Impaired In Vivo Immune Responses in Patients with Melancholia

1993 ◽  
Vol 162 (5) ◽  
pp. 651-657 ◽  
Author(s):  
Ian Hickie ◽  
Catherine Hickie ◽  
Andrew Lloyd ◽  
Derrick Silove ◽  
Denis Wakefield
Keyword(s):  
Immune Responses ◽  
Delayed Type Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Melancholic Depression ◽  
Skin Responses ◽  
Severity Of Depression ◽  
Depressive Subtypes ◽  
Control Study

Previous attempts to establish a relationship between impaired cell-mediated immunity (CMI) and major mood disorders have been limited by a failure to explore the relevance of depressive subcategories or to assess CMI by in vivo methods. In this case-control study CMI was assessed in 57 patients with major depression (31 with melancholic, 26 with non-melancholic disorders), and in age- and sex-matched controls by both in vitro and in vivo immunological techniques. Compared with control subjects and patients with non-melancholic depression, patients with melancholia demonstrated reduced in vivo CMI as assessed by delayed-type hypersensitivity (DTH) skin responses. Although increasing age, severity of depression, hospital admission for treatment, and reported weight loss are correlates of melancholia, none of these factors alone, or in combination, accounted for the differences in DTH responses observed between the two depressive subtypes. These data suggest that impaired CMI in vivo may be limited to those with melancholic disorders. At this stage the factors which account for this effect are unclear.

scholarly journals Inhibition of Local Immune Responses by the Frog-Killing Fungus Batrachochytrium dendrobatidis

2014 ◽  
Vol 82 (11) ◽  
pp. 4698-4706 ◽  
Author(s):  
J. Scott Fites ◽  
Laura K. Reinert ◽  
Timothy M. Chappell ◽  
Louise A. Rollins-Smith
Keyword(s):  
Immune Responses ◽  
Batrachochytrium Dendrobatidis ◽  
Single Injection ◽  
Delayed Type Hypersensitivity ◽  
Chytrid Fungus ◽  
Content Type ◽  
Adaptive Immune ◽  
Secondary Injection

ABSTRACTAmphibians are suffering unprecedented global declines. A leading cause is the infectious disease chytridiomycosis caused by the chytrid fungusBatrachochytrium dendrobatidis. Chytridiomycosis is a skin disease which disrupts transport of essential ions leading to death. Soluble factors produced byB. dendrobatidisimpair amphibian and mammalian lymphocytesin vitro, but previous studies have not shown the effects of these inhibitory factorsin vivo. To demonstratein vivoinhibition of immunity byB. dendrobatidis, a modified delayed-type-hypersensitivity (DTH) protocol was developed to induce innate and adaptive inflammatory swelling in the feet ofXenopus laevisby injection of killed bacteria or phytohemagglutinin (PHA). Compared to previous protocols for PHA injection in amphibians, this method induced up to 20-fold greater inflammatory swelling. Using this new protocol, we measured DTH responses induced by killed bacteria or PHA in the presence ofB. dendrobatidissupernatants. Swelling induced by single injection of PHA or killed bacteria was not significantly affected byB. dendrobatidissupernatants. However, swelling caused by a secondary injection of PHA, was significantly reduced byB. dendrobatidissupernatants. As previously describedin vitro, factors fromB. dendrobatidisappear to inhibit lymphocyte-mediated inflammatory swelling but not swelling caused by an inducer of innate leukocytes. This suggests thatB. dendrobatidisis capable of inhibiting lymphocytes in a localized response to prevent adaptive immune responses in the skin. The modified protocol used to induce inflammatory swelling in the present study may be more effective than previous methods to investigate amphibian immune competence, particularly in nonmodel species.

scholarly journals Deglycosylation of the 45/47-Kilodalton Antigen Complex of Mycobacterium tuberculosis Decreases Its Capacity To Elicit In Vivo or In Vitro Cellular Immune Responses

