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Lipid bodies: Structural markers of inflammatory macrophages in innate immunity.

OBJECTIVE AND DESIGN: The correlation between innate immune responses and formation of cytoplasmic lipid bodies (LBs) was investigated in vivo in inflammatory macrophages from rats infected with Trypanosoma cruzi, the intracellular parasite which causes Chagas' disease. MATERIAL AND METHODS: We used an experimental model of high-dose irradiation prior to infection, which depletes the humoral and cellular immune responses except for the phagocytic activity of macrophages. Rats, irradiated or not, were infected with T. cruzi and macrophages from different origins (peritoneum, heart, uterus) were studied by transmission electron microscopy (TEM). RESULTS: As documented by quantitative TEM, innate immune responses induced prominent formation, structural changes and intracellular interactions of LBs. LBs significantly increased their size and changed their osmiophilia in response to both infection alone and when macrophages were challenged with irradiation-induced increased parasite load. Remarkably, a consistent LB-phagolysosome association was identified. LBs were surrounding, attached to or internalized by phagolysosomes. CONCLUSIONS: We demonstrated that LBs are dynamic organelles notably involved in the host response to acute T. cruzi infection, an event that may be important for pathogen control during innate immunity. Our findings highlight LBs as structural markers of the innate immune responses in phagocytic cells.

Animals↗

A longitudinal study of circulating immune complexes, dna antibodies and complement in patients with systemic lupus erythematosus: an analysis of their relationship to disease activity.

The relationship between immune complex, DNA binding and complement levels and disease activity was studied in twenty-seven patients with systemic lupus erythematosus. Detailed longitudinal studies revealed a good correlation between immune complex levels and disease activity. In addition, a good correlation was obtained, in general, between immune complex and DNA binding values, and an inverse correlation between these values and the haemolytic activity of C1, C2 and C4. CH50 and C3 measurements, on the other hand, were found to be less consistent at reflecting short term fluctuations in disease activity. Statistical analysis of IC, DNA binding and complement values revealed a higher incidence and mean value of immune complexex in active disease compared with inactive disease. These high levels of immune complexes were associated with elevated values of DNA binding and low values of CH50 and C3. The highest values of immune complexes were found in samples with concomitantly abnormal values of DNA binding, CH50 and C3. It is concluded that the measurement of immune complexes in SLE patients is a useful procedure, not only in aiding diagnosis, but also in monitoring disease activity and response to therapy. The results also indicate that serial studies of immune complexes, DNA binding and complement can be of value in the long term management of individual patients.

Antibodies↗

Correlates of cell-mediated immunity in Candida albicans-colonized gnotobiotic mice.

Germfree athymic (nu/nu) and euthymic (nu/+) mice were colonized with a pure culture of Candida albicans. Correlates of cell-mediated immunity (lymphocyte proliferation and footpad responses to C. albicans antigens) and in vivo clearance of mucosal infections were assessed at different time intervals after alimentary tract colonization. C. albicans hyphae infected the dorsal surface of the tongue and the cardial section of the stomach in both nu/nu and nu/+ mice within 1 week after colonization with a pure culture of C. albicans. With time after colonization and infection with C. albicans, nu/+ mice manifested positive lymphocyte proliferation and positive footpad responses to Candida antigens that appeared to correlate with the capacity to clear Candida hyphae from the dorsal surface of the tongue and in the stomach. Conversely, nu/nu mice could not clear mucosal candidosis (in the stomach and on the tongue) and did not manifest either lymphocyte proliferation or footpad swelling in response to C. albicans antigens. These studies indicated that T-cell-mediated immunity may play a role in the acquired resistance of mice to mucosal candidosis. Since neither nu/nu nor nu/+ mice developed a progressive systemic disease, T cells apparently do not play a prominent role in murine resistance to systemic candidosis of endogenous origin.

Animals↗

Correlation of cell-mediated immunity against porcine reproductive and respiratory syndrome virus with protection against reproductive failure in sows during outbreaks of porcine reproductive and respiratory syndrome in commercial herds.

