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At least 343 records · Page 19Linked to original sources

In vitro induction of tumour-specific immunity. I. Development of optimal conditions for induction and assay of cytotoxic lymphocytes.

A microculture system for in vitro induction of tumour-specific immunity with syngeneic spleen cells and plasma-cell tumours is described. The system generates cytoxic lymphocytes assessed by their ability to lyse 51Cr-labelled target cells in a microcytotoxicity assay. Both the inductive and effector phases are subject to many variables in material and methodology and the optimal conditions are defined in this study. Of particular importance are the responder- to stimulator-cell ratios, the presence of 2-mercaptoethanol, the day of harvest, the method of target-cell 51Cr labelling, and preincubation of the cytotoxic lymphocytes prior to assay.

Animals↗

Increased levels of high-density lipoprotein cholesterol are ineffective in inhibiting the development of immune responses to oxidized low-density lipoprotein and atherosclerosis in transgenic rabbits expressing human apolipoprotein (apo) A-I with severe hypercholesterolaemia.

High levels of high-density lipoprotein (HDL) cholesterol have been reported to protect against the development of atherosclerosis in humans by increasing reverse cholesterol transport and inhibiting the oxidation of low-density lipoprotein (LDL) due to the paraoxonase content of HDL. The purpose of the present study was to assess if there are any relationships between in vivo increases in serum levels of immunological LDL oxidation markers [autoantibodies against oxidized LDL, autoantibodies against malondialdehyde-modified LDL, LDL immune complexes and anti-cardiolipin autoantibodies], paraoxonase activity and the development of atherosclerosis in control rabbits and in transgenic rabbits expressing human apolipoprotein (apo) A-I. A total of 13 apo A-I transgenic rabbits and 18 non-transgenic littermates were fed on a cholesterol-rich diet (0.4%, w/w) for 14 weeks, and were monitored at weeks 0, 2, 6, 10 and 14. Aortic atherosclerotic lesions were measured at the end of this period. Human apo A-I transgenic rabbits with high HDL cholesterol levels were not protected against the development of atherosclerosis when they were fed on a cholesterol-rich diet which induced dramatic hypercholesterolaemia. Immunological markers of LDL oxidation increased and serum paraoxonase activity decreased similarly in control and transgenic rabbits. In conclusion, the present study demonstrates that high HDL cholesterol levels are ineffective in inhibiting increases in immunological markers of LDL oxidation and the development of atherosclerosis in a mammal with severe hypercholesterolaemia.

Animals↗

Requirement of CD80+ costimulation for rejection of ocular tumors and termination of immune privilege.

Immune privilege in the anterior chamber of the eye is very effective at preventing elimination of ocular tumors that express weak tumor antigens. We previously demonstrated that DBA/2 mice immunized in the flank with a P815 tumor cell vaccine that expressed CD80/IL-12 was unable to terminate immune privilege and prevent tumor growth in the anterior chamber. In the present study, we determined whether expression of costimulatory signals on tumor cells injected via an ocular route would terminate immune privilege. We observed that CD80-positive tumors were always rejected from the anterior chamber. However, the pattern of tumor rejection was dramatically different depending upon whether the mice were either naïve, or immunized in flank against the tumor cells. Naïve mice that received an anterior chamber injection of CD80-positive tumors did not develop immune privilege and displayed strong delayed hypersensitivity (DH) against the tumor cells. Moreover, the ocular tumors were rejected by ischemic necrosis that induced atrophy of the eye and phthisis. When immunized mice received an identical injection of tumor cells in the anterior chamber, they also did not develop immune privilege and displayed strong DH. However, tumor rejection was considerably different and occurred without destruction of normal ocular tissue, or phthisis. To determine if immune privilege was restored in these eyes, mice received a second injection of P815 cells (CD80-negative) into the anterior chamber 2weeks after the first CD80-positive tumors were eliminated. Surprisingly, immune privilege was not restored and the P815 tumors were eliminated completely, again without phthisis. We conclude that specific rejection of ocular tumors with minimal destruction of the eye requires systemic immunization and expression of CD80 costimulatory signals on tumors within the eye.

Animals↗

The effect of aging on cognate function and development of immune memory.

