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PubMedDate not supplied

Immune effector mechanisms in malaria.

That humans in endemic areas become immune to malaria offers encouragement to the idea of developing protective vaccines. However natural immunity is relatively inefficient, being bought at the cost of substantial childhood mortality, and current vaccines are only partially protective. Understanding potential targets and mechanisms of protective immunity is important in the development and evaluation of future vaccines. Some of the problems in identifying such targets and mechanisms in humans naturally exposed to malaria may stem from conceptual and methodological issues related to defining who in a population is susceptible, problems in defining immune responsiveness at single time points and issues related to antigenic polymorphism, as well as the failure of many current approaches to examine functional aspects of the immune response. Protective immune responses may be directed to the pre erythrocytic parasite, to the free merozoite of the blood stage parasite or to new antigens induced on the infected red cell surface. Tackling the methodological issues of defining protection and immune response, together with studies that combine functional assays with new approaches such as allelic exchange and gene knock out offer opportunities for better defining key targets and mechanisms.

Adolescent↗

PubMed1995

Local and systemic immune response to inactivated Candida albicans in mice.

To improve our understanding of the role natural-immunity cells play in regulating the immune response to Candida albicans (CA) we compared local versus systemic effects of intraperitoneal inoculations with inactivated CA cells in mice. Peritoneal exudate cells (PECs) and spleen cells (SCs) were recovered from CD2F1 mice after 5 intraperitoneal CA injections (2 x 10(7) cells/mouse on days -14, -10, -7, -3 and 0 (CA-5d) with respect to in vitro assays performed at 2 h, 24 h, 3 days and 5 days). Northern blot analysis revealed that 2 h after CA-5d, PECs expressed a high level of IL-2, IFN-gamma, IL-1 beta and a low level of IL-10 and TNF-alpha mRNAs, while IL-4 and IL-5 mRNAs were absent, suggesting the development of TH1 subset. At 24 h, while IL-2 mRNA remained high, IL-1 beta and IFN-gamma expression had decreased and IL-10 and TNF-alpha mRNAs were no longer detectable. Instead, in spleens of CA-treated mice, examined up to 5 days after CA-5d, only IL-2 and IL-1 beta mRNAs were detectable, but the expression level was similar to that of untreated control mice. CA-5d induced a high level of natural-killer (NK)/lymphokine-activated-killer (LAK) activity in the peritoneal cavity but did not affect spleen NK activity. After CA-5d, the proliferative response of PECs to mitogens and CA antigens was also different from that of SCs. Unfractionated PECs were unable to proliferate in response to concanavalin A (Con A), IL-2, CA cells and CA cell wall mannoprotein, but after removal of the nylon-wool-adherent fraction, the nonadherent peritoneal cells (Nad-PECs) showed a significant proliferative response to mitogens. After depletion of NK cells by anti-asialo-GM1 antibody plus complement, the proliferative response of Nad-PECs to Con A and CA increased further. Contrary to the PEC response, unfractionated SCs from the same animals responded very well to mitogens and CA antigens and the proliferative response was significantly higher compared to that of SC from control mice. In conclusion, these results cast some light on the mechanisms by which NK cells and macrophages regulated the development of the local specific response to CA: activated NK cells, by producing IFN-gamma, favor the development of TH1 subset, while suppressor macrophages keep proliferation of T lymphocytes under control because of the presence of highly activated NK cells.

Animals↗

PubMed1992

The IgG subclass antibody response to an inhalant antigen (Dermatophagoides pteronyssinus) during the first year of life: evidence for early stimulation of the immune system following natural exposure.

This study investigates the early humoral immune response following natural exposure to an inhalant antigen (Dermatophagoides pteronyssinus) in 36 babies, from birth until 1 year of age. The total IgG and subclass 1 and 4 D. pteronyssinus-specific antibody levels were assayed in sera collected at 7 days, 3 and 12 months by ELISA. After an initial fall, due to the progressive loss of maternal antibodies, an IgG specific response to D. pteronyssinus was seen between 3 and 12 months. This was restricted to the IgG1 subclass when the values at 12 months were significantly higher than those detected at the third month (P less than 0.001, paired t test). No D. pteronyssinus-specific IgG4 antibody was detected in any subject at any of the time points tested. The present study demonstrates that inhalant as well as food antigens are able to stimulate the immune system during the first year of life and that the antibodies produced are of the IgG1 subclass.

