Pathogenesis and Immunity of HIV在线视频

As we recall in the last session,
我们先回忆一下之前的课程

HIV has affinity for CD4 expressing
HIV对CD4阳性T细胞和髓样细胞

T cells and myeloid cells,
具有高亲和力

which is the major determinant
这是致病机制中

in disease pathogenesis.
主要的决定因素

HIV-induced immunodeficiency:
HIV诱导的免疫缺陷:

AIDS
AIDS

results from the great reduction
是由CD4阳性T淋巴细胞数量

of CD4 T cells.
大量减少所导致

How does the virus
病毒是如何

destroy the target cells?
破坏靶细胞的？

There are direct and indirect
有直接破坏和间接破坏

mechanisms.
两种机制

HIV can destroy the target cells
HIV可以通过出芽

as a result of budding.
破坏靶细胞

Continuous formation of viruses
新合成的病毒

budding from the infected cell surface
不断从被感染的细胞出芽

causes cell damage,
引起细胞破坏

increased permeability,
细胞膜通透性增高

and finally cell lysis.
最后导致细胞裂解

CD4 T cells
CD4阳性T细胞

can be infected with
可以被结合在其他细胞上

the cell-bound HIV
的HIV感染

or by cell-to-cell
也可以在与树突状细胞结合后

transmission of virus
通过细胞间接触

upon binding to the DCs.
进而被感染

The HIV infection
HIV感染

causes syncytia formation
可诱导细胞融合形成多核细胞

and interferes with cell metabolism,
并且干扰细胞代谢

leading to the cells lysis.
导致细胞裂解

Furthermore,
另外

large amounts of nonintegrated
大量未整合的

circular DNA
环状DNA

induce infected T cells
可诱导被感染的T细胞

to commit a type of inflammatory cell
发生炎性死亡

suicide (pyroptosis).
即细胞焦亡

Pyroptosis may lure more
细胞焦亡可募集更多未激活的

unactivated T cells to the site
T细胞到达死亡细胞集中的区域

and also succumb to pyroptosis.
也发生细胞焦亡

At the same time,
同时

the immune response to HIV
HIV诱导的免疫反应

controls viral infection
不仅可控制病毒感染

but also contributes to pathogenesis.
同时也是致病机制之一

Cytotoxic T cells
细胞毒性T细胞

NK cells
自然杀伤细胞

can induce immune cytolysis,
可引起细胞溶解

resulting in the killing
导致CD4阳性T细胞

of CD4 T cells.
被杀伤

On the whole,
总的看来

HIV infection
HIV感染

alters the functions of T cells,
可改变T细胞

dendritic cells,
树突状细胞

and macrophages.
以及巨噬细胞的功能

Virus reduces CD4 T cell numbers,
病毒可以减少CD4阳性T细胞的数量

helper-cell activation of CD8 T cells
抑制辅助细胞对CD8 T细胞

and macrophages.
和巨噬细胞的激活

On the other hand,
另一方面

HIV takes advantages of several ways
HIV可利用几种方式

to escape the immune control.
逃避免疫防御

We can see in the table:
从表格中可以看到

gp120 undergoes mutation
gp120发生变异和

and heavy glycosylation,
高度糖基化

and hence
能改变

alters its antigenicity
病毒的抗原性

and evade immune clearance.
有利于逃避免疫清除

Direct cell-to-cell spread
直接的细胞间接触传播

and syncytia formation
和多核细胞的形成

also attribute to
也促进了病毒

escape of antibody detection.
逃避抗体的监视

Moreover,
此外

persistent infection of dendritic cells,
树突状细胞

macrophages,
巨噬细胞和

and CD4 T helper cells
CD4辅助T细胞的持续感染

may lead to loss of activators
可导致免疫活化

and controllers of the immune system.
和调控功能丧失

Ultimately,
最终

the entire
整个免疫系统

immune system is compromised.
受到抑制

If this progresses,
如果病程继续进展

the final result
最后会导致

will be immunodeficiency.
免疫缺陷

The course of HIV disease
艾滋病的病程

parallels the reduction
与CD4阳性T细胞数量减少

in CD4 T cell numbers
以及血液中病毒载量

and the amount of virus in the blood.
密切相关

There is a large
淋巴结内

burst of virus production
有大量病毒

and viral replication
复制

in the lymph nodes,
与产生

causing disruption of structure
从而导致淋巴结结构破坏

and function.
与功能障碍

CD4 T cell number
在艾滋病晚期

drops greatly
CD4阳性T 细胞的数量

in the late course of disease.
急剧下降

Finally,
最后

the patient becomes immunodeficient.
患者发生免疫功能缺陷

Loss of CD4 T cells affects
CD4阳性T细胞的减少

both cellular
影响细胞免疫

and humoral immune responses.
和体液免疫应答

The patients are susceptible
患者容易发生

to opportunistic diseases
机会感染性疾病

and malignancy.
和恶性肿瘤

In addition,
另外

HIV-infected
被HIV感染的

microglial cells
小胶质细胞

destroy neural function,
会损伤神经细胞

causing neurologic abnormalities.
从而导致神经系统功能异常

The flow diagram
下面这个流程图

depicts the pathogenesis of HIV.
很好的展示了HIV的致病机制

We can see,
我们可以看到

HIV causes lytic
HIV可导致

and latent infection of macrophages,
巨噬细胞、树突状细胞

dendritic cells,
CD4阳性T细胞

and CD4 T cells,
的裂解和潜伏感染

and affects neuron functions.
也可影响神经元的功能

The consequences
其后果

are immunodeficiency
是免疫缺陷

and AIDS-related dementia.
和AIDS相关性痴呆

As you all known,
众所周知

HIV is
HIV是

the causative agent of
获得性免疫缺陷综合征

Acquired Immune Deficiency Syndrome
(AIDS)的

(AIDS).
病原体

AIDS is one of the most
AIDS是

devastating epidemics ever recorded.
最致命的流行病之一

without treatment,
若不进行治疗

most HIV-infected individuals
绝大多数HIV感染者

will become symptomatic,
会出现症状

and ultimately succumb to the disease.
并最终死亡

What is the course of HIV infection?
HIV感染的病程是怎样的?