OBJECTIVE: To determine whether cell-mediated immunity against porcine reproductive and respiratory syndrome (PRRS) virus is correlated with protection against reproductive failure in sows during clinical outbreaks of PRRS in commercial herds. DESIGN: Outbreak investigation in 4 swine breeding herds. ANIMALS: 97 sows. PROCEDURES: On each farm, blood samples were collected from sows with clinical signs (abortion or increased fetal death; case sows) and from clinically normal sows (control sows). The intensity of the cell-mediated immune (CMI) response was determined by use of an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. Multiple logistic regression analyses and t tests were used to compare ELISPOT assay values between case and control sows. Multiple linear regression was used to investigate associations between cell-mediated immunity and the magnitude of clinical signs. RESULTS: In 2 farms, case sows had lower ELISPOT assay values than control sows. A negative association between the intensity of the CMI response and the number of pigs born dead per litter was detected on 1 farm. In 1 farm, no association was detected between the intensity of the CMI response and protection against reproductive failure. CONCLUSIONS AND CLINICAL RELEVANCE: Evidence that a strong CMI response was correlated with protection against clinical PRRS was detected in 3 of 4 farms. However, farms and sows within farms varied considerably in their immune responsiveness and in the degree to which they were protected clinically. Increasing cell-mediated immunity within infected herds has the potential to decrease clinical reproductive disease, but only if the sources of intra- and interfarm variation in the intensity of cell-mediated immunity to PRRS virus can be identified.

Abortion, Veterinary↗

Live attenuated HIV vaccines: pitfalls and prospects.

PURPOSE OF REVIEW: When simian immunodeficiency virus (SIV) deleted in the nef gene caused no disease in macaques and provided protection against wild-type SIV challenge, hopes were high that the removal of nef would convert a pathogenic immunodeficiency virus into a live attenuated vaccine. We seek to highlight recent studies focused on several major issues regarding live attenuated AIDS viruses as vaccine candidates: (1). safety, (2). efficacy, (3). the correlates of immune protection, and (4) the molecular determinants for lentiviral virulence or attenuation. RECENT FINDINGS: Nef-deletion mutants have retained virulence; compared with wild-type SIV, disease progression was slowed but not abrogated. After long-term observation, all adult macaques given SIVmac239delta3 exhibited immune dysfunction; over 50% had T-cell depletion, and 18% developed AIDS. Vaccine efficacy has been disappointing, with limited or no cross-protection and no protection against homologous virus challenge years after initial vaccination. To date, the correlates of protective immunity have defied precise definition; no dominant mechanism has yet emerged. Data from passive serum transfer and CD8+ T-cell depletion studies have raised the possibility that alternate mechanism of protection may be operative. Due to relentless viral replication and continuous selective pressure, initially benign viruses can generate virulent progeny with unpredictable genotypes. SUMMARY: Neither safety nor efficacy of the current live attenuated primate immunodeficiency virus vaccines has withstood the test of time. However, such viruses are invaluable tools to address two key questions: (1). what are the correlates of protection, and (2). what are the molecular determinants of viral immunopathogenesis?

AIDS Vaccines↗

Immunization practices of primary care practitioners and their relation to immunization levels.

OBJECTIVES: To assess variations in immunization practices and attitudes among primary care providers and to relate these characteristics to the immunization levels of their patients. SETTING: Monroe County, New York. DESIGN: Survey of pediatricians (n = 96) and family practitioners (n = 44) to assess immunization practices and attitudes and medical chart reviews for 1884 patients of 32 physicians who practice in the city of Rochester to measure immunization levels. ANALYSIS: Tabular analyses for survey responses (chi 2 test and Fisher's Exact Test); logistic regression to assess the relation between provider responses and measured immunization levels. RESULTS: Responses by pediatricians and family practitioners were similar. Most providers did not routinely immunize during acute-illness visits but did immunize during follow-up or chronic-illness visits. Few used tracking systems to identify underimmunized children. Most practitioners immunized children who had colds but withheld immunizations from children who had fevers or otitis media. Most providers agreed with expanding immunization programs to include sick visits, health department clinic visits, and community site visits, but most thought that they should not be provided at emergency department visits, except for very-high-risk children. Immunization levels at 10 months of age were positively correlated with private practice setting (P = .001) but negatively correlated with immunizing at acute- (P < .01) or chronic-illness (P < .05) visits, Medicaid coverage (P < .05), and high rates of appointments that were not kept (P < .001). CONCLUSIONS: Primary care providers' immunization practices and attitudes vary and do not always follow established guidelines for immunization delivery. Many providers of high-risk children are already attempting to improve immunization delivery by using patient reminders and by immunizing children at acute- or chronic-illness visits. Improving provider immunization practices to deliver childhood immunizations more effectively must be part of our efforts to resolve this nation's childhood immunization problem.

