Insufficient Immune Response Research Articles

Parasites in Emsian-Eifelian Favosites (Anthozoa, Tabulata) from the Holy Cross Mountains (Poland): changes of distribution within colony

Abstract Organisms of unknown biological affinities, assigned to the genus Chaetosalpinx , are known to infest Palaeozoic tabulate corals and stromatoporoids. Analysis of distribution of these parasites, performed on Emsian–Eifelian material of Favosites goldfussi (Anthozoa, Tabulata) from the Northern Region of the Holy Cross Mountains (Poland), shows that parasites were absent in the early astogenetical stages, and that during astogeny both the absolute number of parasites per colony and the number of parasites per polyp were increasing. The latter can reach 2.7 parasites per polyp. Preferred settling places are in corallite corners (junction of three individuals), but dense infestation also produced settlement in the corallite walls (between two individuals). Probable causes of the increase are insufficient protection by host's cnidae, insufficient immune system response, and parasite ability to adapt to the host's defences.

Immune responses in hepatitis C virus infection and mechanisms of hepatitis C virus persistence

Immune responses against hepatitis C virus (HCV) play a crucial role in the pathogenesis of chronic hepatitis C. HCV infection often persists and leads to chronic hepatitis and eventually cirrhosis. Accumulated data suggest that HCV proteins suppress host immune responses through the suppression of functions of immune cells, such as cytotoxic T lymphocytes, natural killer cells, and dendritic cells. They also suppress the type 1 interferon signaling system. The resulting insufficient immune responses against HCV lead to the sustained infection. The appropriate control of immune responses would contribute to the eradication of HCV and the improvement of hepatitis, but there are still many issues to be clarified. This review describes the scientific evidence to support these emerging concepts, and will touch on the implications for improving antiviral therapy.

Tied to the mast

Duke researchers suggest that small molecule mast cell activators might function as intranasal adjuvants to enhance the typically weak or insufficient immune response to nasal vaccines. However, some researchers raise questions about the potential for unwanted inflammatory effects.

HCV and innate immunity

Hepatitis C virus (HCV) is a single-strand, positive sense RNA virus belonging to the flaviviridae family. HCV develops persistent infection in >70% of infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Once chronic infection is established in patients with HCV, spontaneous viral clearance fails, although how HCV remains persistently infecting the liver is largely unknown. Insufficient immune response, involving antiviral innate immune response including dendritic cells (DCs), has been focused. A number of controversial studies have been reported as to HCV genome replication and HCV-mediated immune responses in human DCs. A tantalizing point of these earlier studies is the lack of the system for viral propagation in HCV. Recently, an in vitro system was exploited to propagate HCV particles using the JFH1 strain. In this review, we review the previous reports about the subversion of innate immunity by HCV and show the innate response of monocyte-derived dendritic cells (MoDCs) against the JFH1 strain. We could not observe HCV direct interaction with MoDC maturation. MoDCs maturated by phagocytosing HCV-infected apoptotic cells containing virus-derived dsRNA, which interacted with TLR3 in the phagosomes. All of these data suggests the importance of TLR3 signal for the induction of anti-HCV innate immunity.

Monocyte‐derived dendritic cells from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile

Chronic hepatitis C virus (HCV) infection is characterized by an insufficient immune response, possibly owing to impaired function of antigen-presenting cells such as myeloid dendritic cells (DCs). Therapeutic vaccination with in vitro generated DCs may enhance the immune response. Subsets of DCs can originate from monocytes, but the presence of HCV in monocytes that develop into DCs in vitro may impair DC function. Therefore, we studied the presence of HCV RNA in monocytes and monocyte-derived DCs from chronic HCV patients. Monocytes were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) for 6 days, and then with GM-CSF, IL-4, tumour necrosis factor-alpha (TNF-alpha), prostaglandin E2, IL-1beta and IL-6 for 2 days to generate mature DCs. HCV RNA was assessed by polymerase chain reaction. Surface molecules were assessed by flow cytometry. Cytokine production was assessed by cytokine bead array. HCV RNA was present in monocytes in 11 of 13 patients, but undetectable in mature DCs in 13 of 13 patients. The morphology of patient DCs was comparable with DCs from healthy controls, but the percentage of cells expressing surface molecules CD83 (P=0.001), CD86 (P=0.023) and human leucocyte antigen-DR (P=0.028) was lower in HCV patients. Compared with control DCs, patient DCs produced enhanced levels of IL-10 (P=0.0079) and IL-8 (P=0.0079), and lower levels of TNF-alpha (P=0.032), IL-6 (P=NS) and IL-1beta (P=0.0079). Patient and control DCs did not produce IL-12. Monocyte-derived DCs from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile.

