-
The Journal of Investigative Dermatology Feb 2007It has been well established that Toll-like receptors (TLRs) are expressed by keratinocytes and respond to their respective ligands to initiate immune responses.... (Review)
Review
It has been well established that Toll-like receptors (TLRs) are expressed by keratinocytes and respond to their respective ligands to initiate immune responses. However, it appears that keratinocytes, via differential activation of TLRs, may play a key role in determining the type of subsequent cutaneous immune response generated against a particular pathogen.
Topics: Antibody Formation; Humans; Keratinocytes; Skin; Toll-Like Receptors
PubMed: 17228303
DOI: 10.1038/sj.jid.5700559 -
Current Opinion in Chemical Biology Jun 2007Over the past decade, microarrays have revolutionized the scientific world as dramatically as the internet has changed everyday life. From the initial applications of... (Review)
Review
Over the past decade, microarrays have revolutionized the scientific world as dramatically as the internet has changed everyday life. From the initial applications of DNA microarrays to uncover gene expression patterns that are diagnostic and prognostic of cancer, understanding the interplay between immune responses and disease has been a prime application of this technology. More recent efforts have moved beyond genetic analysis to functional analysis of the molecules involved, including identification of immunodominant antigens and peptides as well as the role of post-translational glycosylation. Here, we focus on recent applications of microarray technology in understanding the detailed chemical biology of immune responses to disease in an effort to guide development of vaccines and other protective therapies.
Topics: Antibody Formation; Carbohydrates; Genome; Humans; Immunity, Cellular; Infections; Oligonucleotide Array Sequence Analysis; Population Surveillance
PubMed: 17500025
DOI: 10.1016/j.cbpa.2007.01.727 -
The Journal of Clinical Investigation Jan 2022We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted... (Randomized Controlled Trial)
Randomized Controlled Trial
We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted intervention in the LEAP clinical trial. We identified an association between peanut-specific IgG4 and HLA-DQA1*01:02 that was only observed in the presence of sustained oral peanut protein exposure. The association between IgG4 and HLA-DQA1*01:02 was driven by IgG4 specific for the Ara h 2 component. Once peanut consumption ceased, the association between IgG4-specific Ara h 2 and HLA-DQA1*01:02 was attenuated. The association was validated by observing expanded IgG4-specific epitopes in people who carried HLA-DQA1*01:02. Notably, we confirmed the previously reported associations with HLA-DQA1*01:02 and peanut allergy risk in the absence of oral peanut protein exposure. Interaction between HLA and presence or absence of exposure to peanut in an allergen- and epitope-specific manner implicates a mechanism of antigen recognition that is fundamental to driving immune responses related to allergy risk or protection.
Topics: 2S Albumins, Plant; Alleles; Antibody Formation; Antigens, Plant; Arachis; Child; Female; HLA-DQ alpha-Chains; Humans; Immunoglobulin G; Male; Peanut Hypersensitivity
PubMed: 34981778
DOI: 10.1172/JCI152070 -
Cellular & Molecular Immunology Jul 2016Bacterial flagellin is a unique pathogen-associated molecular pattern (PAMP), which can be recognized by surface localized Toll-like receptor 5 (TLR5) and the cytosolic...
Bacterial flagellin is a unique pathogen-associated molecular pattern (PAMP), which can be recognized by surface localized Toll-like receptor 5 (TLR5) and the cytosolic NOD-like receptor (NLR) protein 4 (NLRC4) receptors. Activation of the TLR5 and/or NLRC4 signaling pathways by flagellin and the resulting immune responses play important roles in anti-bacterial immunity. However, it remains unclear how the dual activities of flagellin that activate the TLR5 and/or NLRC4 signaling pathways orchestrate the immune responses. In this study, we assessed the effects of flagellin and its mutants lacking the ability to activate TLR5 and NLRC4 alone or in combination on the adaptive immune responses against flagellin. Flagellin that was unable to activate NLRC4 induced a significantly higher antibody response than did wild-type flagellin. The increased antibody response could be eliminated when macrophages were depleted in vivo. The activation of NLRC4 by flagellin downregulated the flagellin-induced and TLR5-mediated immune responses against flagellin.
Topics: Animals; Antibody Formation; Antibody Specificity; Apoptosis Regulatory Proteins; Calcium-Binding Proteins; Cell Death; Down-Regulation; Female; Flagellin; Interleukin-18; Interleukin-1beta; Macrophages; Mice, Inbred BALB C; Recombinant Proteins; Signal Transduction; Toll-Like Receptor 5
PubMed: 25914934
DOI: 10.1038/cmi.2015.33 -
The Journal of Experimental Medicine Oct 1953The ability of an adjuvant and its individual constituents to induce the production of Cx-reactive protein in rabbits has been studied. It was found that the adjuvant...
The relationship between the acute phase response and antibody production in the rabbit. II. The stimulation of Cx-reactive protein response by certain adjuvants and the relation of this response to the enhancement of antibody formation.
The ability of an adjuvant and its individual constituents to induce the production of Cx-reactive protein in rabbits has been studied. It was found that the adjuvant stimulated rabbits to produce large amounts of the acute phase protein for 3 to 6 days. Melted aquaphor blended with saline stimulated the production of Cx-reactive protein for 3 or 4 days. Mineral oil was less effective in stimulating the production of the protein than either adjuvant or aquaphor. Heat-killed Jamaica strain tubercle bacilli suspended in mineral oil did not induce the Cx-protein response. The ability of subcutaneously administered adjuvant without antigen incorporated in the saline phase to potentiate the antibody response of rabbits to the intravenously administered antigens, C-reactive protein and human gamma globulin, was investigated. It was found that the adjuvant-treated animals produced more precipitating antibody to the two intravenously administered antigens than did the control animals given intravenous antigen alone.
