scholarly journals Differences in Components at Delayed-Type Hypersensitivity Reaction Sites in Mice Immunized with Either a Protective or a Nonprotective Immunogen of Cryptococcus neoformans

2002 ◽  
Vol 70 (2) ◽  
pp. 591-600 ◽  
Author(s):  
Kasie L. Nichols ◽  
Sean K. Bauman ◽  
Fredda B. Schafer ◽  
Juneann W. Murphy
Keyword(s):  
Cryptococcus Neoformans ◽  
Specific Antigen ◽  
Intradermal Injection ◽  
Delayed Type Hypersensitivity ◽  
Protective Mechanism ◽  
Cell Mediated Immunity ◽  
Reaction Site ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
A Cell

ABSTRACT Cell-mediated immunity is the major protective mechanism against Cryptococcus neoformans. Delayed swelling reactions, i.e., delayed-type hypersensitivity (DTH), in response to an intradermal injection of specific antigen are used as a means of detecting a cell-mediated immune (CMI) response to the antigen. We have found previously that the presence of an anticryptococcal DTH response in mice is not always indicative of protection against a cryptococcal infection. Using one immunogen that induces a protective anticryptococcal CMI response and one that induces a nonprotective response, we have shown that mice immunized with the protective immunogen undergo a classical DTH response characterized by mononuclear cell and neutrophil infiltrates and the presence of gamma interferon and NO. In contrast, immunization with the nonprotective immunogen results in an influx of primarily neutrophils and production of tumor necrosis factor alpha (TNF-α) at the DTH reaction site. Even when the anticryptococcal DTH response was augmented by blocking the down-regulator, CTLA-4 (CD152), on T cells in the mice given the nonprotective immunogen, the main leukocyte population infiltrating the DTH reaction site is the neutrophil. Although TNF-α is increased at the DTH reaction site in mice immunized with the nonprotective immunogen, it is unlikely that TNF-α activates the neutrophils, because the density of TNF receptors on the neutrophils is reduced below control levels. Uncoupling of DTH reactivity and protection has been demonstrated in other infectious-disease models; however, the mechanisms differ from our model. These findings stress the importance of defining the cascade of events occurring in response to various immunogens and establishing the relationships between protection and DTH reactions.

Effects of psoriasis treatment on genital warts: a case report

2019 ◽  
Vol 30 (8) ◽  
pp. 828-830 ◽  
Author(s):  
Marco Campoli ◽  
Elisa Cinotti ◽  
Michele Fimiani ◽  
Michele Pellegrino ◽  
Linda Tognetti ◽  
...  
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Clinical Manifestations ◽  
Genital Warts ◽  
Immunosuppressive Drugs ◽  
Additional Treatment ◽  
Cell Mediated Immunity ◽  
Complete Regression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha

The use of immunosuppressive drugs predisposes to infections, as they block the most important stage in antiviral defense, which is the cytotoxic T-lymphocyte HLA-dependent response. We report a case of extensive genital warts in a young woman on therapy for psoriasis with cyclosporine, afterwards successfully treated with an anti-tumor necrosis factor alpha (TNF-α) agent. Cyclosporine may predispose to the reactivation of latent infections and may favor the clinical manifestations of human papillomavirus (HPV)-related diseases, due to the inhibition of cell-mediated immunity that plays a crucial role in controlling HPV infections. In the literature the relationship between HPV and TNF-blockers has not yet been clearly defined. Our case underlines that the prompt interruption of cyclosporine can induce a complete regression of warts without any additional treatment and adds evidence to the possible use of anti-TNF-α in patients with psoriasis and genital warts.

scholarly journals Screening for Toxoplasma gondii-Regulated Transcriptional Responses in Lipopolysaccharide-Activated Macrophages

2006 ◽  
Vol 74 (3) ◽  
pp. 1916-1923 ◽  
Author(s):  
Chiang W. Lee ◽  
Soumaya Bennouna ◽  
Eric Y. Denkers
Keyword(s):  
Toxoplasma Gondii ◽  
Defense Mechanisms ◽  
Transcriptional Response ◽  
Interleukin 12 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Transcriptional Responses ◽  
Necrosis Factor Alpha ◽  
Reverse Transcription Pcr ◽  
Tnf Α

