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The role of HLA-A*6802-restricted CD8+ T cells in chlamydial disease was investigated in human ocular infections. Peptides with predicted binding motifs for HLA-A*6802 were synthesized using sequences based on chlamydial antigens, major outer membrane protein (MOMP), macrophage infectivity potentiator (MIP) and heat shock protein (hsp70). Peptides were pooled according to Chlamydia trachomatis protein type and serovar, and were tested in 51Cr-release cytotoxic T lymphocyte (CTL) and enzyme-linked immunospot (ELISPOT) assays, using peripheral blood mononuclear cells (PBMC) isolated from subjects living in trachoma-endemic communities in The Gambia. Significant CTL activity or interferon-gamma release was not detected in any of the subjects, suggesting either that HLA-A*6802 CD8+ T cells may not be important in ocular infections or that the peptides chosen did not represent epitopes. [ABSTRACT FROM AUTHOR]

The protection provided by BCG against pulmonary tuberculosis ranges from nil to over 90%. While BCG protects against the more serious forms of tuberculosis, it is not known whether or not it protects patients with pulmonary tuberculosis from death. In a study designed to look at the effects of immunotherapy with M. vaccae as an adjunct to chemotherapy in 285 adult Gambian patients treated for proven pulmonary tuberculosis, we examined the association between the presence or absence of a BCG scar and mortality. The data showed that subjects who had a BCG scar were significantly younger than those who did not, and were less likely to have nutritional oedema. During the course of treatment, none of the 85 patients who had a BCG scar died compared to 35 of 200 patients (17.5%) who did not (P < 0.001). In these Gambian patients with pulmonary tuberculosis, prior vaccination with BCG may have provided substantial protection against death. However, there is the possibility that this finding is the result of confounding by other factors or has arisen from bias. Researchers with similar data need to investigate this question as this association, if true, could have major implications for BCG vaccination. [ABSTRACT FROM AUTHOR]

Little is known about cellular cytotoxicity to measles virus during natural measles infection which is still a major cause of death in many parts of the world. Therefore we measured the ability of peripheral blood mononuclear cells (PBM) from children with measles to kill Hela cells persistently infected with measles virus. In a 6-hr 51CR-release assay antibody-independent cellular cytotoxicity was shown to be low during the acute stage of measles. This rose to a maximum 1 week after the onset of the rash and fell rapidly on recovery 2 to 3 weeks later. The respective means values for the three periods (expressed as specific immune release of 51Cr) were 7.9 ± 8.4%, 31.0 ± 16.4% and 6.1 ± 7.7%. Killing in this assay was not effected by T lymphocytes, for concentration of these cells by three different methods failed to increase cytotoxic power. In contrast peripheral blood mononuclear cells depleted of T lymphocytes showed greatly increased antibody-independent cellular cytotoxicity. Antibody-dependent cellular cytotoxicity was not found to vary significantly with the stage of measles. The mean values were 30.0 ± 13.6%, 26.6 ± 11.7% and 23.9 ± 12.1% for the periods 0-2, 3.14 and 15-30 days after the onset of the rash. Both antibody-independent and antibody-dependent cellular cytotoxicity of PBM were lowered by layering these cells on immune complexes fixed to plastic or by incubating them with normal rabbit γ-globulin. Antibody-dependent cellular cytotoxicity was also lowered in the presence of 10% acute-phase autologous plasma. We concluded that antibody-independent cytoxocity was effected either by natural killer cells or by K cells using traces of antibody present in the assay. Antibody-dependent cellular cytotoxicity which is due to K cells may be modulated by circulating immune complexes during the course of disease. [ABSTRACT FROM AUTHOR]

This work tests the hypothesis that the increased severity of measles in malnourished children is related to the immune response of the host to the virus. Peripheral blood mononuclear cells (PBM) from well-nourished and malnourished children who had not had measles were infected in vitro with measles virus. The yield of virus from the cells of malnourished children was significantly greater than the yield from well nourished children. This was not due to lack of interferon as both types of cells produced similar amounts on challenge with measles virus. Antibody-independent and antibody-dependent cellular cytotoxicity to Hela cells persistently infected with measles virus was measured on average 1 week after the onset of the measles rash. Mononuclear cells from malnourished children killed infected Hela cells as well as cells from well-nourished children in both types of assay. There was also no significant difference in the ability of serum from the two groups of children to lyse PMB which were infected with measles virus. However, plasma from malnourished children was found to depress proliferation of lymphocytes in the presence of PHA or Candida antigen to a greater degree than plasma from well-nourished children. We conclude that the severity of measles in the malnourished may well be related to the immune response for if their cells are abnormally susceptible to infection and if this infection is followed by a normal cellular and humoral immune response severe and extensive allergic damage would result. The reaction in turn may generate immunosuppressive factors in the patient's plasma thus making the child susceptible to secondary infections. [ABSTRACT FROM AUTHOR]

