Immune responses to vaginal or systemic infection of BALB/c mice with herpes simplex virus type 2.

The temporal relationships among the humoral and cellular immune responses were defined in BALB/c mice after vaginal or systemic infection with herpes simplex virus type 2 (HSV-2). After vaginal infection, mice showed evidence of clinical vaginitis on days 4 to 6 and HSV-2 replication was detected locally in the vaginal secretions, cervix, vagina, and uterus before the virus subsequently spread to the central nervous system. Death from encephalitis occurred between 7 and 10 days after infection. Vaginal infection was associated with significant delayed type hypersensitivity and splenic proliferative cell-mediated immune responses which appeared during the acute infection and waned by 3 weeks. There was almost no evidence of a systemic neutralizing antibody response at any time after vaginal infection. In contrast to the local vaginal infection, systemic i.v. HSV-2 infection induced a humoral response as well as the two cellular immune responses. Although both cellular immune responses appeared during the acute infection (days 6 to 14) and persisted for approximately 5 weeks, the humoral response appeared in surviving animals and persisted for at least 4 months. Thus, vaginal HSV-2 infection was associated primarily with transient cellular immune responses, whereas i.v. HSV-2 infection induced prolonged systemic humoral and cellular immune responses.     

A prolonged immune response to antigen delivered in poly (epsilon-caprolactone) microparticles

A single dose vaccine formulation which induces both humoral and cell-mediated immune responses over a prolonged period would provide a potent weapon against infectious disease. We have used a water-in-oil-in-oil, solvent evaporation method for generating poly epsilon-caprolactone microparticles and tested their ability to induce an immune response against the model antigen ovalbumin. We hypothesized that the initial release of antigen from the surface of the poly epsilon-caprolactone microparticles would act as the priming dose and that the delayed release over the following months, due to diffusion from or break-down of the microparticles, would act as a boost to the immune response. Ovalbumin encapsulated in the poly epsilon-caprolactone microparticles was able to induce both antibody and cell-mediated immune responses. However our results suggest that the spontaneous release had little effect on the immune response. Despite this the response was maintained for at least 8 months following a single immunization. Both humoral and cell-mediated immune responses were induced in mice. This simple method of vaccine formulation offers a cost-efficient way to deliver antigen in a single dose to the immune system.     

Mycoplasma pulmonis depresses humoral and cell-mediated responses in mice

Humoral and cell-mediated immune responses to sheep red blood cells (SRBC) were studied in mice infected experimentally with Mycoplasma pulmonis. The hemagglutinating (HA) antibody against SRBC was evaluated at 0, 3, 5, 7, 14, 21 and 28 days postinfection (PI). Antibody tiers during all days PI were depressed significantly (p less than 0.05) in infected mice as compared to noninfected controls. The HA antibody, which is of the IgM class, peaks at day 5 PI. There is no shift in the kinetics of the humoral response in M. pulmonis infected mice. Cellular immune responses were evaluated by a delayed-type hypersensitivity (DTH) reaction and the lymphocyte transformation technique. Mice were sensitized at 0,3,5,7,14, 21 and 28 days PI with SRBC and challenged by footpad injection of SRBC 7 days later. The DTH reaction measured at 24 hours after challenge was depressed significantly (p less than 0.05) in all infected animals. After a transient enhancement on day 3 PI, the DTH responses remained depressed through day 28 PI. The lymphocyte transformation test showed a significantly (p less than 0.05) depressed response except on days 5 and 7 PI. These results indicate that M. pulmonis infection in mice suppresses the humoral antibody and cell-mediated immune responses.     

Cell-mediated and humoral immune responses in mice during experimental infection with Mycoplasma pulmonis

Cell-mediated and humoral immune responses in mice after challenge exposure with Mycoplasma pulmonis were investigated. The cell-mediated immune response was determined by means of the delayed-type footpad swelling and the humoral immune response by means of the indirect haemagglutination test. Delayed-type footpad swelling and serum antibody titres were detected at one week after the challenge exposure and persisted for 7 weeks until the end of the experiment. However, there was a poor correlation between the degree of delayed-type footpad swelling and that of serum antibody titre. Delayed-type footpad swelling in mice with gross pneumonic lesions was less than that of mice with no gross lesions. A weak negative linear correlation was observed between the delayed-type footpad swelling and the number of M. pulmonis isolated from lungs.     

Immunology of Dermatophytosis

The immune response to infection by dermatophytes ranges from a non-specific host mechanism to a humoral and cell-mediated immune response. The currently accepted view is that a cell-mediated immune response is responsible for the control of dermatophytosis. Indeed, some individuals develop a chronic or recurrent infection mediated by the suppression of a cell-mediated immune response. The immune response to Trichophyton is unusual in that this fungus can elicit both immediate hypersensitivity (IH) and delayed-type hypersensitivity (DTH) in different individuals when they are submitted to a skin test reaction. Understanding the nature and function of the immune response to dermatophytes is an exciting challenge that might lead to novel approaches in the treatment and immunological prophylaxis of dermatophytosis.     

