Immunobiology

Albuminuria was strongly predicted by GN score (r = 0.62-0.81, p < 0.001). Thus, C5aR-signaling in BM-derived cells is essential in this accelerated LN model, an effect cancelled in mice with global C5aR deficiency. The relevant cell(s) through which C5aR signals enhance disease is the topic of ongoing studies.

common polymorphism Y402H in CFH domain 7 is associated with host susceptibility to S. pyogenes infections and that a recombinant CFH construct consisting of domains 5-7 (CFH5-7) can impair complement evasion and survival of S. pyogenes in human blood. E. coli and S. aureus are the most common bacterial pathogens isolated from blood culture of patients with sepsis but neither is known to bind CFH directly on its surface. While working with S. pyogenes we had used these species as negative controls but surprisingly found that survival of some isolates was impaired in the presence of the CFH5-7. Therefore, we wanted to study whether the Y402H polymorphism is associated with host susceptibility to sepsis caused by E. coli or S. aureus and to use blood isolates to study whether CFH5-7 could impair survival of these bacteria in serum or full blood in vitro. Human DNA was isolated from blood culture samples of septic patients for genotyping of the Y402H polymorphism. Several bacterial blood isolates were incubated in pool of fresh normal human sera (E. coli) or lepirudin anticoagulated blood (S. aureus) and their survival in vitro with or without CFH5-7 fragment was analyzed using a modification of most probable number method (MPN) and the pour plate method. The 402hh genotype was more frequent in patients with E. coli or S. aureus sepsis (n = 58) than in Finnish blood donors (n = 350) (p = 0.05) indicating that the Y402H polymorphism is associated with sepsis caused by these pathogens. Survival of some E. coli and S. aureus isolates in serum or blood, respectively, was also impaired in the presence of CFH5-7 indicating that CFH domain 7 is involved in immune evasion by these pathogens.

Murine monoclonal antibodies, HB88A, B29A and DH59B separately identify the CD2 T lymphocyte molecule, a unique pan-B lymphocyte surface marker and a pan-granulocyte/monocyte surface molecule, respectively, in the horse. Specificity was shown by two-color immunofluorescent flow cytometry and immunofluorescent microscopy. MAb HB88A reacted with a 52 kDa pan-T lymphocyte molecule present on 75 % ± 7 of peripheral blood lymphocytes (PBL) (n = 15 horses). It also reacted with lymphocytes restricted to T lymphocyte dependent areas of lymph node and spleen. Specificiry of mAb HB88A to CD2 was demonstrated by its reactivity to COS 7 cells which expressed a transfected 1.5 kb equine lymphocyte c-DNA clone having 77.5 % overall sequence homology with human CD2 c-DNA. MAb B29A reacted with a pan-B lymphocyte specific cell surface complex, 143, 72, 50, 40, 27 and 14.5 kDa, present on 19% ± 7 of PBL (n = 15 horses). This complex has not been described in the horse or other species. MAb DH59B reacted with a 96 kDa pan-granulocyte/monocyte specific surface protein and identified macrophages and Kupffer cells in equine tissue sections. Together these mAbs can be used to identify and quantitate the major constituents of equine leukocytes. Abbreviations: PBL = peripheral blood lymphocytes; FACS = fluorescent-activated cell sorting; PBS = phosphate-buffered saline; mAb = monoclonal antibody; PBMC = peripheral blood mononuclear cells; r-XIgM = fluorescein-labeled polyclonal rabbit anti-equine IgM antibody; BSA = bovine serum albumin; PBS-BSA = PBS with 0.5 % BSA and 0.02 % sodium azide; PAGE = polyacrylamide gel electrophoresis mAbs define equine leukocytes . 49

Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate (r ¼ 0.40; po0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B.