Topics: Acute-Phase Reaction; Adjuvants, Immunologic; Animals; Antibodies; Antibody Formation; Antigens; C-Reactive Protein; Proteins; Rabbits
PubMed: 13096658
DOI: 10.1084/jem.98.4.321 -
Microbes and Infection Dec 1999Natural killer (NK) cells are a third lymphocyte population especially important in innate immunity. NK cells may also have an important role in the regulation of... (Review)
Review
Natural killer (NK) cells are a third lymphocyte population especially important in innate immunity. NK cells may also have an important role in the regulation of acquired immunity. These lymphocytes spontaneously produce large amounts of both active and latent transforming growth factor-beta (TGF-beta). NK-cell-derived TGF-beta1 enabled activated CD8(+) T cells to inhibit antibody production by blocking the induction of this response. Production of lymphocyte-derived TGF-beta is decreased in systemic lupus erythematosus. Insufficient levels of this cytokine in SLE and other autoimmune diseases may contribute to defective T regulatory cell function characteristic of this and other autoimmune diseases. NK cells are found in mucosal tissues and the TGF-beta spontaneously released by these cells could contribute to the usual tolerogenic response of T cells to antigens presented at these sites. Thus, in addition to its well known immunosuppressive effects, TGF-beta could have an equally important role in the generation of regulatory T cells.
Topics: Animals; Antibody Formation; Autoimmune Diseases; Humans; Killer Cells, Natural; Mice; T-Lymphocytes; Transforming Growth Factor beta
PubMed: 10611759
DOI: 10.1016/s1286-4579(99)00253-1 -
Bioscience Reports Jan 2019The reductionist approach is prevalent in biomedical science. However, increasing evidence now shows that biological systems cannot be simply considered as the sum of...
The reductionist approach is prevalent in biomedical science. However, increasing evidence now shows that biological systems cannot be simply considered as the sum of its parts. With experimental, technological, and computational advances, we can now do more than view parts in isolation, thus we propose that an increasing holistic view (where a protein is investigated as much as a whole as possible) is now timely. To further advocate this, we review and discuss several studies and applications involving allostery, where distant protein regions can cross-talk to influence functionality. Therefore, we believe that an increasing big picture approach holds great promise, particularly in the areas of antibody engineering and drug discovery in rational drug design.
Topics: Allosteric Regulation; Antibody Formation; Drug Discovery; Humans; Immunoglobulins; Protein Engineering
PubMed: 30630879
DOI: 10.1042/BSR20181958 -
The Journal of Experimental Medicine Sep 1959When rabbits were fed S(35)-labelled amino acids and simultaneously injected with antigen at the peak of antibody production, the circulating antibody became rapidly...
When rabbits were fed S(35)-labelled amino acids and simultaneously injected with antigen at the peak of antibody production, the circulating antibody became rapidly labelled within a few hours with the isotope. The specific radioactivity of antibody was measured as antibody was allowed to decline in the absence of antigenic stimulation. At various times, in different animals, antigen was reinjected and circulating antibody was measured for specific radioactivity. The initial antibody which appeared after the antigenic stimulus always had a higher specific activity than antibody circulating just prior to the reinjection. The appearance of antibody of higher specific activity was demonstrated to be a specific response to the antigen which was reinjected. It was concluded that there is a reservoir of antibody which is stabilized in tissue and which is not in equilibrium with that in circulation. A mechanism for this stabilization is suggested and discussed from previous investigations demonstrating the long retention of antigen in liver tissue.
Topics: Animals; Antibodies; Antibody Formation; Antigens; Liver; Rabbits
PubMed: 13826708
DOI: 10.1084/jem.110.3.355 -
The Keio Journal of Medicine Mar 1999More than 20 years have passed since the concept that the skin has its own associated immune system was first proposed by Streilein. This proposal was advanced in part... (Review)
Review
More than 20 years have passed since the concept that the skin has its own associated immune system was first proposed by Streilein. This proposal was advanced in part on evidence that cutaneous contact hypersensitivity (CH) reactions are closely correlated with Langerhans cells (LC). Recent reports have demonstrated that LC have neural connectivity with cutaneous nerve termini containing calcitonin gene-related peptide (CGRP), suggesting that a link exists between innervation and immune responses in the skin. Here we discuss the neural components which have recently been found to be participants in skin-associated lymphoid tissue (SALT). In part, discovery of a functional link between the nervous system and SALT is based on studies in which cutaneous immunity was impaired by ultraviolet-B radiation (UVR). The deleterious effects of UVR on cutaneous immunity include failed CH induction and promotion of hapten-specific tolerance, effects that are mediated by tumor necrosis factor-alpha and interleukin-10, respectively. The source of these cytokines after UVR appears to be dermal mast cells. Evidence indicates that mast cells are triggered to release these cytokines in response to CGRP, which is released from UVR-damaged cutaneous nerve endings. Moreover, a substance P agonist was able to reverse the deleterious effects of UVR on CH induction, rendering the mice able to develop intense CH. These observations indicate that two cell types not originally included in the SALT concept are critical to the functional integrity of cutaneous immunity: mast cells and cutaneous nerves. We propose that cutaneous nerves dictate whether antigen applied to or arising within skin will lead to sensitivity or tolerance.
Topics: Animals; Antibody Formation; Lymphoid Tissue; Mice; Skin; Ultraviolet Rays
PubMed: 10206015
DOI: 10.2302/kjm.48.22 -
American Journal of Transplantation :... Jul 2017
Topics: Antibody Formation; Antilymphocyte Serum; Islets of Langerhans; Risk Factors; Tissue Donors
PubMed: 28251813
DOI: 10.1111/ajt.14253