Macrophage transformation of mononuclear cells following primary and secondary experimental immunization with measles vaccine

Cell-mediated and humoral immune response was studied in guinea pigs receiving two immunizations with live measles vaccine l-16 in doses of 1000 TCD50/0.5 ml at an interval of 45 days. The results of this study showed that the maximum level of the macrophagal transformation of mononuclears and the most intensive synthesis of antimeasles antibodies were observed on day 10 after booster immunization. The intensification of cell-mediated and humoral immune response was found to depend on the initial immunological background. The animals having had high values of cell-mediated response before booster immunization showed a decrease in these values, while an increase in antibody titers in such animals was transitory.     

The methods for correcting with specific and nonspecific immunomodulators the immunopathological processes arising from the administration of a staphylococcal vaccine]

In mice immunized with staphylococcal vaccine the arresting of graft-versus-host reaction under the influence of small doses of staphylococcal vaccine, hyperimmune antistaphylococcal serum, cyclophosphamide, antilymphocytic serum has been demonstrated. Small doses of staphylococcal vaccine stimulated the production of antibodies to staphylococci and dermal extract in the animals, previously immunized with this vaccine, with the simultaneous suppression of cell-mediated immune reactions to both antigens. Immunosuppressing agents have been found to inhibit humoral and cell-mediated immune response to microbial antigen and dermal extract. No influence of vermox and levamisole on the outcome of the graft-versus-host reaction has been registered; the latter preparation has been found to intensify cell-mediated immune reactions to microbial and tissue antigens.     

Cell-mediated immune response after vasectomy in rats.

This study investigated the development of a cell-mediated immune response after vasectomy in Swiss Albino rats, by comparing the development of the thymus-dependent lymphoid tissue of the regional testicular lymph node and the spleen in vasectomized and in sham-operated control animals. Frozen sections were used and thymus-dependent regions were stained by immunocytochemistry. After vasectomy, the areas occupied by the paracortex in the lymph node sections showed a significant increase in size; the thymus-dependent regions of the spleen, in contrast, showed no change. The regional lymph node, rather than the spleen, seems to be important in cell-mediated and humoral immune responses to vasectomy.     

The immunoregulatory properties of reaferon

The influence of human recombinant alpha-interferon (reaferon) on cell-mediated and humoral immune response has been studied. Experimental facts on the blast transformation of lymphocytes, humoral immune response and the reaction of delayed hypersensitivity are presented. The study has shown that reaferon possesses the main immunoregulatory properties, characteristic of natural human leukocytic alpha-interferon. Manifestation of these properties depends on the dose of preparation and the time of its use.     

Murine defense mechanism against Candida albicans infection. I. Collaboration of cell-mediated and humoral immunities in protection against systemic C. albicans infection

Mice immunized with viable C. albicans cells demonstrated a high incidence of cell-mediated and a low incidence of humoral immune response. There was good agreement between the final survival rate of C. albicans infected mice and the rate of simultaneous cell-mediated and humoral immune response acquisition. Immunized mice with positive delayed hypersensitivity (DTH) against C. albicans crude antigen showed significant protection against intravenous challenge with C. albicans. Furthermore, the transfer of immunoglobulins from rabbit anti-C. albicans serum to DTH-positive mice enhanced protection, while it did not protect control mice against a subsequent challenge with C. albicans. These results suggest that cell-mediated immunity plays a major role and humoral immunity a side role in the defense mechanism(s) of C. albicans infected mice.     

Factors of the local immune defence of the reproductive tract in pregnant women with vaginosis

Clinico-immunological examination of 99 pregnant women with diagnosed vaginosis and 132 pregnant women without genital infection as a control group, was carried out. The immunological factors of cervical and vaginal secretions in pregnant women before and after local treatment were studied. The conclusion was made that the established changes in the cell-mediated and humoral factors of the immune resistance of the reproductive system could probably play some pathogenetic role in the development of vaginosis and its relapses in pregnant women. As found in this study, more pronounced changes in the local factors of immune protection (the signs of the functional irritation of neutrophils in combination with the prevalence of sIgA and lysozyme simultaneously with a decrease in the level of IgM and IgG in cervical slime) developed in patients with subsequent relapses of vaginosis, these changes remaining after local treatment. The defects of cell-mediated and humoral factors of cervical and humoral secretions, together with some clinical parameters, were shown to be prognostically unfavorable with respect to the relapses of vaginosis in pregnant women.     

