Inappropriate Immune Response (inappropriate + immune_response)

Distribution by Scientific Domains


Selected Abstracts


CARMA1-mediated NF-,B and JNK activation in lymphocytes

IMMUNOLOGICAL REVIEWS, Issue 1 2009
Marzenna Blonska
Summary:, Activation of transcription factor nuclear factor-,B (NF-,B) and Jun N-terminal kinase (JNK) play the pivotal roles in regulation of lymphocyte activation and proliferation. Deregulation of these signaling pathways leads to inappropriate immune response and contributes to the development of leukemia/lymphoma. The scaffold protein CARMA1 [caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1] has a central role in regulation of NF-,B and the JNK2/c-Jun complex in both B and T lymphocytes. During last several years, tremendous work has been done to reveal the mechanism by which CARMA1 and its signaling partners, B cell CLL-lymphoma 10 and mucosa-associated lymphoid tissue 1, are activated and mediate NF-,B and JNK activation. In this review, we summarize our findings in revealing the roles of CARMA1 in the NF-,B and JNK signaling pathways in the context of recent advances in this field. [source]


Mechanisms of immune suppression by interleukin-10 and transforming growth factor-,: the role of T regulatory cells

IMMUNOLOGY, Issue 4 2006
Alison Taylor
Summary Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific type 1 regulatory (Tr1) cells and T helper (Th) 2 cells appears to be decisive in the development of allergy. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific interleukin-4 (IL-4)-secreting T cells in allergic individuals. Allergen-specific immunotherapy can induce specific Tr1 cells that abolish allergen-induced proliferation of Th1 and Th2 cells, as well as their cytokine production. Tr1 cells utilize multiple suppressor mechanisms, such as IL-10 and transforming growth factor-, (TGF-,) as secreted cytokines and various surface molecules, such as cytotoxic T-lymphocyte antigen 4 and programmed death-1. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors, which depend on CD28 costimulation. IL-10 inhibits CD28 tyrosine phosphorylation, preventing the binding of phosphatidylinositol 3-kinase p85 and consequently inhibiting the CD28 signalling pathway. In addition, IL-10 and TGF-, secreted by Tr1 cells skew the antibody production from immunoglobulin E (IgE) towards the non-inflammatory isotypes IgG4 and IgA, respectively. Induction of antigen-specific Tr1 cells can thus re-direct an inappropriate immune response against allergens or auto-antigens using a broad range of suppressor mechanisms. [source]


DEC-205lo Langerinlo neonatal Langerhans' cells preferentially utilize a wortmannin-sensitive, fluid-phase pathway to internalize exogenous antigen

IMMUNOLOGY, Issue 4 2003
Bernadette M. Bellette
Summary Antigen treatment of neonatal epidermis results in antigen-specific immune suppression. Compared with adult counterparts, neonatal Langerhans' cells (LC) demonstrate an impaired ability to transport antigen to the lymph node (LN). As it is possible that neonatal LC have a reduced ability to endocytose antigen, we evaluated the acquisition of endocytic function, the expression of uptake receptors and the internalization of soluble and small particulate antigens in neonatal, juvenile and adult mice. Although LC from 4-day-old mice were weakly positive for the mannose-type receptor, Langerin, they were capable of internalizing fluorescein isothiocyanate (FITC)-dextran, but to a lesser extent than LC from 6-week-old mice. However, when ratio data were calculated to account for variations in fluorescence intensity at 4°, it was demonstrated that neonatal LC continued to internalize antigen over a longer period of time than adult mice and, as the ratios were much higher, that neonatal cells were also relatively more efficient in antigen uptake. When receptors for mannan and mannose were competitively blocked, LC from neonatal mice, but not adult mice, could still efficiently internalize FITC,dextran. Consequently, the uptake of FITC,dextran, in part, occurred via alternative receptors or a receptor-independent fluid-phase pathway. A feasible pathway is macropinocytosis, as LC from 4-day-old mice demonstrated a reduction in FITC,dextran internalization by the macropinocytosis inhibitor, wortmannin. Evidence of a functional macropinocytosis pathway in neonatal LC was further supported by internalization of the soluble tracer Lucifer Yellow (LY). We conclude that neonatal LC preferentially utilize a wortmannin-sensitive, fluid-phase pathway, rather than receptor-mediated endocytosis, to internalize antigen. As neonatal LC are capable of sampling their environment without inducing immunity, this may serve to avoid inappropriate immune responses during the neonatal period. [source]


DNA VACCINES AND ALLERGIC DISEASES

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006
Kaw Yan Chua
SUMMARY 1Allergic diseases are characterized by inappropriate immune responses to common environmental antigens. The prevalence of these diseases has been increasing worldwide for reasons that are not exactly clear. 2Current treatment is largely symptomatic. Because the initial observation that simple plasmid DNA injections resulted in in vivo protein expression and induction of adaptive immune responses to the encoded antigen, the potential of modifying the allergic immune responses by DNA vaccination so as to treat and prevent these diseases has been explored extensively. 3In the present paper we review preclinical studies using animal models of allergic diseases, with an emphasis on DNA vaccine design, for house dust mite allergens-related allergic asthma. [source]