1999 ◽  
Vol 67 (11) ◽  
pp. 5567-5572 ◽  
Author(s):  
Félix Romain ◽  
Cynthia Horn ◽  
Pascale Pescher ◽  
Abdelkader Namane ◽  
Michel Riviere ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Delayed Type Hypersensitivity ◽  
Cellular Immune Responses ◽  
Antigen Complex ◽  
Cellular Immune ◽  
Living Bacteria

ABSTRACT A protection against a challenge with Mycobacterium tuberculosis is induced by previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). The 45/47-kDa antigen complex (Apa) present in culture filtrates of BCG of M. tuberculosis has been identified and isolated based on its ability to interact mainly with T lymphocytes and/or antibodies induced by immunization with living bacteria. The protein is glycosylated. A large batch of Apa was purified from M. tuberculosis culture filtrate to determine the extent of glycosylation and its role on the expression of the immune responses. Mass spectrometry revealed a spectrum of glycosylated molecules, with the majority of species bearing six, seven, or eight mannose residues (22, 24, and 17%, respectively), while others three, four, or five mannoses (5, 9, and 14%, respectively). Molecules with one, two, or nine mannoses were rare (1.5, 3, and 3%, respectively), as were unglycosylated species (in the range of 1%). To eliminate the mannose residues linked to the protein, the glycosylated Apa molecules were chemically or enzymatically treated. The deglycosylated antigen was 10-fold less active than native molecules in eliciting delayed-type hypersensitivity reactions in guinea pigs immunized with BCG. It was 30-fold less active than native molecules when assayed in vitro for its capacity to stimulate T lymphocytes primed in vivo. The presence of the mannose residues on the Apa protein was essential for the antigenicity of the molecules in T-cell-dependent immune responses in vitro and in vivo.

scholarly journals A review of the leishmanin skin test: A neglected test for a neglected disease

2021 ◽  
Vol 15 (7) ◽  
pp. e0009531
Author(s):  
Jessica Carstens-Kass ◽  
Kayla Paulini ◽  
Patrick Lypaczewski ◽  
Greg Matlashewski
Keyword(s):  
Skin Test ◽  
Surrogate Marker ◽  
Epidemiological Studies ◽  
Interferon Γ ◽  
Delayed Type Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Leishmanin Skin Test ◽  
Mesh Terms

The leishmanin skin test (LST) has been used for decades to detect exposure and immunity to the parasite Leishmania, the causative agent of the neglected tropical disease leishmaniasis. In the LST, Leishmania antigen (leishmanin) is intradermally injected into the forearm. In an individual who has been previously infected, a delayed-type hypersensitivity (DTH) reaction results in a measurable induration at the site of the injection, indicating that previous exposure to Leishmania has resulted in the development of cell-mediated immunity. LST positivity is associated with long-lasting protective immunity against reinfection, most notably as reported for visceral leishmaniasis (VL). Despite efforts over the past few decades, leishmanin antigen is no longer produced under good manufacturing practice (GMP) conditions anywhere in the world. Consequently, the use of the LST in epidemiological studies has declined in favor of serological and molecular tests. In this review, we provide a historical overview of the LST and justification for the reintroduction of leishmanin. A GMP-grade leishmanin can be used to detect immunity in vivo by the LST and can be investigated for use in an interferon-γ release assay (IGRA), which may serve as an in vitro version of the LST. The LST will be a valuable tool for surveillance and epidemiological studies in support of the VL elimination programs and as a surrogate marker of immunity in vaccine clinical trials. Methods A review of the literature was conducted using PubMed as the primary database, with MeSH terms “leishmanin skin test” OR “Montenegro test” OR “Montenegro skin test.” Articles written in English that describe the history or standardization of leishmanin, the use of leishmanin in an IGRA, or the use of the LST in epidemiological studies or vaccine trials were prioritized in our appraisal of the literature.