Selenium Supplementation Restores Innate and Humoral Immune Responses in Footrot-Affected Sheep

Dietary selenium (Se) alters whole-blood Se concentrations in sheep, dependent upon Se source and dosage administered, but little is known about effects on immune function. We used footrot (FR) as a disease model to test the effects of supranutritional Se supplementation on immune function. To determine the effect of Se-source (organic Se-yeast, inorganic Na-selenite or Na-selenate) and Se-dosage (1, 3, 5 times FDA-permitted level) on FR severity, 120 ewes with and 120 ewes without FR were drenched weekly for 62 weeks with different Se sources and dosages (30 ewes/treatment group). Innate immunity was evaluated after 62 weeks of supplementation by measuring neutrophil bacterial killing ability. Adaptive immune function was evaluated by immunizing sheep with keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. At baseline, FR-affected ewes had lower whole-blood and serum-Se concentrations; this difference was not observed after Se supplementation. Se supplementation increased neutrophil bacterial killing percentages in FR-affected sheep to percentages observed in supplemented and non-supplemented healthy sheep. Similarly, Se supplementation increased KLH antibody titers in FR-affected sheep to titers observed in healthy sheep. FR-affected sheep demonstrated suppressed cell-mediated immunity at 24 hours after intradermal KLH challenge, although there was no improvement with Se supplementation. We did not consistently prevent nor improve recovery from FR over the 62 week Se-treatment period. In conclusion, Se supplementation does not prevent FR, but does restore innate and humoral immune functions negatively affected by FR.     

Immunomodulation activity of new vaccines for pertussis prophylaxis--acellular pertussis vaccine and adsorbed DPT vaccine with acellular component

The immunomodulating activity of acellular pertussis vaccine (APV) and adsorbed DPT vaccine with acellular pertussis component (DPTA vaccine) was studied. The study revealed that only large doses of APV, 10 immunizing doses (ID), suppressed humoral and cell-mediated response to sheep red blood cells (SRBC). 1 ID produced no influence on the formation of antibody producing cells, but increased the development of delayed hypersensitivity (DH) to SRBC. The modulation of cell-mediated immune response, induced by APV, returned to normal after the injection of purified staphylococcal toxoid, used as immunomodulator, in doses of 0.15 BU per mouse and 1.5 BU per mouse. DPTA vaccine containing 1 ID, as well as 10 ID, produced no immunomodulating effect. This was established by the evaluation of humoral response to SRBC in CBA mice and the study of the formation of DH to SRBC in BALB/c mice. As indicated by the total of the presented data, the inclusion of APV into DPTA vaccine enhanced the immunological safety of its pertussis component.     

Immunogenicities of haemocyanins from the giant African snail (Achatina fulica) and the keyhole limpet (Megathura crenulata).

1. The immunogenicities of the giant African snail (Achatina fulica) haemocyanin (AFH) and the keyhole limpet (Megathura crenulata) haemocyanin (KLH) were compared by determining their capacities to induce humoral and cell-mediated immune response in rats. 2. KLH was found to be more immunogenic than AFH, and this was attributed to the fact that KLH contains more moieties, and probably more antigenic determinants than AFH. 3. Since AFH was found capable of stimulating both humoral and cell-mediated immunity, it was suggested that it could be used as an antigen for the investigation of immune responses.     

Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.

Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been previously employed in this system, we observed that the humoral immune response to EIAV required a 6- to 8-month period in which to fully mature. During this time frame, EIAV-specific antibody evolved gradually from a population characterized by low-avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high levels, neutralizing activity, and predominantly conformational epitope specificity. Analyses of the cell-mediated immune response to EIAV revealed CD4+ and CD8+ major histocompatibility complex-restricted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent within 3 to 4 weeks postinfection, temporally correlating with the resolution of the primary viremia. After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally infected ponies, with some animals having readily detectable CTL activity while others had little measurable CTL activity. Thus, in contrast to the initial viremia, it appeared that no single immune parameter correlated with the resolution of further viremic episodes. Instead, immune control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system mechanisms to suppress viral replication that effectively functions only after the immune system has evolved to a fully mature state 6 to 8 months postinfection. These findings strongly imply the necessity for candidate EIAV and other lentivirus vaccines to achieve this immune system maturation for efficacious immunological control of lentivirus challenge.     

