مروري بر مكانيسمهاي دخيل در ايمونوپاتوژنز ويروس SARS-CoV-2

A Review of the Mechanisms Involved in the Immunopathogenesis of SARS-CoV-2

ﮐﺮوﻧﺎوﯾﺮوسﻫﺎ ﺑﻪ ﺧﺎﻧﻮاده ﮐﺮوﻧﺎ وﯾﺮﯾﺪه ﺗﻌﻠﻖ داﺷﺘﻪ و ﺳﻪ وﯾﺮوس ﺑﯿﻤﺎري زاي MERS-CoV ،SARS-CoV و 2-SARS-CoV ﺟﺰء اﯾﻦ ﺧﺎﻧﻮاده ﻣﺤﺴﻮب ﻣﯽﺷﻮﻧﺪ. ﻫﺮ ﺳﻪ وﯾﺮوس ﺑﺎﻋﺚ اﯾﺠﺎد اﺧﺘﻠﺎﻟﺎت ﺗﻨﻔﺴﯽ در اﻧﺴﺎن ﻣﯽﮔﺮدﻧﺪ. 2-SARS-CoV ﯾﮏ RNA وﯾﺮوس ﺑﺎ اﻧﺪازه ﺣﺪود nm 80-160 و ﺳﺎﯾﺰ ژﻧﻮﻣﯽ ﺣﺪود kb 27-35 ﻣﯽﺑﺎﺷﺪ ﮐﻪ ﺑﯿﻤﺎري 19-COVID را اﯾﺠﺎد ﻣﯽﮐﻨﺪ. ﻋﻠﺎﯾﻢ اﺑﺘﻠﺎ ﺑﻪ اﯾﻦ ﺑﯿﻤﺎري ﺷﺎﻣﻞ ﺗﺐ، ﺳﺮﻓﻪ ﺧﺸﮏ، ﺧﺴﺘﮕﯽ، ﺿﻌﻒ ﻋﻀﻠﺎﻧﯽ، ﺗﻨﮕﯽ ﻧﻔﺲ، ﺧﻠﻂ، ﺳﺮدرد و اﺳﻬﺎل ﻣﯽ ﺑﺎﺷﺪ. ﻣﻄﺎﻟﻌﺎت ﻣﺨﺘﻠﻒ ﻧﺸﺎن دادهاﻧﺪ ﺑﺎ اﻧﺘﻘﺎل وﯾﺮوس -SARS 2-CoV از ﻃﺮﯾﻖ ﮔﯿﺮﻧﺪه ACE2 ﺳﻄﺢ ﺳﻠﻮلﻫﺎي آﻟﻮﺋﻮﻟﺎر ﻧﻮع دو و CD147 ﺳﻠﻮلﻫﺎي رﯾﻮي، ﺳﻪ اﺗﻔﺎق اﺻﻠﯽ ﺷﺎﻣﻞ اﺧﺘﻠﺎﻟﺎت ﺗﻨﻔﺴﯽ، ﻟﻨﻔﻮﭘﻨﯽ و ﻃﻮﻓﺎن ﺳﺎﯾﺘﻮﮐﺎﯾﻨﯽ رخ ﻣﯽدﻫﺪ ﮐﻪ ﺑﻪ دﻟﯿﻞ ﻋﺪم ﺗﻨﻈﯿﻢ ﭘﺎﺳﺦﻫﺎي اﻟﺘﻬﺎﺑﯽ ﺳﯿﺴﺘﻢ اﯾﻤﻨﯽ و اﻓﺰاﯾﺶ ﻧﺎﮔﻬﺎﻧﯽ ﺗﻮﻟﯿﺪ ﺳﺎﯾﺘﻮﮐﺎﯾﻦﻫﺎ ﻣﻮارد ﭘﻨﻮﻣﻮﻧﯽ، از دﺳﺖ رﻓﺘﻦ ﻋﻤﻠﮑﺮد رﯾﻪ، ﺳﻨﺪرم زﺟﺮ ﺗﻨﻔﺴﯽ ﺣﺎد )ARDS(، ﺷﻮك و ﺣﺘﯽ ﻣﺮگ اﺗﻔﺎق ﻣﯽاﻓﺘﺪ. ﮔﯿﺮﻧﺪهﻫﺎي ﺳﯿﺴﺘﻢ اﯾﻤﻨﯽ ذاﺗﯽ ﺷﺎﻣﻞ TLR3 و TLR7 )ﮔﯿﺮﻧﺪهﻫﺎي اﻧﺪوزوﻣﺎل( و RIG-I و 5-MDA )ﮔﯿﺮﻧﺪهﻫﺎي ﺳﯿﺘﻮزوﻟﯽ( ﻧﻘﺶ ﻣﻬﻤﯽ در ﺷﻨﺎﺳﺎﯾﯽ RNA، وﯾﺮوس 2-SARS-CoV دارﻧﺪ. درﮔﯿﺮ ﺷﺪن اﯾﻦ ﮔﯿﺮﻧﺪهﻫﺎ ﻣﻮﺟﺐ ﺗﻮﻟﯿﺪ اﻧﻮاع ﻣﺨﺘﻠﻒ ﺳﺎﯾﺘﻮﮐﺎﯾﻦﻫﺎ، اﯾﻨﺘﺮﻓﺮونﻫﺎي ﺗﯿﭗ 1 و ﻣﺪﯾﺎﺗﻮرﻫﺎي اﻟﺘﻬﺎﺑﯽ ﻣﯽﺷﻮﻧﺪ. در ارﺗﺒﺎط ﺑﺎ ﺳﯿﺴﺘﻢ اﯾﻤﻨﯽ اﮐﺘﺴﺎﺑﯽ-ﺳﻠﻮﻟﯽ ﻟﻨﻔﻮﺳﯿﺖﻫﺎي Th2 ،Th1 و Th17 ﺑﺎ ﺗﻮﻟﯿﺪ ﺳﺎﯾﺘﻮﮐﺎﯾﻦ، ﻟﻨﻔﻮﺳﯿﺖﻫﺎي CTL) T CD8( ﺑﺎ ﺗﻮﻟﯿﺪ ﭘﺮﻓﻮرﯾﻦ، ﮔﺮاﻧﺰﯾﻢ و ﺳﺎﯾﺘﻮﮐﺎﯾﻦ ﻧﻘﺶ دﻓﺎﻋﯽ ﺧﻮد را ﻋﻠﯿﻪ وﯾﺮوس 2-SARS-CoV اﯾﻔﺎ ﻣﯽﮐﻨﻨﺪ. ﻓﻌﺎﻟﯿﺖ اﯾﻤﻨﯽ اﮐﺘﺴﺎﺑﯽ-ﻫﻮﻣﻮرال در اﻏﻠﺐ ﺑﯿﻤﺎران ﺑﺎ ﺗﻮﻟﯿﺪ IgM )ﺣﺪود 9 روز ﺑﻌﺪ از ﺷﺮوع ﺑﯿﻤﺎري( و IgG )ﺣﺪود 2 ﻫﻔﺘﻪ ﺑﻌﺪ از ﺷﺮوع ﺑﯿﻤﺎري( ﻣﺸﺨﺺ ﻣﯽﺷﻮد. وﯾﺮوس -SARS 2-CoV از ﻣﮑﺎﻧﯿﺴﻢ ﻫﺎﯾﯽ ﺷﺎﻣﻞ اﯾﺠﺎد اﺧﺘﻠﺎل در ﺗﻮﻟﯿﺪ اﯾﻨﺘﺮﻓﺮون ﻫﺎي ﻧﻮع I، ﮐﺎﻫﺶ ﺑﯿﺎن MHC-II ،MHC-I و اﻓﺰاﯾﺶ ﺑﯿﺎن 3-Tim و 1-PD و اﻟﻘﺎي ﺧﺴﺘﮕﯽ در ﻟﻨﻔﻮﺳﯿﺖﻫﺎي T cell exhaustion) T( ﺑﺮاي ﻓﺮار از ﭘﺎﺳﺦﻫﺎي ﺳﯿﺴﺘﻢ اﯾﻤﻨﯽ اﺳﺘﻔﺎده ﻣﯽﮐﻨﺪ. در اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﻣﺮوري، ﺟﺪﯾﺪﺗﺮﯾﻦ اﻃﻠﺎﻋﺎت ﻣﺮﺗﺒﻂ ﺑﺎ ﻣﮑﺎﻧﯿﺴﻢﻫﺎي دﺧﯿﻞ در اﯾﻤﻮﻧﻮﭘﺎﺗﻮژﻧﺰ وﯾﺮوسﻫﺎي ﺗﻨﻔﺴﯽ ﺑﻪ وﯾﮋه 2-SARS-COV ﻧﮕﺎرش ﺷﺪه اﺳﺖ.

