Malaria infection alters the expression of B-cell activating factor resulting in diminished memory antibody responses and survival.

Malaria is a major cause of morbidity worldwide with reports of over 200-500 million infected individuals and nearly 1 million deaths each year. Antibodies have been shown to play a critical role in controlling the blood stage of this disease; however, in malaria-endemic areas antibody immunity is slow to develop despite years of exposure to Plasmodium spp. the causative parasite.

Dendritic cells: the Trojan horse of malaria?

Malaria, caused by Plasmodium spp., is responsible for over 200 million infections worldwide and 650,000 deaths annually. Until recently, it was thought that blood-stage parasites survived and replicated in hepatocytes and red blood cells exclusively.

Are plasmacytoid dendritic cells the misguided sentinels of malarial immunity?

Dendritic cells (DCs), the sentinels of immunity, reside in almost every organ of the body. These cells are responsible for initiating immune responses against infectious agents. DCs are divided into different subsets based on their biological functions, with plasmacytoid DCs (pDCs) and conventional DCs (cDCs) being two major populations.

Plasmodium immunomics.

The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. No malaria vaccine has yet been licensed.

Sequence map of the 2 Mb Giardia lamblia assemblage A chromosome.

The gut protozoan parasite, Giardia lamblia (Assemblage A), has 5 major chromosomes, 1 of which is 2 Mb, as determined from gel separations of whole chromosomes. We originally published a physical map of this chromosome and, now, using the sequence data from 46 chromosome-specific probes, have produced a sequence map of the 2 Mb chromosome. Comparison of the probe sequences with the Giardia genome database (http://GiardiaDB.

Metronidazole resistance in Trichomonas vaginalis from highland women in Papua New Guinea.

Background: The prevalence of the sexually transmissible protozoan parasite Trichomonas vaginalis in the highlands of Papua New Guinea (PNG) has been reported to be as high as 46% and although not previously studied in Papua New Guinea, clinical resistance against metronidazole (Mz), the drug most commonly used to treat trichomoniasis, is well documented worldwide. This study was primarily aimed at assessing resistance to Mz in T. vaginalis strains from the Goroka region.

Acquired immunity to malaria.

Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection.

Soluble CD38 significantly prolongs the lifespan of memory B-cell responses.

The development and maintenance of memory B cells (MBC) is dependent on germinal centres (GC) with follicular dendritic cell (FDC) networks. We have previously shown that FDC networks within GC of the spleen express a novel ligand for CD38 and that the administration of soluble CD38 induces an expansion of these cellular structures. We therefore used adoptive transfer studies to investigate whether the expansion of FDC networks with soluble CD38 affected the generation and maintenance of antigen-specific MBC.

What really happens to dendritic cells during malaria?

As dendritic cells (DCs) initiate all adaptive and some innate immune responses, it is not surprising that DC function during malaria is the subject of intensive investigations. However, the results of these investigations have so far been controversial. Here, we discuss various aspects of these studies, including the influence of the species and strain of Plasmodium on DC function, the effects of Plasmodium infection on the activation of CD8(+) T cells by DCs, the effects of haemozoin and the effects of Plasmodium infections on DC Toll-like-receptor signalling.

Systemic tumor necrosis factor generated during lethal Plasmodium infections impairs dendritic cell function.

Dendritic cells (DCs) initiate innate and adaptive immune responses including those against malaria. Although several studies have shown that DC function is normal during malaria, other studies have shown compromised function. To establish why these studies had different findings, we examined DCs from mice infected with two lethal species of parasite, Plasmodium berghei or P.

Colorectal carcinogenesis: road maps to cancer.

This review explores the chief genetic and epigenetic events that promote pathological progression in colorectal carcinogenesis. This article discusses the molecular and pathological basis for classifying colorectal neoplasia into suppressor, mutator and methylator pathways. These differing mechanisms of genomic instability are associated with specific cancer characteristics, and may provide the opportunity for more effective prevention and surveillance strategies in the future.

A case for whole-parasite malaria vaccines.

Malaria causes morbidity in 300-500 million people each year and claims 2-3 millions lives annually, mostly children in sub-Saharan Africa. In 1983, the cloning of malaria antigens offered great promise for developing a viable subunit vaccine. However, an efficacious human vaccine is still not available.

Dendritic cell biology during malaria.

Malaria is an infectious disease that causes serious morbidity and mortality worldwide. The disease is associated with a variety of clinical syndromes ranging from asymptomatic to lethal infections involving anaemia, organ failure, pulmonary and cerebral disease. The molecular and cellular factors responsible for the differences in disease severity are poorly understood but parasite-specific immune responses are thought to play a critical role in pathogenesis.

Virulent Avian Giardia duodenalis Pathogenic for Mice.

