免疫系統(tǒng)主要分為先天免疫系統(tǒng)和獲得性免疫系統(tǒng)（后天免疫系統(tǒng)）兩種類型,。美國(guó)加州大學(xué)圣地亞哥分校醫(yī)學(xué)院的一項(xiàng)新研究則首次發(fā)現(xiàn)了一種器官獨(dú)有的先天免疫系統(tǒng),。該研究勾勒出了肺臟制定其對(duì)微生物入侵的抵抗策略的一種獨(dú)特機(jī)制的輪廓,。這些研究結(jié)果發(fā)表在4月18日的《免疫》（Immunity）雜志上,。研究人員指出,，這種肺臟特有的先天免疫應(yīng)答可能將肺部因過度炎癥反應(yīng)導(dǎo)致的損傷最小化。
眾所周知,，身體的呼吸道長(zhǎng)期被暴露在吸入的顆?；蛭⑸镏小７闻K中微小的空氣囊泡alveola是呼吸系統(tǒng)和循環(huán)系統(tǒng)進(jìn)行氣體交換的場(chǎng)所,，它們受到alveolar巨噬細(xì)胞的保護(hù),，從而避免入侵微生物的侵害。
巨噬細(xì)胞是身體炎性反應(yīng)有關(guān)的白細(xì)胞,，它時(shí)刻警惕入侵者并將其殺死,。Alveolar巨噬細(xì)胞是身體中獨(dú)特的一種巨噬細(xì)胞，這是因?yàn)樗鼈兊幕顒?dòng)會(huì)受到由肺臟上皮細(xì)胞表達(dá)的化合物TGFβ的抑制,。
由于alveola所處的微環(huán)境非常獨(dú)特（長(zhǎng)期被微生物等包圍）,，如果巨噬細(xì)胞免疫系統(tǒng)持續(xù)地處于戰(zhàn)備狀態(tài)就可能使它遭到破壞，很容易導(dǎo)致自身免疫疾病中常見到的炎癥,。因此,，alveola具有一種復(fù)雜的免疫系統(tǒng)以抑制巨噬細(xì)胞處于穩(wěn)定狀態(tài)，并在需要抵抗入侵微生物時(shí)被活化,，然后再次被抑制——這種循環(huán)是alveola微環(huán)境特有的,。
剖析這種免疫機(jī)制能夠使研究人員了解到如何能人為延長(zhǎng)alveolar巨噬細(xì)胞的活化狀態(tài)的信息，而這些信息將在抵御任何新的能夠影響下呼吸道的生物恐怖制劑中具有重要意義,。
研究數(shù)據(jù)揭示出了alveolar巨噬細(xì)胞如何避過TGFb的抑制作用一段時(shí)間以完成免疫任務(wù)的一個(gè)復(fù)雜環(huán)路,。這個(gè)過程通過一套細(xì)胞表面受體（integrins，粘合素或整合素）調(diào)節(jié)TGFβ活動(dòng)來完成,。
這種調(diào)節(jié)使得alveolar巨噬細(xì)胞只在非常有限的時(shí)間里展現(xiàn)“殺手”的冷酷面,。粘合素使TGFβ短時(shí)間失活,，之后肺中的一種叫做MMP9的酶再將其功能恢復(fù)。也就是說,，巨噬細(xì)胞醒來一會(huì),，該系統(tǒng)自己的酶就又會(huì)活化抑制因子使它們?cè)俅纬了?/p>
補(bǔ)充:
integrin，國(guó)內(nèi)將譯為粘合素,、整合素等,，本書暫命名為粘合素。integrin是最初在1986年提出的概念,，描述一個(gè)膜受體家族,，此家族的粘附分子主要介導(dǎo)細(xì)胞與細(xì)胞外基質(zhì)的粘附，使細(xì)胞得以附著而形成整體(integration),故得名,。此外,，粘合素家族的粘附分子還介導(dǎo)白細(xì)胞與血管內(nèi)皮細(xì)胞的粘附。
粘合素家族的粘附分子都是由α,、β兩條鏈由非共價(jià)鍵連接組成的異源雙體(heterodimer),α,、β鏈均為Ⅰ類穿膜蛋白。目前已知至少有14種α亞單位和8種β亞單位,除α7和αIEL外,，其它粘合素分子亞單位均已基因克隆成功,。粘合素分子在體內(nèi)分布很廣泛，多數(shù)粘合素分子可以表達(dá)于多種組織細(xì)胞,，如VLA組的粘合素分子在體內(nèi)廣泛分布于各種組織細(xì)胞,；而多數(shù)細(xì)胞可同時(shí)表達(dá)數(shù)種不同的粘合素分子。對(duì)體外哺乳動(dòng)物來源的細(xì)胞系粘合素分子表達(dá)研究發(fā)現(xiàn),，每一種細(xì)胞系可同時(shí)表達(dá)2～10種不同的粘合素分子,，但不同類型的細(xì)胞表達(dá)粘合素分子的種類是不同的。
Researchers reveal lung's unique innate immune system
For the first time, scientists have documented an organ-specific innate immune system. In research published in the April 18 edition of the journal Immunity, scientists at the University of California, San Diego (UCSD) School of Medicine outline the unique mechanism by which the lung shapes its defensive strategies against microbial invasion.
“This innate immune response is specific to the lung, and was probably designed to minimize collateral damage to lung tissue caused by unchecked inflammation,” said Eyal Raz, M.D., Professor of Medicine at UCSD School of Medicine.
The body’s respiratory tract is constantly exposed to inhaled particles or microorganisms. The alveola – tiny air sacs in the lung where exchanges of gases between the respiratory and circulatory systems takes place – are protected from invading microbes by the alveolar macrophage.
Macrophages are white blood cells involved in the inflammatory response throughout the body, cells normally on the alert for invaders to kill. Alveolar macrophages are unique among macrophages in the body, because their activation is inhibited by TGFb, a compound expressed in the lung by epithelial cells.
“Because the microenvironment of the alveola is a delicate one, it would be damaged if the macrophage immune system was in a constant battle-ready status,” said Raz. “This could readily lead to the type of inflammation we see in autoimmune diseases of the lung such as asthma.”
Therefore, the alveola possess a complex immune system in which the macrophage is repressed in its steady state, activated when called upon to fight invading microorganisms, and then re-repressed, in a circuit that is unique to this microenvironment.
“Dissecting this immune mechanism provides us with the knowledge of how we might prolong the activation status of alveolar macrophages. This knowledge could prove to be essential in combating any novel microbial agents that could infect the lower airways, such as a new flu strain or bioterrorist agents,” said Raz.
The researchers’ data outlines a complex circuit in which the alveolar macrophages circumvent the inhibition by TGFb for brief period of time, in order perform their immune task. This is accomplished through regulation of TGFb activity by a set of cell surface receptors, proteins called integrins.
This regulation allows the alveolar macrophages to take on their “killer” function – the ability of macrophages to engulf invading microorganisms – but only for a very limited period of time. The mediating role of TGFb, briefly inactivated by the integrin, is then restored by one of the lung’s own enzymes, the MMP9.
“Basically, the macrophages wake up for a while, but the system’s own enzymes activate the inhibitor that puts them back to sleep,” said Kenji Takabayshi, Ph.D., first author of the study.
Other contributors to this paper include Maripat Corr, Tomoko Hayashi, Vanessa Redecke, Lucinda Beck, and Donald Guiney of the Department of Medicine at UCSD School of Medicine; and Dean Sheppard, Lung Biology Center, University of California, San Francisco.
University of California–San Diego
