流感對你的身體做了什麼？它為何讓你如此難受？

流感為什麼會讓你頭痛欲裂，肌肉酸痛？

作者 Laura Haynes

日期 February 12, 2018

翻譯 貓鷹

審校 阿金

在美國，每年有5%到20%的人會感染流感病毒。這其中平均有20萬人需要住院接受治療，多達5萬人因此喪生。隨著年齡的增長，免疫系統將會變得脆弱，這使得65歲以上的老人成為易感人群。此外，老人還更容易受到伴隨流感產生的長期傷殘折磨，特別對於住院治療的人而言。

我們都知道流感的癥狀包括發燒、咳嗽、喉嚨痛、肌肉酸痛、頭痛和疲勞。但究竟是什麼造成了如此多的損傷？當你對抗流感時，你的身體內又在發生什麼？

我在康涅狄格大學醫學院（University of Connecticut School of Medicine）專攻免疫學，我的實驗室著眼於探索流感如何影響身體，以及我們的身體如何對抗病毒。令人生趣的是，許多攻擊病毒的體內防禦機制也會引起與流感相關的癥狀。

流感是如何進入你的身體的？

流感病毒會感染呼吸道，包括鼻腔、喉部和肺部。病毒通常通過空氣或手指接觸傳播至口腔、鼻子或眼睛的粘膜。緊接著，它沿著呼吸道傳播，通過細胞表面的特定分子，與排列在肺氣道的上皮細胞相結合。一旦進入細胞，病毒便劫持細胞的蛋白生成機制，生產病毒蛋白，並製造更多的病毒顆粒。一旦成熟的病毒顆粒製造完成，它們將被從細胞里釋放出來，繼續入侵感染鄰近的細胞。

流感在呼吸道中佔據了一席之地，但卻會讓人感覺很糟糕

這一過程會造成肺部損傷，不過流感的大部分癥狀實際上是由免疫系統對病毒的防禦反應引起的。最初的免疫反應涉及到人體先天免疫系統細胞，例如巨噬細胞和中性粒細胞。這些細胞表達能夠感知病毒存在的受體，隨後，它們通過產生稱為細胞因子與趨化因子的類激素小分子發出警報，提醒身體：「你已經遭受病毒感染！」

細胞因子協調免疫系統的其他「成員」以各自適當的方式對抗入侵病毒，而趨化因子則將這些「成員」引導到感染部位。參與反應過程的其中一種細胞稱為 T 淋巴細胞（T lymphocytes），這是一種能對抗感染的白細胞。有時它們也被稱為「士兵細胞」。當T細胞特定識別出流感病毒蛋白後，它們開始在肺部和喉嚨周圍的淋巴結中增殖。這會導致淋巴結腫大，產生疼痛感。

幾天後，這些T細胞移動到肺部，開始殺死被病毒感染的細胞。這一過程會造成大量類似於支氣管炎的肺部損傷，加重現有的肺部疾病，使呼吸變得困難。此外，免疫反應造成肺部黏液積聚，這會導致身體將咳嗽作為一種反射機制來清理呼吸道。通常，在健康的人體內，由 T 細胞在肺部引起的損傷是可逆的，但當反應過激時甚至會導致死亡。

流感特異性 T 細胞的正常功能對有效清除肺部病毒至關重要。當 T 細胞功能下降，比如隨著年齡的增長或者使用免疫抑製藥物時，病毒清除時間將會更久。這會延長感染時間，導致更嚴重的肺部損傷。也可能激發包括繼發細菌性肺炎（secondary bacterial pneumonia）在內的併發症，而這常常是致命的。

為何你會頭痛欲裂？

雖然正常情況下，流感病毒完全被控制在肺部，不過流感的幾種癥狀卻是全身性的，包括發燒、頭痛、疲勞和肌肉酸痛。為了更好地應對流感感染，由肺部內先天免疫細胞產生的細胞因子和趨化因子因此變得能夠影響整個身體系統——它們進入血液，從而造成了上述癥狀。發生這種情況時，就會出現一連串複雜的生物學現象。

此時，一種炎症細胞因子白介素-1（Interleukin-1）會被激活。白介素-1對於病毒殺手——T細胞的生成很重要，但它也會影響到大腦下丘腦調節體溫的部分，便會引起發燒和頭痛。

對抗流感感染的另一個重要細胞因子是「腫瘤壞死因子－α」。它在肺部有著直接抗病毒的效果。但在流感和其他類型的感染中，它也可能導致發燒和食欲不振，使人變得疲勞和虛弱。

l.

健康的人體T細胞 Flickr/NIAID.com, CC BY-SA

為何你會肌肉酸痛？

我們的研究還揭示了流感感染影響身體的另一個方面。

眾所周知，肌肉酸痛和虛弱是流感感染的主要癥狀。在動物模型的研究里，我們發現流感感染會增加肌肉退化基因的表達，而腿部骨骼肌的肌肉構建基因表達則會減少。

從功能上看，流感感染也會影響行走能力，削弱腿部力量。重要的是，在年輕人中，這些影響是短暫的，將會隨著感染的清除而恢復正常。

相比之下，這些影響在老年人身上停留的時間更長。這至關重要，因為腿部穩定性和腿部力量的降低可能會導致老年人在恢復期更容易摔倒。甚至會造成長期傷殘，使得老人需要藉助拐杖或者輪椅，從而限制了自己的行動能力和獨立性。

我們實驗室的研究人員認為，流感感染對肌肉的影響是免疫系統對病毒反應中另一個意想不到的結果。我們目前正致力於確定免疫反應中何種因素導致此類影響，並嘗試找到避免它的方法。

因此，當你飽受流感折磨之時，你大可放心，因為你的身體正在奮力反抗。它在不懈地抵抗肺部病毒的傳播，殺死被感染的細胞。

相關論文信息

一

[論文標題] T-Cell Immunity to Influenza inOlder Adults: A Pathophysiological Framework for Development of More EffectiveVaccines

[論文作者] Janet E. McElhaney, George A.Kuchel, et al.