Early in 1995, a sulphur-crested cockatoo captured in the wild died along with several other cage mates, apparently of an overwhelming, acute infection of Giardia. Trophozoites isolated from the dead bird and established in traditional Giardia axenic medium were infective to mice and established chronic infections associated with weight gain impairment. Genetically and morphologically, the Giardia isolated from the bird belonged to the duodenalis group.

Vaccine-induced immunity to malaria parasites and the need for novel strategies.

History shows that vaccines are most easily developed for those organisms that induce natural immunity after a single infection. For malaria, partial antiparasite immunity develops only after several years of endemic exposure. Evidence suggests that this inefficient induction of immunity is partly a result of antigenic polymorphism, poor immunogenicity of individual antigens, the ability of the parasite to interfere with the development of immune responses and to cause apoptosis of effector and memory T and B cells, and the interaction of maternal and neonatal immunity.

The endangered Illidge's ant blue butterfly (Acrodipsas illidgei) from an intertidal habitat managed for mosquito control.

Acrodipsas illidgei is an endangered butterfly inhabiting mangrove forests in southeastern Queensland, Australia. Concern over the effects of mosquito control activities prompted a broad-scale survey for the species at Coomera Island, in southeastern Queensland. The butterfly was recorded on the edge of an old-growth mangrove forest in close proximity to mosquito control runnels.

Why do B cells produce CD40 ligand?

The CD40-CD40 ligand (CD40L) interaction is one of the most important receptor-ligand interactions that occurs during a T dependent immune response. However, while CD40L is expressed on a range of cell types including activated T cells and B cells, dendritic cells granulocytes, macrophages and platelets, only CD40L on T cells is considered by most immunologists when planning experiments or analysing data. The current theory professes that T cells expressing CD40L can provide signals to B cells that induce proliferation, immunoglobulin class switching, antibody secretion, rescue from apoptosis at different times during the life of a B cell and also has a role in the development of germinal centres and the survival of memory B cells.

Identification of novel protective antigens from Anaplasma marginale.

A successful recombinant vaccine against Anaplasma marginale remains elusive, despite intensive study of the protective, though variable major surface antigens. As an alternative approach to the discovery of additional antigens, crude parasite material was subjected to conventional protein fractionation, coupled with vaccination and parasite challenge trials, without making assumptions as to the nature or location of these antigens. This has lead to the identification of four novel antigens that, in microgram amounts, have significant protective effects in vaccination trials.

Orally administered Giardia duodenalis extracts enhance an antigen-specific antibody response.

We have identified novel adjuvant activity in specific cytosol fractions from trophozoites of Giardia isolate BRIS/95/HEPU/2041 (J. A. Upcroft, P.

Production of interleukin-10 by peripheral blood mononuclear cells from residents of a marshland area in China endemic for Schistosoma japonicum.

Interleukin-10 (IL-10) cytokine production was assessed using peripheral blood mononuclear cells (PBMC) from 67 individuals living in an area endemic for schistosomiasis japonica in China (Dongting Lake, Hunan Province), and 11 control subjects from a non-endemic part of the same Province. Production of IL-10 was measured following in vitro stimulation of PBMC using whole parasite extract (SWAP) or a panel of recombinant Schistosoma japonicum antigens (22-kDa tegumental membrane-associated antigen, glyceraldehyde-3-phosphate dehydrogenase, paramyosin, 14-kDa fatty acid-binding protein and 28-kDa glutathione S-transferase) which are of recognized interest in the development of protective immunity to schistosomiasis. Significantly, PBMC isolated from the exposed population compared with the non-exposed population produced higher levels of IL-10.

Drug targets and mechanisms of resistance in the anaerobic protozoa.

The anaerobic protozoa Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica infect up to a billion people each year. G. duodenalis and E.

Different transporters for tri-iodothyronine (T(3)) and thyroxine (T(4)) in the human choriocarcinoma cell line, JAR.

We investigated transport systems for tri-iodothyronine (T(3)) and thyroxine (T(4)) in the human choriocarcinoma cell line, JAR, using a range of structurally similar compounds to determine whether these thyroid hormones are transported by common or different mechanisms. Saturable T(3) but not saturable T(4) uptake was inhibited by a wide range of aromatic compounds (nitrendipine, nifedipine, verapamil, meclofenamic acid, mefenamic acid, diazepam, phenytoin). Nitrendipine and diazepam were the most effective inhibitors of saturable thyroid hormone uptake.

Peptide-MHC class I tetrameric complexes display exquisite ligand specificity.

The production of synthetic MHC-peptide tetramers has revolutionized cellular immunology by revealing enormous CD8(+) T cell expansions specific for peptides from various pathogens. A feature of these reagents, essential for their staining function, is that they bind T cells with relatively high avidity. This could, theoretically, promote cross-reactivity with irrelevant T cells leading to overestimates of epitope-specific T cell numbers.