a crucial aspect of this work was that whilst worm burdens in immune serum-treated animals were moderately lower in the first 3 weeks after infection, a marked further loss occurred after the 4th week of infection. Thus, in addition to fewer worms completing the tissue phase of development in immune serum-treated recipients,

and the development of smaller stunted, less fecund worms, the surviving population was subsequently expelled some 4–5 weeks after the transfer of immune serum, long after most of the transferred antibodies would have been lost from the circulation by normal catabolism. These findings prompted the idea that one role of antibodies in this host–parasite system was to neutralize Sitaxentan the immunomodulatory factors (IMF) secreted by the parasites to facilitate their own survival [47] and that in the absence of effective mucosal immunodepression from adult worms, the mice were able to mount the characteristic intestinal inflammatory response that had been described and dissected so well in the case of Trichinella spiralis and Nippostrongylus brasiliensis [5, 6, 48]. Later on, it was demonstrated clearly that far from being insusceptible to mucosal responses, as had been thought earlier, when intense intestinal inflammatory responses were induced in mice by heterologous challenge, adult H. p.

Human monocyte-derived DCs exposed to MUC-1 with sialylated core 1 (sialyl-T, ST) oligosaccharides, similar to those found in epithelial tumours in vivo, display a modified phenotype with decreased expression of costimulatory

molecules (CD86, CD40), Ag-presenting molecules (DR and CD1d) and differentiation markers (CD83). Besides, markers associated with immature DC phenotype, such as, CD1a and CD206 (mannose receptor), are increased in its expression [46]. Further, by altering the cytokine repertoire of monocyte – derived DCs and switch them into IL-10high IL-12low expressing antigen presenting cells (APCs), the tumour derived mucin cripple DCs immunostimulatory (Th 1 dependent) capacity and represses their functional differentiation and maturation [47]. Mucin-dependent regulation of DC functions BMS-777607 concentration results in inadequate/impaired presentation of tumour antigens to T cells resulting in tolerance to TAAs and converts them

into suppressor/regulatory T cells [47]. Increased secretion of IL-10 interns causes T cell tolerance and anergy (Fig 2). Although direct implication of MUC-1/DF 3 antigen in the apoptosis of activated T cells [48] is partially retracted, fresh studies on T cell suppression and induction of tolerance by MUC-1 suggest that upon

MUC-1 challenge, expression of αβTCR and CD28 gets downregulated on CD8+ T cells resulting in the absence of detectable CTL activity and induction of find more peripheral tolerance [26]. Active CTLs that infiltrate the pancreatic tumour microenvironment Reverse transcriptase become cytolytically anergic and are tolerized to MUC-1 antigen, partly due to tumour microenvironment and to the presence of CD4+ CD25+ T regulatory cells that secrete IL-10 [49]. MUC-1 also suppresses the T cell proliferation, which can be reversed by IL2 [27]. However, the inhibition of cytolytic activity of human natural killer (NK) cells by ovarian cancer CA125 antigen could not be reversed by IL2 and did not involve alterations in proliferation or apoptotic induction, but related to major downregulation of CD16, suggesting that different mucins or its carbohydrate epitopes have different immune suppressive effects [50]. Thus, while expression of Sialyl Tn antigen on colorectal cancer mucins inhibits natural killer T (NKT) cell cytotoxicity [51], aberrant glycosylated forms of Lea/Leb glycans on colorectal cancers interact with DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) – C-type lectins – and impair its differentiation and functions [52], thereby influencing the prognosis of the cancer.

A complete periodontal evaluation was performed at each of the three sampling intervals for supragingival plaque, pocket depth, recession and bleeding upon probing [47,48] at four sites on each tooth: distobuccal, buccal, mesiobuccal and lingual (premolar, first and second molar) in each quadrant. Attachment level values were calculated from the pocket depth and recession measures [47,49]. Missing teeth or teeth that could not be scored were noted. A gingival bleeding score, following determination of the pocket depth measure, was obtained. Ligatures were tied Palbociclib on the first and second molar and second premolar teeth (teeth five, six and seven) using 3–0

silk sutures. To promote inflammation, the animals in the experimental group were placed on a soft chow diet, consisting of commercial chow biscuits soaked in warm water for 10 min and drained [50]. The Composite Index of Periodontal Disease (CIPD) was developed to provide a single index value that would incorporate measures of both disease extent and severity and included weighted measures of gingival bleeding and attachment loss (unpublished data). For the CIPD we weighted the variables such that the measure of destructive disease (CAL) and the extent of destruction (% of sites with CAL >2 mm) were increased in contribution to the CIPD. The CIPD

results demonstrated substantial heterogeneity of clinical presentation of the baboons, not dissimilar from that reported in human populations. A CIPD of <20 is consistent with relative Volasertib price gingival health in non-human primates; 20–<50 represents gingivitis; 50–<75 mild periodontitis; 75–<100 moderate periodontitis; and >100 severe periodontitis. Blood (approximately 10 ml) was obtained by femoral venipuncture into red-topped vacutainer tubes. The blood was allowed to clot for 1 h, centrifuged for 15 min at 3000 g and the serum removed and the serum prepared and stored at −70°C after separation into 0·5–0·75-ml aliquots. A panel of acute phase reactants, including C-reactive protein (CRP), bactericidal