One-third of the global human population harbours Mycobacterium tuberculosis in dormant form. This dormant or latent infection presents a major challenge for global efforts to eradicate tuberculosis, because it is a vast reservoir of potential reactivation and transmission. This article explains how the pathogen evades the host immune response to establish a latent infection, and how it emerges from a state of latency to cause reactivation disease. This review highlights the key factors responsible for immune evasion and reactivation. It concludes by identifying interesting candidates for drug or vaccine development, as well as identifying unresolved questions for the future research.

List of abbreviations: 2-AG, 2-arachidonoylglycerol 5-HIAA, 5-hydroxyindoleacetic acid AA-5-HT, N-arachidonoyl-serotonin ACTH, adrenocorticotrophic hormone BDNF, brain-derived neurotrophic factor BLA, basolateral amygdala CB, cannabinoid CCK, cholecystokinin CRF, corticotrophin releasing factor DOPAC, 3,4-dihydroxyphenylacetic acid ERK, extracellular signal-regulated kinase FAAH, fatty acid amide hydrolase FCA. Fear-conditioned analgesia GABA, gamma-aminobutyric acid HPA, hypothalamo-pituitary-adrenal MGL, monoacylglycerol lipase mRNA, messenger ribonucleic acid PAG, periaqueductal grey PTSD, post-traumatic stress disorder PVN, paraventricular nucleus RVM, rostral ventromedial medulla

Towards the end of the 1990s, the two opposing theories on immunosurveillance and immunostimulation were extensively studied by researchers in an attempt to understand the complex mechanisms that regulate the relation between tumors and the host's immune system. Both theories probably have elements that would help us to comprehend how the host can induce anti-tumor clinical responses through stimulation of the immune system and which could also give us a deeper insight into the mechanisms of tumor immunosuppression. The model that most resembles the behavior of tumor cells in terms of growth, infiltration and suppression of the immune system of the environment in which they live is undoubtedly that of the embryonic cell. The fetus behaves like an allogenic transplant within the mother's body, using every means it has to escape from and defend itself against the mother's immune system. The majority of these mechanisms are the same as those found in tumor cells: antigenic loss, lack of expression of classic HLA-I molecules, production of immunosuppressive cytokines, induction of lack of expression of costimulatory molecules in antigen presenting cells, and induction of apoptosis in infiltrating lymphocytes, with activation of a type Th2 regulatory lymphocyte response. A careful and comparative study of key mechanisms capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells could prove immensely valuable in designing new strategies for anti-tumor immunotherapy.

Hemocytes play an important role in internal defense in mollusk bivalves; they are generally divided into granular and hyaline types, where the granules possess molecules to combat foreign particles. We investigated the morphology, staining reactions, and immune-related activities of hemocytes from the pectinid lions-paw scallop Nodipecten subnodosus. We showed that, in contrast to the conditions in most bivalves and similar to other pectinids, no granular cells were observed; only very few semi-granular cells were present and the large majority of cells were hyalinocytes and blast-like cells. The cytoplasm in many hyalinocytes showed vesicles of various sizes, but none with the staining characteristics of typical granules. When hemolymph was removed from these scallops, the plasma did not clot and the hemocytes rapidly adhered to one another in suspension. When living hemocytes were placed on a glass surface, they clustered into groups of various sizes; within minutes, pseudopods extended from the cells and outward migration began. Many cells spread to form extensive networks of flat cells, and other undifferentiated cells did not spread and kept a rounded morphology. Some hemocytes were immunologically active because they phagocytize Escherichia coli bacteria. Hemocytes expressed the carbohydrates residues N-acetyl-d-glucosamine, ␣-d-glucose, ␣-d-mannose, and ␣-L-fucose moieties, and cytochemical assays showed activity of acid phosphatase, specific esterase, and non-specific esterase, enzymes commonly associated with lysosomes and immunologic activity. These observations serve as a useful tool for further investigation of morphofunctional studies and physiological status of scallops.

