Transcript Subclinical infection

C24 Viral infection and immunity
樊晓晖 教授
第24章 病毒的感染与免疫
Section I Mode of viral infection
Direct person-to-person
spread.
Horizontal Transmission
vertical infection
Relies on PERSISTENCE of the agent
to transfer infection from parents to
offspring.
Transmission and portal of entry
• Vertical transmission
• Horizontal transmission
Several forms of vertical
transmission can be distinguished:
• 1.Neonatal infection at birth, e.g.
gonorrhorea, AIDS.
• 2.Infection in utero e.g. syphilis, CMV,
Rubella (CRS), AIDS.
• 3. Germ line infection - via ovum or sperm.
第24章 病毒的感染与免疫
Section II
Types of viral infection
Inapparent infection
( Subclinical infection) .
1、
Apparent infection
Acute infection
2、
Chronic infection
3、
chronic
Persistent Infection
latent
Slow virus infections
第24章 病毒的感染与免疫
Persistent Infection
• ① Chronic Infection ：Virus can be
continuously detected ; mild or no clinical
symptoms may be evident.
• ② Latent infection ：The Virus persists in an
occult, or cryptic, from most of the time. There will be
intermittent flare-ups of clinical disease , Infectious
virus can be recovered during flare-ups . Latent virus
infections typically persist for the entire life of the host
• ③ Slow virus infection ： A prolonged incubation
period, lasting months or years, daring which virus
continues to multiply. Clinical symptoms are usually
not evident during the long incubation period .
带状疱疹(水痘病毒感染
后潜伏在脊髓后跟N节)
Mechanism of Persistent Infection
•
•
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Immunity is weak；
Viral antigenicity is weak；
Viruses is in protective position；
Viral variation；
Viral genes integration.
第24章 病毒的感染与免疫
•Processes and fates of infections
1. local
Infection processes：2. systemic
1. die
Infection fates：
2. Subclinical infection
3. Abortive infection
4. Recover
•Animal model
第24章 病毒的感染与免疫
Section III Pathogenicity of viruses
I. Effects of viral infection on cells
• According to the interaction
host cells and viruses
between
cytocidal effect
include
Steady state infection
Apopotosis
Transformation
Integrated viral infection
Formation of inclusion body
Cytocidal infection
•Severe，cells lyse and die
•Occur in non-enveloped virus
•Cause
Cytopathological effects(CPE)
Cells rounding
Degeneration,
Aggregation
Loss of attachments to substrate
上皮细胞epithelial cells – 腺病毒adenovirus
uninfected
slides from CDC
early infection
late infection
上皮细胞epithelial cells –
呼吸道合胞病毒respiratory syncytial virus
uninfected
slides from CDC
respiratory syncytial virus
纤维母细胞fibroblastic cells –
单纯疱疹病毒herpes simplex virus
uninfected
slides from CDC
early infection
late infection
纤维母细胞fibroblastic cells –
脊髓灰质炎病毒poliovirus
uninfected
slides from CDC
early infection
late infection
Pathogenicity:
Viral early
protein
•Blocking
synthesis
of
Some
cellular protein and nucleic
capsid
acid
destroy
•Toxicity of viral protein
injury
•Affect cellular lysosome
•Alter the cellular organ 。
稳定状态感染
Steady state infection
•Enveloped viruses,
•Without lyses of cells
•Release by budding
•Change of cell membrane
•Formation of auto
and fusing of cells
antigen
Fig A multinucleate giant cell
细胞凋亡 apoptosis
HIV
Cell transformation,
SV40
Integration of viral genes
•DNA viruses and retro-viruses
•The viral genetic information
may become integrated as DNA in
the cellular genome or may
persist as episomal DNA in these
surviving cells.
•Oncogenic transformation occur
•New antigen appears.
Interaction between viruses
and hosts
• Types of infection.
–HBV:
steady
and
integration
infection
–Herpesviruses:
Cytocidal,steady
and integration infections.
–Most viruses, only one type
infection
二、 Effects of virus infection on
immune system
• Inhibit or destroy immune system
• Pathological
effects
caused
by
caused
by
humorol immunity
• Pathological
effects
cellular immunity
Inhibit
or
immune system
•HIV
•Measle virus
destroy
Pathological effects
by humorol immunity
caused
• Viruses infect cells, new Ag
present on cell membrane →type
Ⅱ
hypersensitivity damage
cells
• Viral Ag combines with Ab,
precipitate on basic membrane
of blood vessel→ type III 型
hypersensitivity damage cells.
Pathological effects caused
by cellular immunity
•Viruses infect cells, new Ag
present on cell membrane
→recognized by specific CTL)
type IV
hypersensitivity
kills cells
Section 4 Anti-virus immunity
IFN
Innate immunity
（ nonspecific）
NK cells
Humorol immunity
Adaptive immunity
（ specific）
Cellular immunity
IFN
• Interferons are proteins produced by
cells infected with viruses, or exposed to
certain other agents, which protect other
cells against virus infection or decrease
drastically the virus yield from such cells.
