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At least 163 records · Page 9Linked to original sources

Cellular immunity against Theileria parva and its influence on parasite diversity.

Theileria parva, a tick-borne parasite of African cattle, causes a fatal disease known as East Coast fever. Cattle that recover from the disease develop strong parasite-specific MHC-class I-restricted cytotoxic T-lymphocyte responses. Protection can be transferred between immune and naïve calves in the CD8+ T cell fraction emanating from a responding lymph node. In vitro studies suggest that this response requires input from activated CD4+ T cells. The T parva life cycle involves developmental stages in mammalian and tick hosts and can lead to a number of different endemic scenarios for the disease. These range from a stable situation with high prevalence of herd infection, but low fatality rates, to a low prevalence/high fatality scenario. The impact on endemic stability is an important consideration for the design of vaccine implementation strategies. For subunit vaccines targeted at T parva schizonts, the principal issue in this regard is whether development of the piroplasm stage is blocked by immunity.

Animals↗

Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma-associated antigen in patients.

Induction of immunity against antigens expressed on tumor cells might prevent or delay recurrence of the disease. Six patients operated on for colorectal carcinoma were immunized with human monoclonal anti-idiotypic antibodies (h-Ab2) against the mouse 17-1A anti-colon carcinoma antibody, mimicking a nominal antigen (GA733-2). All patients developed a long-lasting T-cell immunity against the extracellular domain of GA733-2 (GA733-2E) (produced in a baculovirus system) and h-Ab2. This was shown in vitro by specific cell proliferation (DNA-synthesis) assay as well as by interleukin 2 and interferon gamma production and in vivo by the delayed-type hypersensitivity reaction. Five patients mounted a specific humoral response (IgG) against the tumor antigen GA733-2E (ELISA) and tumor cells expressing GA733-2. Epitope mapping using 23 overlapping peptides of GA733-2E revealed that the B-cell epitope was localized close to the N terminus of GA733-2. Binding of the antibodies to the tumor antigen and to one 18-aa peptide was inhibited by h-Ab2, indicating that the antibodies were able to bind to the antigen as well as to h-Ab2. The results suggest that our h-Ab2 might be able to induce an anti-tumor immunity which may control the growth of tumor cells in vivo.

Adult↗

Humoral and cellular immune functions are not compromised by the anticarcinogenic Bowman-Birk inhibitor.

Previous studies have demonstrated that the soybean-derived Bowman-Birk protease inhibitor (BBI) is effective as a cancer chemopreventive agent in several animal model systems. Proteases represent a key component of several aspects of immune function; therefore the immune system is a primary target for potential toxicity. The present investigation examines the effect of dietary and intraperitoneally administered BBI on antibody response to keyhole limpet hemocyanin and delayed-type hypersensitivity response to dinitrochlorobenzene. Primary antibody response was not altered by BBI treatment; however, an elevated secondary response was observed in animals receiving dietary BBI at two weeks of age. This effect was not observed at later time points. No change in delayed-type hypersensitivity response was observed in any of the treatment groups.

Animals↗

In vitro activation of cellular immune response to Gross virus-induced lymphoma.

Spleen cells from W/Fu rats 40 days or more after immunization with a syngeneic Gross virus-induced leukemia were unreactive in direct cytotoxic assays. Incubation of these immune cells at 37 degrees C for 12 hr or longer, in the absence of antigen, resulted in the appearance of specific cytotoxic reactivity. Other lymphoid cells from the immune rats also were activated upon in vitro incubation, but to a lesser extent. Experiments were performed to define the necessary conditions and the mechanism for the in vitro incubation. Activation was temperature dependent, occurring at 37 degrees C but not at 4 degrees C. Immune serum suppressed the activation, but normal rat serum also had some inhibitory activity. Passage of immune cells through a nylon column, before preincubation, prevented activation. In contrast, exposure to nylon after preincubation did not remove cytotoxic reactivity. These findings demonstrate the reversal of a central inhibition of immune cell activity. The explanations offered for this phenomenon included change in surface characteristics of the immune cells during in vitro incubation, and the possible need for an adherent helper cell.

AKR murine leukemia virus↗

The mediator of cellular immunity. VII. Localization of sensitized lymphocytes in inflammatory exudates.

Peritoneal exudates induced in rats infected with Listeria monocytogenes contain sensitized lymphocytes which can protect normal recipients against a Listeria challenge. The protective cells arise in lymphoid tissue remote from the peritoneal cavity. Those formed in the caudal lymph nodes of subcutaneously infected rats are delivered to the thoracic duct and hence to the blood from where they are drawn into exudates. Immunoblasts are the most immature members of this protective cell population and they alone among the cells in central lymph localize in exudates induced by killed bacteria. They do so in substantial numbers, but only during the early postinduction period. The "homing" of immunoblasts to inflammatory foci seems to be determined by a general property of the cells rather than their immunological commitment; however, the intense inflammation induced by organisms to which an animal has been specifically sensitized is accompanied by an exuberant influx of immunoblasts into lesions. Sensitized lymphocytes that extravasate in the inflamed peritoneal may generate more of their own kind, but some give rise to small lymphocytes. The latter also have protective properties and, with time, comprise an increasing portion of the protective cell population. The results imply that the tissue disposition of sensitized lymphocytes in the body is determined by a complementary relationship between blood-borne immunoblasts and vascular endothelium in inflamed tissue. The results also provide a plausible explanation for the concentration of sensitized lymphocytes at sites of microbial implantation where they alone would be expected to collaborate with monocyte-derived macrophages in the control of infection.