Influence of dietary protein on selected measures of humoral and cellular immunity in the cotton rat Sigmodon hispidus

1993 ◽  
Vol 71 (3) ◽  
pp. 579-586 ◽  
Author(s):  
M. R. Vestey ◽  
S. T. McMurry ◽  
R. L. Lochmiller
Keyword(s):  
Dietary Protein ◽  
Inbred Strains ◽  
Lymphoid Organ ◽  
Delayed Type Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Humoral And Cellular Immunity ◽  
Laboratory Rodents ◽  
Cotton Rats

Small-mammal populations are subject to unpredictable and often dramatic fluctuations in numbers, but the mechanisms underlying this phenomenon are largely unclear. It has been suggested that protein is an important nutritional factor limiting survival, so we explored the effect of protein intake on the immunocompetence of cotton rats (Sigmodon hipsidus). In vivo and in vitro measures of both humoral and cell-mediated immunity were examined in a series of four protein-feeding trials (with weanlings, juveniles, subadults, and adults), using animals randomly assigned to an isocaloric diet containing either 4 or 16% crude protein. The response of lymphoid organ mass and cellularity to low dietary protein was variable, the spleen being more sensitive to dietary protein than the thymus. The ability of splenic lymphocytes to respond to in vitro stimulation with mitogens was unaffected by dietary protein, while the capacity of weanling and subadult cotton rats fed 4% protein to mount a delayed-type hypersensitivity response was enhanced. Nonspecific immunity (complement activity) was reduced in juveniles fed 4% protein. Dietary protein did not influence the ability of subadults or adults to generate a specific antibody response. These data suggest that cotton rats are less sensitive to dietary protein level than many inbred strains of laboratory rodents, younger animals may be at greater risk, and nutritional history may influence the response of a population to a reduction in available dietary protein.

scholarly journals Proteomic Analysis of and Immune Responses to Ehrlichia chaffeensis Lipoproteins

2008 ◽  
Vol 76 (8) ◽  
pp. 3405-3414 ◽  
Author(s):  
Haibin Huang ◽  
Mingqun Lin ◽  
Xueqi Wang ◽  
Takane Kikuchi ◽  
Heather Mottaz ◽  
...  
Keyword(s):  
Immune Responses ◽  
Leukemia Cell ◽  
Signal Peptidase ◽  
Leukemia Cell Line ◽  
Delayed Type Hypersensitivity ◽  
Ehrlichia Chaffeensis ◽  
Processing Enzymes ◽  
Mammalian Expression

ABSTRACT Ehrlichia chaffeensis is an obligately intracellular gram-negative bacterium and is the etiologic agent of human monocytic ehrlichiosis (HME). Although E. chaffeensis induces the generation of several cytokines and chemokines by leukocytes, E. chaffeensis lacks lipopolysaccharide and peptidoglycan. Bioinfomatic analysis of the E. chaffeensis genome, however, predicted genes encoding 15 lipoproteins and 3 posttranslational lipoprotein-processing enzymes. The present study showed that by use of multidimensional liquid chromatography followed by tandem mass spectrometry, all predicted lipoproteins as well as lipoprotein-processing enzymes were expressed by E. chaffeensis cultured in the human promyelocytic leukemia cell line HL-60. Consistent with this observation, a signal peptidase II inhibitor, globomycin, was found to inhibit E. chaffeensis infection and lipoprotein processing in HL-60 cell culture. To study in vivo E. chaffeensis lipoprotein expression and host immune responses to E. chaffeensis lipoproteins, 13 E. chaffeensis lipoprotein genes were cloned into a mammalian expression vector. When the DNA constructs were inoculated into naïve dogs, or when dogs were infected with E. chaffeensis, the animals developed delayed-type hypersensitivity reactions at cutaneous sites of the DNA construct deposition and serum antibodies to these lipoproteins. This is the first demonstration of lipoprotein expression and elicitation of immune responses by a member of the order Rickettsiales. Multiple lipoproteins expressed by E. chaffeensis in vitro and in vivo may play key roles in pathogenesis and immune responses in HME.

scholarly journals The pH-Sensitive Fusogenic 3-Methyl-Glutarylated Hyperbranched Poly(Glycidol)-Conjugated Liposome Induces Antigen-Specific Cellular and Humoral Immunity

