Mechanisms of immunosensitization to metals (IUPAC Technical Report)

Moehle

2014

Humoral immunity allows the body to mount a defense against pathogens and foreign substances, and to respond with memory to subsequent exposures. The molecular participants may also recognize selfstructures, leading to attack on the body and autoimmune disease. The main players in humoral immunity are antibody-producing B lymphocytes, and several classes of T lymphocytes. This review deals with the molecular details of recognition of antigens by soluble antibodies, and of substances presented to receptors on the surfaces of T cells (TCRs). The prototype antibody consists of a dimer of dimers, two heavy (H) chains and two light (L) chains, with antigen recognition capacity lying in variable "head" regions of an H-L pair. Most crystallographic studies are done with this substructure, called a F ab fragment, bound in a soluble antigen complex. Homologous to this arrangement, the prototype TCR consists of two chains (α and β) that complex not soluble antigen, but usually a short peptide or other small molecule presented by proteins of the major histocompatibility complex. In each case a general background on the historical development of understanding the molecular recognition interface is given, followed by a number of examples of crystal structures from the recent literature that have allowed us to refine our understanding of the complex recognition process. Variations on the prototypical structures are also considered. The spectrum of recognition strategies involves interplay of lock-and-key with flexibility, varying degrees of entropic and enthalpic contributions, surface shaping by entrapped water molecules, and combinations of stabilizing hydrogen bonding, electrostatic interactions, salt bridging, and van der Waals forces. Preeminent in the recent literature are details of antibody binding to influenza A and human immunodeficiency viral antigens. Both viral antigens and attempts to understand autoimmunity are prominent in the recent TCR literature.

Section: Metal Ion Recognitionmentioning

confidence: 99%

Structural aspects of molecular recognition in the immune system. Part I: Acquired immunity (IUPAC Technical Report)

Moehle

2014

“…Nickel is the most common immunosensitizer of all metals [56]. In the past, nickel allergies were observed mainly in the workplace.…”

Section: Nickelmentioning

confidence: 99%

Lymphocyte subpopulations in human exposure to metals (IUPAC Technical Report)

Schwenk¹,

Klein

2008

Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without theAbstract: Numerous species of metal ions cause immunosensitization in humans. Possible approaches to determine those occupational and environmental exposures to metals that result in immunological changes include lymphocyte transformation assay, cytokine profiling, and measurement of lymphocyte subpopulations. In two previous papers, we considered lymphocyte transformation assay [1] and cytokine profiling [2]. Here we review the effects of exposures to metals on lymphocyte subpopulations. Specific consideration is given to beryllium, chromium, cobalt, nickel, palladium and platinum, cadmium, gold, mercury, and lead. Analysis of the scientific literature shows that immunosensitizing metals may have influences on the lymphocyte subset composition, but only in a few instances does exposure to metals cause reproducible shifts of lymphocyte subpopulations. If lymphocyte subpopulations are analyzed, each diagnostic step, including indication, sample handling, analytic procedure, and data interpretation, should adhere to good quality assurance and quality control.

“…Cobalt, another sensitizing metal [54], occurs together with Cr in alloys used for prosthetic devices. Cytokine production was studied in PBMCs retrieved from patients with loosening Co/Cr-alloy hip prostheses [59].…”

Section: Cobaltmentioning

confidence: 99%

Cytokine profiles in human exposure to metals (IUPAC Technical Report)

Klein

Schwenk

2006

Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without the need for formal IUPAC permission on condition that an acknowledgmentAbstract: Immunosensitization to metal ions through occupational and environmental exposure has been described in earlier papers from this project. Here we discuss the possible role of cytokine profiling in demonstrating and understanding this phenomenon. The cytokines are a large family of polypeptides exerting autocrine, paracrine, and/or endocrine effects. They include interleukins (ILs), interferons (IFNs), and growth factors. They may be grouped as pro-inflammatory (e.g., IL-1, IL-6, IL-12, IL-18, TNF-α), anti-inflammatory (e.g., IL-10), or those regulating T-helper (TH) cell function. The latter are subdivided into those associated with TH1 (e.g., IL-2, IL-12, IFN-γ, TNF-β) or TH2 (e.g., IL-4, IL-5, IL-13) cell function. Because different types of immune reactions (e.g., immediate reaction vs. delayed-type hypersensitivity) differentially involve TH1 and TH2 cells, measurement of cytokine production in response to metal ions can potentially give insight into underlying immune mechanisms and responses. Examples are given for species of Ni, Cr, Co, Hg, Cd, and Be; and in less detail for species of Fe, Pt, Pd, and Rh. Antibodies are available commercially that allow for the determination of many cytokines, and such measurements are most usefully performed with body fluids, supernatants from stimulated lymphocyte cultures, or lysates of lymphocytes or other biopsied cells. The predominant methods include enzyme-linked immunosorbent assay (ELISA) and flow cytometric measurement of the cytokine, bioassay of its activity in cell culture, and polymerase chain reaction (PCR) assessment of its mRNA level. In practice, levels of individual cytokines are highly variable between individuals, and reliable reference values are generally lacking. Ratios of cytokines are more informative than absolute concentrations, and biological variability in cytokine production dictates that repeated testing is necessary to confirm trends. Determining cytokine profiles is presently of questionable diagnostic utility in individual cases of metal sensitization, but is providing mechanistic insights in a research context.