permeability inducing factor (BPI) and lipopolysaccharide binding protein (LBP) were quantified using an enzyme-linked immunosorbent assay (ELISA) Rutecarpine developed in our laboratory (i.e. CRP) or obtained commercially (BPI, LBP; Hycult Biotechnology, Cell Sciences, Canton, MA, USA). Various serum cytokines/chemokines, including interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α (CCL3), regulated upon activation, normal T cell expressed and secreted (RANTES) (CCL5), IL-12p40 and MCP-1 (CCL2) were measured using a multiplex beadlyte assay on a Luminex IS-100 (Millipore, Billerica, MA, USA). PGE2 levels were assessed using a commercial ELISA kit (Assay Design, Ann Arbor, MI, USA).

28 Chagnac et al.29 demonstrated that renal hyperperfusion and hyperfiltration in severe obesity and hyperfiltration injuries can lead to the final pathway of glomerulosclerosis HKI-272 cell line especially when the size of functioning nephron mass is substantially reduced. As a result, obesity might have more adverse effects in renal transplant recipients. A major limitation in our study is the relatively small sample size. Moreover, the underweight patients (BMI <18.5) in our study were not analyzed separately because of the limited number of patients. More patients should be recruited in order to see if Asian renal transplant recipients

with low BMI values have a higher mortality when compared with recipients with normal BMI values. Furthermore, lack of data for those with primary non-functioning kidneys was another limitation in this study because obese patients tend to experience more surgical problems which may result in early technically-caused graft loss. Finally, our obese patients were older and had a higher incidence of DM, so survival analysis could still

be biased because both were independent predictors of graft outcome. However, with the use selleck chemicals llc of a multivariate model of factors associated with graft failure over time, we demonstrated that obesity was associated with decreased long-term graft survival independent of confounding factors such as DM and age. In conclusion, our study demonstrated that obesity was significantly associated with poor renal graft function and decreased patient and graft survival in Asian renal transplant recipients. In addition, overweight was associated with a lower estimated GFR. However, no significant difference in patient and graft survival could be demonstrated between the overweight group and the normal group. Further studies are required to

validate the optimal target BMI in our renal transplant recipients. Moreover, we also showed that obesity, older age, Aspartate presence of pre-transplant DM and acute rejection were all independent risk factors for graft failure in our patients. “
“Aim:  Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non-haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes-related acceleration of renal damage after ischaemia–reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non-haematopoietic erythropoietin derivative, against ischaemia–reperfusion-induced acute kidney injury in diabetic mice. Methods:  C57BL/6J mice with and without streptozotocin-induced diabetes were subjected to 30 min unilateral renal ischaemia–reperfusion injury at 1 week after induction of diabetes.

These results suggest that MS activates human PDL cells to express immune/defence genes encoding cytokines, chemokines, defensins and TLRs via a SIRT1 pathway. Orthodontic tooth movement is achieved by the remodelling of alveolar bone and periodontal ligaments (PDL) in response to mechanical loading [1]. The host response to orthodontic force has been described as an aseptic and transitory inflammation, Palbociclib mouse mediated by a variety of endogenous mediators such as cytokines and chemokines, which are involved in adaptive and innate immunity [2]. Chemokines are a superfamily of small chemotactic cytokines recognized

as regulators of inflammatory reactions, and Selleckchem U0126 the development of an appropriate immune response by co-ordinating leucocyte recruitment [3]. Mechanical stress (MS) or loading increases the production of chemokines and chemokine receptors, including interleukin (IL)-8 receptor in osteoblasts [4], IL-8 in human periodontal ligament (PDL) cells [5] and IL-11 and IL-8 in

human PDL cells [6]. A study has reported recently that chemokines such as monocyte chemoattractant protein (MCP)-1, regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP)-2 are up-regulated during rat orthodontic tooth movement [5]. However, an equibiaxial tensile strain of a low magnitude inhibits IL-1β-induced synthesis of IL-1β, IL-6 and IL-8 in PDL cells [7]. Furthermore, Lee et al. [8] reported that compressive stress

in PDL cells had no significant effect on IL-8 expression. In vivo, IL-1, IL-6, IL-8, IL-11 and tumour necrosis factor (TNF)-α are produced by inflammatory cells and periodontal tissue cells upon the application of orthodontic force [9]. The mechanisms involved in host immune responses to MS, however, are not completely understood. One host defence mechanism that involves activation of an innate immune response following exposure to the external environment is the production of defensins, small cationic anti-microbial mafosfamide peptides that are classified into the α- and β-defensin subfamilies [10]. Human β-defensin 1 (hBD-1) is expressed constitutively in epithelial cells, whereas hBD-2 and hBD-3 are expressed inducibly by bacteria, Candida albicans and inflammatory cytokines such as TNF-α and IL-1β[11]. Toll-like receptors (TLRs) are a transmembrane receptor family that plays a pivotal role in the modulation of immune response by recognizing pathogen-associated molecular patterns [12]. This recognition subsequently stimulates a sequence of signalling mechanisms, resulting ultimately in the production of various cytokines that serve as a link between innate and specific immune mechanisms.