Immunological memory is one of the central features of the immune system and can be described as the ability of the immune system to respond more efficiently to a second encounter with the same pathogen. The immune system is dramatically affected by age-related changes and it is becoming apparent that immune memory exhibits significant defects as a result of aging. Although immune memory generated during youth functions well into old age, that generated later in life functions poorly. Importantly, age-related defects in the cognate helper function of CD4(+) T cells can potentially influence the development of both humoral and cell-mediated immune memory. These defects ultimately result in aged individuals who exhibit reduced responses to both infections and vaccinations.

Aging↗

Exercise and immune function. Recent developments.

Comparison of immune function in athletes and nonathletes reveals that the adaptive immune system is largely unaffected by athletic endeavour. The innate immune system appears to respond differentially to the chronic stress of intensive exercise, with natural killer cell activity tending to be enhanced while neutrophil function is suppressed. However, even when significant changes in the level and functional activity of immune parameters have been observed in athletes, investigators have had little success in linking these to a higher incidence of infection and illness. Many components of the immune system exhibit change after prolonged heavy exertion. During this 'open window' of altered immunity (which may last between 3 and 72 hours, depending on the parameter measured), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. However, no serious attempt has been made by investigators to demonstrate that athletes showing the most extreme post-exercise immunosuppression are those that contract an infection during the ensuing 1 to 2 weeks. This link must be established before the 'open window' theory can be wholly accepted. The influence of nutritional supplements, primarily zinc, vitamin C, glutamin and carbohydrate, on the acute immune response to prolonged exercise has been measured in endurance athletes. Vitamin C and glutamine have received much attention, but the data thus far are inconclusive. The most impressive results have been reported in the carbohydrate supplementation studies. Carbohydrate beverage ingestion has been associated with higher plasma glucose levels, an attenuated cortisol and growth hormone response, fewer perturbations in blood immune cell counts, lower granulocyte and monocyte phagocytosis and oxidative burst activity, and a diminished pro- and anti-inflammatory cytokine response. It remains to be shown whether carbohydrate supplementation diminishes the frequency of infections in the recovery period after strenuous exercise. Studies on the influence of moderate exercise training on host protection and immune function have shown that near-daily brisk walking compared with inactivity reduced the number of sickness days by half over a 12- to 15-week period without change in resting immune function. Positive effects on immunosurveillance and host protection that come with moderate exercise training are probably related to a summation effect from acute positive changes that occur during each exercise bout. No convincing data exist that moderate exercise training is linked with improved T helper cell counts in patients with HIV, or enhanced immunity in elderly participants.

Aged↗

The effect of treatment with eprinomectin on lungworms at early patency on the development of immunity in young cattle.

An experiment was carried out to study the effect of topical application of eprinomectin at early patency on the build up of infection and development of protection against Dictyocaulus viviparus in young cattle. Three groups of six calves were used and parasitological and blood variables were monitored at weekly intervals throughout the trial. At the start of the experiment calves in groups A and B were experimentally inoculated with 100 D. viviparus infective third-stage larvae (L3) for five consecutive days, whereas calves in group C served as uninfected controls. The calves in group A were each treated with eprinomectin (0.5mg/kg bodyweight) in a pour-on formulation at early patency at day 24 post the first inoculation, whereas the calves in groups B and C were left untreated. Seven weeks following anthelmintic treatment all groups were challenged with 1500 L3. Another 4 weeks later the animals were sacrificed and established worms in the lungs were counted. Moderate transient signs of lungworm disease occurred both in groups A and B. However, group B calves were found to be about 8 times more resistant than those in group A, whereas the naive infection controls in Group C was found to be about 35 times more susceptible to infection. Also the ELISA values showed that the course of infection was different between experimental groups. The eosinophil counts prior to and at the time of slaughter indicate that immunity was involved in the protection and the response was correlated with previous exposure and worm load. Weight gains differed significantly, but only between groups A and C and between groups B and C that on an average were approximately 13kg heavier at the termination of the experiment. It was concluded that eprinomectin was effective against established adult lungworms. However, the untreated calves (group B) developed a more marked resistance to lungworms compared to those that were subjected to anthelmintic treatment at early patency (group A). On the other hand, the cumulative number of excreted larvae was on an average 43 times higher in group B as compared to group A. Consequently, infected calves that remain out on pasture should be treated. This will restrain transmission of the parasite despite the fact that immunity is deteriorated.