Administration, Inhalation↗

PubMed1996

Electrochemotherapy with bleomycin in SA-1 tumor-bearing mice--natural resistance and immune responsiveness.

Electrochemotherapy is an antitumor treatment that utilizes locally delivered electric pulses to increase the effectiveness of chemotherapeutic drugs in cells and tissues. Electric pulses permeabilize tumor cells to allow nonpermeant drugs such as bleomycin to enter the cells. Although preclinical data indicate that immune responsiveness of the organism is important for obtaining cures of the tumors after electrochemotherapy with bleomycin, it is not known how electrochemotherapy affects the immune system of the organism. The aim of the study was to determine the effects of electrochemotherapy with bleomycin on natural resistance and immune responsiveness. Natural resistance was evaluated by phagocytic and intracellular killing activity (oxidative burst) in monocytes and polymorphonuclear granulocytes from venous blood, and immune responsiveness by blast transformation of spleen mononuclear cells to mitogens. The percentage of monocytes in venous blood able to elicit oxidative burst was significantly increased 7 days after the electrochemotherapy and returned to normal values after 14 days. In addition, increased blast transformation of spleen mononuclear cells by stimulation with concanavalin A (T lymphocytes activity) was found 14 days after electrochemotherapy treatment. The results of our study demonstrate that electrochemotherapy with bleomycin affects the immune system of the organism

Animals↗

PubMed1992

Immunity to Haemophilus influenzae type b on sample population from central Italy.

A study on natural immunity to Haemophilus influenzae type b (Hib) was carried out in the province of Siena on 474 subjects ranging in age from 3 days to 70 years. The titration of antibody to capsular polysaccharide (PRP) was performed by the radioantigen-binding assay (RABA) method. A total of 66.67% of the population studied presented an antibody level considered to be protective (greater than or equal to 0.15 microgram ml-1). Seropositivity was 5.7% in the 5-7 month age group and 29.09% in the 8-17 month age group. This rose progressively in successive age groups reaching 79.54% between 4 and 6 years old and a value greater than 90% after 7 years old. From 3 to 17 months even the geometric mean of antibodies to PRP was below the protective limit. Our data indicate that, even in Italy, the majority of the infant population is not protected against H. influenzae, and therefore that vaccination should also be introduced in this country.

Adolescent↗

PubMed1999

Exercise and immune function: effect of ageing and nutrition.

Strenuous exercise is followed by lymphopenia, neutrophilia, impaired natural immunity, decreased lymphocyte proliferative responses to mitogens, a low level of secretory immunoglobulin A in saliva, but high circulating levels of pro- and anti-inflammatory cytokines. These exercise-induced immune changes may provide the physiological basis of altered resistance to infections. The mechanisms underlying exercise-induced immune changes are multifactorial and include neuroendocrinological and metabolic mechanisms. Nutritional supplementation with glutamine abolishes the exercise-induced decline in plasma glutamine, but does not influence post-exercise immune impairment. However, carbohydrate loading diminishes most exercise effects of cytokines, lymphocyte and neutrophils. The diminished neutrophilia and elastase (EC 3.4.21.37) responses to eccentric exercise in elderly subjects were enhanced to levels comparable with those of young subjects by fish oil or vitamin E supplements. However, although vitamin C supplementation may diminish the risk of contracting an infection after strenuous exercise, it is not obvious that this effect is linked to an effect of vitamin C on exercise-induced immune changes. In conclusion, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗

PubMed2006

Interactions between natural killer cells, cortisol and prolactin in malaria during pregnancy.