In mice, monoclonal antibody (mAb) to the al integrin abrogate gastro-intestinal damage during graft-versus-host-disease (GVHD), suggesting anti al mAb as candidates for treatment in humans as well. Our current data show that one such reagent, mAb 1B3.1, when immobilized to plastic wells via rabbit-anti murine (ram) immunoglobulin (Ig) induces a protein kinase-dependent spreading of activated human T cells. Furthermore, it significantly increases the proliferative response, and expression of interleukin-2 (IL-2) receptors (R) and CD69, of resting T cells, expressing minimal integrin on the cell surface, to sub-optimal stimulation by anti-C03 mAb. We found, in addition, that mAb IB3.1 a) immuno-precipitates a 1~1 integrins from cell-surface iodinated canine epithelial cells b) is highly reactive with canine T cells after their activation and c) inhibits adhesion of canine T cells to collagen IV: Despite the potential ability of the mAb to co-activate T cells in vitro, two dogs that received 4 injections of 0.5-0.3 mg/Kg of mAb 1B3.1 remained healthy, developing only marginal transient lymphopenia. Injection of 0.75mg/Kg in a third dog induced a more marked lymphopenia, and an additional dose of 1.0 mg/Kg 2 weeks later was followed by gastrointestinal hemorrhage. Importantly, the lymphopenia was associated with a greater and more persistent decrease of C08+ than of C04+ T cells, leading to an increase in the C04/C08 ratio 24 hours after the injection. Thus, despite it's co-activating effects in vitro, administration of this mAb in vivo is feasible when appropriately dosed, and may have immuno-modulatory effects.

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic waterimmersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-a) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-a levels. These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

Antigen presenting cell (APC) function is central to the development of an effective anti-viral immune response. Among APC, monocytes, macrophages and dendritic cells (DC) form the principal non-T cell compartment involved in in vivo HIV infection, and these cells play important and well-established roles in multiple aspects of viral pathogenesis. HIV infection may result in APC defects, which could ultimately contribute to the loss of CD4 + T cell responses observed early in HIV infection, when the CD4 + T cell number is still within the normal range. Extensive in vitro studies have demonstrated that the envelope glycoproteins of HIV-1 exert profound influences on various cell populations of the immune system, including hematopoietic progenitors, T and B lymphocytes, monocytes/ macrophages and DC, as well as on neuronal cells. The demonstration of the presence of envelope proteins both free in the circulation and bound to the surface of CD4 + cells suggests that gp120 interactions with non-infected cells can influence cellular functions in vivo, thus contributing to the immunopathogenesis of AIDS. This paper provides an overview of the present knowledge on gp120 binding, signal transduction triggering and interference with macrophage and DC functions and it highlights the importance of this interaction in the pathogenesis of AIDS.

C1q binds to many non-self and altered-self-materials. These include microorganisms, immune complexes, apoptotic and necrotic cells and their breakdown products, and amyloids. C1q binding to amyloid fibrils found as extracellular deposits in tissues, and subsequent complement activation are involved in the pathology of several amyloid diseases, such as Alzheimer's disease. Prion diseases, such as scrapie also involve formation of amyloid by polymerization of the host prion protein (PrP). Complement activation is likely to contribute to neuronal damage in the end stages of prion diseases, but is also thought to participate in the initial infection, dissemination and replication stages. Infectious prion particles are likely to bind C1q and activate the complement system. Bound complement proteins may then influence the uptake and transport of prion particles by dendritic cells (DCs) and their subsequent proliferation at sites such as follicular DCs. r