ABSTRACT Toxoplasma gondii-infected macrophages are blocked in production of the proinflammatory cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) upon activation with lipopolysaccharide (LPS). Here, we used pathway-focused cDNA arrays to identify additional T. gondii-regulated transcriptional responses. Parasite infection decreased 57 (inclusive of IL-12 and TNF-α) and increased expression of 7 of 77 LPS-activated cytokine and cytokine-related genes. Interestingly, we found that the LPS-induced transcriptional response of the anti-inflammatory cytokine IL-10 was synergistically increased by T. gondii, results that we validated by conventional reverse transcription-PCR and enzyme-linked immunosorbent assay. Importantly, although the parasite exerted disparate effects in LPS-signaling leading to TNF-α versus IL-10 production, both responses required functional Toll-like receptor 4. We suggest that these effects represent parasite defense mechanisms to avoid or delay induction of antimicrobial activity and/or T-cell-mediated immunity during Toxoplasma infection.

scholarly journals Specific Antibody to Cryptococcus neoformans Alters Human Leukocyte Cytokine Synthesis and Promotes T-Cell Proliferation

1998 ◽  
Vol 66 (3) ◽  
pp. 1244-1247 ◽  
Author(s):  
Anna Vecchiarelli ◽  
Cinzia Retini ◽  
Claudia Monari ◽  
Arturo Casadevall
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cryptococcus Neoformans ◽  
Specific Antibody ◽  
Human Leukocyte ◽  
T Cell Proliferation ◽  
Cell Mediated Immunity ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Addition of a monoclonal antibody which binds theCryptococcus neoformans capsule to suspensions of human monocytes, T lymphocytes, and cryptococcal cells (i) enhances interleukin-1β (IL-1β), tumor necrosis factor alpha, and IL-2 production; (ii) reduces IL-10 secretion; and (iii) promotes T-cell proliferation. The ability of specific antibody to influence cytokine production and lymphoproliferation suggests a mechanism by which humoral immunity can influence cell-mediated immunity.

scholarly journals Mechanisms Involved in the Pathogenesis of Sepsis Are Not Necessarily Reflected by In Vitro Cell Activation Studies

1998 ◽  
Vol 66 (11) ◽  
pp. 5372-5378 ◽  
Author(s):  
Claudia R. Amura ◽  
R. Silverstein ◽  
D. C. Morrison
Keyword(s):  
Cell Activation ◽  
Endotoxic Shock ◽  
Peritoneal Macrophages ◽  
In Vitro Studies ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
In Vitro Systems ◽  
A Cell

ABSTRACT It is thought that lipopolysaccharide (LPS) from gram-negative bacteria contributes significantly to the pathogenesis of septic shock. In vitro studies to address the mechanisms involved in this process have often investigated human monocytes or mouse macrophages, since these cells produce many of the mediators found in septic patients. Targeting of these mediators, especially tumor necrosis factor alpha (TNF-α), has been pursued as a means of reducing mortality in sepsis. Two experimental approaches were designed to test the assumption that in vitro studies with macrophages accurately predict in vivo mechanisms of LPS pathogenesis. In the first approach, advantage was taken of the fact that on consecutive days after injection of thioglycolate into mice, increased numbers of macrophages could be harvested from the peritoneum. These cells manifested markedly enhanced levels of in vitro TNF-α, interleukin 6 (IL-6), and nitric oxide production in response to LPS. In d-galactosamine-sensitized mice, however, thioglycolate treatment significantly decreased mortality due to LPS, as well as levels of circulating TNF-α and IL-6. Anti-TNF-α treatment confirmed this cytokine’s role in the observed lethality. In a second experimental approach, we compared the mouse macrophage-stimulating potencies of different LPS preparations with their lethalities to mice. In these studies, the in vitro macrophage-stimulating profiles presented by rough-LPS and smooth-LPS preparations were the reverse of their relative lethal potencies in vivo. In conclusion, peritoneal macrophages appear not to be the major cells responsible for the overall host response during endotoxic shock. These findings underscore the importance of verifying the correlation of in vivo systems with in vitro systems when attributing specific functions to a cell type.

