Characterization of the immunological memory state generated in mice susceptible to Leishmania major following exposure to low doses of L. major and resulting in resistance to a normally pathogenic challenge

BALB/c mice are susceptible to a high-dose infection of the protozoan Leishmania major, which induces a parasite-specific antibody, Th2-like response, exclusive of a significant and protective cell-mediated Th1 component. We have shown, in contrast, that infection with a low number of parasites induces cell-mediated immunity exclusive of antibody production, and results in resistance to substantial subsequent high-dose infection. Low-dose exposure thus constitutes effective vaccination. In the present study, we analyze lymphokine production by parasite-specific T cells from these low-dose exposed, resistant mice and from normal, susceptible mice following high-dose infection. Two findings stand out. First, the parasite-specific T cells in mice rendered resistant appear not to be in an activated, effector state at the time of parasite challenge, as assessed by lack of lymphokine production on short-term stimulation with parasite antigens, but to be rather in a memory state. Second, the ratio of parasite antigen-dependent production of interferon-γ to that of interleukin-4 by spleen cells of low-dose exposed and normal mice upon high-dose challenge takes a dramatically different course. This ratio is similar in both groups of mice shortly after challenge, but increases dramatically in the resistant and declines dramatically in the control mice over a period of weeks, such that these ratios differ by about 60-fold 12 weeks after the high-dose challenge. In addition, we show that a similar state of resistance occurs following low-dose infection with a more virulent strain of L. major. In toto, our observations suggest that resistance may be generally achievable by low-dose exposure and may be associated with a memory state which, when activated by parasite challenge, results in the evolution of the response over weeks such that the protective, Th1 component becomes ever more dominant over the Th2 component.     

Listeria--review of epidemiology and pathogenesis.

Listeria monocytogenes (commonly called Listeria) is a Gram-positive facultatively intracellular foodborne pathogen often found in food and elsewhere in nature. It can cause a rare but serious disease called listeriosis, especially among pregnant women, the elderly or individuals with a weakened immune system. In serious cases, it can lead to brain infection and even death. Listeria is more likely to cause death than other bacteria that cause food poisoning. In fact, 20 to 30% of food borne listeriosis infections in high-risk individuals may be fatal. Recent technological developments have increased the ability of scientists to identify the cause of foodborne illnesses. L. monocytogenes has been used as a model organism for the study of intracellular parasitism. Whilst the basic mechanisms of cellular pathogenesis have been elucidated by a series of elegant studies, recent research has begun to focus upon the gastrointestinal phase of L. monocytogenes infection. Epidemiological studies of outbreaks of human disease now demonstrate that the pathogen can cause gastroenteritis in the absence of invasive disease and associated mortality. Elucidation of whole genome sequences and virulence determinants have greatly contributed to understanding of the organism and its infection pathways.     

Comparative cytological study of lymph node tuberculosis in HIV-infected individuals and in patients with diabetes in a developing country

Tuberculosis (TB) is a common infection affecting patients with human immunodeficiency virus (HIV) and diabetes mellitus (DM). With the increasing incidence of HIV infection and DM in a developing country like India, TB is definitely on the rise. In a given population, one expects to see these three diseases in varying combinations, such as HIV and TB, DM and TB, HIV and DM with TB. In such combinations TB may lack the characteristic clinical and histological picture due to the associated depressed cell-mediated immunity seen in both diseases and TB may have an unusual clinical presentation and cytology picture. In this retrospective study of 36 months, from January 1997 to December 1999, 109 cases diagnosed cytologically as tuberculous lymphadenitis and tested for HIV infection and investigated as well for DM were selected. Forty-six (42%) were nondiabetic HIV patients, 13 (12%) were non-HIV DM patients, and 50 (46%) had TB without HIV infection or DM. The coexistence of both HIV and DM was not noted. The cytomorphological characteristics supplemented by culture studies of each of these three groups were compared in detail and based on these four cytological patterns, Pattern 1, Pattern 2, Pattern 3, and Pattern 4 emerged and were characterized. This study highlights the usefulness of cytomorphology of the lymph nodes to characterize the cytopathological profile of TB in both HIV and DM, which have many clinical and immunological similarities, and indirectly postulate the extent of immune suppression and evolve effective strategies in the management of coexisting diseases. Such a comparative study has not been carried out in the past.     