Low levels of complement components C3 C4 and factor B were found in the sera of most patients with early and advanced Gambian trypanosomiasis. C3 levels increased after treatment with melarsoprol (Mel B). Nearly all patients had high serum 1gM levels and a significant correlation was found between high serum 1gM levels and low serum C3 levels. concentrations of cryoglobulins, which contained 1gM and C3 were found in most of the sera tested. Formation of large molecular weight 1gM complexes may play an important part in producing the low C3 levels found in patients with Gambian sleeping sickness. [ABSTRACT FROM AUTHOR]

Free light chains were detected in the cerebrospinal fluid (CS F) of most patients with advanced trypanosomiasis but not in the CSF of patients with early trypanosomiasis or in the CSF of controls. Immunofluorescence showed free light chains in CSF plasma cells and morular cells, suggesting local production of light chains within the central nervous system. We believe that the presence of free light chains in the CSF of patients with advanced trypanosomiasis is a reflection of their disordered immunoglobulin synthesis and is in keeping with the view that the marked IgM synthesis seen in patients with this disease is due to the action of a mitogen and not the result of specific immune stimulation. [ABSTRACT FROM AUTHOR]

The antigen detectable by counter-current immunoelectrophoresis in the cerebrospinal fluid and sera of patients with group A meningoeoccal meningitis was found to be a high molecular weight polysaccharide. Its composition was deduced from its immunochemical identity with a known group A meningoeoccal polysaccharide which has previously been shown to be a polymer of N-acetyl, O-acetyl mannosamine phosphate. [ABSTRACT FROM AUTHOR]

Presents the results of pilot studies of hepatitis B virus (HBV) immunization of children in the Gambian villages of Keneba and Manduar. Children were followed for up to four years to assess the effect of vaccination on the established pattern of HBV infection.

Children living in hyperendemic malarious regions have high immunoglobulin levels and an increased frequency of Burkitt's lymphoma. In a study of Gambian children which endeavours to explain these findings we showed that acute P. falciparum malaria caused spontaneous activation and growth of their B lymphocytes in vitro. A high proportion of these cells contained Epstein Barr nuclear antigen (EBNA). In ancillary experiments aimed at explaining these findings. CD4 helper cells from adult donors were destroyed with monoclonal antibody and complement. This manoeuvre resulted in loss of cytotoxic T cell control of their B lymphocytes when infected with Epstein Barr virus (EBV). In children with acute malaria., both spontaneous immunoglobulin and antibody production by B cells was increased yet CD4 helper cell control over these cells, as measured by responses to pokeweed mitogen, was found to be intact. Spontaneous and concanavalin A-driven lymphocyte proliferation was depressed. We infer from these findings that in patients with P. falciparum malaria loss of cytotoxic T cell control of the EBV in B cells, possibly due to destruction or dysfunction of a subset of CD4 cells responsible for induction ot suppressor/cytotoxic CD8 cells, leads to activation and proliferation of foci of B cells containing EBV. The expanded pool and rapid turnover of these cells may increase chances of malignant transformation leading to the genesis of Burkitt's tumor. Partial loss of suppressor mechanisms coupled with normal CD4 helper/inducer activity may result in high serum levels of immunoglobulin which are characteristic of persons living in malarious regions. [ABSTRACT FROM AUTHOR]

Supernatants from Epstein-Barr virus (EBV)-stimulated B lymphocytes obtained from two adult Gambians who were partially immune to malaria markedly inhibited the growth of Plasmodium falciparum in vitro (55-95% inhibition). When 22 separate colonies were derived by micromanipulation from one of these primary cultures and their supernatants assayed, the degree of inhibition correlated with levels of IgG fluorescent antibody and total IgG. The inhibitory anti-P. falciparum IgG immunoprecipitated an antigen of mol. wt 195,000, identified as the major schizont surface glycoprotein by dual biosynthetic labelling with 3H-glucosamine or -35S-methionine. Other studies on the analogous schizont surface protein of rodent malarias have shown that this antigen stimulates protective immunity. Production of this inhibitory antibody by adult Gambians may therefore contribute to their immunity to malaria. Human antibodies produced by EBV-stimulated B lymphocytes may be used to identify other important P. falciparum antigens and have potential applications for immunotherapy. [ABSTRACT FROM AUTHOR]