Coronaviruses belong to the Coronaviridae family and three SARS-CoV, MERS-CoV and SARS-CoV-2 pathogens are found in this family, all of which cause respiratory disorders in human beings. SARS-CoV-2 is a RNA virus of approximately 80-160 nm in size and genomic size of approximately 27-35 kb which causes COVID-19. Symptoms of COVID-19 include fever, dry cough, fatigue and muscle weakness, shortness of breath, sputum, headache, diarrhea and muscle inflammation. It causes death in the elderly, people with hypertension, a history of cardiovascular diseases, people with diabetes, cancer, impaired immune system, transplanted, and all people with immunocompromised weakness. Various studies have shown that three major events are respiratory disorders, lymphocytopenia, and cytokine storm as SARS-CoV-2 is transmitted through the ACE-2 receptor on the surface of alveolar type 2 lung cells; in which case, pneumonia, loss of lung function, acute respiratory distress syndrome (ARDS), shock and even death occur because of the failure in the adjustment of inflammatory responses from immune system and proliferation of cytokines. As the virus enters the cells, receptors of intrinsic immune system-TLR3, TLR7 (endosomal receptors) and RIG-I and MDA-5 (cytosolic receptors) detect the RNA of the virus. Involvement of the receptors ends up with the production of different types of cytokines such as type I interferons and inflammation. In respect of acquired cellular immune system of Th1, Th2, and Th17 lymphocytes with cytokine production, the lymphocytes T CD8+ (CTL) play their part by producing perforin, granzyme and cytokine. Humoral-acquired immune activity can be determined in most patients by producing IgM (9 days after disease onset) and IgG (two weeks after disease onset). SARS-CoV-2 makes use of mechanisms such as disruption in the production of type I interferons, reduction of MHC-I, MHC-II expression, and increase of Tim-3 and PD-1 expression on the surface of CTL cells (T cell exhaustion) in order to evade the immune system. In this paper, we present a review of the most recent data on the immunopathogenic mechanisms of the infection with respiratory viruses, especially SARS-CoV-2.