The history of IgG glycosylation and where we are now.

IgG glycosylation is currently at the forefront of both immunology and glycobiology, likely due in part to the widespread and growing use of antibodies as drugs. For over four decades, it has been recognized that the conserved N-linked glycan on asparagine 297 found within the second Ig domain of the heavy chain (CH2) that helps to comprise Fc region of IgG plays a special role in IgG structure and function. Changes in galactosylation, fucosylation and sialylation are now well-established factors, which drive differential IgG function, ranging from inhibitory/anti-inflammatory to activating complement and promoting antibody-dependent cellular cytotoxicity. Thus, if we are to truly understand how to design and deploy antibody-based drugs with maximal efficacy and evaluate proper vaccine responses from a protective and functional perspective, a deep understanding of IgG glycosylation is essential. This article is intended to provide a comprehensive review of the IgG glycosylation field and the impact glycans have on IgG function, beginning with the earliest findings over 40 years ago, in order to provide a robust foundation for moving forward.

[Pooled Human Immunoglobulin Preparations as Immunomodulating Drugs].

It is time to celebrate the 125th anniversary of the first successful attempt to develop and use a specific high-titer antitoxic serum for treating diphtheria, a deadly infectious disease. This was followed by major advances in passive immunotherapy 75 years ago (production of pooled human IgG for subcutaneous injection) and 50 years ago (widespread technology for producing immunoglobulin preparations for intravenous administration). More than 200 tons of pooled human IgG are produced per year worldwide. The preparation is used primarily for IgG substitution in patients with primary and secondary immunodeficiencies, as well as for an immunomodulating treatment of a growing number of autoimmune and inflammatory diseases. These preparations contain the pooled IgG antibody repertoire of a large population of healthy plasma donors. This repertoire includes antibodies that neutralize pathogens and their factors of virulence, anti-idiotypic antibodies, and antibodies to other foreign and own proteins, as well as to carbohydrate antigens. Naturally polyspecific antibodies that are present in all healthy individuals play an important role as a first-line defense against bacteria and viruses. After exposure to protein-modifying agents, some IgG molecules can acquire the ability to bind novel structurally unrelated antigens. This phenomenon is referred to as induced polyspecificity. The list of these protein-modifying molecules was shown to include low-pH buffers, free heme, pro-oxidative ferrous ions, reactive oxygen species, etc. Such modified antibody preparations may have a therapeutic potential, since their administration to animals with experimental sepsis or aseptic systemic response syndromes significantly improved survival rates, while the same dose of the native preparation had no effect. We also hypothesize that the aggressive protein-modifying molecules released in sites of inflammation and tissue damage could also modify the antigen-binding behavior of surface immunoglobulin B cell receptors and the structurally related T cell receptors. This "specificity editing" of both types of receptors may play a major role in the body's defense mechanisms.

The search for an endogenous schizogen: the strange case of taraxein.

In 1956, Dr. Robert Galbraith Heath, Chair of Psychiatry and Neurology at Tulane University School of Medicine in New Orleans, announced that he and colleagues had discovered a protein they called taraxein in the blood of schizophrenic patients that caused symptoms of schizophrenia when injected into healthy volunteers. Heath's claim received wide public and professional attention. Researchers quickly tried to confirm the discovery. These efforts, which were rigorous and in some cases conducted in consultation with the Tulane researchers, failed. Nevertheless, for the next four decades Heath continued to defend his claim. This article recounts the scientific developments that led up to Heath's putative discovery and it explores the scientific findings for and against the taraxein theory of schizophrenia.

Phages, antibodies and de-monstration.

Using examples from the field of molecular genetics and immunology, this paper examines the argumentative strategy underlying the use of electron micrographs as decisive evidence for previously uncertain or disputed claims. Scientists often resort to visual imagery in order to demonstrate the factual status of their claims and thus to compel assent from their peers, therefore bypassing other forms of argumentation such as propositional reasoning. The particular form of demonstration discussed in this article resorts to the use of photography rather than drawings and diagrams. While the mechanical objectivity of micrographs certainly adds to their evidential strength, the pictures we examine derive part of their power from their arrangement in a sequence that mimics experimental operations. The visual argument tracks the textual report of the steps in a biochemical or molecular genetic experiment, with which it becomes intimately associated. We conclude that much of the evidential strength conveyed by the articles we analyze is to be sought less in the extrinsic attributes of the instrumentation they mobilized than in the specific material and argumentative practices enacted by those particular uses of the instrument.

Finally! The Brambell receptor (FcRB). Mediator of transmission of immunity and protection from catabolism for IgG.

F. W. Rogers Brambell was the father of the field of transmission of immunity, which he entered 50 years before the present era. As part of his quantitative and temporal studies on transmission, he defined the first Fc receptor system for IgG, and furthermore recognized the link between transmission of passive immunity from mother to young and protection from catabolism for IgG. This article provides a historical overview of the efforts of Professor Brambell and summarizes the subsequent elaboration of the details of the physiology and molecular biology of this remarkable receptor system.