A crustin-like antimicrobial peptide from the haemocytes of giant tiger shrimp, Penaeus monodon was partially characterized at the molecular level and phylogenetic analysis was performed. The partial coding sequence of 299 bp and 91 deduced amino acid residues possessed conserved cysteine residues characteristic of the shrimp crustins. Phylogenetic tree and sequence comparison clearly confirmed divergence of this crustin-like AMP from other shrimp crustins. The differential expression of the crustin-like AMP in P. monodon in response to the administration of various immunostimulants viz., two marine yeasts (Candida haemulonii S27 and Candida sake S165) and two ␤-glucan isolates (extracted from C. haemulonii S27 and C. sake S165) were noted during the study. Responses to the application of two gram-positive probiotic bacteria (Bacillus MCCB101 and Micrococcus MCCB104) were also observed. The immune profile was recorded pre-and post-challenge white spot syndrome virus (WSSV) by semi-quantitative RT-PCR. Expressions of seven WSSV genes were also observed for studying the intensity of viral infection in the experimental animals. The crustin-like AMP was found to be constitutively expressed in the animal and a significant down-regulation could be noted post-challenge WSSV. Remarkable down-regulation of the gene was observed in the immunostimulant fed animals pre-challenge followed by a significant up-regulation post-challenge WSSV. Tissue-wise expression of crustin-like AMP on administration of C. haemulonii and Bacillus showed maximum transcripts in gill and intestine. The marine yeast, C. haemulonii and the probiotic bacteria, Bacillus were found to enhance the production of crustin-like AMP and confer significant protection to P. monodon against WSSV infection.

Cytotoxicity is one of the major defence mechanisms against both virus-infected and tumor cells. Radioactive 51 chromium ( 51 Cr) release assay is a ''gold standard'' for assessment of natural killer (NK) cytolytic activity in vitro. Several disadvantages of this assay led us to design alternative tools based on flow cytometry analysis. Four different fluorescent dyes, calcein acetoxymethyl ester (CAM), carboxyfluorescein succinimidyl ester (CFSE), Vybrant DiO (DiO) and MitoTracker Green (MTG) were tested for labeling of NK target K-562 cells. Target staining stability, spontaneous release of fluorochromes and subsequent accumulation in bystander unstained cells were measured using fluorimetry and flow cytometry. Healthy donor peripheral blood mononuclear cells and affinity column purified NK cells were used as effectors coincubated with target K-562 cells at different E:T ratios for 3 h and 90 min, respectively. Fluorescent probe 7-amino-actinomycin D was used for live and dead cell discrimination. Bland-Altman statistical method was applied to measure true agreement for all CAM-51 Cr, CFSE-51 Cr, DiO-51 Cr and MTG-51 Cr pairs analyzed.

The immune response of ruminants to Johne's disease has been long associated with a cell mediated immune (CMI) response in the early stages of infection with a switch to an antibody response later as the disease manifests. This study examines the immune response in sheep to Mycobacterium avium subspecies paratuberculosis (Map) infections, specifically the antigen-specific interferon gamma (IFN-␥) and antibody responses as surrogates of T helper-1 (Th1) and Th2 immunity. The difference in IFN-␥ production between paucibacillary and multibacillary diseased animals was also examined. The results show that sheep are more likely to have a combined antibody and IFN-␥ response (seen in 50% of the animals) rather than a switch from an IFN-␥ to antibody response (39%). Multibacillary diseased animals were found to have a decrease in functional ability to produce IFN-␥ from cells stimulated with MAPspecific antigens and non-specific mitogens. This indicates that the immune responses to Map infections are more complex than thought, where both antibody and cellular immunity may play key roles in the early stages of disease manifestation or resistance. The loss of the cellular response in multibacillary animals may be an indication that the entire immune response is dysfunctional, with the cell mediated responses becoming affected first.

To compare the concentrations of cytokines belonging to Th17 axis (interleukin (IL)-17 and IL-23) and Th1 axis (IL-12 and interferon (IFN)-gamma) in obese and lean women, and to investigate their relationships with the proinflammatory adipokine leptin, proinflammatory cytokine macrophage migration inhibitory factor (MIF) and anthropometric and metabolic parameters of obesity. Cross-sectional study. Twenty-six obese women (age 20-52 years, body mass index (BMI): 30-48 kg/m(2)) and 20 healthy lean women (age 23-46 years, BMI: 18-25 kg/m(2)). Plasma levels of cytokines and leptin, BMI, waist circumference (WC) and insulin resistance index HOMA (homeostatic model assessment). Blood concentrations of IL-17, IL-23, MIF and leptin, but not IL-12 or IFN-gamma, were higher in obese compared with lean women (P=0.002, 0.046, 0.006 and 0.002, respectively). There was a positive correlation between IL-17 and IL-23 (r(s)=0.530), which was at the border of statistical significance (P=0.065). Neith...

Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs that links innate and adaptive immunity. They sense viral and bacterial pathogens and release high levels of Type I interferons (IFN-I) in response to infection. pDCs were shown to contribute to inflammatory responses in the steady state and in pathology. In atherosclerosis, pDCs are involved in priming vascular inflammation and atherogenesis through production of IFN-I and chemokines that attract inflammatory cells to inflamed sites. pDCs also contribute to the proinflammatory activation of effector T cells, cytotoxic T cells, and conventional DCs. However, tolerogenic populations of pDCs are found that suppress atherosclerosis-associated inflammation through down-regulation of function and proliferation of proinflammatory T cell subsets and induction of regulatory T cells with potent immunomodulatory properties. Notably, atheroprotective tolerogenic DCs could be induced by certain self-antigens or bacterial antigens that suggests for great therapeutic potential of these DCs for development of DC-based anti-atherogenic vaccines.

Host defence peptides (HDPs) are short cationic molecules produced by the immune systems of most multicellular organisms and play a central role as effector molecules of innate immunity. Host defence peptides have a wide range of biological activities from direct killing of invading pathogens to modulation of immunity and other biological responses of the host. HDPs have important functions in multiple, clinically relevant disease processes and their imbalanced expression is associated with pathology in different organ systems and cell types. Furthermore, HDPs are now evaluated as model molecules for the development of novel natural antibiotics and immunoregulatory compounds. This review provides an overview of HDPs focused on their antimicrobial-immunomodulatory duality.

Inflammation plays an important role in protective immunity against fungi, including the opportunistic pathogen, Aspergillus fumigatus. The balance between pro-inflammatory and anti-inflammatory cytokines is a key determinant of infection outcome. Since macrophage migration inhibitory factor (MIF) is an upstream regulator of many cytokines, we analyzed herein the role of endogenous MIF in the host control of hematogenously disseminated aspergillosis using MIF −/− mice. As revealed by their mortality rate, MIF −/− mice were more susceptible to disseminated infection than WT mice. Moreover, pharmacologic inhibition of MIF with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester, (ISO-1) increased the susceptibility of WT mice to lethal infection. The higher tissue fungal burden early in sublethal infection indicated increased susceptibility of MIF −/− mice to sublethal infection as well. Substantial down-regulation of innate and acquired antifungal responses, characterized by decreased production of IL-1␤, IL-6, TNF-␣, IFN-␥ and IL-17 in the spleen was noted in sublethally infected MIF −/− mice. In contrast, IL-4 was higher in MIF −/− than in WT mice. Taken together, our findings show that MIF contributes to host resistance against progressive invasive A. fumigatus infection by controlling downstream pro-inflammatory versus anti-inflammatory cytokine production thus determining the outcome of infection.