Multiple Cytokine and Acute-Phase Protein Gene Transcription in West Greenland Sledge Dogs (Canis familiaris) Dietary Exposed to Organic Environmental Pollutants

Exposure levels of persistent organic pollutants, such as polychlorinated biphenyls and DDTs, are high in Arctic apex predators and Inuit peoples and are suspected to have negative impacts on their immune systems. We conducted a controlled generational study on liver tissue and ethylenediaminetetraacetic acid blood cytokine and acute-phase protein (APP) mRNA expressions using reverse transcriptionase-polymerase chain reaction in West Greenland sledge dogs (Canis familiaris); contaminated minke whale (Balaenoptera acutorostrata) blubber serves as dietary pollutant source. Two of seven blood cytokine expressions (IL-6 and IL-12) and three of five APP expressions (haptoglobin [HP], heat shock protein, and fatty acid-binding protein [FABP]) were lowest in the exposed group, whereas the remaining five blood cytokine expressions (IL-2, IL-10, IFN-gamma, TNF-alpha, and TGF-beta) and two APP expressions (MT1 and MT2) were highest in the exposed group. In liver tissue, three cytokine expressions (IL-10, IFN-gamma, and TNF-alpha) and two APP expressions (MT1 and MT2) were highest in the exposed group, and the remaining cytokine and APP expressions were lowest in the exposed group. Of these, the liver tissue expression of HP and FABP was significantly lowest in the exposed group (both p < 0.05). As a consequence of our findings, we suggest that a daily intake of 50 to 200 g polluted whale blubber is associated with a genotoxic decrease in HP and FABP gene expression in the liver of sledge dog and possibly of other top mammalian marine predators and consumers in the Arctic, indicating a restricted acute-phase reaction and insufficient immune response. Finally, HP and FABP liver expression appear to be new and sensitive biomarkers of organohalogen compound exposure.

Vaccination in special situations

To review the indications, contraindications and efficacy of vaccination in some special situations: immunosuppression, prematurity, pregnancy and post-exposure situations. Systematic review of articles published during the two last decades, found in MEDLINE, SciELO and Lilacs databases; guidelines of Programa Nacional de Imunizações (Brazilian National Immunization Program), 2001 to 2004, and of Programa Nacional de DST/AIDS (Brazilian National STD/AIDS Program), 2004. Abstracts published in national and international pediatric and infectious disease congress annals during the last five years were also consulted. Some special situations, such as immunosuppression, prematurity, pregnancy and exposure to infectious diseases increased the risk of diseases or adverse post-vaccination events. In these situations, special vaccines or special vaccination schedules are indicated, or vaccines should be postponed or even forbidden. In general, toxoid or inactivated vaccines can be used, considering the possibility of insufficient immune response. For immunosuppressed patients, in accordance with the type of immunosuppression, live virus or bacterial vaccines should be avoided, because of the risk of vaccine agent spread. Immunization should include not only the patient, but his/her home and day-care contacts as well. Knowledge about the schedule indicated for each situation improves the chances of better vaccine protection and decreases the risk of adverse events. Immunosuppressed or immunodeficient patients whose post-vaccine antibody titers are not available should be considered susceptible when exposed to infectious disease, and all the available prophylactic measures should be implemented, even when the vaccination schedule is correct.

Inhibition of Interferon-γ Signaling in Oligodendroglia Delays Coronavirus Clearance without Altering Demyelination

Infection of the central nervous system (CNS) by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces an acute encephalomyelitis associated with demyelination. To examine the anti-viral and/or regulatory role of interferon-γ (IFN-γ) signaling in the cell that synthesizes and maintains the myelin sheath, we analyzed JHMV pathogenesis in transgenic mice expressing a dominant-negative IFN-γ receptor on oligodendroglia. Defective IFN-γ signaling was associated with enhanced oligodendroglial tropism and delayed virus clearance. However, the CNS inflammatory cell composition and CD8+ T-cell effector functions were similar between transgenic and wild-type mice, supporting unimpaired peripheral and CNS immune responses in transgenic mice. Surprisingly, increased viral load in oligodendroglia did not affect the extent of myelin loss, the frequency of oligodendroglial apoptosis, or CNS recruitment of macrophages. These data demonstrate that IFN-γ receptor signaling is critical for the control of JHMV replication in oligodendroglia. In addition, the absence of a correlation between increased oligodendroglial infection and the extent of demyelination suggests a complex pathobiology of myelin loss in which infection of oligodendroglia is required but not sufficient.

Neurodermitis

Squamous cell conjunctival carcinomas (SCCC) are rare. We report on a 34-year-old patient with neurodermatitis and chronic conjunctivitis who presented with a therapy-resistant corneal ulcer induced by mechanical irritation diagnosed as SCCC. Chronic blepharoconjunctivitis seems to sustain the development of SCCC in patients with neurodermatitis because of their insufficient immune response.