A typical course of HIV disease
典型的HIV感染病程：

undergoes 3 stages
从无症状

from an asymptomatic disease
发展到免疫缺陷

to immunodeficiency.
主要经历三个阶段

The 1st stage is
第一阶段是

acute infection
急性感染期

followed by clinical latency.
和随后的临床潜伏期

Many individuals
许多患者

experience flu-like symptoms,
大约在感染后

occurring approximately
的2-4周出现

2 to 4 weeks after exposure.
类似流感的症状

During this acute phase,
在急性感染期

HIV infection is spreading
HIV入侵后并扩散

and the viral load
血液和其他体液

in the blood and other body fluids
中的病毒载量

can be quite high,
明显升高

increasing the risk of transmission
传染他人的风险

to others.
也随之增高

P24 antigen and viral RNA
血液中可以检测到P24抗原

can be detected,
和病毒RNA

while anti-HIV antibodies
但在这个阶段

are not detectable in this period.
无法检测到HIV抗体

During the asymptomatic period,
在无症状潜伏期

the viral replication continues,
病毒持续复制

leading to gradual decline
导致CD4阳性T细胞

of CD4 T cells.
数量逐步下降

Viral load can be also measured,
检测病毒载量

which plays a major role
对评估患者的

in evaluation of the patient’s
状态和预后

status and prognosis.
十分重要

The HIV antibodies
这个时期可以检测到

can appear in this phase.
HIV抗体

The 2nd stage
第二阶段

is subclinical immune dysfunction
是亚临床免疫功能紊乱期

with CD4 T cell counts
CD4阳性T细胞

continuing to fall.
数量持续下降

The individuals may present with
患者可能出现

Acquired immune deficiency
AIDS相关综合征

syndrome-Related Complex(ARC) symptoms
的症状

such as fever,
如发热

weight loss,
体重下降

GI problems
胃肠道疾病

and muscle pains,
肌肉疼痛

and generalized
和全身

enlargement of lymph nodes.
淋巴结肿大

As the immune system collapses,
随着免疫系统的严重缺损

opportunistic infections develop.
患者开始出现机会性感染

Without treatment,
如果不进行治疗

what is the final fate
感染者最终

of infected individual?
会发生什么？

In the 3rd stage,
第三阶段

most HIV patients
大多数HIV感染者

eventually progress to full-blown AIDS,
最终会进入典型AIDS期

when CD4 T cell counts
当CD4阳性T细胞

are less than 200/µl
＜200个/μl

and viral load is larger than
病毒载量

75,000 copies/ml.
＞75,000拷贝/ml

At this time,
这时

they show significant diseases
患者会出现明显的临床疾病

including
包括

generalized enlargement of lymph nodes,
全身性淋巴结肿大

fever,
发热

opportunistic infections,
机会性感染

cancers,
肿瘤

HIV wasting syndrome,
HIV消耗综合征

and AIDS-related dementia.
AIDS相关性痴呆

AIDS patients are
AIDS患者容易出现

susceptible to opportunistic infection.
机会性感染

In this table,
从表格中

we may see
我们可以看到

the common infectious diseases
引起机会性感染的

caused by various agents in AIDS.
常见病原体

The relevant agents including
相关的病原体包括