Adolescent↗

Stress, affective disorders, and immune function.

Increasing scientific evidence supports age-old observations that psychosocial factors are closely associated with the pathogenesis of certain physical and mental illnesses. The immune system appears to play a primary mediating role. Whereas acute stress may initiate a transient immunologically protective response, prolonged or poorly controlled psychosocial stressors may result in depression of different components of the immune system. These responses may be related to, or independent of, changes in the neuroendocrine system. As the rather prolific literature in this infant area of psychoneuroimmunology reveals, there are many complex levels of interaction that require further investigation. There is clearly a need for long-term prospective studies that will identify individuals at risk for those numerous diseases in which psychosocial factors and impaired immune function play a pathogenic role. In addition to correlating altered immune function over time with changes in the physical environment, these studies should include psychologic profiles, life-event inventories, and psychiatric interviews in an effort to delineate the role of psychosocial factors as the stimulus for and as the response to the disease process. One of the many positive outcomes of this multifactorial approach to illness is that it will alter the physician's approach to disease and thus to patients as they are evaluated and treated in the psychosocial context in which they live. As Hippocrates said, "It is more important to know what sort of a person has a disease than to know what sort of disease a person has."

Autoimmune Diseases↗

Chronic immune activation and inflammation in the pathogenesis of AIDS and cancer.

Infection with the human immunodeficiency virus (HIV) invariably leads to the development of acquired immunodeficiency syndrome (AIDS) in most infected humans, yet does so rarely, if at all, in HIV-infected chimpanzees. The differences between the two species are not due to differences in cellular receptors or an inability of the chimpanzee to be infected, but rather to the lack of pan-immune activation in the infected primate. This results in reduced apoptotic death in CD4+ T-helper lymphocytes and a lower viral load. In humans the degree of chronic immune activation correlates with virus load and clinical outcome with high immune activation leading to high viral loads and the more rapid progression to AIDS and death. The type of immune perturbation seen in HIV-associated AIDS is similar to that of chronic graft-versus-host disease (GVHD) where reduced cell-mediated immune (CMI) responses occur early in the course of the disease and where humoral responses (HI) predominate. A reduced CMI response occurs in a number of chronic infectious diseases, including tuberculosis and leishmaniasis. More recently, it has become increasingly apparent that the CMI response is suppressed in virtually all malignant diseases, including melanoma and colorectal and prostate cancer. This raises the possibility that, as the malignant process develops, the cancer cells evolve to subvert the CMI response. Moreover, the reduced CMI response seen in colorectal cancer (CRC) patients is completely reversed following curative surgery strongly supporting the hypothesis that CRC can suppress the systemic immune response. Wound healing, ovulation, embryo implantation, and fetal growth are all associated with suppressed CMI and neovascularization (the formation of new blood vessels) or angiogenesis (the formation of new blood vessels from an existing vasculature). If unresolved, wound healing results in chronic inflammation, which can give rise to the phenomenon of "scar cancers." Indeed all the chronic inflammatory conditions known to be associated with the subsequent development of malignant disease, including chronic obstructive airway disease (COPD), ulcerative colitis (UC), and asbestosis, give rise to similar proangiogenic, suppressed CMI, and HI-predominant environments. In keeping with this CMI-associated cytokines such as interleukin (IL)-2 and interferon (IFN)-gamma tend to be antiangiogenic, whereas HI cytokines such as IL-6 tend to be proangiogenic. Furthermore, chronic immune activation leads to the synthesis and release of factors such as macrophage inflammatory protein (MIP)-1 that inhibit apoptosis through suppression of p53 activity. The "Golden Triangle" of suppressed CMI, angiogenesis, and reduced apoptosis would provide the ideal environment for the serial mutations to occur that are required for the development of malignant disease. If the observed association is relevant to carcinogenesis, then treatments aimed at reducing the components of these inflammatory conditions may be useful both in the setting of chemoprevention and the therapeutic management of established disease.

Acquired Immunodeficiency Syndrome↗

The effects of host immunity on virulence-transmissibility relationships in the rodent malaria parasite Plasmodium chabaudi.

