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皮肤免疫学 – 译学馆
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皮肤免疫学

Immunology in the skin

皮肤免疫学
自然免疫学
动画制作:Arkitek Scientific
赞助:Janssen
The skin is the body’s primary barrier
皮肤是机体的主要屏障
against physical insults and microbial pathogens.
能抵御机械性损伤和病原微生物
It represents a unique environment in which immune cells interact with skin cells,
它的特点是免疫细胞与皮肤细胞相互作用
to maintain tissue homeostasis and induce immune responses.
以维持组织内稳态 并诱导免疫应答
The skin is composed of epidermis, dermis, and subcutaneous fatty region.
皮肤由表皮 真皮和皮下脂肪层组成
Commensal bacteria, fungi and viruses living on the skin
皮肤上的共生细菌 真菌和病毒
have beneficial effects in the protection against pathogens and in wound healing.
对阻止病原体入侵 伤口愈合有益
The epidermis is composed of highly specialized epithelial cells
表皮是由高度分化的上皮细胞组成
known as keratinocytes.
即角质形成细胞
They are continuously replenished from
基底角质形成细胞虽然只有一层
just one layer of basal keratinocytes which divide frequently.
但它不断地分裂 更新表皮细胞
Dead cells called corneocytes form the outermost layer,
死亡细胞被推到最外层 形成角质细胞层
and are largely responsible for the barrier function of the skin.
皮肤的屏障功能主要由它负责
In the dermis, cells known as fibroblasts
真皮层的细胞为成纤维细胞
secrete elastin and collagen fibers
它分泌弹性蛋白和胶原纤维
that form dense extracellular matrix.
形成致密的细胞外基质
Blood capillaries irrigate the dermis,
毛细血管滋养真皮层
while lymph fluid is drained through lymphatic vessels to lymph nodes,
而淋巴液通过淋巴管流向淋巴结
specialized immune structures
这是一个特异性的免疫器官
in which immune cells are activated after pathogen encounter.
里面的免疫细胞接触病原体后被激活
Diverse and functionally specialized immune cells populate the skin.
皮肤内分布着功能各异的免疫细胞
In the epidermis,
在表皮层
a specialized subset of dendritic cells
有树突状细胞的一个特殊亚群
called Langerhans cells, sample antigen.
称为郎格汉斯细胞 能采样抗原
They project dendrites upward towards the cornified epithelial layer
它们将树突伸到角质化的上皮层
and sample bacterial antigens such as toxins.
采样细菌抗原 如毒素
Langerhans cells appear to be both anti-inflammatory and activatory
朗格汉斯细胞似乎能根据微环境的不同
depending on context.
发挥抗炎或激活作用
Dendritic cell in the dermis
真皮中的树突状细胞 能高效地捕获死细胞
are highly efficient to capturing dead cells,
能高效地捕获死细胞
and presenting antigen
并呈递抗原给T细胞 如病毒 及其他细胞内病原体
such as viruses, other intracellular pathogens,
如病毒 及其他细胞内病原体
or skin associated self antigen to T cells.
或皮肤相关的自身抗原
If dendritic cells are the immune sentinels,
如果树突状细胞是免疫哨兵
T cells are the immune effectors.
T细胞是免疫效应器
Healthy skin contains more than twice the number of T cells found in the blood.
健康皮肤中的T细胞数量是血液中的两倍多
Most of them are memory T cells,
这些主要是记忆性T细胞
that have previously encountered antigen
它们曾接触过抗原
and can be rapidly reactivated.
再次接触能迅速活化
T cells in the epidermis are mostly CD8⁺ T cells,
表皮层的T细胞主要是CD8⁺T细胞
a subset that become cytotoxic and kill target cells upon activation.
这个亚群一旦活化 就有细胞毒性 能杀死靶细胞
They are long-term residents in the epidermis,
它们长期寄居于表皮
mostly disconnected from the circulation.
很少进入血液循环
T cells in the dermis are mostly helper CD4⁺ T cells,
真皮中的T细胞主要是辅助性CD4⁺T细胞
which have a more modulatory role in the immune response.
它们在免疫应答中主要发挥调节作用
A variety of other immune cells,
还有多种其他的免疫细胞
such as natural killer cells, eosinophils,
如 真皮层中的NK细胞 嗜酸性粒细胞
and mast cells are present in the dermis,
以及肥大细胞
and might be involved in the allergic reactions in the skin.
它们可能参与皮肤过敏反应
Dendritic cell and keratinocytes sense tissue damage,
树突状细胞和角质形成细胞感应组织损伤
such as wounds or cuts
例如 创伤 刀伤
or lesions that occur when latent herpes virus reactivates.
或潜伏的疱疹病毒再次活化后导致的皮损
And they do that through evolutionarily conserved receptors,
它们通过进化上保守的受体
that recognize pathogen derived molecular patterns,
来识别病原体来源的分子模式
or host derived molecules,
或宿主来源的分子
that are exposed by cell death, such as DNA.
