Transcript Unifying problems all viruses must solve

Prevention and control of
microbial infections
Domitory 2222
Department of medicine
From
Shandong university
Prevention and Control of
Microbial Infection
Interaction of microbes with host
immune system determines
- outcome of an infection and disease
- ways to control those infections
- effects on populations
Three things
all viruses must do
1 - Replicate to make progeny
2 - Spread and transmission
3 - Evade host defenses
3. Evade host defenses
• Evade anti-viral defenses
• Struggle between virus and host
• Virus must evade long enough to
replicate and transmit, or establish
latent or persistent infection
• Disease is unintended consequence of
how a virus solves three problems
Types of Prevention and
Control
• Natural defenses
• Host immune defenses
• Vaccines- prevent viral infection
• Antiviral chemotherapy- reduce viral
disease after infection
Types of host defenses
• Natural barrier defenses
• Innate defenses
(phagocytes, complement, interferon, NK )
• Adaptive immune defenses
(antibodies, NK cell)
Natural host defenses
- defend against a variety of microbes
- include
• skin epidermis layer
• pH and enzymes of stomach
• ciliation of respiratory tract
• mucosal surfaces
• blood brain barrier
Activation of immune
response
• Natural barrier is breached
• Innate immune system quick response
(complement and macrophages)
(natural killer, neutrophils, monocytes)
• Cytokine activation eg. TNF, IFN-g
• Dendritic cells communicate to adaptive
system by migrating to lymph node
Adaptive host defenses
• Humoral immunity
–antibody mediated immune responses
–antibodies, IgA, IgM, IgG
–interferons
•Cellular immunity
–cytotoxic T-cells lyse infected cells
–Interferons and other cytokines
Weaknesses of immune
defenses
• Innate
- recognizes bacteria better than viruses
- some viruses sneak past host detection
• Adaptive
- specific but slow to react
- less efficient in infants and aged
Preventions and controls:
Vaccines
• Prime immune response without
causing actually viral disease
• Properties of viral vaccines
– given usually before disease encounter
– can be given once or repeated
– can vary in protection
Historical perspective
• Vaccine success stories
smallpox, yellow fever, measles, rubella
• Criteria for eradication
- no animal reservoire
- effective vaccine available
- one stable virus strain
- easily recognizable disease
- infection provides lifelong immunity
Vaccine types
• Usually provided before infection
– Live attenuated
adenovirus,measles,rubella
– Killed
influenza,rabies,cholera
– Subunit vaccines
hepatitis B ,tetanus
Prevention and controls:
Anti-virals
• Goals
of chemotherapy
- reduce severity of disease
- specifically interrupt events unique to
replication of virus
- do not adversely affect the host
Anti-viral considerations
-
give after or during infection
selective toxicity
defined target site
side effects
duration and range of effectiveness
development of resistance
economical market
Some current anti-virals
– Ribavirin (virazole)
– Amantadine (adamantanamine)
– Azidothymidine (AZT)
– WIN 51711 (Disoxaril)
– Ganciclovir (DHPH)
Viral survival strategies
•
•
•
•
Gain entry
Multiply at local site
Find suitable niche
Overcome or subvert host defenses
- outrun
- antigenic change
- hide in host
- mimic host component
- inactivate/down-regulate host response
How to determine that a virus
causes a certain disease:
Koch’s postulates
• Microbe must be associated with infectious
disease
• Isolate virus from diseased host and prepare
a pure culture
• Inoculate pure culture into healthy host who
becomes sick with the same disease
• Isolate the same microbe from the new sick
host
Koch’s molecular postulates
• Gene or factor should be associated
with pathogenic condition or phenotype
• Inactivate or alter this gene should lead
to measurable decrease in virulence or
pathogenicity
• Specifically replace gene should restore
virulence