[發表時間] 2016/02/25

[發表期刊]Front. Immunol

[論文摘要] One of the most profound publichealth consequences of immune senescence is reflected in an increasedsusceptibility to influenza and other acute respiratory illnesses, as well as aloss of influenza vaccine effectiveness in older people. Common medicalconditions and mental and psychosocial health issues as well as degree offrailty and functional dependence accelerate changes associated with immunesenescence. All contribute to the increased risk for complications of influenzainfection, including pneumonias, heart diseases, and strokes that lead tohospitalization, disability, and death in the over 65 population. Changes inmucosal barrier mechanisms and both innate and adaptive immune functions convergein the reduced response to influenza infection, and lead to a loss ofantibody-mediated protection against influenza with age. The interactions ofimmune senescence and reduced adaptive immune responses, persistentcytomegalovirus infection, inflammaging (chronic elevation of inflammatorycytokines), and dysregulated cytokine production, pose major challenges to thedevelopment of vaccines designed to improve T-cell-mediated immunity. In olderadults, the goal of vaccination is more realistically targeted to providingclinical protection against disease rather than to inducing sterilizingimmunity to infection. Standard assays of antibody titers correlate withprotection against influenza illness but do not detect important changes incellular immune mechanisms that correlate with vaccine-mediated protectionagainst influenza in older people. This article will discuss: (i) the burden ofinfluenza in older adults and how this relates to changes in T-cell function,(ii) age-related changes in different T-cell subsets and immunologic targetsfor improved influenza vaccine efficacy in older, and (iii) the development ofcorrelates of clinical protection against influenza disease to expedite theprocess of new vaccine development for the 65 and older population. Ultimately,these efforts will address the public health need for improved protectionagainst influenza in older adults and 「vaccine preventable disability.」

二

[論文題目] Macrophages and Neutrophils:Regulation of the Inflammatory Microenvironment in Autoimmunity and Cancer

[論文作者] Michal A. Rahat,1 Seth B. Coffelt,et al.

[發表時間] 2016/05/04

[發表期刊]Mediators of Inflammation

三

[論文題目] Secondary Bacterial InfectionsAssociated with Influenza Pandemics

[論文作者] Denise E. Morris, David W. Cleary,and Stuart C. Clarke.

[發表時間] 2017/06/23

[發表期刊]Front Microbiol.

[論文編號] doi: 10.3389/fmicb.2017.01041

[論文摘要] Lower and upper respiratoryinfections are the fourth highest cause of global mortality (Lozano et al.,2012). Epidemic and pandemic outbreaks of respiratory infection are a majormedical concern, often causing considerable disease and a high death toll, typicallyover a relatively short period of time. Influenza is a major cause of epidemicand pandemic infection. Bacterial co/secondary infection further increasesmorbidity and mortality of influenza infection, with Streptococcus pneumoniae,Haemophilus influenzae, and Staphylococcus aureus reported as the most commoncauses. With increased antibiotic resistance and vaccine evasion it isimportant to monitor the epidemiology of pathogens in circulation to informclinical treatment and development, particularly in the setting of an influenzaepidemic/pandemic.

四

[論文題目] Aging augments the impact ofinfluenza respiratory tract infection on mobility impairments, muscle-localizedinflammation, and muscle atrophy

[論文作者] Jenna M. Bartley, Sarah J. Pan, etal.

[發表時間] 2017/02/07

[發表期刊]Aging

[論文摘要] Although the influenza virus onlyinfects the respiratory system, myalgias are commonly experienced duringinfection. In addition to a greater risk of hospitalization and death, olderadults are more likely to develop disability following influenza infection;however, this relationship is understudied. We hypothesized that upon challengewith influenza, aging would be associated with functional impairments, as wellas upregulation of skeletal muscle inflammatory and atrophy genes. Infectedyoung and aged mice demonstrated decreased mobility and altered gait kinetics.These declines were more prominent in hind limbs and in aged mice. Skeletalmuscle expression of genes involved in inflammation, as well as muscle atrophyand proteolysis, increased during influenza infection with an elevated andprolonged peak in aged mice. Infection also decreased expression of positiveregulators of muscle mass and myogenesis components to a greater degree in agedmice. Gene expression correlated to influenza-induced body mass loss, althoughevidence did not support direct muscle infection. Overall, influenza leads tomobility impairments with induction of inflammatory and muscle degradationgenes and downregulation of positive regulators of muscle. These effects areaugmented and prolonged with aging, providing a molecular link betweeninfluenza infection, decreased resilience and increased risk of disability inthe elderly.

喜歡這篇文章嗎？立刻分享出去讓更多人知道吧！