Animals↗

Management of malignant melanoma: new developments in immune and gene therapy.

Thus far, the use of classical anti-cancer treatment modalities had only rarely a beneficial impact on the prognosis of patients with metastatic melanoma. We as physicians have therefore the obligation as well as the chance to develop and test new therapeutic strategies. Our growing knowledge about the genetic basis of melanoma provides one platform to fulfil this task. Another one comes from our increasing understanding of the molecular and cellular mechanisms involved in the induction/modulation of immune responses, as well as the progress made in the field of identification of melanoma antigens, and allows for the development of a new generation of vaccines. The aim of this article is to discuss several of these new concepts towards the use of immune and gene therapy of melanoma.

Antigens, Neoplasm↗

[Correction of immunity disorder developing after craniocerebral trauma].

The article presents some data concerning influence of humoral factor received from blood serum of injured animals on humoral and cell immune response of animals. The results show that administration of humoral factor prevents stress-induced devastation of thymus, improves humoral immune response to antigen test (sheep erythrocytes) and restores hypersensitivity of decelerated type (HDT) reactions. Immune stimulating effects are observed both right after cranial trauma and some time later -- 5-7 days after the injury.

Adjuvants, Immunologic↗

Haemophilus influenzae disease and immunization in developing countries.

Haemophilus influenzae is one of the leading causes of severe bacterial infection in children of developing regions, causing 30% of the cases of culture-positive pneumonia and 20%-60% of the cases of bacterial meningitis. In infants and children, the majority of isolates from cerebrospinal fluid and blood and 16%-38% of pulmonary isolates are H. influenzae type b. The availability of several new polysaccharide-protein conjugate vaccines for the prevention of invasive disease due to H. influenzae type b prompts this review of the epidemiology of H. influenzae disease in the developing world and of the characteristics of current H. influenzae type b vaccines. To develop a strategy for use of H. influenzae type b vaccines in developing countries, the following data are needed: the age-specific attack rates of H. influenzae type b disease and the immunogenicity and efficacy of these vaccines in young infants in developing countries. Should H. influenzae type b vaccines prove to be inadequate for the prevention of H. influenzae pneumonia, the use of non-type b H. influenzae vaccines may be necessary.

Bacterial Capsules↗

Development of immune responsiveness to Ascaris suum antigens in pigs vaccinated with ultraviolet-attenuated eggs.

Pigs fed Ascaris suum eggs attenuated by short wave ultraviolet-radiation developed resistance to challenge infection. Per os inoculation of pigs on three successive weeks with 10,000 eggs irradiated to total exposures of 150,100 and 75 microW-min/cm2, respectively, resulted in an 88% reduction in the number of larvae recovered from the lungs 7 days after challenge with 10,000 infective eggs. Peripheral blood lymphocytes (PBL) from vaccinated pigs were specifically stimulated in vitro to incorporate tritiated thymidine by egg hatching fluid (Ea) and by excretory-secretory products obtained from cultures and from cultures of third-stage larvae developing to fourth-stage (L3-4). PBL were also specifically stimulated by living L2. Ea and L2 stimulated pig PBL significantly at 7 days after the first inoculation; responses to L2-3 and L3-4 developed 7 days after a second inoculation. The antigen-responsive cells in the PBL population were non-immunoglobulin-bearing lymphocytes. Antibodies to Ea and L2-3 were not detected in the serum of vaccinated pigs, and only 3 of 7 pigs had low concentrations of serum antibodies to L3-4.

Animals↗

Treatment of junin virus-infected guinea pigs with immune serum: development of late neurological disease.

Guinea pigs infected with Argentine hemorrhagic fever virus (Junin) were treated with pooled, homologous convalescent sera. Use of 15,000 or 5,000 therapeutic units of immune sera prevented all signs of illness when administered within 24 hr of infection. We could also prevent illness and death in infected guinea pigs as late as 6 days after infection if we used more antisera (30,000 therapeutic units/kg). In some treatment groups, surviving animals developed a late neurological syndrome with prominent rear-limb paralysis. Treated animals typically expressed higher viral titers in the brain than in any other organ. There appeared to be no acute exacerbation of disease by antibody administration. Our data suggest that, after replicating peripherally, Junin virus infects the brain where circulating immunoglobulins may not eliminate viable virus. Subsequent replication of virus in the brain may generate a neurological phase of the illness. Histological examination of brains from guinea pigs in treatment groups favoring the neurological phase of illness showed encephalitis, meningitis, and swollen astrocytes, suggestive of neuronal degeneration. There is likely a delicate balance among presence of virus in the brain, the amount of antibody transported into the central nervous system, and the occurrence of this late neurological aspect of experimental Argentine hemorrhagic fever. Further study of this model may elucidate factors relevant in understanding the continuing problem of the late neurological syndrome seen in some human cases of Argentine hemorrhagic fever treated with immune plasma.

