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The major strategy to reduce the impact of schistosomiasis is the development of a defined antigen vaccine. It has recently been reported that the 62-kDa antigen known as S. mansoni calreticulin (SmCaR), is a good T- and B-cell antigen and represents a potential vaccine candidate. In the present study the immune response to SmCaR was evaluated in individuals resistant to schistosomiasis. Lymphoproliferative response and cytokine production to SmCaR was assessed in 30 schistosomiasis resistant and healthy individuals. Only 10% of the schistosomiasis resistant individuals showed significant proliferative response to SmCaR while all of them showed significant proliferative response to soluble adult warm antigen (SAWA). On the other hand, 20-30% of the schistosomiasis resistant individuals showed detectable levels of IL-2, IL-4 and IFN-gamma after stimulation with SmCaR, and 59% of them showed had anti SmCaR IgM specific antibodies. These findings suggest that SmCaR might be a potential vaccine antigen.

In the present work we studied: (a) biochemical changes; (b) serum immunoglobulins (IGs); and (c) mitogenecity of peripheral blood lymphocytes (PBL) in workers directly exposed to high concentrations of pollutants in several sectors of a major copper company in Alexandria. These sectors included the aluminum utensils refining of copper semicontinuous aluminum casting, brass foundries, and steel furnaces. Toxicants in these sectors included aluminum, hexachloroethan, silica, cadmium, copper, mercury, lead, abestos, nickels, zinc, silver, carbon iron, and sulfate present in high concentrations in the sectors where workers are directly exposed. Administrative personnel (indirectly exposed) were included as positive controls; negative controls were people living in areas of Alexandria where the concentrations of these toxicants are extremely low. All personnel of the aluminum utensils area showed reduction in serum levels of IgG, IgA, and IgM assayed by enzyme-linked immunosorbent assay (ELISA) while workers directly exposed in the other sectors showed elevated Igs. Mitogenic activity in cultured PBL assayed by 3H-thymidine uptake was impaired in all plant personnel. However, experimentals showed increases in the interleukins IL-2, IL-4, IL-6, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha and-beta (TNF-alpha and beta) assayed by ELISA. Changes were directly related to duration of exposure. Some workers showed autoimmune symptoms such as arthritis and spondylitis. Allergic manifestations were also recorded. Thus, abnormalities were greatest in directly exposed workers, while other plant personnel showed some form of toxicity in the parameters studied. Clinical significance of the immunologic abnormalities seen is under further study.

The effects of 1/1000 field recommended concentration of the organophosphorus compounds; edifenphos and glyphosate on the immune response and protein contents were investigated after different time intervals. The cell mediated immune response assessed by proliferative response of splenocytes to mitogens; phytohemagglutinin (PHA) and concanavalin A (Con A) for T cell and lipopolysaccharide (LPS) for B cell decreased significantly in tems of the level of stimulation index in the treated fish and reached maximal depression after 4 weeks. Humoral immunity assessed as splenic antibody plaque forming cells (PFC) measured after 5 days in vitro immunization to sheep erythrocytes (SRBC's) were suppressed in a concentration dependent pattern by the two compounds. The estimated ED50 for the PFC/10(6) cells of edifenphos and glyphosate were 1.48 x 10(-2) uM and 1.65 x 10(-2) uM respectively. The data also showed that serum antibody titres in the treated fish were decreased in a time dependent manner. The total protein content of serum treated with the two pesticides was decreased after different time periods compared with control. The blood serum of treated and untreated Tilapia nilotica were analyzed electrophoretically for protein components and the percentage of proteins in each fraction was determined.

Cell mediated immune reactivity of chronic schistosomiasis patients was tested in vitro by peripheral blood mononuclear cell (PBMN) responses against phytohemagglutinin P (PHA), Candida albicans extract, soluble schistosomal antigenic preparations derived from eggs (SEA), adult worms (SWAP) and cercariae (CAP), before and after treatment of the patients with parziquantel. The patient population was from villages in the Qalyub province, Egypt, that are endemic for Schistosoma mansoni and S. haematobium. Patients were studied immediately before, and at 1, 3, 6, and 9 months after chemotherapy. Egg counts were done on stool and urine specimens taken simultaneously with blood samples. There was a significant increase in PBMN responses to SWAP and CAP but not to SEA, PHA or C. albicans in 27 patients (age 8-65) 1 month after treatment. Eleven patients treated 1.5 years previously did not show such elevated responses 1 month after re-treatment. Three months after treatment higher mean responses were observed to SWAP, CAP, SEA, and PHA, but not to C. albicans in 24 patients (age 6-26). Significant increases in PBMN responses to SWAP and CAP, but not to SEA, PHA or C. albicans were obtained at 6 months after treatment in 12 patients (age 6-30). By 9 months after treatment in a group of 11 patients (age 8-25) SWAP and CAP responses were still elevated as were SEA and C. albicans induced reactivities. The PBMN responses of 10 patients were followed longitudinally at pretreatment, 3-, 6-, and 9-month post-treatment times. In general, elevated responses were maintained throughout this period to the schistosomal preparations. Unrelated responses occasionally fluctuated but were not consistently altered over time.

The effect of histamine on cell-mediated immune responses of chronic schistosomiasis patients was tested by peripheral blood mononuclear cell (PBMN) reactions to phytohemagglutinin-P (PHA) and soluble schistosomal antigenic preparations derived from eggs (SEA) or adult worms (SWAP). PBMN responses to PHA were suppressed by exogenous histamine (10(-5)M), and the addition of cimetidine (CIM) (10(-4)M), an H2-receptor antagonist, reversed this suppressive effect. Histamine primarily suppressed PBMN responses to suboptimal and optimal PHA concentrations. Exogenous histamine (10(-5)M) also suppressed PBMN responses of 27 schistosomiasis patients to SEA and SWAP, respectively. The addition of CIM (10(-4)M) to suppressed cultures reversed the effect of exogenous histamine. Most importantly, the addition of CIM to schistosomal antigen-induced cultures, without exogenous histamine, significantly increased patients' PBMN responses to SEA and SWAP. The mean optimal increase in SEA responses of 19 patients was 390%. With SWAP-induced responses of 21 patients this increase was 165%. The use of 10(-4)M diphenhydramine (DPH), an H1-receptor antagonist, resulted in general suppression of both PHA-induced and schistosomal antigen-induced PBMN responses. Lower concentrations of DPH lead to variable responses but did not result in consistent abrogation of the histamine-induced suppression. These data imply that an histamine-induced, H2-receptor-mediated suppressor circuit often helps modulate antigen-specific responsiveness of PBMN from patients with chronic schistosomiasis.