Intensive Treatment for Childhood Acute Lymphoblastic Leukemia Reduces Immune Responses to Diphtheria, Tetanus, and Haemophilus influenzae Type b

Immunity to diphtheria toxoid (D), tetanus toxoid (T), and Haemophilus influenzae type b (Hib) is affected in children with acute lymphoblastic leukemia (ALL). The aims were to examine immunity and to compare the response to immunization at 1 or 6 months after treatment. Thirty-one patients were immunized with DT and conjugated Hib vaccine (ActHib) at 1 month or 6 months after treatment of ALL with the NOPHO 92 protocol. Antibody levels were determined before and 3 weeks after vaccination. Specific T and Hib antibody-secreting cells of IgG/IgA/IgM isotypes were analyzed in peripheral blood using an ELISPOT technique. All specific antibody levels decreased during ALL treatment, and protective levels after treatment were noted for 17% against D, 33% against T, and 100% against Hib. No high-risk patient had full D or T protection after treatment. After vaccination all the standard- and intermediate-risk patients achieved full protection against D, T, and Hib. The high-risk group showed insufficient immune response (full protection after vaccination: D 56%, T 22%, Hib 78%). No difference was found between vaccination at 1 month or 6 months after treatment. The poor antibody production in the high-risk group correlated to low numbers of antibody-secreting cells. Nonprotective antibody levels against D, T, and Hib after childhood ALL are more common than previously thought. Insufficient immune response was restricted to the high-risk group and was related to a low number of memory B cells in this study. Immunizations should be included in follow-up after childhood ALL, and the policy should be adapted to treatment intensity.

Molecular epidemiology of malaria in cameroon. IX. Characteristics of recrudescent and persistent Plasmodium falciparum infections after chloroquine or amodiaquine treatment in children.

In the absence of a firmly established gene responsible for chloroquine and amodiaquine resistance in Plasmodium falciparum, surveillance of resistance to these first-line drugs in Cameroon needs to be performed by in vivo or in vitro tests for drug resistance. These 2 methodological approaches to define drug resistance were shown to be complementary and concordant in a majority of cases at our study sites, but discordant results may be observed in a few cases, probably as a result of acquired immunity and low plasma drug levels. To further examine the nature of recrudescent and persistent parasitemia after treatment with chloroquine or amodiaquine, the clinical response of children aged < 5 years, presumably with insufficient immune response, was assessed, and the in vitro response of the corresponding isolates was determined if treatment or parasitological failure occurred. Genotyping of pretreatment and posttreatment isolates was performed by polymerase chain reaction to distinguish between recrudescence and reinfection. Plasma drug levels were measured at the time of therapeutic failure by high-performance liquid chromatography. All cases of therapeutic or parasitological failure observed on or before Day 14 were due to the persistence or recrudescence of the original parasite populations present before treatment, with or without selection and appearance of new populations. Most parasites were characterized by elevated 50% inhibitory concentrations for chloroquine and amodiaquine at the time of clinical or parasitological failure. In some children, recrudescence was explained by the absence of drug in the plasma. The simultaneous analysis of clinical and in vitro responses, plasma drug level measurement, and genotyping may yield results that may explain the reasons for therapeutic failure, help establish the threshold level for in vitro resistance, and provide a set of more accurate tools to describe the epidemiology of drug-resistant P. falciparum while awaiting for the identification of the chloroquine and amodiaquine resistance gene or genes.

A 5-year follow-up on antibody response after diphtheria and tetanus vaccination in hemodialysis patients

Chronic renal failure is associated with a T-cell-dependent immune defect. In the past, various studies have focused on the insufficient immune response to vaccination of hemodialysis patients. An impaired vaccination response rate has been reported for vaccines against hepatitis B, influenza, tetanus, diphtheria, and others. However, no data exist on the long-term success of vaccination against tetanus and diphtheria in these patients. The aim of the present study is to investigate seroresponse to tetanus and diphtheria vaccination over a 5-year period. Antibody levels were determined by enzyme immunoassay. Antidiphtheria antibody levels of 31 hemodialysis patients were determined 5 years after vaccination. After 5 years, 10 of 31 patients (32%) had a protective antibody level against diphtheria (≥0.1 IU/mL), whereas 12 months after vaccination, 26 of 71 patients (37%) were protected. Also, mean antibody levels significantly decreased. Furthermore, antitetanus antibody levels of 21 patients simultaneously vaccinated against tetanus and diphtheria were investigated. After 5 years, 15 of 21 patients (71%) were protected compared with 46 of 71 patients (65%) in the hemodialysis collective studied after 12 months. In the interval between 1 and 5 years after vaccination, significantly more patients in the initial nonresponder group had died than in the responder group; therefore, the overall protection rate observed in vaccinated patients increased. Our results provide evidence that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid. Therefore, detection of individual antibody concentrations may be indicated to decide on revaccination. © 2001 by the National Kidney Foundation, Inc.