Candida albicans
白色念珠菌

or other fungi,
或者其他真菌

viruses capable of reactivation,
潜伏后可再激活的病毒

parasites,
寄生虫

and Tuberculous bacillus
结核分枝杆菌

or other bacteria
或者其他可以

can result in significant infections.
引起严重感染的细菌

The pictures here
这张图

show the lung
展示的是

with Pneumocystis carinii infection
发生了肺孢子菌性肺炎

in an AIDS patient.
AIDS患者的肺部病变

Pneumocystis carinii pneumonia (PCP)
肺孢子菌性肺炎（PCP）

is one of the major complications
是AIDS最主要的

of AIDS.
并发症之一

As you can see,
如图所见

Candida infections
假丝酵母菌的感染

is another overt
也是AIDS中

manifestation of AIDS.
常见的并发症

Oral candidiasis (thrush),
假丝酵母菌

causing the appearance of sores
可以导致

in the mouth ,
鹅口疮

and systemic candidiasis
全身性念珠菌病

are common problems for AIDS patients.
这些都是AIDS患者常见疾病

Prolonged and severe viral infections
持续严重的病毒感染

including reactivation of the
例如疱疹病毒的再激活

herpesviruses also often occur.
也常在AIDS患者中出现

The immunodeficiency
免疫缺陷

may involve the onset of the malignancy.
可导致恶性肿瘤的发生

As the table shows,
如图表所示

the most notable is Kaposi sarcoma.
最常见是卡波西肉瘤

Lymphomas are also prevalent.
淋巴瘤也很常见

What can you find in these two pictures?
在这两张图片中你发现了什么？

There are the lesions of
皮肤上有

Kaposi sarcoma on the skin.
卡波西肉瘤的病灶

The cancer is
这种肿瘤与

associated with a herpes virus infection
疱疹病毒8型（HHV-8）的感染

(HHV-8),
有关

which is rare in healthy people.
但在健康人中很罕见

Lymphomas are also
淋巴瘤也是AIDS患者

prevalent in AIDS patients
常见的恶性肿瘤

such as
如

Hodgkin and non-Hodgkin lymphomas.
霍奇金淋巴瘤和非霍奇金淋巴瘤

At the same time,
同时

the AIDS patients
AIDS患者

will develop HIV wasting syndrome,
会出现HIV消耗综合征

characterized by
主要特征是

enlargement of lymph nodes,
淋巴结肿大

fever,
发热

weight loss,
体重下降

malaise,
乏力

opportunistic infections,
机会性感染

diarrhea,
腹泻

night sweats,
盗汗

and fatigue.
和疲劳

Furthermore,
此外

some AIDS patients
一些AIDS患者

exhibit manifestations of
会出现AIDS痴呆综合征（ADC）

AIDS dementia complex(ADC)
的临床表现

(including HIV encephalopathy
（包括HIV脑病

and AIDS-related dementia).
和 AIDS相关性痴呆

Overall,
总体上

late-stage
在最后一个阶段

generally are burdened with tuberculosis
患者一般会出现

pneumonia,
肺结核

severe diarrhea,
严重的腹泻

various malignancies,
各种恶性肿瘤

or AIDS-related dementia.
或AIDS相关性痴呆等疾病

Without treatment,
未进行治疗者

the patients would succumb
通常在

in 9 to 11 years.
9-11年内死亡

Till now,we have finished the session.
到此，我们已经学完了这一节

Next part ,
下节课

we will discuss about
我们将会讨论

the epidemiology
HIV的流行病学特征

and lab diagnosis of HIV.
和实验室诊断方法