Cell-mediated immunity during natural measles infection.

Natural measles causes prolonged depression of cell-mediated immunity yet little is known as to how the infection influences lymphocyte function. Therefore, we studied the properties and function of lymphocytes during and after measles. The number and proportion of circulating thymus-derived lymphocytes was low during the acute stage of measles, and at this time 37% of these cells showed positive immunofluorescent staining for measles virus after stimulation with phytohemagglutinin. 7% of B cells were shown to contain virus but their numbers did not alter during the infection. Acute-phase lymphocytes, when stimulated, yielded infective virus and half were killed on incubation with autologous serum and complement. In acute measles the increase in [(3)H]-thymidine uptake of lymphocytes when stimulated with an optimal dose of PHA was normal in media with 10% fetal calf serum and low in media containing 10% autologous serum: the mean values were 56.8+/-34.1 and 23.7+/-25.9 cpm x 10(3) per 10(6) lymphocytes, respectively. Stimulation of acute-phase lymphocytes by Candida antigen was also low in media containing autologous serum averaging 1.2 x 10(3) cpm per 10(6) lymphocytes. On recovery 4-6 wk later this rose significantly to 18.9+/-19.8. The mean migration index of leukocytes to heat-killed candida cells in acute measles was 0.84+/-SD 0.08, and this fell significantly to 0.75+/-SD 0.08 4 wk later. Thus, depletion of T cells, an inhibitor of lymphocyte proliferation in the serum and a possible defect in antigen processing, interacts to depress cell-mediated immunity in measles.

Mitogenic activity of an extract of Trypanosoma gambiense.

An extract obtained by repeated freeze/thawing of a freshly isolated strain of Trypanosoma gambiense caused stimulation of lymphocytes obtained from healthy adult donors and from cord blood. The active factor had some stimulatory effect on purified B and T lymphocytes and in two of five subjects increased IgM production by lymphocytes cultured in vitro. A trypanosome-derived mitogenic factor may play some part in the pathogenesis of the hypergammaglobulinaemia characteristic of African trypanosomiasis.

Lymphocyte changes in acute malaria.

Lymphocyte sub-populations were studied in children with acute malaria. Depletion of T cells was found associated with an increased proportion of null cells. K cell activity for chicken red cells was also increased and it is likely that some of the increased number of null cells were K cells. An increase in K cell activity in acute malaria could be part of a protective immune response.

Partial characterization of a malaria mitogen.

Supernatants from 24-hour cultures of Plasmodium falciparum-infected human red blood cells stimulated lymphocytes from both malaria immune and malaria non-immune donors. Both T and B lymphocytes responded. Amalaria parasite-derived mitogen may play some part in the pathogenesis of the hypergammaglobulinaemia characteristic of malaria.

T- and B-lymphocyte subpopulations in the tropical splenomegaly syndrome (TSS).

Lymphocyte subpopulations in thirty-nine patients with the tropical splenomegaly syndrome (TSS) were studied using the E-rosette, EAC rosette and direct immunofluorescent staining techniques. In the peripheral blood a decrease in the percentage of T-lymphocytes was found which was accompanied by an increase in the percentage and number of B-lymphocytes. These abnormalities reverted towards normal on treatment. Splenic aspirates contained an increased proportion of T-lymphocytes. The relative T-cell lymphoenia in TSS is probably due to specific trapping or non-specific sequestration of lymphocytes in the liver and splen. B-cell lymphocytosis is probably due to persistent antigenic or mitogenic stimulation by malaria.

Cellular immunity in patients with meningococcal disease and in vaccinated subjects.

Cell-mediated immunity was studied in patients with group A meningococcal meningitis and in normal subjects given group A meningococcal vaccine. Lymphocytes responsiveness to phytohaemagglutinin and to meningococcal antigens was markedly depressed in patients with acute meningococcal infection. This defect was present when lymphocytes were cultured in autologous or foetal calf serum. Patients also showed a transient increase in the degree of inhibition produced by whole group A meningococci in leucocyte migration assays. Meningococci of other groups produced a similar degree of inhibition. Vaccination with group A meningococcal polysaccharide vaccine had no effect on lymphocytes responsiveness to meningococcal antigens or on the inhibitory effect of group A meningococci on leucocyte migration.

Evidence for familial immune defect in meningococcal meningitis.

Twenty-six patients who had recovered from group A meningococcal meningitis were vaccinated with group C meningococcal polysaccharide and tetanus toxoid. Their haemagglutinating antibody response was measured two weeks later and compared with those of 22 siblings and 39 controls. Patients and siblings had a significantly lower antibody response to the group C vaccine but not to tetanus toxoid. This suggests that patients susceptible to meningococcal disease may have an immune defect involving their response to meningococcal polysaccharides.

Antigenic diversity among Onchocerca volvulus in Nigeria, and immunological differences between onchocerciasis in the savanna and forest of Cameroon.

Onchocerciasis is a remarkably chronic infection and, in West Africa, there are distinct clinical and pathological differences between the disease in the savanna and in the forest. Experiments were carried out to see whether antigenic diversity among Ochocerca volvulus worms might contribute to these features. Extracts of adult worms and or microfilariae were analysed by disc electrophoresis on polyacrylamide gels and showed a remarkable diversity of protein patterns but no consistent savanna/forest or Nigeria/Cameroon differences. Indirect haemagglutination using cross-absorbed sera was used to look for antigenic diversity or identity between different O. volvulus worms. Sera of patients were absorbed with antigens extracted from worms taken from those paitents and then titrated against sheep erythrocytes coated with the same antigens. It was shown that an adult Onchocerca volvulus could be either antigenically identical with, or distinct from, another worm taken from the same patient. In one Nigerian village identity was shown in two instances nad diversity in five. Microfilariae lack some antigens possessed by adult worms. This test has shown consistent savanna/forest differences in worm antigen patterns and antibody responses. In order to explain the pattern of these differences it was necessary to postulate that forest patients possessed antibodies to another worm which had antigens in common with savanna Onchocerca. The relevance of these findings to the pathology and prevention of onchocerciasis is discussed.