Natural killer cells derived from pluripotent hematopoietic stem cells are important cells of the immune system that have two main functions: a cytolytic activity and a cytokine-producing capacity. These functions are tightly regulated by numerous activating and inhibitory receptors, including newly discovered receptors that selectively trigger the cytolytic activity in a major histocompatibility complex independent manner. Based on their defining function of spontaneous cytotoxicity without prior immunization, natural killer (NK) cells have been thought to play a critical role in immune surveillance and cancer therapy. New insights into NK cell biology have suggested their major roles in the control of infections, particularly in Plasmodium falciparum infection and in fetal implantation. P. falciparum is the main protozoan parasite responsible for malaria causing 200-300 million clinical cases and killing over 3 million people each year. This review provides an update on NK cell function, ontogeny and biology in order to better understand the role of NK cells in pregnancy in regions where malaria is endemic. Understanding mechanisms of NK cell functions may lead to novel therapeutic strategies for the treatment of human disease, in general, and particularly in the fight against malaria.

Cell Death↗

PubMed1999

Placental transfer of IgG antibodies against Haemophilus influenzae type b capsular polysaccharide in Brazilian term and preterm newborns.

Placental transfer of antibodies to polysaccharide antigens is still a controversial subject. The incidence of invasive Haemophilus influenzae type b (Hib) infections is high in countries where the vaccine has not been included in routine immunization schedules. In the present work, we proposed to evaluate the natural immune response to Hib capsular polysaccharide in term and preterm Brazilian newborns and their respective mothers. Although the means, medians, and ranges of antibody titres in paired maternal and cord sera from preterm neonates were similar, the maternal levels were slightly higher than the cord levels and a poor correlation between these levels was verified. Term neonates showed similar antibody levels to those of their respective mothers and a very significant correlation between these levels was observed.

Antibodies, Bacterial↗

PubMed1991

Mosquitoes, leeches and medicine in Charleston, South Carolina (1670-1861).

Charleston, South Carolina, USA has a rich history extending over 300 years. The plantations of the Carolina Low Country produced rice, indigo and cotton. Mosquitoes, which abounded in the wetlands, transmitted diseases such as Yellow Fever and epidemics occurred almost every year. African slaves, however, had a natural immunity to the disease and, together with the climate and the nature of the work, this shaped the economic and social system of the area. Physicians offered all sorts of cures to deal with the medical problems of the area and apothecaries also sold many nostrums including leeches. Newspaper advertisements reveal that these bloodsuckers were extensively used for many decades.

Animals↗

PubMed2000

Effects of exercise on lymphocytes and cytokines.

OBJECTIVES: To review results on exercise induced changes in the immune system following strenuous and moderate exercise. METHODS: A literature search over the past 15 years was conducted using Medline and selected papers. RESULTS: After intense long term exercise, the immune system is characterised by concomitant impairment of the cellular immune system and increased inflammation. Thus low concentrations of lymphocytes, suppressed natural immunity, suppressed lymphocyte proliferation, and suppressed levels of secretory IgA in saliva are found simultaneously with high levels of circulating proinflammatory and antiinflammatory cytokines. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. The clinical consequences of the exercise induced immune changes have not formally been identified, but the exercise effect on lymphocyte dynamics and immune function may be linked to the exercise effects on resistance to infections and malignancy and the cytokine response may be linked to muscle damage or muscle cell growth. CONCLUSIONS: Moderate exercise across the life span seems to increase resistance to upper respiratory tract infections, whereas repeated strenuous exercise suppresses immune function. It is premature to offer advice on nutrition to athletes in order to alter the exercise induced immunosuppression found after exercise.

Animals↗

PubMedDate not supplied

Salivary lysozyme levels in patients with primary immunodeficiencies.

BACKGROUND: Lysozyme is a muramidase that acts on the peptideoglycan wall of Gram positive bacteria, causing cell death. It plays part in innate immunity and is present in blood, external fluid, as well in lysossomal granules of the phagocytes. Primary Immunodeficiencies are a diverse group of illnesses that, as a result of abnormalities of the immune system, increase susceptibility to infection. Among the examples of impaired natural immunity are defects in phagocytes and in the complement system. Innate immunity could be important in protecting mucosas against infections in patients with different forms of primary immunodeficiencies. The aim of this study was to investigate lysozyme concentrations in saliva from patients with primary immunodeficiencies. METHODS: Lysozyme levels in saliva samples from 34 patients with primary immunodeficiency (30 children and adolescents between the age of 3-13 years and 4 adults between the age of 20-33) and 60 age-matched healthy controls (49 children and adolescents between the ages of 3-15 and 11 adults between the ages of 22-42) were determined by the lysoplate method. RESULTS: There was no statistically significant difference between the lysozyme concentrations in the saliva of the immunodeficient subjects and those of the healthy controls. CONCLUSION: The results in the present work clearly show that salivary lysozyme levels in primary immunodeficient patients are equivalent to those found in healthy controls, suggesting that this enzyme still represents a remaining (but not a compensatory mechanism), contributing to the protection of there patients against infections.

