On the solution of mathematical models of herd immunity in human helminth infections

The general solution of the mathematical model of herd immunity to human helminth infections recently proposed by Anderson and May [3] is obtained. The numerical solution of a more accurate biological model is indistinguishable from the corresponding exact solution of a more tractable mathematical model. Computer simulations of some particular cases of this model support the notion that both ecological and immunological factors determine the observed convex patterns of age-prevalence and age-intensity curves of human helminth infections.This work was made thanks to the advise and support of Dr. Robert M. May while the author was Postdoctoral Fellow at Princeton University     

Expression of herpes simplex virus glycoprotein D on antigen presenting cells infected with vaccinia recombinants and protective immunity

We studied the effect of the temporal regulation of herpes simplex virus (HSV) type 1 glycoprotein D (gD-1) expression in Ia⁺ epidermal cells (EC) and macrophages on virus specific immunity and protection from HSV-2 challenge. gD-1 was expressed on the surface of cells infected with a vaccinia recombinant containing gD-1 under the control of an early vaccinia virus promoter (VP176). It was not expressed in cells infected with a recombinant (VP254) in which gD-1 is controlled by a late vaccinia virus promoter. BALB/c mice immunized with both recombinants seroconverted to HSV-2 as determined by neutralization. However, HSV specific delayed type hypersensitivity (DTH) responses were significantly (p<0.025) higher in VP176 than VP254 immunized animals. Both VP176 and VP254 immunized mice were protected from severe neurological disease due to HSV-2 challenge at 14 days post immunization, but long term protection was observed only in VP176 immunized mice.     

Correlation of immunomodulatory and therapeutic activities of interferon and interferon inducers in metastatic disease

The mechanism of therapeutic activity of recombinant murine interferon-gamma (rMu IFN-gamma) and the IFN inducer polyinosinic-polycytidylic acid solubilized with poly-L-lysine in carboxy methyl cellulose (pICLC) in treating metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the organ with tumor) were tested after 1 and 3 weeks of rMu IFN-gamma or pICLC administration (intravenous, three times a week). In these studies, natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocytes (CTL) (against specific and nonspecific targets), and macrophage tumoricidal and tumoristatic activities were measured. rM IFN-gamma and pICLC had therapeutic activity and immunomodulatory activity in most assays of immune function examined. Specific CTL activity of pulmonary parenchymal mononuclear cells (PPMC), but not in splenocytes or peripheral blood lymphocytes (PBL), during week 3 and not during week 1, correlated with the therapeutic activity of rMu IFN-gamma and of pICLC. Macrophage tumoricidal activity in PPMC, but not in alveolar macrophages, also correlated with the therapeutic activity of rMu IFN-gamma, but the opposite was true for the therapeutic activity of pICLC. NK activity of PPMC, but not of splenocytes or PBL, during week 1 correlated with the therapeutic activity of pICLC; in contrast, NK activity at any site did not correlate with the therapeutic activity of rMu IFN-gamma. LAK activity at any site did not correlate with the therapeutic activity of either agent.     

Daily relaxation modifies serum and salivary immunoglobulins and psychophysiologic symptom severity

This study investigated the effect of daily relaxation on concentrations of serum immunoglobulins A, G, and M and secretion rates of salivary immunoglobulin A (S-IgA). Twenty-four volunteers were randomly assigned to practice a relaxation technique daily for 3 weeks and 16 to a waiting list control condition. Blood and saliva samples were collected before and after a supervised 20-min relaxation session at the beginning and end of the 3-week practice period. S-IgA secretion rate increased significantly (p<.001) after 20 min of relaxation. A longer-term practice effect also occurred in that the increase in secretion rate in before to after relaxation samples was higher (p=.014) in subjects who had practiced relaxation once a day for 3 weeks than in waiting list control subjects practicing for the first time. Serum IgA (p<.001), IgG (p<.001), and igM (p<.05) increased significantly over the 3-week practice period. Relaxation may be a self-regulating strategy affecting both humoral and cellular divisions of the immune system.Parts of this paper were presented at the annual meeting of the Biofeedback Society of America, March 1987. Materials for the IgA assays were provided by Cooper Biomedical, Malvern, Pennsylvania.     

Clinical studies on cell-mediated immunity in patients with renal cell carcinoma: interleukin-2 and interferon-γ production of lymphocytes

Summary The authors examined interleukin-2 (IL-2) production and interferon (IFN) production of peripheral blood mononuclear cells in 28 patients with renal cell carcinoma and 17 control subjects. The peripheral blood was obtained prior to the initiation of therapeutic procedures. The patients were divided into two groups according to tumor size, 5 cm and >5 cm. The production of IL-2 and IFN was measured by immunoradiometric assay. As a result, in the patients with tumors >5 cm, IL-2 and IFN production was impaired. However, in the patients with tumors 5 cm, IFN production was enhanced, though IL-2 production was not significantly different from that of the control subjects. There was no significant correlation between IL-2 production and IFN production.     