Rearing environment effects on immune defence in blue tit Cyanistes caeruleus nestlings

Rearing conditions may influence ontogeny and functioning of the immune system. Activation of different mechanisms involved in host disease resistance and their internal regulation can be affected by intrinsic and extrinsic factors influencing development. I investigated how rearing environment can influence associations between humoral and cellular constituents of immune defence in nestling blue tits (Cyanistes caeruleus). The ability to mount a cell-mediated immune response was estimated as a hypersensitivity reaction to phytohaemagglutinin, and the ontogeny of humoral immunity was determined by assessing circulating levels of total IgG in 15-day-old nestlings. Heterogeneity in rearing conditions was evoked by placing nest-boxes in areas differing in habitat structural characteristics, and examining natural variation in nest ectoparasite infestations, hatching date, brood size and brood sex-ratio. Habitat characteristics, parasitism and hatching date may shape associations between different components of the immune system in developing birds. I discuss the effects of rearing conditions on the interaction between different arms of the immune system and the implications for understanding negative correlations within the immune system at the individual and brood level.     

Indices of immunity and allergy in patients with viral hepatitis treated with prodigiozan

The immune and allergic status of patients with acute viral hepatitides A and B after treatment with prodigiosan, a bacterial lipopolysaccharide preparation, was studied. The drug produced as stimulating effect on cell-mediated and humoral immunity. The development of delayed specific drug sensitization was registered in two-thirds of the patients, which correlated with the regression of clinicobiochemical manifestations of hepatitis.     

Condition dependence, multiple sexual signals, and immunocompetence in peacocks

Condition-dependent expression of secondary sexual charactersand measures of immune function in a cohort of similarly agedmale blue peafowl Pavo cristatus was used to test whether differentsexual signals provide information about different aspectsof phenotypic quality. A measure of cell-mediated immunityand the heterophil—lymphocyte ratio demonstrated conditiondependence, but a measure of humoral immunity was not condition dependent. Only train length demonstrated condition-dependentexpression, while the number and the size of ocelli in thetrain did not show significant condition dependence. Althoughresidual train length (after controlling for the number andthe size of ocelli in the train) reliably reflected the magnitudeof two condition-dependent measures of immunocompetence (positively with cell-mediated immunity and negatively with humoral immunity),residual size of ocelli was negatively related to cell-mediatedimmunity. Different features of the complex train were relatedin different ways to measures of immunocompetence.     

Characteristics of the immune response to a single peroral administration of different doses of corpuscular pertussis vaccine

The effect of oral administrations of different doses of pertussis vaccine on the humoral and cell-mediated responses of systemic immunity and on the immunomorphological transformation of the mucous membrane of the small intestine was studied in (CBA X C57BL/6)F1 mice. On day 28 after the administration of all the tested doses of pertussis vaccine the animals were found to have a high degree of protection from the development of meningoencephalitis induced by the inoculation of Bordetella pertussis in the absence of specific hemagglutinins in their blood sera. At the same time the formation of spontaneous and immune rosette-forming cells and splenocytes was found to be inversely related to the administered dose. The immunomorphological transformation observed in the mucous membrane of the small intestine and in the lymphoid tissue associated with the small intestine was indicative of the stimulation of local immunity. The results thus obtained suggest that a single oral administration of pertussis vaccine to mice stimulates cell-mediated and humoral reactions of local immunity and induces the development of systemic cell-mediated immunity.     

Cellular and Humoral Cross-Immunity against Two H3N2v Influenza Strains in Presumably Unexposed Healthy and HIV-Infected Subjects

Human cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States. Pre-existing humoral and cellular immunity has been recognized as one of the key factors in limiting the infection burden of an emerging influenza virus strain, contributing to restrict its circulation and to mitigate clinical presentation. Aim of this study was to assess humoral and cell-mediated cross immune responses to H3N2v in immuno-competent (healthy donors, n = 45) and immuno-compromised hosts (HIV-infected subjects, n = 46) never exposed to H3N2v influenza strain. Humoral response against i) H3N2v (A/H3N2/Ind/08/11), ii) animal vaccine H3N2 strain (A/H3N2/Min/11/10), and iii) pandemic H1N1 virus (A/H1N1/Cal/07/09) was analysed by hemagglutination inhibition assay; cell-mediated response against the same influenza strains was analysed by ELISpot assay. A large proportion of healthy and HIV subjects displayed cross-reacting humoral and cellular immune responses against two H3N2v strains, suggesting the presence of B- and T-cell clones able to recognize epitopes from emerging viral strains in both groups. Specifically, humoral response was lower in HIV subjects than in HD, and a specific age-related pattern of antibody response against different influenza strains was observed both in HD and in HIV. Cellular immune response was similar between HD and HIV groups and no relationship with age was reported. Finally, no correlation between humoral and cellular immune response was observed. Overall, a high prevalence of HD and HIV patients showing cross reactive immunity against two H3N2v strains was observed, with a slightly lower proportion in HIV persons. Other studies focused on HIV subjects at different stages of diseases are needed in order to define how cross immunity can be affected by advanced immunosuppression.