Here we examined the impact of host immunity on relationships between parasite virulence, transmission rate, intrinsic growth rate and host recovery rate in the rodent malaria parasite, Plasmodium chabaudi. Groups of naïve and immunized mice were infected with 1 of 10 cloned lines of parasites and their infection dynamics were monitored for 19 days. We found that (1) host immunity reduced the growth rate, virulence, transmission rate and infection length, with a consequent 3-fold reduction in life-time transmission potential, (2) clone means for these traits ranked similarly across naïve and immunized mice, (3) regression slopes of transmission potential on growth rate, virulence and infection length were similar in naive and immunized mice, (4) virulence and infection length were positively correlated in immunized but not naïve mice, and (5) for a similar level of parasite growth rate and virulence, transmission potential and infection length were lower in immunized than naïve mice. Thus host immunity reduced all these fitness traits in a manner consistent with direct parasite-driven biological links among them. These results support the basic assumption underlying our theory that predicts that anti-disease vaccines will select for higher virulence in those microparasites for which virulence is integrally linked to transmission.

Animals↗

The influence on pretransplant blood transfusions from random donors on immune parameters affecting cadaveric allograft survival.

The number of pretransplant blood transfusions (BT) from random donors influences the recipient's immune response status and suppressor cell number and function, as well as allograft survival. The 54% one-year survival rate for 104 cadaveric renal allograft recipients treated with azathioprine and prednisone was divisible into two groups: 74.5% in 51 patients receiving greater than 5 BT and 34% for 53 patients with less than 5 BT (P less than 0.02). Transfusions enhanced the benefit of HLA A, B, and DR compatibility on graft survival: 33 recipients of well-matched grafts (less than 2 A, B, and 0-1 DR mismatches) had a one-year survival rate of 94% when pretreated with greater than 5 BT, compared with 38% when receiving less than 5 BT (P less than 0.05). The graft survival of 73% (36/49) displayed by patients determined preoperatively to be weak immune responders was significantly better than the 36% survival (20/55) demonstrated by strong immune responders (P less than 0.01). The transfusion history correlated with immune responder status: 76% (39/51) of patients receiving greater than 5 BT were weak immune responders, whereas 81% (43/53) of patients receiving less than 5 BT were strong immune responders (P less than 0.001). Ninety-two percent (12/13) of patients with greater than 5 BT, but only 58% (10/17) of patients with less than 5 BT, had a normal number of OKT8+ T suppressor cells. Only 1 X 10(5) mononuclear cells from patients with greater than 5 BT rather than 4 X 10(5) cells from patients with less than 5 BT caused 50% suppression of a third-party MLC. Thus, patients receiving greater than 5 BT are more likely to display weak immune responses, normal numbers of OKT8 cells, strong suppressor function in vitro, and prolonged allograft survival.

Antibodies, Monoclonal↗

IgM anti-phenolic glycolipid I and IgG anti-10-kDa heat shock protein antibodies in sera and immune complexes isolated from leprosy patients with or without erythema nodosum leprosum and contacts.

The aim of the present work was to evaluate the levels of anti-PGL-I and anti-10-kDa heat shock protein antibodies in serum and immune complexes isolated from leprosy patients, convivients and controls. Leprosy patients with erythema nodosum leprosum or without it were included and a comparative study was done to investigate intergroup differences. Immune complexes were precipitated from serum by polyethylene glycol 3.5%; antibody levels were measured in sera and in dissociated immune complexes by ELISA. Serum antibody levels were then correlated with immune complex-associated antibody levels. The results showed that the erythema nodosum leprosum group differed from controls, contacts and non-erythema patients in their immune complex levels. IgM anti-PGL-I and IgG anti-10-kDa heat shock protein antibodies were constituents of the immune complexes in patients with erythema nodosum leprosum, who exhibited a significant difference in their immune complex composition compared with controls, contacts and non-erythema patients; while free antibody levels (anti-PGL-I and anti-10-kDa) did not differentiate between erythema and non-erythema patients, the measurement of immune complex-associated antibodies demonstrated a significant difference between the two clinical conditions. Furthermore, the measurement of immune complex-associated anti-PGL-I IgM made it possible to differentiate between contacts and controls. The significance of these results is discussed.

Adolescent↗

Effect of age and degree of immune activation on cytochrome P450 3A4 activity after influenza immunization.