Passive immunization protects guinea pigs from lethal toxoplasma infection

Abstract The cellular and humoral interactions that contribute to protective immunity in toxoplasmosis were studied by adoptive transfer of selective cell populations or immune serum and its fractions into normal syngeneic strain 2 guinea pigs. The results of this study with the RH strain of Toxoplasma gondii confirm and extend the findings of previous studies by showing that the passive transfer of parasite-sensitized T cells or of immune serum from previously infected donors protected recipient guinea pigs against lethal toxoplasmosis. An additional key finding was that similar levels of complete protection against lethal infection occurred in guinea pigs receiving partially purified anti- Toxoplasma immunoglobulins or immune cells that had been enriched for B cells prior to transfer. Cells residing in the spleen, lymph nodes and peritoneal cavity, but not the thymus, were equally effective in conferring immunity to challenged recipients. In addition, cell titration experiments revealed that guinea pigs could survive T. gondii infection by infusing them with as little as 2 × 10⁷ sensitized T cells or B cells. Unlike protection mediated by T cells, protection against lethal disease occurring in the B cell recipients was associated with the formation of Toxoplasma antibodies. These findings illustrate the major role of both humoral and cell-mediated immunity in affording protection against toxoplasmosis based on a guinea pig model of the human disease.     

A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs

Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.     

Complete resistance to challenges with Hymenolepis nana cysticercoids derived from mouse, rat and beetle in mice

and 1986. Complete resistance to challenges with Hymenolepis nana cysticercoids derived from mouse, rat and beetle in mice. International Journal for Parasitology 16: 623–628. When BALB/c and dd strains of mice were given eggs of Hymenolepis nana, they all became completely resistant not only to challenge with mouse-derived cysticercoids but also to challenges with rat-derived and beetle-derived cysticercoids. Serum IgG antibodies at 47–60 days post egg inoculation reacted strongly with these three different host-derived cysticercoids when examined by IFA test, but IgA and IgM isotypes reacted very weakly. Antibodies of infected mouse sera (IgG, IgM and IgA were examined) reacted not only with the protoscolex (scolex of the excysted juvenile) but also with the outer cyst wall. By contrast, uninfected mouse sera and immune sera prepared seven days post cysticercoid inoculation did not react at all. Antigens of both cyst wall and protoscolex appeared to be of parasite origin and not of host origin, and appeared similar in parasites from the different host species.     

The influence of level of infection of rats with Nippostrongylus brasiliensis on the haematology and phospholipase activity and mast cell numbers in the small intestine and colon

The haematology and phospholipase activity and mast cell numbers of the small intestine and colon of rats was studied 10 days after infection with various numbers of larvae of N. brasiliensis. A significant reduction in the RBC occurred after infections with 200 and 5000 larvae but not with 1000 larvae. Hb was significantly reduced after infection with 200 larvae and increases in the MCV and MCH indicated the development of a macrocytic anaemia. Reticulocyte count was increased at all levels of infection except after 200 larvae. WBC was increased at all levels of infection except in the 5000 larvae group. Lymphocytes were significantly increased in all groups except those infected with 5000 larvae. Neutrophils increased only at the lower levels of infection. The most marked changes occurred in eosinophil numbers, significant increases occurring with increasing levels of infection. However, after infection with 5000 larvae the numbers were significantly lower than after infection with 200 or 1000 larvae. Phospholipase activity, which is believed to be related to tissue eosinophil levels, was significantly increased at all infection levels in the proximal small intestine. Significant increases in the distal ileum and colon occurred mainly after infection with 1000 and 5000 larvae. Mast cell numbers did not change significantly at any infection level. It is suggested that the pathology observed, here in the form of anaemia, is multifactorial in origin and is largely a function of the immune response, the development and expression of which is dependent on the level of infection, with suppression of immune damage occurring at the high levels of infection when pathogenesis may involve a direct effect of the worms.     

Taenia solium: cell reactions to the larva (Cysticercus cellulosae) in naturally parasitized, immunized hogs

In hogs naturally infected with Taenia solium larvae (i.e., Cysticercus cellulosae), we studied the host response induced by antigens obtained from the larvae. Histopathological studies of cysticerci removed after 4 and 8 weeks of immunization showed an intense inflammatory reaction surrounding the larvae. The response was greater in the 8-week specimens. A dense layer of eosinophils was in close contact with the external membrane of the bladder wall and, in several cases, the eosinophils had infiltrated this tegument. Many eosinophils were seen in the spiral canal of larvae. This infiltration by eosinophils increased with time. Preparations from the 8-week samples showed many degenerated and disrupted eosinophils whose granules were found in close contact with the outer membrane of the larval tegument and, in some cases, had entered through the broken surface of this structure. More than 90% of the larvae were found in various stages of degeneration; the rest were completely destroyed and surrounded by a mass of eosinophils. After immunization, peripheral blood eosinophilia increased to 17%, whereas the eosinophilia of the control hog was 4% throughout the study. The larval worms removed from control hogs showed intact structures, with a low degree of infiltration by eosinophils and a discrete inflammatory reaction surrounding the bladder wall of the larvae.