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Published January 20, 2022 | Version v1
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Innate Immune Response and Immune Evasion in Viral Infections

  • 1. Department of Medical Microbiology, Gulhane Training and Research Hospital, Ankara, Turkey

Description

Özet

Virüsler insanlarda çoğunlukla asemptomatik veya geçici hastalıklara neden olurlar. Bununla beraber bazı virüsler kalıcı hasar, kronik veya persistan enfeksiyonlar, ciddi seyirli ve yüksek mortaliteli enfeksiyonlar ve neoplastik transformasyona neden olabilmeleri nedeniyle önem taşırlar. Virüsler neden oldukları salgınlarla insanlık tarihinde yıkıcı etkileri ile toplumsal hafızalarda da önemli izler bırakmışlardır. En önemli halk sağlığı sorunları arasında yer alan viral enfeksiyonlarla mücadele (çocuk felci, kızamık, kızamıkçık gibi) ulusal sağlık otoriteleri ve uluslararası kuruluşların büyük çabaları ile devam etmektedir. Bağışıklık sistemimiz fetal dönemden başlamak üzere yaşam boyu viral enfeksiyon tehditleri ile karşı karşıya kalmakta ve immün öğrenme süreçlerinden geçerek mücadelesini sürdürmektedir. İmmün sistem geleneksel bakışla doğuştan (nonspesifik) ve edinsel/adaptif (spesifik) bağışıklık alt başlıklarına ayrılır. Bununla beraber bu iki sistem arasında keskin bir sınır bulunmamakta ve her iki sistem birbiri ile birçok noktada kesişmektedir. Doğuştan gelen bağışıklığın bir derece özelleşmiş reseptörleri (TLR alt tipleri gibi) veya görece spesifik görevler için farklılaşan hücre tipleri (dentritik hücre alt tipleri) patojenlere karşı ilk savunma hattını oluşturan bu sistemin fiziksel ve kimyasal bariyerlerden başlamak üzere giderek artan derecelerde spesifik görevler üstlendiğini de göstermektedir. Doğuştan gelen bağışıklık sistemi ayrıca uzun süreli hafıza, klonal çoğalma ve yüksek derecede özgül antikor yanıtları ile etkene spesifik ve hızlı yanıtlar üreten adaptif immün sistemi aktive etmekle de görevlidir. Viral enfeksiyonların temizlenmesi için efektif yanıtların üretilmesinde bu iki sistemin koordineli ve dengeli çalışması önem arz eder. Proinflamatuar ve antiinflamatuar sitokinler veya sitotoksik ve süpressör hücreler arasındaki dengeler bunun bir örneğidir. Bu denge bozulduğunda veya eksik kaldığında ciddi seyirli, kronik veya yüksek mortaliteli enfeksiyonlar gelişebildiği gibi, aşırı ve kontrolsüz yanıtlar da doku ve organlarda ciddi ve kalıcı hasarlara neden olabilmektedir. Son derece karmaşık bir sistem içerisinde başarılı bir enfeksiyon için virüslerin immün sistemin defans mekanizmalarından, kontrol ağlarından ve klerens süreçlerinden kaçması gerekmektedir. Farklı doku ve organlara tropizm gösteren her bir virüs immün sistemden kaçışını ve enfeksiyon oluşturabilmesini sağlayan spesifik özelliklerle donatılmıştır. Viral enfeksiyonlar sırasında virüslere ait proteinler insan vücudunda yüzlerce protein ile etkileşmekte (virüs-konak etkileşim ağı) ve viral replikasyon enfekte hücrelerin veya bazı durumlarda olduğu gibi doku ve organ düzeyinde temel fonksiyonların kaybedilmesine neden olmaktadır. Viral enfeksiyonlara karşı gelişen immün yanıtın iyi anlaşılması bu enfeksiyonlarla mücadelede bireysel korunma, etkinliği yüksek aşıların üretilmesi ve koruyucu sağlık politikalarının geliştirilmesi için büyük önem taşır. Bu derlemede insan enfeksiyonları ile ilişkili virüslere karşı verilen doğuştan immün yanıta genel bir bakış sunulmuştur.

Abstract

Viruses cause mostly asymptomatic or transient illnesses in humans. However, some viruses are important because they can cause permanent damage, chronic or persistent infections, serious infections with high mortality‎, and neoplastic transformation. Viruses have left important traces in social memories with their devastating effects in human history with causing epidemics. The fight ‎against viral infections (such as polio, measles, rubella), which are among the most important public health ‎problems continues with great efforts of national health authorities and international organizations. ‎ Our immune system is faced with lifelong, starting from the fetal period, viral infection threats and ‎continues its struggle by going through immune learning processes. ‎‎ The immune system is traditionally divided into innate (nonspecific) and acquired/adaptive (specific) immunity parts. However, there is no sharp boundary between these two systems, and both systems intersect with each other at many points. In addition, partially specialized receptors of innate immunity (such as TLR subtypes) or cell types that differentiate for relatively specific tasks (dendritic cell subtypes) show that this system, which is the first line of defense against pathogens, performs increasingly specific tasks, starting with physical and chemical barriers. ‎The innate immune system is also responsible for activating the adaptive immune system, which produces agent specific and rapid responses with long-term memory, clonal expansion, and highly specific antibody responses. The coordination and balance of these two systems is important in generating effective responses for clearing viral infections. The balance between pro-inflammatory and anti-inflammatory cytokines or cytotoxic and suppressor cells is an example of this situation. When this balance is disrupted or deficient, serious, chronic, or high-mortality infections may develop, and severe and permanent damages to tissues and organs‎ could have been caused by excessive and unregulated responses. For a successful infection in an extremely complex system, viruses must escape from the defense mechanisms, control networks and clearance processes of immune system. Each virus that shows tropism to different tissues and organs is equipped with specific characteristic that enable it to escape from the immune system and cause infection. During viral infections, viral proteins interact with hundreds of proteins in the human body (virus-host interaction network), and viral replication causes the death of infected cells or, in some cases, essential functions at the tissue and organ level. ‎ A better understanding of the immune response against viral infections is of great importance for ‎individual protection in the fight against these infections, for the production of highly effective vaccines ‎and the development of preventive health policies. This review provides an overview of the immune response to viruses associated with human ‎infections.

Notes

Viral Enfeksiyonlarda Doğuştan Gelen Bağışıklık Yanıt ve İmmün Kaçış

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