The work of immunologists, cell biologists and parasitologists in the field of leishmaniasis has not only provided important insights into the immunopathogenesis of this disease, but also yielded fundamental contributions to our understanding of basic immunological phenomena and of host-parasite interactions. The ability of recombinant interferon-y to induce the microbicidal activity of phagocytes and the opposite effect of inhibitory cytokines was first demonstrated with Leishmania-infected macrophages. The selective development of protective and disease-mediating CD4+ T lymphocytes as well as their differential influence on the course of the disease has been long investigated in the murine Leishmania major model and now represents one of the best examples for the in vivo induction of type 1 versus type 2 T helper lymphocytes. At the same time, this model has also been extensively used for immunization studies and cytokine therapy, which shed light on the functions of cytokines in vivo as well as on the mechanism(s) of disease resistance and susceptibility. In this review we will discuss the present picture of the cytokine network in murine L. major infections. Abbreviations: APC = antigen-presenting cell; ASF = activation suppression factor; CGRP = calcitonin-gene related peptide; GM-CSF = granulocyte macrophage colonystimulating factor; gp 63 = 63 kDa surface glycoprotein of Leishmania; lFN = interferon; IL = interleukin; iNOS = inducible nitric oxide synthase; LC = Langerhans cells; L. major = Leishmania major; L-NMMA = N G monomethyl-L-arginine; LPG = lipophosphoglycan; LPS = bacterial lipopolysaccharide; mAb = monoclonal antibody; MDF = macrophage-deactivating factor; NK cells = natural killer cells; NO = nitric oxide; RNl = reactive nitrogen intermediates; ROl = reactive oxygen intermediates; scid = severe combined immunodeficiency; sIL-4R = soluble IL-4 receptor; SLA = soluble leishmanial antigen; TCR = T cell receptor; Tho (ThI, Th2) = type 0 (type 1, type 2) T helper cells; TNF-a = tumor necrosis factor-a fected BALB/c mice into protected normal or nude BALB/c mice (34, 40, 42) (R, E) • transfer of CD4+ T cells from s.c. immunized BALBI c mice into naive BALB/c mice (48) (E)

An unexplored nexus in Drosophila Immune deficiency (IMD) pathway is TGF-beta Activating Kinase 1 (TAK1), which triggers both immunity and apoptosis. In a cell culture screen, we identified that Lysine at position 142 was a K63-linked Ubiquitin acceptor site for TAK1, required for signalling. Moreover, Lysine at position 156 functioned both as a K63 and a K48-linked Ubiquitin acceptor site, also necessary for TAK1 activity. The deubiquitinase Trabid interacted with TAK1, reducing immune signalling output and K63-linked ubiquitination. The three tandem Npl4 Zinc Fingers and the catalytic Cysteine at position 518 were required for Trabid activity. Flies deficient for Trabid had a reduced life span due to chronic activation of IMD both systemically as well as in their gut where homeostasis was disrupted. The TAK1-associated Binding Protein 2 (TAB2) was linked with the TAK1-Trabid interaction through its Zinc finger domain that pacified the TAK1 signal. These results indicate an elaborate and multi-tiered mechanism for regulating TAK1 activity and modulating its immune signal. We will discuss why trabid-deficient flies exhibited a dramatically reduced life span and explore how different tissues exhibit variable levels of tolerance to persistent immune signalling.

Respiratory viral infections have been implicated in the origin of, protection from and exacerbation of allergy-related symptoms in a variety of ways. Viral infections are closely linked to infantile wheezing. Severe bronchiolitis in early infancy may predispose to chronic childhood asthma as well as allergic sensitization; alternatively it could represent a marker of susceptible individuals. In contrast, repeated mild infections in early life may have a protective role in the development of asthma or atopy by driving the immune system towards Th1 responses. However, evidence on this hypothesis is not consistent as far as respiratory viruses are concerned. Several factors, including the presence of an atopic environment, timing of exposure and severity of the infection, interactively contribute to the allergy-infection relationship. In the present report, recent data on the role of viral infections in the development and progression of allergy and asthma are reviewed.

Plants are equipped with a range of defence mech- anisms against herbivorous insects. In cruciferous species, jasmonic acid, salicylic acid, and ethylene along with glucosinolates and their hydrolysis prod- ucts play important roles in plant protection and plant- insect communication. In turn, a number of herbivores have adapted to plants that contain glucosinolates. As a result of adaptation to their

Macrophage migration inhibitory factor (MIF) was first described as a cytokine 50 years ago, and emerged in mammals as a pleiotropic protein with pro-inflammatory, chemotactic, and growthpromoting activities. In addition, MIF has gained substantial attention as a pivotal upstream mediator of innate and adaptive immune responses and with pathologic roles in several diseases. Of less importance in mammals is an intrinsic but non-physiologic enzymatic activity that points to MIF's evolution from an ancient defense molecule. Therefore, it is not surprising that mif-like genes also have been found across a range of different organisms including bacteria, plants, protozoa, helminths, molluscs, arthropods, fish, amphibians and birds. While Genebank analysis identifying mif-like genes across species is extensive, contained herein is an overview of the nonmammalian MIF-like proteins that have been most well studied experimentally. For many of these organisms, MIF contributes to an innate defense system or plays a role in development. For parasitic organisms however, MIF appears to function as a virulence factor aiding in the establishment or persistence of infection by modulating the host immune response. Consequently, a combined targeting of both parasitic and host MIF could lead to more effective treatment strategies for parasitic diseases of socioeconomic importance.