scholarly journals Induction of Interleukin-12 and Gamma Interferon Requires Tumor Necrosis Factor Alpha for Protective T1-Cell-Mediated Immunity to Pulmonary Cryptococcus neoformans Infection

2002 ◽  
Vol 70 (6) ◽  
pp. 2959-2964 ◽  
Author(s):  
Amy C. Herring ◽  
John Lee ◽  
Roderick A. McDonald ◽  
Galen B. Toews ◽  
Gary B. Huffnagle
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 12 ◽  
Cell Mediated Immunity ◽  
Pulmonary Eosinophilia ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT The development of T1-cell-mediated immunity is required to clear a pulmonary Cryptococcus neoformans infection. The objective of these studies was to determine the mechanism by which tumor necrosis factor alpha (TNF-α) augments the development of pulmonary T1 immunity to C. neoformans infection. TNF-α expression was detected in lavage sample cells at days 2, 3, and 7 following C. neoformans infection. The numbers of CFU in the lung were not different between control and anti-TNF-α-treated mice at any time point examined during the afferent phase of the response (days 0 to 7). However, neutralization of TNF-α prevented the initiation of pulmonary clearance during the efferent phase of the response (day 14). Administration of anti-TNF-α monoclonal antibody (day 0) diminished the lung levels of TNF-α, interleukin-12 (IL-12), and gamma interferon (IFN-γ) induced by C. neoformans at day 7 postinfection. Neutralization of TNF-α (day 0) also altered the IFN-γ/IL-4 ratio in the lung-associated lymph nodes at day 7 following C. neoformans infection. Anti-TNF-α-treated mice developed a pulmonary eosinophilia at day 14 postinfection. Consistent with the pulmonary eosinophilia, anti-TNF-α-treated mice exhibited elevated serum immunoglobulin E and inhibition of the anticryptococcal delayed-type hypersensitivity response, indicating a shift toward a T2 response. Neutralization of IL-12 also prevented lung leukocyte production of IFN-γ in response to the infection. These findings demonstrate that afferent-phase TNF-α production is essential for the induction of IL-12 and IFN-γ and neutralization of early TNF-α results in a T2 shift of the T1/T2 balance of antifungal immunity.

scholarly journals POTENTIATION OF T-CELL-MEDIATED IMMUNITY BY SELECTIVE SUPPRESSION OF ANTIBODY FORMATION WITH CYCLOPHOSPHAMIDE

1974 ◽  
Vol 139 (6) ◽  
pp. 1529-1539 ◽  
Author(s):  
P. H. Lagrange ◽  
G. B. Mackaness ◽  
T. E. Miller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Formation ◽  
Specific Antigen ◽  
Cell Activity ◽  
Antigenic Stimulation ◽  
Delayed Type Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Inhibitory Influence ◽  
Resting Cells

Delayed-type hypersensitivity (DTH) appears in mice immunized with less than an optimal immunogenic dose of sheep red blood cells (SRBC), but is blocked progressively as antibody production increases in response to larger doses of SRBC. Treatment with cyclophosphamide (CY) was shown to release T cells from this inhibitory influence of the humoral response, and cause enhancement of DTH. The magnitude of this enhancing effect on T-cell activity was markedly dependent on the time of treatment relative to the time of immunization, and on the time chosen for measuring DTH. The reasons for these pronounced effects of timing are threefold: (a) CY given before antigenic stimulation has a long-lasting effect on antibody formation, but no apparent effect on the precursors of activated T cells. (b) After antigenic stimulation, T cells also become susceptible to CY. (c) The production of a nonspecific participant (monocyte) in the DTH reaction is also suppressed by CY, though the supply of circulating monocytes is not immediately affected by the drug. The differential effect of CY on T and B lymphocytes depends on the differing physiological states of the majority of cells that make up these two populations. The former are resting cells that are insensitive to CY until exposed to specific antigen, while the latter are drawn from a rapidly replicating precursor pool and are susceptible to CY at all times.