Interferon itself is not directly the antiviral agent, but it is the inducer of one or
many anti-viral mechanisms
Interferon inducing agents
• (1) Viruses.
• (2) dsRNA is a potent inducer, both viral
intermediates, and synthetic polyI-C.
• (4) Certain Bacterial infections, and the
production of endotoxin.
• (5) Metabolic activators/inhibitors.
Mitogens for gamma induction, also a
variety of tumor promoters induce IFNs. ,
in particular PTA-phorbol tetradecanoate
acetate, butyrate, dexamethasone
Kinds and sources IFNs
Kinds
INF-α
Principal cell source
Epithelium
and leukocytes
IFN-β
type I
Fibroblasts
IFN-γ T lymphocytes
typeⅡ IFN
IFN
Mechanism of action
• Release from an initial infected cell occurs
• IFN binds to a specific cell surface receptor on an
other cell
• IFN induces the “antiviral state” : synthesis of
protein kinase, 2’5’ oligoadenylate synthetase, and
ribonuclease L
• Viral infection of the cell activates these enzymes
• Inhibition of viral and cellular protein synthesis
occurs
Application of IFNs
•Anti viral infection
•Anti tumor treatment
•Immuoregulation。
Diseases currently treated with
IFN-alpha and IFN-beta
• hepatitis C
• hepatitis B
• papilloma warts and early trials with cervical
carcinoma
• Kaposi sarcoma of AIDS,
• colon tumors
• kidney tumors ( usually in combination with other
drugs).
• Basal cell carcinoma
• Breast cancer combined with tamoxifan.
Nature killer/ NK cell
•NK cells are Activated by IFN-alpha/beta
•NK cells are Activated by IFN-alpha and IL-2
and
Activate macrophage
•NK cells target and kill virus infected cells
NK cell
Macrophages
• Macrophages filter ciral particles from
blood
• Macrophages inactivate opsonized virus
particles
• Macrophages present viral antigen to
CD4 T cells
Complement
• Enhancing neutralization of Antibody
• Enhancing phagocytosis of virus
particles
• Lysis
二
Specific
immunity
•humorol
•cellular
anti-viral
Overview of Specific immunity
• specific recognition and selective
elimination of foreign molecules.
• Involves specificity, diversity, memory, and
self/nonself recognition.
Humorol immunity
• Abs against viruses
–NeutrolizationAb:IgG、IgM、IgA
–nonneutrolizing: otherantibody
• Extracellular viral infections
Antibody
IgG
Function
Memory
Blood and
tissue
IgM
Primary
response
Clear viruses in
blood
-
IgA
Mucus
immunit
y
C: classic
pathway
C : C3 pathway
+++
-
-
-
+
placenta
+++
-
-
ADCC
++
-
-
Antibody
Antibody neutralizes extracellular virue:
it blocks viral attachment proteins
it destablilizes viral structure
Antibody opsonizes virus for phagocytosis
Antibody promotes killing of target cell by the complement cascade
and antibody-dependent cellular cytotoxicity
Antibody resolves lytic viral infections
Antibody blocks viremic spread to target tissue
IgM is an indicator of recent or current infection
IgG is more effective than LgM
Secretory IgA is important for protecting mucosal surfaces
Neutralization antibody
•Neutralization ：
Neutralization antibody
binds virus to terminate
the viral infectivity
Mechanism of neutralization Ab:
• Block viruses to attach and
penetrate
• Virus combine with Ab to immune
complex, facilitate the
phygocytosis of macrophage
• Ab combines with enveloped
virus, activate complement to
lyse virus
Cellular immunity
•Intracellular viral infection
•CTL
•DTH
Maintaining duration of
anti-viral immunity
•Varied by different viruses,
•Factors
–Viral antigenecity is single
or steady
–Viramia
–Variation of virus surface
Ags.
Summary
• The ability of viruses to cause disease can be viewed on two
distinct levels: (1) the changes that occur within individual cells
and (2) the process that takes place in the infected patient.
• The fundamental process of viral infection is the viral replication
cycle in a host cell. The cellular response to that infection may
range from cell death or cancer to no apparent effect.
• The host response to an invading virus will depend upon the types
of the infectious agent and where it is encountered.
• Virus infections may be clinical, sub -clinical, acute, chronic,
latent, and delayed.
• Interferons (IFNs) are host - coded proteins of the large cytokine
family that inhibit viral replication and can modulate humoral
and cellular immunity.
• Host defenses against viruses fall into two major categories: (1)
nonspecific, of which the most important are interferons; and (2)
specific, including both humoral and cell-mediated immunity.
复习思考题
何为垂直传播？何为水平传播？
病毒感染的类型有哪些？
病毒对宿主细胞有哪些直接作用？
名词解释： 水平传播（horizontal
transmission）潜伏感染（latent
infection）整合（integration）包涵
体（inclusion body）
• 试简述干扰素的概念、种类、作用及其
抗病毒的主要机制
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