Anaemia is a frequent complication of chronic infectious diseases but the exact mechanisms by which it develops remain to be clarified. In the present work, we used a mouse model of mycobacterial infection to study molecular alterations of iron metabolism. We show that four weeks after infection with Mycobacterium avium BALB/c mice exhibit a moderate anaemia, which cannot be explained by elevated hepatic hepcidin mRNA expression. Instead, the mice respond with increased mRNA expression of ferroportin (Slc40a1), ceruloplasmin (Cp), hemopexin (Hpx), hemeoxygenase-1 (Hmox1) and lipocalin-2 (Lcn2). Both the anaemia and the mRNA expression changes of iron-related genes are largely absent in C.D2 mice which bear a functional allele of the Nramp1 gene. These data suggest that anaemia due to a chronic infection with M. avium develops independently of elevated hepcidin expression and possibly involves ferroportin and/or lipocalin-2.

The CD300 glycoproteins are a family of related leucocyte surface molecules that modulate a diverse array of cell processes via their paired triggering and inhibitory receptor functions. All family members have a single Ig-V like domain and they share a common evolutionary pathway. At least one member of the family has undergone significant positive selection (ranked second in the top 50) indicating a need to maintain some crucial function. Here we have reviewed the CD300 family members, and their expression on cells of the monocyte and dendritic cell lineages. The consequences of CD300 molecule expression by these leucocyte lineages are only now beginning to be understood. The ability to fine tune monocyte and dendritic cell function and immune responses highlights several potential options to exploit these molecules as therapeutic targets in chronic inflammatory diseases, allergy and other disease states.

We report here the development of hybrid cell producing monoclonal antibodies (MAbs) specific for HBsAg using hybridoma technology. BALB/c mice were immunized with a mixture of HBsAg subtype "ad" and subtype "ay." Spleen and lymph nodes were used as a source of high-titer antibody producing lymphocytes and removed and fused with myeloma cells of F0 origin separately. In the five fusion experiment, enzyme-linked immunosorbent assay (ELISA) tests showed that among 1594 hybridomas only 5 hybrids (9D12, 2B7, 4G5, 2G3, and 6E7) reacted with HBsAg. These MAbs were characterized for use in the development of diagnostic kits based on sandwich ELISA test system. The MAbs were conjugated with horseradish peroxidase (HRP) and used in the quick sandwich ELISA system. This system is a quite practical and time-saving test system when compared with common and commercial sandwich ELISA for diagnosis of hepatitis B surface antigen in human serum.

We have recently described the existence of two subsets of porcine monocytes based on the expression ofCD163. In this study we compare the expression of a number of cell surface antigens in CD163+ and CD 163-monocyte subsets using three-color flow cytometry. These monocyte subsets show differences with respect to the expression of MHC class II antigens (SLA-DR and DQ) and a variety of adhesion molecules (CDlla, wCDllc, wCD29, CD49d) that are expressed at higher levels on CD 163+monocytes, and of CD 14 that is higher expressed by CD 163-cells. These differences on phenotype could reflect differences in the ability of these two subsets to migrate to tissues and may account for the higher allostimulatory capacity of CD 163+ cells. In some aspects, the phenoype of CD 163+ monocytes resembles that of mature macrophages. In vitro serum-induced maturation of monocytes into macrophages lead to the expression of SWC9 together with an increase in the expression of CD 163 and a reduction in that of CD 14. These results delineate a maturation pathway where CDI4 hi CDI63-SWC9-monocytes develop into CDI4 1 oCDI63+SWC9-monocytes and these cells into CDI4 1 oCDI63+SWC9+ macrophages. Abbreviations: mAb = monoclonal antibody, FSC = forward-scatter, MFI = mean fluorescence intensity, PAM = porcine alveolar macrophages, PBMC = peripheral mononuclear blood cells, PMT = photomultiplier tubes, SSC = side-scatter.