Risk factors for HIV infection in injection drug users and evidence for onward transmission of HIV to their sexual partners in Chennai, India

OBJECTIVES: Determining HIV prevalence in injection drug users (IDUs) and their regular sex partners in Chennai, India. METHODS: A total of 226 IDUs and their regular sex partners were enrolled during April-July 2003. After informed consent was obtained, a semistructured questionnaire was administered and serum was tested for HIV antibody. RESULTS: The HIV seroprevalence was 30% (68/226) in IDUs and 5% in their regular sex partners (11/226). While in 25% of couples only the male partner was HIV positive, 5% of the couples were concordant for HIV infection and 70% were HIV negative. Fifty-seven percent of the HIV-positive IDUs and 45% of the HIV-infected women thought that they had "no chance" or "very little chance" of getting HIV, reflecting low HIV risk perception. More than 20% IDUs reported borrowing or lending of injection equipment. In univariate analyses "sex" and "condom use" with sex workers had no bearing but "more than twice a day injecting frequency," "history of incarceration," "tattoos," "recruitment from northern part of the city," and ever-injecting drugs in drug-selling places had significant association with HIV infection in IDUs. In an adjusted model, the odds of HIV infection were 2 times higher among IDUs who had ever injected drugs in drug-selling places and 6 times higher in those who were recruited from the northern part of central Chennai. CONCLUSION: Reducing sharing of injection equipment and unsafe tattooing through targeted and environmental interventions, increasing HIV risk perception, and promoting safer sex practices among IDUs and their sex partners are urgent program needs.     

Interleukin 10 protects mice against staphylococcal enterotoxin B-induced lethal shock.

We investigated the ability of interleukin 10 (IL-10) to protect mice against lethal shock induced by staphylococcal enterotoxin B (SEB). Treatment of mice with IL-10 prevented the death of mice injected with SEB in a dose-dependent manner. IL-10-mediated protection was apparent when administered either prior to or concurrent with SEB but was less effective when administered following SEB injection. This observation indicates that IL-10 is capable of regulating T-cell activation in vivo.     

The refined crystal structure of cowpea mosaic virus at 2.8 A resolution

Comoviruses are a group of plant viruses in the picornavirus superfamily. The type member of comoviruses, cowpea mosaic virus (CPMV), was crystallized in the cubic space group I23, a = 317 A and the hexagonal space group P6(1)22, a = 451 A, c = 1038 A. Structures of three closely similar nucleoprotein particles were determined in the cubic form. The roughly 300-A capsid was similar to the picornavirus capsid displaying a pseudo T = 3 (P = 3) surface lattice. The three beta-sandwich domains adopt two orientations, one with the long axis radial and the other two with the long axes tangential in reference to the capsid sphere. T = 3 viruses display one or the other of these two orientations. The CPMV capsid was permeable to cesium ions, leading to a disturbance of the beta-annulus inside a channel-like structure, suggesting an ion channel. The hexagonal crystal form diffracted X rays to 3 A resolution, despite the large unit cell. The large ( approximately 200 A) solvent channels in the lattice allow exchange of CPMV cognate Fab fragments. As an initial step in the structure determination of the CPMV/Fab complex, the P6(1)22 crystal structure was solved by molecular replacement with the CPMV model determined in the cubic cell.     

Molecular characterization of two soybean-infecting begomoviruses from India and evidence for recombination among legume-infecting begomoviruses from South [corrected] South-East Asia

The complete nucleotide sequences of two soybean-infecting begomoviruses have been determined from central and southern parts of India. Sequence analyses show that the isolate from central India is a strain of Mungbean yellow mosaic India virus (MYMIV) and the southern Indian isolate is a strain of Mungbean yellow mosaic virus (MYMV). Multiple DNA B components could be detected with the soybean strain of Mungbean yellow mosaic virus species. The nucleotide sequence similarity between the DNA A components of the two isolates is higher (82%) than that between the corresponding DNA B components (71%). Analyses of the common region of the genomic components of these two virus isolates indicate considerable divergence in the origin of replication (ori), which did not impair their infectivity as demonstrated for the central Indian isolate by agroinfection with partial tandem repeats (PTRs) of the genomic components. Detailed sequence and phylogenetic analyses reveal the distribution and possible recombination events among legume-infecting begomoviruses from South-East Asia.     

Design, fabrication, and characterization of a tissue-equivalent phantom for optical elastography

We suitably adapt the design of a tissue-equivalent phantom used for photoacoustic imaging to construct phantoms for optical elastography. The elastography phantom we consider should have optical properties such as scattering coefficient, scattering anisotropy factor, and refractive index; mechanical properties such as storage and loss modulus; and acoustic properties such as ultrasound velocity, attenuation coefficient, and acoustic impedance to match healthy and diseased tissues. The phantom is made of poly (vinyl alcohol) (PVA) and its mechanical, optical, and acoustic properties are tailored by physical cross-linking effected through subjecting a suitable mix of PVA stock and water to a number of freeze-thaw cycles and by varying the degree of hydrolysis in the PVA stock. The optical, mechanical, and acoustic properties of the samples prepared are measured by employing different techniques. The measured variations in the values of optical scattering coefficient, scattering anisotropy factor, and refractive index and storage modulus are found to be comparable to those in normal and diseased breast tissues. The acoustic properties such as sound speed, acoustic attenuation coefficient, and density are found to be close to the average values reported in the literature for normal breast tissue.