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Transcript
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