Publications by authors named "Heinz Kohler"

Immune Jumping in Autoimmune Long-Covid.

Monoclon Antib Immunodiagn Immunother

October 2024

This Long-Covid disease, mild or severe, is multiorgan or system-wide, spanning from fatigue to clotting abnormalities and autoantibody. The spectrum of different symptoms in Long-Covid diseases makes it difficult to point to a common immunopathogenic etiology. Different immune pathways are presented and critically evaluated.

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In view of the tremendous emissions of toxic gases and particulate matter (PM) by low-power firewood-fueled fireplaces, there is an urgent need for effective measures to lower emissions to keep this renewable and economical source for private home heating available in the future. For this purpose, an advanced combustion air control system was developed and tested on a commercial fireplace (HKD7, Bunner GmbH, Eggenfelden, Germany), complemented with a commercial oxidation catalyst (EmTechEngineering GmbH, Leipzig, Germany) placed in the post-combustion zone. Combustion air stream control of the wood-log charge combustion was realized by five different control algorithms to describe all situations of combustion properly.

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The quality of wood combustion processes can be effectively improved by achieving the automated control of the combustion air feed. For this purpose, continuous flue gas analysis using in situ sensors is essential. Besides the successfully introduced monitoring of the combustion temperature and the residual oxygen concentration, in this study, in addition, a planar gas sensor is suggested that utilizes the thermoelectric principle to measure the exothermic heat generated by the oxidation of unburnt reducing exhaust gas components such as carbon monoxide (CO) and hydrocarbons (CH).

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What Can We Learn from Research with Monoclonal Antibody 1F7?

Monoclon Antib Immunodiagn Immunother

December 2022

1F7 is a monoclonal antibody that recognizes an idiotypic determinant expressed on primate antibodies binding to HIV-1 and hepatitis C proteins. This monoclonal antibody was used as a tool to dissect the immune response in humans infected with HIV-1 and hepatitis B. Furthermore, 1F7 was also used to manipulate the immune response against HIV-1 in macaques.

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The PubMed data set was scanned with the title and abstract term "Idiotype" followed by secondary searches with "Vaccine" and "Clinical trial." The retrieved references were analyzed from the period before and after hybridoma technology (1975). In 1963, Oudin and Kunkel discovered that antibodies against antibodies can be raised to identify determinants unique to an antibody termed idiotype or individual antigenic determinant.

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In this report we provide a hypothesis of how intravenous immunoglobulin (IvIg) (pooled therapeutic normal IgG) mitigates the severe disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The disease is caused by an overreaction of the innate immune system producing a cytokine storm and inflicting multiple organ damage. Our interpretation of IvIg therapy hinges on a recent analysis of the immune dysregulation in Covid-19 infection.

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In this hypothesis, we address the biological/immunological pathway leading to severe disease or death after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune response is described with "original antigenic sin" (OAS) whereby previous infections influence the response to future virus encounters. We cite evidence for OAS-induced immunopathology in HIV-1 disease.

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The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines.

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Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding.

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Natural antibodies have diverse functions in maintaining immune homeostasis and in the regulation of autoimmune response. Yet there might be other important functions of natural antibodies for human medicine such as the ability of natural antibodies to shape and induce antibody immune responses. I propose that natural antibodies, present in IVIG, could be used to prevent autoimmune reactions and to enhance the immune response to vaccination.

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The homophilic potential emerges as an important biological principle to boost the potency of immunoglobulins. Since homophilic antibodies in human and mouse sera exist prior environmental exposure, they are part of the natural antibody repertoire. Nevertheless, hemophilic properties are also identified in induced antibody repertoire.

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In this review, we trace the concept and potential functional role of regulatory idiotypes in the immune response to human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus, and hepatitis C virus (HCV). A major idiotype involved in these viral infections is recognized and defined by a murine monoclonal antibody (1F7). Antibodies expressing the idiotype defined by 1F7 are dominant in HIV-1 infection and are also found on many broadly neutralizing antibodies against HIV-1.

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A novel vaccine concept is discussed based on recent evidence of a "back-boost" effect in Influenza infection. The initial immune response to the infection is imprinted through an immune memory pathway. The immune memory in the back-boost mechanism could be used in reversed order as a "forward-boost" in the proposed vaccine concept.

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The present work describes a field survey aiming at assessing the impact of a sewage treatment plant (STP) effluent on fish health by means of biomarkers. Indigenous fish were absent downstream of the STP. To elucidate the reason behind this, brown trout (Salmo trutta f.

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MoO3 nanostructures have been grown in thin film form on five different substrates by RF magnetron sputtering and subsequent annealing; non-aligned nanorods, aligned nanorods, bundled nanowires, vertical nanorods and nanoslabs are formed respectively on the glass, quartz, wafer, alumina and sapphire substrates. The nanostructures formed on these substrates are characterized by AFM, SEM, GIXRD, XPS, micro-Raman, diffuse reflectance and photoluminescence spectroscopy. A detailed growth model for morphology alteration with respect to substrates has been discussed by considering various aspects such as surface roughness, lattice parameters and the thermal expansion coefficient, of both substrates and MoO3.

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Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic's epicenter in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We identified one correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer Ab production and neonatal FcR-mediated concentration of these Abs on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry.

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We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium.

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A homophilic peptide from the T15 plasmacytoma inhibits growth of murine and human B cell tumors. This finding confirms the hypothesis that B cell malignancies are driven by a self-binding epitope in the B cell receoptor (BCR) proposed as the pathogenesis of chronic lymphocytic leukemia (CLL).

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Antibodies (Abs) induced during infections with immunodeficiency viruses are subject to a form of original antigenic sin, termed repertoire freeze. This phenomenon encompasses conditions in which antigen (Ag)-specific B-cells and free Ab induced against early viral variants recognize viral escape mutants sufficiently to compete for Ag with naïve B-cells. As previously activated Ag-specific Abs and B-cells are more abundant than their naïve counterparts, they out-compete naïve B-cells and can be selected to undergo repeated rounds of somatic hypermutation and affinity maturation that drive repeated rounds of immune selection and viral escape.

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This review recalls the history of homophilic antibody discovery and adaptation for cancer immunotherapy. Homophilic antibodies are a rare type of murine monoclonal antibody produced by plasmacytomas. They are self-binding in solid-phase assays and, in solution, are in an equilibrium of monomers and dimers.

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A basic tenet of antibody-based immunity is their specificity to antigenic determinates from foreign pathogen products to abnormal cellular components such as in cancer. However, an antibody has the potential to bind to more than one determinate, be it an antigen or another antibody. These observations led to the idiotype network theory (INT) to explain immune regulation, which has wax and waned in enthusiasm over the years.

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Previously we increased the potency of therapeutic antibodies in targeting, induction of apoptosis, and growth inhibition in vitro and in vivo by chemically conjugating a homophilic peptide to the antibody. Here, we describe the construction of a chimeric fusion gene derived from the murine anti-CD20 antibody (1F5) variable region, with an engineered homophilic domain at the C-terminus of the human IgG1 sequence. The construct was expressed in CHO suspension cells and purified.

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Aim: To evaluate the ability of anti-ricin A-chain antibodies, delivered intracellularly, to protect against ricin-induced cytotoxicity in RAW264.7 cells.

Methods: Anti-deglycosylated ricin A-chain antibody and RAC18 anti-ricin A-chain monoclonal antibody were delivered intracellularly by encapsulating in liposomes or via conjugation with the cell-penetrating MTS-transport peptide.

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