Using a mouse model of neonatal respiratory distress syndrome (RDS), we demonstrate a central role for macrophage migration inhibitory factor (MIF) in lung maturation at the developmental stage when human neonates are most susceptible to RDS. We prematurely delivered mouse pups at embryonic day 18, during the early saccular stage of pulmonary development. Only 8% of the prematurely delivered pups genetically deficient in MIF survived 8 h vs 75% of wild-type controls (p < 0.001). This phenotype was corrected when pups of all genotypes were bred from dams heterozygote for MIF deficiency. Local production of MIF in the lung increased at embryonic day 18, continued until full-term at embryonic day 19.5, and decreased in adulthood, thus coinciding with this developmental window. The lungs of pups genetically deficient in MIF were less mature upon histological evaluation, and demonstrated lower levels of vascular endothelial growth factor and corticosterone-two factors that promote fetal lung maturation. In vitro studies support a role for MIF in surfactant production by pulmonary epithelial cells. In a cohort of human neonates with RDS, higher intrapulmonary MIF levels were associated with a lower likelihood of developing bronchopulmonary dysplasia, a sequelae of RDS (p < 0.03). This study demonstrates for the first time a role for MIF in lung maturation, and supports a protective role for MIF in newborn lung disease.

The primary biologic roles of C1 inhibitor (C1-INH) are the regulation of activation of the classical complement pathway and of the contact system of kinin formation. Heterozygosity for deficiency or dysfunction of Cl-INH results in hereditary angioedema (HAE). This deficiency results in loss of homeostasis with unregulated complement and contact system activation. Due to the consequent CI-INH consumption, plasma levels of CI-INH in patients with HAE are decreased below 50% of normal.

This experiment is design to find the values of rate of role at different free stream velocity. A wing of moderate aspect ratio place in wind tunnel and find the rolling rate at three different velocities. In this report we are evaluate Lp value for two different wings. One wing is elliptical type given in handout and one is carrying out in the experiment was straight tapered plan-form figures are given below, with the sharp end. Then at the end compare the experimental Lp with the theoretical Lp value which will estimate by using the strip theory. When an aircraft flying in steady state flight, as both wing produce same amount of lift because both wings are flying at the same velocity and have same angle of attack. If pilot deflect aileron so that one wing produce more lift then the other wing. It only can when one aileron deflect down side and other deflect top side. Then aircraft begin to roll and will continue until the other side of the wing will not show resistance. Lateral aerodynamics derivative Lp involves yaw and rolling moment. Yaw moment is about y-axis and rolling moment about x-axis.

Tuberculosis (TB) remains a leading cause of death with more than 8 million cases every year and 1.4 million deaths worldwide, representing one of the three most impacting infectious diseases for human health. 1 One of the reasons for the limited success in the combat of TB is the lack of new drugs to shorten disease treatment, which typically lasts at least 6 mo. As a result, immunotherapy for TB has gained new attention because it may also provide an adjuvant effect for conventional chemotherapy by improving the immune response of the patient against the bacillus. In this regard, three candidates for TB immunotherapy have been discussed specifically in the literature: (1) M. vaccae, (2) a post-infection vaccine called RUTI made from detoxified, fragmented M. tuberculosis cells, and (3) a DNA vaccine encoding the heat-shock protein 65 of M. leprae (DNA-hsp65). 2-4 M. vaccae is the only immunotherapy that has been tested in TB patients and, despite high individual variability, it showed some improvement in treatment outcome. 5