STUDY OBJECTIVE: To measure age- or sex-related changes in cytochrome P450 (CYP) activity secondary to influenza vaccination. DESIGN: Open-label, single-dose study. SETTING: General clinical research center at a university hospital. SUBJECTS: Fifteen healthy volunteers aged 22-51 years. INTERVENTION: Each subject was given an erythromycin breath test (ERMBT) to measure CYP3A4 activity before influenza immunization and again on day 7 after immunization. Blood was drawn before immunization and on day 28 after immunization to measure influenza antibody concentrations. MEASUREMENTS AND MAIN RESULTS: Age of subject and change in ERMBT results after influenza immunization were correlated (correlation coefficient -0.624, p < 0.015). However, no correlations could be made between antibody concentrations after influenza immunization or change in antibody concentrations from baseline and age. CONCLUSION: Decreases in CYP3A4 activity after influenza immunization are associated with increasing age. The decreases in CYP3A4 activity, however, are not associated with influenza antibody concentrations. This study bears repeating in an older cohort since the study sample did not include elderly individuals.

Adult↗

[Induction of anti-tumor immunity by HSP gp96-peptide complexes].

AIM: To immunize the mice with gp96-peptide complexes extracted and purified from different kinds of malignant tumor cells and to observe anti-tumor immunity induced by the complexes. METHODS: HSP gp96-peptide complexes were extracted and purified from different kinds of malignant tumor cells. Mice were immunized subcutaneously with the complexes from different sources at different doses. Then the mice were challenged with 2 x 10(5) tumor cells on the seventh day after the last immunization. Tumor incidence, weight and histology were observed and compared with those of control group. At the meantime, cytotoxicity activity and nitric oxide production of mouse peritoneal macrophages were detected in vitro after being stimulated with gp96-peptide complexes. RESULTS: The SDS-PAGE and Western blot showed that gp96-peptide complexes were purified successfully. The anti-tumor immunity was correlated with the dose of the complex and the immunized mice could resist the challenge of homogeneous tumor cells. NO secreted from the peritoneal macrophages stimulated with the complex was significantly higher than that of control group and the tumoricidal activity of the macrophages in vitro was markedly promoted by the complex. CONCLUSION: Mice immunized with appropriate dose of gp96-peptide complexes from H22 tumor cells can resist the challenge of syngeneic tumor cells. NO secreted by macrophages stimulated with the complex might play a key role in the anti-tumor immunity.

Animals↗

Changes in lymphocyte subsets and immune competence in very advanced age.

To study the changes in immune system during aging and their effects on patient survival, immune functions of 18 very old (92-107 years) hospital patients were tested. After three years follow-up, the survival of patients and the correlation of immune capacity to lifetime were determined. In the very old patients, the frequency of T lymphocytes was significantly lower than in young adults. This decrease was attributed more to the CD8-positive than to CD4-positive cell subset, leading to generally high CD4/CD8 ratios. The mitogenic responses to phytohemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), were decreased significantly in cultures with isolated lymphocytes, while in whole blood cultures the responses to PHA and PWM but not to Con A were reduced. In very advanced age, there was a significant decrease in the number of B cells, and the ability to produce IgM in vitro was decreased. During the follow-up time, 15 out of the 18 patients died. However, their lifetime was not in correlation with any single immune parameter.

Aged↗

Immune adherence of nascent hepatitis B surface antigen-antibody complexes in vivo in humans.

Upon i.v. injection into humans, pre-formed immune complexes bind complement and adhere to complement receptor type I (CR1, CD35) on erythrocytes (immune adherence). However, in most circumstances antigen and antibody react in the presence of complement; such nascent immune complexes may have properties different from pre-formed immune complexes. To define whether nascent immune complexes would also adhere to erythrocytes in vivo in humans, we studied immune complexes that formed upon i.v. injection of radiolabelled hepatitis B surface antigen (HBsAg) into immunized volunteers (eight subjects with anti-HBsAb levels ranging from undetectable to 50 U/ml.; and three control non-immune individuals). Immune complexes formed immediately in the subjects with detectable levels of specific antibody, and the clearance rate of these immune complexes correlated with the anti-HBsAb level (r = 0.78, P < 0.01). A fraction of the circulating immune complexes bound to erythrocytes in the three individuals with the highest antibody level (8-15% at 10 min). The effect of CR1 number per erythrocytes was analysed in two subjects with similar antibody levels and immune complexes clearance rates: immune adherence was higher in the subject with more CR1 per erythrocytes. The same immune complexes model studied in vitro provided similar results: a fraction of nascent immune complexes bound to human erythrocytes; this immune adherence was observed only when immune complexes formed in the presence of antibody excess, and correlated with CR1 number per erythrocytes (r = 0.99, P < 0.01). Finally, adherence of nascent HBsAg-antibody immune complexes to platelets was demonstrated in rabbits. Although immune adherence involves only a small fraction of nascent immune complexes at any given time, it may be essential for the safe disposal of large nascent immune complexes.

