• Fintetuning for antibodies

    From ScienceDaily@1337:3/111 to All on Fri Jul 14 22:30:26 2023
    Fintetuning for antibodies
    The strength of the immune reaction triggered by antibodies can be
    regulated

    Date:
    July 14, 2023
    Source:
    Friedrich-Alexander-Universita"t Erlangen-Nu"rnberg
    Summary:
    Antibodies are crucial, not only for treating tumors and infections.

    Sometimes, however, the immune reaction they trigger can be too
    strong and end up causing more damage, for example in the case of
    people infected with Covid-19. Problems such as these can often
    be avoided by finetuning antibodies, according to new research.


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    ==========================================================================
    FULL STORY ========================================================================== Antibodies are crucial, not only for treating tumors and
    infections. Sometimes, however, the immune reaction they trigger can
    be too strong and end up causing more damage, for example in the case
    of people infected with Covid-19. Problems such as these can often be
    avoided by finetuning antibodies, as Prof. Dr. Falk Nimmerjahn from Friedrich-Alexander-Universita"t Erlangen-Nu"rnberg (FAU) and two of
    his colleagues in the Netherlands and in the UK have now reported in thejournal_Nature_Immunology.

    In his laboratories, the FAU researcher is carrying out research into immunoglobulin G, or IgG in short, that provides long-lasting protection against infection in the bodies of humans and animals. These biomolecules
    that are often used in modern medicine consist of two long and two short
    chains of proteins that link together to form a Y-shaped structure. For
    many years, research and medicine has focused on the two top branches of
    this Y for good reason: the two ends form a type of pocket which smaller structures on the surface of bacteria and other pathogens fit into,
    similarly to a key in a lock.

    Key-lock principle in immune system Just like a locksmith can produce
    very many different locks and the matching keys by only making a few
    slight changes, the immune system also produces very many different
    structures at the ends of immunoglobulins that match to very many
    different pathogens. After an infection with a specific bacterium or
    virus, these IgG created during the immune reaction remain on patrol
    within the body for a very long time and can react extremely rapidly in
    the case of a renewed infection.

    If the key fits the lock, the immunoglobulin attaches to the pathogen
    and marks it for other immune specialists within the immune system. The antibody serves to mark tumor cells or pathogens to make them stand
    out from the huge quantities of cells and harmless microorganisms that circulate throughout the body and take on important functions in the
    bodies of humans and animals.

    Using genetic glue to fight bacteria Once this stage has been
    successfully completed, this is when the backbone of the Y-shaped
    IgG comes into play. It is this backbone that Falk Nimmerjahn is now investigating closely at his Chair of Genetics. Macrophages, killer
    cells and granulocytes take over in the end phase of the battle against
    an infection.

    "We have often observed cells working as a team, with granulocytes
    taking on a suicidal role;" Falk Nimmerjahn explains. Attracted by the
    antibody that has found its target, these cells burst, releasing their relatively sticky genetic material from their core. The bacteria that
    the IgG previously identified as being harmful stick to this matter.

    These microorganisms can be extremely dangerous, but have now been
    rendered helpless, and are easy prey for the macrophages that have also
    been attracted and can now consume the bacteria that the antibodies
    have tracked down and marked. However, the macrophages are often rather aggressive and act with little consideration of possible consequences. If
    time is running out in the race between life and death, collateral damage
    is accepted as being unavoidable, and substances such as oxygen radicals
    and other dangerous products that would normally be rendered harmless are released. For most patients this is of no consequence: The main priority
    is survival, any resulting damage should be able to be repaired later.

    One of the factors modulating the immune reaction involves small posttranslational modifications that are made to the backbone of the immunoglobulin after the antibody has been created. This involves,
    for example, little sugar molecules that are attached to the backbone
    of the immunoglobulin.

    They seem to play a crucial role in the finetuning of the immune
    reaction. "If the right components are missing, it makes the immune
    reaction much more severe," explains Falk Nimmerjahn.

    That can, however, have fatal consequences, for example if a viral
    infection has already severely damaged tissue. If the control mechanism
    on the backbone of the immunoglobulin is adjusted to only attach a little
    sugar and therefore induce a strong reaction, that may cause dangerously
    severe damage to an organ that is already stretched to its limit, such as
    the lung in the event of a viral infection. According to Falk Nimmerjahn,
    "the organism therefore adjusts its control mechanisms very exactly." In
    cases such as this, the control mechanisms are set to trigger a weak
    reaction with many chains of sugar.

    Gaining an exact knowledge of this antibody tuning within the context
    of an immune response is fundamental if we are to improve and increase patients' tolerance of antibodies used to treat tumors and autoimmune
    diseases.

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    Materials provided by Friedrich-Alexander-Universita"t_Erlangen-Nu"rnberg.

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    ========================================================================== Journal Reference:
    1. Falk Nimmerjahn, Gestur Vidarsson, Mark S. Cragg. Effect of
    posttranslational modifications and subclass on IgG activity:
    from immunity to immunotherapy. Nature Immunology, 2023; DOI:
    10.1038/s41590- 023-01544-8 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2023/07/230714114736.htm

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