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فیلم برداری از چگونگی از بین رفتن باکتری ها به کمک سیستم ایمنی

سیستم ایمنی و باکتری‌ها

یکی از اصلی‌ترین استراتژی‌های برخورد سیستم ایمنی با باکتری‌های مهاجم ایجاد حفرات متعدد در پوشش آنها است که در نهایت منجر به مرگ باکتری خواهد شد. جزئیات ایجاد این حفره‌ها که اندازه‌ای در حدود 10nm دارند به دلیل اندازه بسیار کوچک و پیچیدگی‌های فراوان تاکنون ناشناخته بود.
ایجاد مدل مشابه پوشش باکتری‌ها و تصویر برداری‌های دقیق و پی در پی با استفاده از میکروسکوپ اتمی (atomic force microscopy) بسیاری از زوایای پنهان این فرایند را آشکار می‌کند. کمپلکس پروتئینی موجود در سطح سلول‌های ایمنی که کمپلکس حمله کننده به غی membrane attack complex نام دارد از 18 پروتئین مختلف تشکیل می‌شود. بعد از ایجاد نخستین حفره در باکتری توسط یکی از زیرواحدهای کمپلکس به نام C9 سیسم ایمنی مکث کوتاهی خواهد کرد. این مکث که در ابتدا توجیه ناپذیر می‌نمود در واقع مرحله اصلی در تمیز سلول‌های خودی است، به این ترتیب که وجود گیرنده‌های CD59 یکی از عوامل تشخیص سلول‌های خودی و پراکندگی کمپلکس است و در نبود آن سایر اعضای کمپلکس نیز با سرعت فراوان حفره‌های بعدی را ایجاد می‌کنند.
یافته‌های جدید علاوه بر آشکار کردن یکی از مهمترین مکانیسم‌های ایمنی بدن نقش مهمی در افزایش اختصاصیت مداخلات انسانی خواهد داشت.

Filming how our immune system kills bacteria

Date: May 6, 2019
Source: University College London

Summary:
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets. Scientists have now filmed these nanomachines in action, discovering a key bottleneck in the process which helps to protect our own cells.

To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets. UCL scientists have now filmed these nanomachines in action, discovering a key bottleneck in the process which helps to protect our own cells.

immune system against bacterial infections

The research, published in Nature Communications, provides us with a better understanding of how the immune system kills bacteria and why our own cells remain intact. This may guide the development of new therapies that harness the immune system against bacterial infections, and strategies that repurpose the immune system to act against other rogue cells in the body.

In earlier research, the scientists imaged the hallmarks of attack in live bacteria, showing that the immune system response results in ‘bullet holes’ spread across the cell envelopes of bacteria. The holes are incredibly small with a diameter of just 10 nanometres — about 1/10,000 of the width of a human hair.

membrane attack complex | MAC

For this study, the researchers mimicked how these deadly holes are formed by the membrane attack complex (MAC) using a model bacterial surface. By tracking each step of the process, they found that shortly after each hole started to form, the process stalled, offering a reprise for the body’s own cells.

“It appears as if these nanomachines wait a moment, allowing their potential victim to intervene in case it is one of the body’s own cells instead of an invading bug, before they deal the killer blow,” explained Dr Edward Parsons (UCL London Centre for Nanotechnology).

The team say the process pauses as 18 copies of the same protein are needed to complete a hole. Initially, there’s only one copy which inserts into the bacterial surface, after which the other copies of the protein slot into place much more rapidly.

“It is the insertion of the first protein of the membrane attack complex which causes the bottleneck in the killing process. Curiously, it coincides with the point where hole formation is prevented on our own healthy cells, thus leaving them undamaged,” said Professor Bart Hoogenboom (UCL Physics & Astronomy).

To film the immune system in action at nanometre resolution and at a few seconds per frame, the scientists used atomic force microscopy. This type of microscopy uses an ultrafine needle to feel rather than see molecules on a surface, similar to a blind person reading Braille. The needle repeatedly scans the surface to produce an image that refreshes fast enough to track how immune proteins get together and cut into the bacterial surface.

The research was led by UCL, and carried out in close collaboration with scientists from Imperial College London, from the Swiss Federal Institute of Technology in Lausanne, and from the University of Leeds.
The work was kindly funded by the Biotechnology and Biological Sciences Research Council, Medical Research Council, Engineering and Physical Sciences Research Council and the European Union.

Story Source:
Materials provided by University College London. Note: Content may be edited for style and length.

Journal Reference:
Edward S. Parsons, George J. Stanley, Alice L. B. Pyne, Adrian W. Hodel, Adrian P. Nievergelt, Anaïs Menny, Alexander R. Yon, Ashlea Rowley, Ralf P. Richter, Georg E. Fantner, Doryen Bubeck, Bart W. Hoogenboom. Single-molecule kinetics of pore assembly by the membrane attack complex. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-10058-7

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