مروری بر مکانیسم‎های دخیل در ایمونوپاتوژنز ویروس SARS-CoV-2

نوع مقاله : مروری

نویسندگان

1 دانشگاه بقیه الله

2 دانشگاه تهران

3 مرکز تحقیقات ویروس شناسی بالینی، دانشگاه علوم پزشکی تهران، تهران، ایران

چکیده

کروناویروس‎ها به خانواده کرونا ویریده تعلق داشته و سه ویروس بیماری زای SARS-CoV، MERS-CoV و SARS-CoV-2 جزء این خانواده محسوب می­شوند. هر سه ویروس باعث ایجاد اختلالات تنفسی در انسان میگردند. SARS-CoV-2 یک RNA ویروس با اندازه حدود  nm160-80 و سایز ژنومی حدود  kb35-27 می‎باشد که بیماری COVID-19 را ایجاد می‎کند. علایم ابتلا به این بیماری شامل تب، سرفه خشک، خستگی، ضعف عضلانی، تنگی نفس، خلط، سردرد و اسهال می باشد. مطالعات مختلف نشان داده‎اند با انتقال ویروس SARS-CoV-2 از طریق گیرنده ACE2 سطح سلول‎های آلوئولار نوع دو و CD147 سلول‎های ریوی، سه اتفاق اصلی شامل اختلالات تنفسی، لنفوپنی و طوفان سایتوکاینی رخ می‎دهد که به دلیل عدم تنظیم پاسخ‎های التهابی سیستم ایمنی و افزایش ناگهانی تولید سایتوکاین‎ها موارد پنومونی، از دست رفتن عملکرد ریه، سندرم زجر تنفسی حاد (ARDS)، شوک و حتی مرگ اتفاق می‎افتد. گیرنده‎های سیستم ایمنی ذاتی شامل TLR3 و TLR7 (گیرنده‎های اندوزومال) و RIG-I و MDA-5 (گیرنده‎های سیتوزولی) نقش مهمی در شناسایی RNA، ویروس SARS-CoV-2 دارند. درگیر شدن این گیرنده‎ها موجب تولید انواع مختلف سایتوکاین‎ها، اینترفرون‎های تیپ 1 و مدیاتورهای التهابی می‎شوند. در ارتباط با سیستم ایمنی اکتسابی-سلولی لنفوسیت‎های Th1، Th2 و Th17 با تولید سایتوکاین، لنفوسیت‎های T CD8+ (CTL) با تولید پرفورین، گرانزیم و سایتوکاین نقش دفاعی خود را علیه ویروس SARS-CoV-2  ایفا می‎کنند. فعالیت ایمنی اکتسابی-هومورال در اغلب بیماران با تولید IgM (حدود 9 روز بعد از شروع بیماری) و IgG (حدود 2 هفته بعد از شروع بیماری) مشخص می‎شود. ویروس SARS-CoV-2 از مکانیسم هایی شامل ایجاد اختلال در تولید اینترفرون های نوع I، کاهش بیان MHC-I، MHC-II و افزایش بیان Tim-3 و PD-1 و القای خستگی در لنفوسیت‎های T (T cell exhaustion) برای فرار از پاسخ‎های سیستم ایمنی استفاده می‎کند. در این مطالعه مروری، جدیدترین اطلاعات مرتبط با مکانیسم‎های دخیل در ایمونوپاتوژنز ویروس‎های تنفسی به ویژه SARS-COV-2 نگارش شده است.

کلیدواژه‌ها


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