如 细胞死亡后释放的DNA
Keratinocytes produce antimicrobial peptides,
角质形成细胞产生的抗菌肽
which can kill bacteria directly.
可以直接杀死细菌
Inflammatory mediators such as interleukin-1 or IL-1
产生的炎症介质 如白介素-1 或 IL-1
which activate dendritic cells,
能激活树突状细胞
and chemokines which recruit neutrophils
产生的趋化因子能募集中性粒细胞
macrophages and T cells.
巨噬细胞 和T细胞
Activated dendritic cells migrate to the lymph nodes,
活化的树突状细胞迁移到淋巴结
where they present antigen from the site of infection to naive T cells,
然后将感染部位的抗原递呈给初始T细胞
priming them to activate
促使T细胞活化
and differentiate into effector T cells.
并分化为效应T细胞
Activated T cells return to the skin
活化的T细胞返回皮肤
and kill infected keratinocytes to control viral infection,
杀死感染的角质形成细胞 控制病毒感染
or secrete signals that recruit additional immune effector cells.
或者分泌细胞因子 募集其他疫效应细胞
Following viral clearance,
病毒清除后
memory CD8⁺ T cells persist in the epidermis
记忆性CD8⁺T细胞继续定居表皮
to provide immunity for further encounters with the same virus.
以后接触相同的病毒时 能提供免疫保护
Immune responses can become dysregulated
免疫应答也可能失调
and cause skin disorders
引起皮肤疾病
such as psoriasis or atopic dermatitis.
如银屑病 或特应性皮炎
Psoriasis is a life long inflammatory skin disease
银屑病是一种终生的炎症性皮肤病
characterized by scaly reddish plaques.
以鳞屑红斑为特点
A combination of environmental and genetic factors
环境和遗传因素
confer susceptibility to the disease.
共同增加了此病的易感性
Physical injury or inflammation
机械性损伤或炎症
can trigger the formation of an acute lesion.
可诱发急性损伤
The antigenic trigger is unknown,
诱发的抗原仍未知
but current models propose that
但目前的模型认为
stressed keratinocytes might release self DNA,
压力过大的角质形成细胞可能会释放自身的DNA
which in complex with an antimicrobial peptide,
它与抗菌肽结合
activates dermal plasmacytoid dendritic cells
再激活真皮浆细胞样树突状细胞
to secrete high amounts of the antiviral mediator interferon.
使其分泌大量抗病毒介质——干扰素
Together with proinflammatory IL-1α released by stressed keratinocytes,
应激性角质形成细胞释放的炎症分子IL-1α
interferon activates dermal dendritic cells
与干扰素一起激活皮肤中的树突状细胞
to promote T cell differentiation.
促进T细胞分化
The earliest recognizable change in the affected skin
受累皮肤最早可见的变化
is the accumulation of T cells and dendritic cells around blood vessels in the dermis.
是真皮血管周围聚集的T细胞和树突状细胞
An overt lesion occurs when CD8⁺ T cells, dendritic cells
当CD8⁺T细胞 树突状细胞
and neutrophils infiltrate the epidermis.
及中性粒细胞浸润表皮时 有显性皮损
中性粒细胞
Specialized subsets of T cells secrete soluble mediators
特殊的T细胞亚群能分泌可溶性介质
like interferon gamma (IFNγ) and IL-17
如 干扰素γ(IFNγ)和IL-17
which stimulate the proliferation of keratinocytes,
它们能促进角质形成细胞的增殖
and this produces a marked thickening of the epidermis.
这会使表皮明显增厚
Signals from the proliferating keratinocytes
增殖的角质形成细胞分泌信号分子
act as chemo attractants for infiltrating neutrophils.
作为趋化因子 促进浸润的中性粒细胞聚集
Crosstalk between immune cells, keratinocytes, and dermal cells,
免疫细胞 角质形成细胞和真皮细胞之间相互应答
thus contribute to tissue remodeling
有助于组织重塑
and amplification of this dysregulated immune response.
但免疫应答失调也会增强
Without treatment, acute psoriatic lesions become chronic lesions.
如不治疗 银屑病的急性皮损会变成慢性
Genetic studies have identified psoriasis associated susceptibility genes,
基因研究揭示银屑病有易感基因
some of them linking Tʜ17 cells,
银屑病的发病机制与Th17相关
the subset of T cells that produce IL-17 to psoriasis pathogenesis.
Th17 即产生IL-17的T细胞亚群
Thus immune cells in the skin
因此皮肤中的免疫细胞
exert important roles in maintaining the barrier function against pathogens,
在抵御病原体 维持屏障功能中 发挥重要作用
but can also become activated by self antigen or harmless antigen
但也可以被自身抗原或无害抗原激活
to cause autoimmunity or allergies.
导致自身免疫或过敏

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视频概述

皮肤即是一道物理屏障,也是重要的免疫屏障。正常的免疫应答对人体有益,异常的免疫应答则会导致疾病。

听录译者

zbz

翻译译者

Raven

审核员

审核员MS

视频来源

https://www.youtube.com/watch?v=_VhcZTGv0CU

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