Animals↗

Varicella-zoster virus-specific cellular immunity in subjects given acyclovir after household chickenpox exposure.

The time course of primary cell-mediated immune responses to varicella-zoster virus (VZV) among persons receiving acyclovir prophylaxis after exposure to chickenpox has not been well defined. Fifteen children who had household exposure to varicella received prophylactic acyclovir (40 mg/kg/day for 7-14 days after exposure) and were studied for development of both antibody and cell-mediated immunity (CMI) to VZV. Twelve developed antibodies and/or CMI; 10 had no symptoms and 2 manifested mild varicella. Two were already immune to varicella and had booster immune responses. One was not infected and subsequently developed full-blown varicella. Although acyclovir given after exposure to VZV is highly effective and does not appear to attenuate the immune response, it remains necessary to confirm whether, in the absence of clinical varicella, persons acquire specific immunity.

Acyclovir↗

Broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors.

Adenovirus serotype 35 (Ad35) is a promising vaccine platform for human immunodeficiency virus (HIV) infection and emerging infectious diseases as it is uncommon in humans worldwide and is distinct from Ad5, the major vaccine serotype for which many individuals have pre-existing immunity. The immunogenicity of a first-generation, replication-competent Ad35-based vaccine was tested in the simian immunodeficiency virus (SIV) rhesus macaque model by evaluating its capacity to boost immunity generated by Ad5-based vectors. A series of four immunizations with replication-defective Ad5 vectors expressing SIVmac239 gag induced high-frequency responses mediated by both CD8(+) and CD4(+) T cells directed against several epitopes. Ad5-specific neutralizing antibody responses that did not neutralize Ad35 were rapidly induced but waned over time. Subsequent immunization with Ad5-based vectors was minimally effective, whereas immunization with Ad35-based vectors generated a strong increase in the frequency of Gag-specific T cells with specificities that were unchanged. While this boosting response was relatively transient, challenge with the distinct pathogenic isolate SIV/DeltaB670 generated robust and selective recall responses to Gag with similar specificities as induced by vaccination that were elevated for 25 weeks relative to controls. Vaccination had measurable albeit minor effects on virus load. Unexpectedly, regional hypervariability within the Gag sequence of SIV/DeltaB670 was associated with mutation of the conserved CD8(+) T-cell epitope CM9 without concurrent flanking mutations and in the absence of immune pressure. These findings support the further development of Ad35 as a vaccine vector, and promote vaccine regimens that utilize serial administration of heterologous adenoviruses.

Adenoviruses, Human↗

Role of cellular immunity in protection against Trypanosoma cruzi in mice.

The importance of antibodies in the maintenance of immunity against Trypanosoma cruzi in mice is emphasized by the failure of either immunization or transfer of immune T cells to afford B cell suppressed mice complete protection against a lethal infection. Both procedures did, however, significantly prolong survival indicating a contributory role for T cells other than simply as helper cells in antibody production. The complete protection afforded intact mice following transfer of immune T cells can be attributed to a significant T cell-mediated augmentation of IgG antibody production.

Animals↗

Time-dose-response studies on cellular immunity.

The time-dose responses to several murine histocompatibility antigens were studied using lymphocytes as an antigen source for immunization and the speed of rejection of skin grafts as an assay of the level of immune responsiveness. It was observed that the weaker the first set response to an antigen the higher the minimal immunizing dose and the lower the tolerizing dose; thus, there was a small "immunizing window." The speed of onset of immune responsiveness and the magnitude of change in it following first antigen contact depended on the "strength" of the antigen. When the antigen was "strong" the level of response increased rapidly following first antigen contact. When the antigen was "weak" a period of tolerance appeared following first antigen contact, which then gave way to a state of immunity; the "weaker" the antigen the longer the interval and the greater the magnitude of tolerance. Increasing the antigen dose tended to magnify and prolong the tolerance. The "weaker" the antigen the longer the interval between first antigen contact and the appearance of immunity. Once established, the level of immunity was not constant. Undulations in the levels of all responses were noted; the "weaker" the antigen the larger the undulations. Possible explanations for the undulations and implications of the time-dose-response curves in immunotherapy are discussed.

Animals↗

Human cellular immune responses to Bordetella pertussis infection.

We have compared the responses of peripheral blood leucocytes from three groups (i) patients suffering from pertussis (whooping cough), (ii) clinical staff caring for those patients and laboratory staff working with Bordetella pertussis, and (iii) staff with no known recent contact with B. pertussis. In vitro stimulation with filamentous haemagglutinin (FHA) caused significant increases in proliferation of only the patient group's lymphocytes. In vitro stimulation with pertussis toxin (PT) caused a large increase in proliferation of lymphocytes from all three groups and in the patient group the increase in proliferation was related to the dose of PT. Interleukin 2 (IL-2) production by leucocytes from all three groups was significantly increased following challenge with FHA or PT. The increases in IL-2 production were greatest in lymphocytes from patients with pertussis. Challenge with toxoided pertussis toxin had no effect on either proliferation or IL-2 production in any of the groups.

Adolescent↗