Adolescent↗

PubMed1992

[Malaria: immune mechanisms and immunization].

In the 1990s, malaria worldwide is still the most important infectious disease. In endemic areas mostly children carry the highest burden of morbidity and mortality. Nevertheless an increasing incidence in adults can be expected. Patterns of disease and immunity within a population may be related to host parasite interactions and recent advances in immunology have contributed to a better understanding at the molecular level. Humoral and cellular responses play a major part in the immunity as well as immunopathology of malaria. Due to their extensive adaptive modulation, it will be extremely difficult to expel malaria parasites from their ecological niche. Most approaches of immunization targeted at different parasite stages, interfere with the acquisition of natural immunity and should thus be pursued with great care if implemented in the field.

Animals↗

PubMed1990

The impact of Hodgkin's disease on the immune system.

Patients with Hodgkin's disease, at presentation or in remission, exhibit a persistent defect in cellular immunity. Natural killer cell mediated cytotoxicity is depressed in untreated patients. Humoral immune function is transiently reduced following treatment. The cellular immune defect appears to be the result of enhanced sensitivity to suppressor monocytes and T-suppressor cells, in addition to abnormal interleukin-2 production. Patients with advanced disease have an inherent T-lymphocyte defect. Reed-Sternberg cells function as antigen-presenting cells for mitogen-induced and mixed lymphocyte T-cell proliferation.

Antibody Formation↗

PubMed1989

Tetanus immunity in kibbutz women.

The clinic records of 1,009 women, aged greater than or equal to 28, who comprised the entire cohort of the six kibbutzim studied, were reviewed concerning basic tetanus immunization and booster injections. Immunization was incomplete in 6.5% of women aged 28 to 39 years (the youngest age-group), 13.7% in those aged 40 to 49, 55% in the 50 to 59 year age-group, and 68.2% in those aged greater than or equal to 60. There were no significant differences between the age-groups regarding the number of booster doses given. Blood samples drawn at random from 120 of the women whose records were surveyed (30 from each age-group) showed that all had a protective titer of antibody to tetanus toxin as determined by the passive hemagglutination method: 15 of them (12.5%) had never received basic immunization or a booster dose. Whatever the method chosen for determining immunity--chart review or antibody titer--the level of protection was lower in the older age-groups. The implications of this finding for future immunization programs, and the possibility that there may be widespread, acquired natural immunity to tetanus in rural communities, are discussed.

Adult↗

PubMed2002

The use of diclazuril in extended withdrawal anticoccidial programs: 2. Immunity to Eimeria tenella challenge after drug withdrawal.

The effect of diclazuril medication on the development of natural immunity to Eimeria tenella was determined. Birds in two treatments, nonexposed, non-challenged (NENC) and nonexposed, challenged (NEC), were from a holding group raised under conditions designed to prevent coccidial infection. Birds in five other treatments, from the same hatch and source as birds in the first two treatments, were from a floor pen study involving a natural exposure to Eimeria spp. These birds were assigned to the current study based on their respective treatments in the original floor pen study as follows: unmedicated (UNM), 66 ppm salinomycin (SAL) + 50 ppm roxarsone in the starter and grower diets to Day 28 (SAL 28), 66 ppm SAL + 50 ppm roxarsone in the starter diet and 1 ppm diclazuril (DIC) in the grower diet to Day 28 (DIC 28) or to Day 35 (DIC 35), or in the grower and finisher diets to Day 42 (DIC 42). Each treatment comprised three floor pens of 10 birds (female) in a randomized complete block design. All birds were fed an UNM finisher diet during the 7-d challenge study. Birds in each treatment, except NENC, were individually inoculated (p.o.) with 1 x 10(5) Eimeria tenella sporulated oocysts on Day 1. Based on bird performance and cecal lesion scores, birds in the DIC 35 and 42 treatments had a low immunity to the challenge infection, birds in the DIC 28 treatment were partially immunized, and the highest levels of immunity were observed in the UNM and SAL 28 treatments.