Animals↗

The role of mucosal immunity in development of an acquired immunodeficiency syndrome (AIDS) vaccine: workshop summary.

As the AIDS pandemic spreads, the importance of developing effective vaccines against the human immunodeficiency virus (HIV) assumes increasing importance. Since prevention of any disease is a preferred goal, extensive efforts are being devoted to development of an effective vaccine capable of preventing HIV infection and/or disease. Although many investigators are studying the systemic immune response to HIV, relatively little is known about the mucosal immune response to HIV. A workshop was held to identify the basic research issues in mucosal immunity which need to be addressed in order to rationally design an effective vaccine against HIV. This summary emphasizes the salient points of the papers presented and identifies the unanswered questions.

Acquired Immunodeficiency Syndrome↗

Origin of Toll-like receptor-mediated innate immunity.

Toll-related receptors (TLR) have been found in four animal phyla: Nematoda, Arthropoda, Echinodermata, and Chordata. No TLR has been identified thus far in acoelomates. TLR genes play a pivotal role in the innate immunity in both fruit fly and mammals. The prevailing view is that TLR-mediated immunity is ancient. The two pseudocoelomate TLRs, one each from Caenorhabditis elegans and Strongyloides stercoralis, were distinct from the coelomate ones. Further, the only TLR gene (Tol-1) in Ca. elegans did not appear to play a role in innate immunity. We argue that TLR-mediated innate immunity developed only in the coelomates, after they split from pseudocoelomates and acoelomates. We hypothesize that the function of TLR-mediated immunity is to prevent microbial infection in the body cavity present only in the coelomates. Phylogenetic analysis showed that almost all arthropod TLRs form a separate cluster from the mammalian counterparts. We further hypothesize that TLR-mediated immunity developed independently in the protostomia and deuterostomia coelomates.

Amino Acid Sequence↗

Autoimmunity: from physiology to pathology. Natural antibodies, mucosal immunity and development of B cell repertoire.

Presence of spontaneously produced immunoglobulins bearing a broad spectrum of "natural" antibody specificities (including autoantibodies) in sera and other body fluids results mainly from inapparent immunization and polyclonal B cell activation by microflora and food antigens occurring mostly on mucosal surfaces. Early postnatal ontogeny in external environment is characterized by rapid growth and functional maturation of secondary lymphatic tissues as a consequence of this "natural" mucosal immunization. Under normal circumstances a state of "oral" tolerance to intestinal antigens is actively established after this period. Studies performed in germ-free, antigen-free and maternal antibody-deprived animals showed that low amounts of natural antibodies (mainly of IgM isotype) are formed without any known cause of stimulation. These "nonstimulated" antibodies, similarly as hybridomas originating from nonimmunized newborns, correspond to the preimmune repertoire of antibodies characterized by poly-specificity, high connectivity and reactivity against self antigens. Together with other innate humoral and cellular factors, they probably represent the first line of anti-infectious resistance. Moreover, due to their connectivity they are supposed to play an important role in B cell repertoire shaping (forming an idiotypic network), through interaction with a broad spectrum of immunological components they act as regulatory molecules, and through their participation in catabolic events they can promote morphogenetic changes during fetal development. Beneficial therapeutic effects of nonspecific gammaglobulin (IVIG) application observed recently in patients with autoimmune diseases suggest that they can influence autoimmune reactivity by a not yet analyzed mechanism. Other functions of natural autoantibodies can be suggested and expected to be found in the near future.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmunity↗

Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition.

Vaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non-attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate-sensitive and -resistant epitopes in 'skin-stage', 'lung-stage' and 'liver-stage' schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species-specific responses, and vaccination-specific responses were examined. No response developed in parallel with serum-mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non-protective CIS.

Animals↗