Thymus-Independent Antigens

Bondada, Subbarao; Garg, Manju

doi:10.1016/b978-0-12-653955-4.50017-8

Cited by 21 publications

(17 citation statements)

References 182 publications

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“…One possible explanation for this observation is that recombinant proteins generated using Escherichia coli were glycosylated, but this requires confirmation. Another explanation is the nonspecific nature of antibodies recognizing TI antigens, which may recognize multiple epitopes against unrelated molecules, usually with a low affinity (12). A more complex explanation involves several principles discovered during attempts to optimize vaccines using polysaccharide-protein conjugates.…”

Section: Discussionmentioning

confidence: 99%

T-Cell-Independent Responses toBorrelia burgdorferiAre Critical for Protective Immunity and Resolution of Lyme Disease

2000

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The humoral immune response to Borrelia burgdorferi during persistent infection is critical to both protective and disease-resolving immunity. This study examined the role of B cells in the absence of T cells during these events, using mice with selected immune dysfunctions. At 6 weeks postinfection, an interval at which arthritis resolves in immunocompetent mice, arthritis severity was equivalent among immunocompetent mice, ␣␤ ؉ -Tcell-deficient mice, and mice lacking both ␣␤ ؉ and ␥␦ ؉ T cells. Arthritis severity was worse in SCID mice, which lack T and B lymphocytes. Carditis regressed in immunocompetent mice and those lacking both ␣␤ burgdorferi. However, only sera from infected immunocompetent mice, but not sera from infected T-cell-deficient mice, were able to resolve arthritis when passively transferred to actively infected SCID mice. These data demonstrate that B-cell activation during a T-cell-independent response may be critical for resolution of arthritis and carditis and that protective antibodies are generated during this response.

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Section: Discussionmentioning

confidence: 99%

T-Cell-Independent Responses toBorrelia burgdorferiAre Critical for Protective Immunity and Resolution of Lyme Disease

2000

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“…In the aged, where mature B cells are present and are only marginally affected in their responses to B cell receptor signaling, the reason for reduced responsiveness to polysaccharide vaccines is not known. The pneumococcal polysaccharides have been classified as thymic-independent antigens, as they do not elicit antigen-specific helper T cells, which can interact with B cells in a cognate manner [10]. However, B cells and M⌽ are required for generating an immune response to polysaccharide antigens.…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages

Chelvarajan

Liu²,

Popa³

et al. 2006

Journal of Leukocyte Biology

131

104

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Aged humans and rodents are susceptible to infection with Streptococcus pneumoniae bacteria as a result of an inability to make antibodies to capsular polysaccharides. This is partly a result of decreased production of proinflammatory cytokines and increased production of interleukin (IL)-10 by macrophages (Mphi) from aged mice. To understand the molecular basis of cytokine dysregulation in aged mouse Mphi, a microarray analysis was performed on RNA from resting and lipopolysaccharide (LPS)-stimulated Mphi from aged and control mice using the Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA analysis demonstrated that at an overall P < 0.01 level, 853 genes were regulated by LPS (169 in only the young, 184 in only the aged, and 500 in both). Expression analysis of systematic explorer revealed that immune response (proinflammatory chemokines, cytokines, and their receptors) and signal transduction genes were specifically reduced in aged mouse Mphi. Accordingly, expression of Il1 and Il6 was reduced, and Il10 was increased, confirming our previous results. There was also decreased expression of interferon-gamma. Genes in the Toll-like receptor-signaling pathway leading to nuclear factor-kappaB activation were also down-regulated but IL-1 receptor-associated kinase 3, a negative regulator of this pathway, was increased in aged mice. An increase in expression of the gene for p38 mitogen-activated protein kinase (MAPK) was observed with a corresponding increase in protein expression and enzyme activity confirmed by Western blotting. Low doses of a p38 MAPK inhibitor (SB203580) enhanced proinflammatory cytokine production by Mphi and reduced IL-10 levels, indicating that increased p38 MAPK activity has a role in cytokine dysregulation in the aged mouse Mphi.

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“…The spleen is important for immune response to these organisms, as splenectomized patients and animals are unresponsive to PS Ag from such bacteria [6,7]. Although part of the defect in Ab responses to bacterial PS Ag is B cell immaturity [8], the possibility that neonatal M⌽ may be defective in providing accessory function to B cells responsive to PS Ag has not been investigated thus far.…”

Section: Introductionmentioning

confidence: 99%

“…TI Ag are divided into two types, based on whether or not they induce immune responses in CBA/N or neonatal wild-type (WT) mice. CBA/N mice, which have an Xlinked, recessive, immune defect (Xid), and neonatal WT mice respond to TI-1 Ag but not to TI-2 Ag [8,9]. Another difference is that at high doses, TI-1 Ag, unlike TI-2 Ag, become mitogenic and invoke a polyclonal response from B cells [5,10].…”

Section: Introductionmentioning

confidence: 99%

Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens

Chelvarajan

Collins

Doubinskaia

et al. 2004

Journal of Leukocyte Biology

103

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Neonates do not respond to thymus-independent (TI) antigens (Ag), making them vulnerable to infection with encapsulated bacteria. The antibody (Ab) response of adult and neonatal B cells to TI Ag requires certain cytokines, which are provided by T cells or macrophages (MPhi). Lipopolysaccharide (LPS) failed to induce neonatal MPhi to produce interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha) mRNA and to secrete IL-1beta, IL-12, and TNF-alpha. However, LPS induced neonates to secrete some IL-6 and three- to fivefold more IL-10 than adults. Accordingly, adding adult but not neonatal MPhi could restore the response of purified adult B cells to trinitrophenol (TNP)-LPS, a TI Ag. Increased IL-10 is causally related to decreased IL-1beta and IL-6 production, as IL-10(-/-) neonatal MPhi responded to LPS by secreting more IL-1beta and IL-6 than wild-type (WT) neonatal MPhi. When cultures were supplemented with a neutralizing Ab to IL-10, WT neonatal MPhi secreted increased amounts of IL-6 and allowed neonatal MPhi to promote adult B cells to mount an Ab response against TNP-LPS. Thus, neonates do not respond to TI Ag as a result of the inability of neonatal MPhi to secrete cytokines, such as IL-1beta and IL-6, probably as a result of an excess production of IL-10. This dysregulated cytokine secretion by neonatal MPhi may be a result of a reduction in expression of Toll-like receptor-2 (TLR-2) and TLR-4 and CD14.

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Thymus-Independent Antigens

Cited by 21 publications

References 182 publications

T-Cell-Independent Responses toBorrelia burgdorferiAre Critical for Protective Immunity and Resolution of Lyme Disease

T-Cell-Independent Responses toBorrelia burgdorferiAre Critical for Protective Immunity and Resolution of Lyme Disease

Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages

Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens

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