Animal Nutritional Physiological Phenomena↗

PubMed2006

Immunization with live Neisseria lactamica protects mice against meningococcal challenge and can elicit serum bactericidal antibodies.

Natural immunity against Neisseria meningitidis is thought to develop following nasopharyngeal colonization with this bacterium or other microbes expressing cross-reactive antigens. Neisseria lactamica is a commensal of the upper respiratory tract which is often carried by infants and young children; epidemiological evidence indicates that colonization with this bacterium can elicit serum bactericidal activity (SBA) against Neisseria meningitidis, the most validated correlate of protective immunity. Here we demonstrate experimentally that immunization of mice with live N. lactamica protects animals against lethal meningococcal challenge and that some, but not all, strains of N. lactamica elicit detectable SBA in immunized animals regardless of the serogroup of N. meningitidis. While it is unlikely that immunization with live N. lactamica will be implemented as a vaccine against meningococcal disease, understanding the basis for the induction of cross-protective immunity and SBA should be valuable in the design of subunit vaccines for the prevention of this important human infection.

Animals↗

PubMed2005

Role of cytokines and chemokines in the regulation of innate immunity and HIV infection.

The earliest defense against microbial infection is represented by the responses of the innate (or natural) immune system, that also profoundly regulates the adaptive (or acquired) T- and B-cell immune responses. Activation of the innate immune system is primed by microbial invasion in response to conserved structures present in large groups of microorganisms (LPS, peptidoglycan, double-stranded RNA), and is finely tuned by different cell types (including dendritic cells, macrophages, natural killer cells, natural killer T cells, and gammadelta T cells). In addition, several soluble factors (complement components, defensins, mannose-binding lectins, interferons, cytokines and chemokines) can play a major role in the regulation of both the innate and adaptive immunity. In this review, we will briefly overview the regulation of some cellular subsets of the innate immune system particularly involved in human immunodeficiency virus (HIV) infection and then focus our attention on those cytokines and chemokines whose levels of expression are more profoundly affected by HIV infection and that, conversely, can modulate virus infection and replication.

Chemokines↗

PubMed2003

Natural selection on immune responsiveness in blue tits Parus caeruleus.

What is the form of natural selection on immune responsiveness? For a population at evolutionary equilibrium, there are two different scenarios. First, it is generally assumed that immune defense has both benefits and costs. If variation in immune responsiveness is due to variation in how individuals trade off these costs and benefits, one would expect immune responsiveness to be subject to stabilizing selection. Second, it is well known that an individual's immune responsiveness is often dependent on its overall condition. If immune responsiveness is condition-dependent, one would expect immune responsiveness to be under positive directional selection. We would therefore expect that the form of natural selection on immune responsiveness depends on the relative magnitude of these two sources of variation: variation in how individuals trade off the costs and benefits of defense, and variation in condition. We measured primary and secondary antibody responsiveness to diphtheria-tetanus vaccine in blue tits during winter and investigated the relationship between responsiveness and survival to the following breeding season. We use responsiveness to these antigens as measures of an individual's ability or propensity to mount an antibody response in case of an infection. Interestingly, different measures of responsiveness were subject to different selective regimes: primary responsiveness to diphtheria was subject to stabilizing selection, whereas secondary responsiveness to tetanus was subject to positive directional selection. In contrast, there was no significant selection on primary responsiveness to tetanus or secondary responsiveness to diphtheria. The finding of stabilizing selection on a measure of responsiveness is evidence that immune defense can incur fitness costs; a central but little-tested assumption of theories of the ecology and evolution of immunological defense. The finding of directional selection on a measure of responsiveness is consistent with the idea that immune responsiveness is condition-dependent, although we cannot rule out the alternative explanation that the population is not at evolutionary equilibrium with respect to this trait.

Age Factors↗