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One of the greatest health-care challenges in the elderly is to ensure that vaccination against infections are optimally effective, but vaccination can only be effective if cells that are capable of responding are still present in the repertoire. The reversing of immunosenescence could be achieved by improving immune responses or altering vaccine formulation. Recent vaccination strategies in the elderly exert low effectiveness. Nutritional interventions and moderate exercise delay T cell senescence. Telomerase activity and expression of toll-like receptors can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of immunostimulatory and anti-inflammatory cytokines show the best practical approach. Reduced dendritic cell activity and co-receptor expression might be increased by interleukin (IL)-2 administration. IL-7 protects both B and T lymphocytes, but IL-2, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone also have a stimulatory effect on thymopoiesis. In animals, several strategies have been explored to produce more efficacious vaccines including high dose vaccines, DNA vaccines with immunostimulatory patch, virosomal vaccines and vaccines containing new adjuvants. Hopefully, one of these approaches will be translated into human therapy in a short time.

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Acta Microbiologica et Immunologica Hungarica
Authors:
F. Kerek
,
G. Szegli
,
Lidia Cremer
,
Andreea-Roxana Lupu
,
Steliana Durbaca
,
Ana Calugaru
,
Aurora Herold
, and
D. Radu

Influence of the novel arthritis drug-substance MCS-18 on the antibody (Ab) production against tetanus toxoid (TT) and diphtheria toxoid (DT) antigens was tested in vivo . Possible involvement of MCS-18 in Toll-like receptor (TLR) signalling pathway was further considered.Materials and methods: Immunization of male CD1 mice was done with subcutaneous injection of TT emulsified in Freund’s Complete (FCA) or Incomplete Adjuvant (FIA) and mixed diversly with MCS-18 and different test substances. To investigate the influence of TLR activation Pam3Cys and lipopolysaccharide (LPS) emulsified in FIA were tested in combinations with MCS-18. Antibody production was analysed in vivo by tetanus-or diphtheria-toxin neutralization test.Results: Immunogenicity of TT was significantly enhanced if administered together with FCA or TLR agonists Pam3Cys or LPS emulsified in FIA. It was shown that MCS-18 attenuated strongly the production of anti-TT Ab if administered together with the Ab elicitor FCA or TLR agonists in various combinations. MCS-18 was also active via oral administration.Discussion: These findings suggest that MCS-18 could be a potent, non-toxic antagonist or a down-regulator of TLR signalling pathway. Investigations on further models are needed to establish if MCS-18 may influence particularly the production of RA-specific auto-antibodies, too.

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European Journal of Microbiology and Immunology
Authors:
Sascha Cording
,
Diana Fleissner
,
Markus M. Heimesaat
,
Stefan Bereswill
,
Christoph Loddenkemper
,
Satoshi Uematsu
,
Shizuo Akira
,
Alf Hamann
, and
Jochen Huehn

are differentially regulated by pro-inflammatory cytokines produced by TLR-activated dendritic cells J Immunol 173 7249 7258 . 41

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.H. Rea B.R. Bloom R.L. Modlin 2005 TLR activation triggers the rapid differentiation of monocytes into macrophages

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endotoxin present in vaccines and other immunotherapeutics lead to TLR activation, with an improved immunization and drug effect as desired outcomes. Acceptable low levels of LPS ‘contaminants’ with adjuvant activity have been named Innate Immune Response

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