Animals↗

Expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES genes in lymph nodes from HIV+ individuals: correlation with a Th1-type cytokine response.

The in vivo response of the immune system after HIV infection in regard to cytokine production and C-C chemokine synthesis is not well known. Here we have analysed cytokine and chemokine mRNA production in lymph nodes with follicular hyperplasia (FHLN) of HIV-infected patients by in situ hybridization using anti-sense mRNA probes. The synthesis of mRNAs for interferon-gamma (IFN-gamma), IL-12p35, IL-12p40, IL-4, and for the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta was compared with that of lymph nodes from non-infected individuals to define HIV-specific events. Only few cells expressing IFN-gamma, RANTES, MIP-1alpha, and MIP-1beta mRNAs were detectable in the T-dependent area of lymph nodes from HIV-negatives. In contrast, in FHLN from HIV+ patients a high number of IFN-gamma, RANTES, MIP-1alpha, and MIP-1beta mRNA-containing cells were detectable. Remarkably, only single individual IL-12p35 mRNA-producing cells were present in the T-dependent area from both HIV+ and HIV lymph nodes. Furthermore, the low number of IL-12p40 mRNA-expressing cells did not differ between HIV+ and HIV- lymph nodes. This indicates that IFN-gamma is expressed independently of IL-12, possibly by a direct T cell-mediated reaction. IL-4 mRNA-producing cells were hardly detectable in infected and control lymph nodes. The same findings were made in a limited number of samples from patients with advanced disease. Thus, these results demonstrate that a high IFN-gamma production is accompanied by a strong expression of MIP-1alpha, MIP-1beta, and RANTES in the lymph node after HIV infection. This favours the idea that a Th1-type immune response correlates with a preferential production of C-C chemokines in FHLN of HIV+ patients.

Adult↗

Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules.

The chimpanzee (Pan troglodytes) is an important model for studying the immune response to several human pathogens, but the study of correlates of immunity has been hindered by the fact that little is known about the epitope-binding specificity of chimpanzee (Patr) class I MHC. In the present study we have characterized the peptide binding specificity of several common Patr class I molecules. Using single amino acid substitution analogs and large peptide libraries, quantitative peptide binding motifs have been derived for Patr A*0101, A*0701, A*0901, B*0101, and B*2401. Each molecule was found to bind peptides using position 2 and the C terminus as main anchor contacts. On the other hand, each Patr molecule is associated with a unique binding specificity, and the range of specificities is similar to that seen amongst HLA alleles. A high degree of cross-reactivity was noted between Patr A*0701 and Patr A*0901, suggesting the existence of a Patr-specific supertype. Consistent with previous studies suggesting that some cross-reactivity may exist between HLA and Patr alleles, Patr A*0901 was found to have an appreciable degree of cross-reactivity with molecules of the HLA A24-supertype. Finally, utilizing motif scans and peptide binding and intracellular cytokine staining assays, 77 hepatitis B virus (HBV)-derived epitopes were identified in five chimpanzees that were recently convalescent from acute HBV infection. Because the Patr alleles studied herein were found to be very common in two different chimpanzee populations, the present data should facilitate the use of chimpanzees for immunological studies.

Amino Acid Motifs↗

TLR9 expression is related to immune activation but is impaired in individuals with chronic immune activation.

Millions of individuals in developing countries are infected with helminths and other chronic infectious diseases, such as HIV-1, which lead to persistent immune activation and unbalanced immune state. We have suggested that the capacity of chronically immune activated individuals to protect themselves, cope with infections, and mount protective immunity following vaccination, is highly impaired. Here we examined the expression of toll-like receptor 9 (TLR9), as an essential component in the recognition of immunostimulating bacterial CpG-DNA motifs, in different subsets of human peripheral blood mononuclear cells (PBMC) obtained from chronically immune activated and non-activated individuals. TLR9 expression was correlated to immune cell activation and was upregulated following phytohemagglutinin or anti-CD3 activation. PBMC obtained from chronically immune activated individuals had a different overall pattern of TLR9 expression, including reduced upregulation of this receptor following additional immune activation, and diminished responsiveness to CpG-DNA stimulation, in comparison to non-activated individuals. These differences may partly account for the reduced capacity of chronically immune activated individuals to mount effective immune responses and strengthen the notion that the host immune background should be considered in the design and trial of potential adjuvants and vaccines.

Adolescent↗