2012 ◽  
Vol 19 (9) ◽  
pp. 1492-1498 ◽  
Author(s):  
Takehisa Hebishima ◽  
Eiji Yuba ◽  
Kenji Kono ◽  
Shin-nosuke Takeshima ◽  
Yoshihiro Ito ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mhc Class I ◽  
Class I ◽  
Delayed Type Hypersensitivity ◽  
Murine Bone Marrow ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Hyperbranched Poly

ABSTRACTWe examined the ability of a novel liposome, surface modified by 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG), to enhance antigen-specific immunityin vitroandin vivoand to function as a vaccine carrier. Murine bone marrow-derived dendritic cells took up ovalbumin (OVA) encapsulated in MGlu-HPG-modified liposomes more effectively than free OVA or OVA encapsulated in unmodified liposomes. Immunization of mice with OVA-containing MGlu-HPG-modified liposomes induced antigen-specific splenocyte proliferation and production of gamma interferon (IFN-γ) more strongly than did immunization with free OVA or OVA encapsulated in unmodified liposomes. The immune responses induced by OVA encapsulated in MGlu-HPG-modified liposomes were significantly suppressed by addition of anti-major histocompatibility complex (MHC) class I and class II monoclonal antibodies, indicating the involvement of antigen presentation via MHC class I and II. Furthermore, delayed-type hypersensitivity responses and OVA-specific antibodies were induced more effectively in mice immunized with OVA encapsulated by MGlu-HPG-modified liposomes than with unencapsulated OVA or OVA encapsulated in unmodified liposomes. These results suggested that MGlu-HPG-modified liposomes effectively induced both cell-mediated and humoral immune responses. Collectively, this study is the first to demonstrate the induction of both cell-mediated and humoral immune responsesin vivoby MGlu-HPG-modified liposomes.

Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion

Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2424-2432 ◽  
Author(s):  
Matthias Gunzer ◽  
Helge Riemann ◽  
Yasmin Basoglu ◽  
Anja Hillmer ◽  
Carsten Weishaupt ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocyte ◽  
Endothelial Activation ◽  
Contact Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Blood Leukocytes

Abstract Toll-like receptor (TLR) ligands lead to the induction of proinflammatory cytokines and are potent enhancers of specific immune responses. We show here that a single systemic dose of R-848, a ligand for TLR7, potently enhanced hapten sensitization during the induction of contact hypersensitivity (CHS). However, R-848 administration also resulted in a rapid and almost complete depletion of leukocytes from the blood. This effect was transient and was associated with general induction of endothelial adhesiveness. In response to R-848, endothelial cells up-regulated adhesion molecules in vitro and in vivo and leukocytes exhibited increased rolling on endothelia in R-848-treated animals. Adhesion molecule induction appeared to be a direct effect, because endothelial cells expressed TLR7 in vitro and in vivo. After R-848 treatment, the tissue residence time of leukocytes was markedly prolonged in all major peripheral organs. The resulting transiently reduced availability of peripheral-blood leukocytes (PBLs) (TRAP) significantly inhibited otherwise potent CHS responses until the effector cells returned. Thus, although TLR7 ligands are effective adjuvants for the induction of cell-mediated immunity, they can transiently inhibit the elicitation of localized immune responses, possibly due to a systemic endothelial activation throughout the vasculature. (Blood. 2005;106:2424-2432)

scholarly journals Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai-Ling Tian ◽  
Qi Wu ◽  
Peng Liu ◽  
Liwei Zhao ◽  
Isabelle Martins ◽  
...  
Keyword(s):  
Stress Response ◽  
Immune Responses ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Serine Residue ◽  
Eif2α Phosphorylation ◽  
Lysosomotropic Agents ◽  
Cultured Human Cells

AbstractThe integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.

scholarly journals Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mauro Di Pilato ◽  
Miguel Palomino-Segura ◽  
Ernesto Mejías-Pérez ◽  
Carmen E. Gómez ◽  
Andrea Rubio-Ponce ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immune System ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Adaptive Immune

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

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