Monocyte-dependent cell death of T lymphocyte subsets in chronic hepatitis C

A high incidence of viral persistence and progression to chronic hepatitis are characteristic features of hepatitis C virus (HCV) infection. Since T lymphocytes play a critical role in virus clearance, their abnormalities in undergoing apoptosis may cause the insufficient antiviral immune responses leading to persistent viral infection. Recent reports have suggested that monocyte-dependent cell death (MDCD) is a mechanism of T lymphocyte apoptosis in chronic viral infection. The current study was designed to monitor apoptosis of CD4 + and CD8 + T lymphocyte subsets in co-culture with CD14 + monocytes under the apoptotic stimuli in patients with chronic hepatitis C. Cell mortalities of CD4 + and CD8 + T lymphocyte subsets from patients exhibiting various degrees of chronic hepatitis C were increased to a greater extent when incubated with CD14 + monocyte subset in medium containing phorbol 12-myristate 13-acetate. The current observations demonstrate that MDCD of CD4 + and CD8 + T lymphocyte subsets may provide a cellular basis for immune dysfunction which results in insufficient viral clearance and progression of liver disease in chronic HCV infection.

Early gene expression of NK cell-activating chemokines in mice resistant to Leishmania major.

Susceptibility of mice to Leishmania major is associated with an insufficient NK cell-mediated innate immune response. We analyzed the expression of NK cell-activating chemokines in vivo during the first days of infection in resistant and susceptible mice. The mRNA expression of gamma interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and lymphotactin was upregulated 1 day after infection in the draining lymph nodes of resistant C57BL/6 mice but not in those of susceptible BALB/c mice. In vivo local treatment of BALB/c mice with recombinant IP-10 shortly after infection resulted in an enhanced NK cell activity in the draining lymph node. The data suggest that although the recruitment of NK cells is normal in susceptible mice, the lack of NK cell-activating chemokines is a factor resulting in a suboptimal NK cell-mediated defense.

Antibody Response to gp E of Tick-Borne Encephalitis Virus: Comparison Between Natural Infection and Vaccination Breakdown

Human sera obtained after tick-borne encephalitis (TBE) without prior vaccination were compared with sera from patients after a vaccination breakdown. Most sera previously shown to have high titers of IgG and IgM against TBE virus as detected in the ELISA and hemagglutination inhibition (HI) tests also reacted in Western blot with TBE virus E protein which is involved in virus neutralization. The serum of a patient with a vaccination breakdown, however, reacted only very weakly with the E protein in the Western blot in spite of a high amount of antibodies detectable in ELISA. Using SDS-denaturated virus as an antigen in ELISA (imitating the blotting condition), this serum revealed a significant reduction in its reactivity with denatured virus compared to the control sera. This indicates that the patient had an insufficient immune response against certain denaturation resistant epitopes which might contribute to development of disease despite vaccination. The analysis of the immune response of human sera at the epitope level revealed a characteristic "fingerprint" for each serum reflecting the genetic control of the production of antibody populations against different antigenic determinants.

Homœopathic therapy for immune disorders

Homeopathic therapy for immune disorders M. JENAER (Brussels) The author's very innovative method of using drugs derives from recent discoveries in the field of immunology, opening an original way of using hom0eopathy. The distinction is made between cancer and viral diseases on the one hand (associated with an insufficient immune response) and autoimmune diseases on the other hand (associated with an exaggerated immune response ) . He also notes that cases with dys-immunity exist i.e. a mixture of insufficient and exaggerated responses related to the syphilis miasm. The following potentized drugs are used: RNA, DNA: Cancer: used in ascending potencies in cases with an identifiable cancer mass. Treatment in this way is stopped when cancer regresses because of fear of pathogenic effect of RNA and DNA, but is continued in a 9c to enhance a new equilibrium between host and tumour. Auto-immune diseases: used in a 15c.

Hepatitis in drug addicts (follow-up study with biopsies) (author's transl)

Viral hepatitis, proven by biopsy in 44 patients known to be drug addicts or confirmed drug takers had serial clinical, biochemical and (half of them) biopsy studies between 1971 and 1974. At the time of the first biopsy the period of addicition averaged 28.8 months. 30 of the 44 patients had had jaundice. At the time of the last biopsy, 20 of the 44 had chronic persisting and three had chronic active hepatitis, i.e. more than half had a chronic form. A further 12 patients had "hippie" hepatitis, a special form of acute viral hepatitis with piecemeal necrosis, histological evidence of possible change to a chronic state. There was no case of complete healing during the period of observation. The high rate of chronic hepatitis is thought to be due to partially insufficient immune response. The clinical and even biochemical course in most of the patients was remarkably mild. Severe clinical forms are rare and were not observed at all in the described group. It would therefore, seem that the prognosis is generally good, in contrast to chronic hepatitis in non-addicts.