scholarly journals Protective effect of cytosine-phosphate-guanosine oligodeoxynucleotide against experimental mastitis induced by Cryptococcus neoformans infection in goats

2017 ◽  
Vol 40 (2) ◽  
pp. 113-123
Author(s):  
Nidhal R. Mahdi
Keyword(s):  
Mammary Gland ◽  
Cryptococcus Neoformans ◽  
Interferon Gamma ◽  
Antibody Titer ◽  
Delayed Type Hypersensitivity ◽  
Phagocytic Index ◽  
Cell Mediated Immunity ◽  
The Right ◽  
High Level ◽  
Phosphate Buffered Saline

     The present study investigated the effect of synthetic non-methylated oligonucleotides containing Cytosine-phosphate-guanosine dinucleotides (Cytosine-phosphate-guanosine oligodeoxynucleotide) on caprine mastitis with Heat Killed Cryptococcus neoformans Ag. 20 healthy local breed does were used with weight ranging of 25-30 Kg and free of mastitis by examination via California Mastitis Test and Somatic Cell Count. The does were allotted into four equal groups, the first group (G1) was treated intramammary with 100μg/kg of Cytosine-phosphate-guanosine oligodeoxy nucleotide on fifth day postpartum in the right mammary gland while the left mammary gland served as control and were infused with sterile phosphate buffered saline. On day 8 postpartum repeat dosages of Cytosine-phosphate-guanosine oligodeoxynucleotide and phosphate buffered saline were infused respectively. On day 9 pp the right mammary gland was infused with 2ml of 2x108 cell/ml of Heat Killed Cryptococcus neoformans Ag. The second group (G2) was infused at day 9 postpartum with 2ml of 2x108 cell/ml of Heat Killed Cryptococcus neoformans Ag in the right mammary gland only. The third group (G3) was left until the challenge test done after one week of immunization in the G1 and G2, by inoculation of 2ml of 5x106 viable C. neoformans in the right mammary gland. The fourth group (G4) was kept as a control receiving 2ml of sterile PBS. Blood samples were collected at 0, 5, 10, 20, 30 and 40 days of the study, to determine the antibody titer by passive haemagglutination assay, while the cell mediated immunity was evaluated by detecting the goat Interferon Gamma by ELISA test and Phagocytic index. Also the cell mediated immunity was determined by delayed type hypersensitivity test after 21 days of immunization. The results showed a significant variation (P≤0.05) between vaccinated groups (G1 and G2) and the control. However, there was a significant increase (P≤0.05) of skin thickness shown after 48 hrs in the G1compared to G2. High level of Interferon Gamma concentration was noticed in the G1 as compared with other groups. Moreover, cell mediated immunity developed effectively in the G1 which was noted by a significant increase (P≤0.05) of phagocytic activity of polymorphonuclear cells. The high level of antibody titer was observed in the G1 as compared with other groups. In conclusion: These results suggest that vaccination with Cytosine-phosphate-guanosine oligodeoxynucleotide plus Heat Killed Cryptococcus neoformans Ag intramammary lead to a good protection of caprine mammary glands against C. neoformans mastitis.

scholarly journals Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats.