Bailey R (Department of Microbiology, Southampton University Medical School, South Academic Block, Southampton General Hospital, Tremona Road, Southampton SO9 4XY, UK), Osmond C, Mabey D C W, Whittle H C and Ward M E. Analysis of the household distribution of trachoma in a Gambian village using a Monte Carlo simulation procedure. 1989, : 944–951. Studies on the household distribution of trachoma have reached conflicting conclusions. This paper describes a cross sectional survey of endemic trachoma in a Gambian village. Cases of active trachoma were mapped, and the compound and household distribution of the disease analysed by a Monte Carlo simulation procedure which takes into account differences in the size and age distribution within individual households. Significant clustering of active trachoma cases both by village compound (p<0.0001) and bedroom (<0.05) were detected supporting the concept that intra-familial transmission of trachoma is important. There was no evidence of spatial clustering of rooms with higher than expected prevalence of trachoma. Clustering of disease in space or time provides important evidence of infectious aetiology and route of transmission. The methods discussed here are generally applicable in the study of other infections diseases. [ABSTRACT FROM PUBLISHER]

Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plasmodium falciparum infection and disease. We have previously described the use of peptides to define malaria-specific CTL epitopes. To determine whether these peptide epitopes are processed intracellularly from the whole antigen we have developed recombinant vaccinia viruses (rVV) expressing three malaria antigens: thrombospondin-related adhesive protein (TRAP), Pfs16 and the C-terminal half of liver-stage antigen (LSA)-1. Target cells infected with recombinant viruses were lysed by malaria-specific CTL from semi-immune African donors. We also tested the ability of cells infected with these recombinant vaccinia viruses to re-stimulate malaria-specific CTL in peripheral blood lymphocytes from malaria immune adults. Two other pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC, a canarypox virus, both expressing malaria antigens were also evaluated for their ability to stimulate malaria-specific CTL in contrast to peptide, none of these viruses successfully re-stimulated CTL from the peripheral blood lymphocytes of semi-immune donors. The ability of human CTL from naturally exposed individuals to recognize processed antigen supports the relevance of these cells in protective immunity to malaria. [ABSTRACT FROM AUTHOR]

114 patients with meningococcal infection were studied; 72 had group C infection and 42 group A infection. 14 patients had acute meningococcaemia, all of whom had group C infection and 9 of whom died. Clinical and laboratory findings were similar in patients with meningitis due to a group A and C organisms, but arthritis and cutaneous vasculitis were more common in patients with group C infection. The overall mortality was 22% in patients with group C infection, and 12% in patients with group A infection, but was the same in both groups when cases of acute meningococcaemia are excluded. [ABSTRACT FROM AUTHOR]

The application of a diagnostic and genotyping technique based on the polymerase chain reaction (PCR) to the study of trachoma epidemiology in the Gambian village of Jali is reported. PCR based on the major outer membrane protein (MOMP) gene of Chlamydia trachomatis appears to be more sensitive than either isolation or antigen detection by enzyme immunoassay; it had a specificity of 95% and sensitivity of 51% against clinical signs. PCR genotyping identified genotypes A and B of Chlamydia trachomatis circulating in Jali. Sequencing revealed a Pst1 restriction endonuclease site in the amplified MOMP gene of some B strains but not others; Pst1 digestion of the PCR product proved an easy method of distinguishing these strains. The distribution of serotypes and B strain variants shows a significant degree of household clustering (p < 0.001). PCR based genotyping combined with strain typing provides a new and powerful epidemiological tool for the study of transmission events in trachoma. [ABSTRACT FROM PUBLISHER]

Increased stimulation of Th2 cytokines may contribute to the development of persistent ocular chlamydial infection, resulting in the blinding pathological changes of trachoma. Proliferation and cytokine production profiles of PBMC in response to stimulation with antigens of Chlamydia trachomatis were compared in 30 patients with severe conjunctival scarring due to trachoma and in 30 age-, sex-and location-matched controls. Interferon-gamma (IFN-γ) and IL-4 were detected at the single-cell level by ELISPOT assay. Transcription of the genes encoding IFN-γ, IL-4 and IL-10 was detected in mRNA isolated from parallel cultures of PBMC using reverse transcriptase-polymerase chain reaction (RT-PCR). Incubation with the chlamydial heat shock protein (hsp)60 resulted in increased numbers of lL-4-producing cells in PBMC isolated from patients with scarring disease and increased secretion of IFN-γ from PBMC of control subjects. Incubation with the chlamydial major outer membrane protein (MOMP) increased the number of IFN-γ-producing cells in the control group only. Messenger RNA encoding IL-4 was only detected in PBMC of patients with scarring disease after in vitro stimulation with chlamydial antigens, but (IFN-γ) mRNA and IL-10 mRNA were also more frequently detected in this group. Thirty-eight subjects were HLA-DRBI and -DQBI typed. Associations were observed between certain HLA class II alleles and cellular immune responses to chlamydial antigens. No HLA associations were found with clinical status, and overall we found no evidence of strong associations and the type of immune response. These data are consistent with a role for Th2 cells and cytokines in the pathogenesis of trachomatous scarring. [ABSTRACT FROM AUTHOR]