1992 ◽  
Vol 175 (3) ◽  
pp. 655-659 ◽  
Author(s):  
M J Day ◽  
A G Tse ◽  
M Puklavec ◽  
S J Simmonds ◽  
D W Mason
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Autoimmune Disease ◽  
Antibody Production ◽  
Specific Antigen ◽  
Reciprocal Relationship ◽  
Delayed Type Hypersensitivity ◽  
A Cell

Immunization protocols that induce high levels of delayed-type hypersensitivity are often associated with low levels of antibody production, whereas alternative immunization strategies can produce the opposite effect. This reciprocal relationship appears to depend, at least in part, on the fact that T cell-derived lymphokines that are predominantly involved in one type of response inhibit the development of those T cells that promote the alternative one. Such a regulatory mechanism is likely to be bistable in that whenever one form of response is established, spontaneous development of the alternative one will be inhibited. We have applied this concept to the control of a cell-mediated autoimmune disease in rats. By covalently linking the autoantigen to anti-IgD antibody, we have targeted it to B cells for presentation to antigen-specific T cells. This form of presentation favors antibody production and may be expected to antagonize the cell-mediated disease-inducing response to the same antigen. To test this hypothesis, use was made of the fact that experimental allergic encephalomyelitis (EAE), when induced with the encephalitogenic peptide of guinea pig myelin basic protein, is purely a cell-mediated disease. The experiments show that Lewis rats, immunized with the peptide in its encephalitogenic form, were protected from disease when simultaneously injected with the peptide coupled to anti-IgD monoclonal antibodies. Control experiments showed that neither peptide nor anti-IgD alone were protective, and the peptide covalently coupled to irrelevant antibodies also failed to protect. Spleen cells from animals protected from disease by the anti-IgD-peptide conjugate, when activated in vitro with the encephalitogen, were able to transfer EAE to naive recipients. The results demonstrate that a cell-mediated immune response can be controlled by appropriate targeting of the specific antigen without inducing T cell anergy and suggest a potential strategy for preventing autoimmune diseases that are essentially cell-mediated in type.

scholarly journals Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection

2008 ◽  
Vol 76 (10) ◽  
pp. 4745-4756 ◽  
Author(s):  
Loïc Guillot ◽  
Scott F. Carroll ◽  
Robert Homer ◽  
Salman T. Qureshi
Keyword(s):  
Immune Response ◽  
Cryptococcus Neoformans ◽  
Innate Immune Response ◽  
Intracellular Signaling ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Innate Immune ◽  
Natural Resistance ◽  
Necrosis Factor Alpha ◽  
Tnf Α

ABSTRACT Genetically regulated mechanisms of host defense against Cryptococcus neoformans infection are not well understood. In this study, pulmonary infection with the moderately virulent C. neoformans strain 24067 was used to compare the host resistance phenotype of C57BL/6J with that of inbred mouse strain SJL/J. At 7 days or later after infection, C57BL/6J mice exhibited a significantly greater fungal burden in the lungs than SJL/J mice. Characterization of the pulmonary innate immune response at 3 h after cryptococcal infection revealed that resistant SJL/J mice exhibited significantly higher neutrophilia, with elevated levels of inflammatory cytokine tumor necrosis factor alpha (TNF-α) and keratinocyte-derived chemokine (KC)/CXCL1 in the airways, as well as increased whole-lung mRNA expression of chemokines KC/CXCL1, MIP-1α/CCL3, MIP-1β/CCL4, MIP-2/CXCL2, and MCP-1/CCL2 and cytokines interleukin 1β (IL-1β) and IL-1Ra. At 7 and 14 days after infection, SJL/J mice maintained significantly higher levels of TNF-α and KC/CXCL1 in the airways and exhibited a Th1 response characterized by elevated levels of lung gamma interferon (IFN-γ) and IL-12/IL-23p40, while C57BL/6J mice exhibited Th2 immunity as defined by eosinophilia and IL-4 production. Alveolar and resident peritoneal macrophages from SJL/J mice also secreted significantly greater amounts of TNF-α and KC/CXCL1 following in vitro stimulation with C. neoformans. Intracellular signaling analysis demonstrated that TNF-α and KC/CXCL1 production was regulated by NF-κB and phosphatidylinositol 3 kinase in both strains; however, SJL/J macrophages exhibited heightened and prolonged activation in response to C. neoformans infection compared to that of C57BL/6J. Taken together, these data demonstrate that an enhanced innate immune response against pulmonary C. neoformans infection in SJL/J mice is associated with natural resistance to progressive infection.

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