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ons/Vaccine.htm
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Ch1.Infections and Vaccines
Ch1.Infections and Vaccines
HOW ORGANISMS EVADE THE IMMUNE RESPONSE
Viruses
Small RNA viruses, such as influenza and HIV
small genomes so can not encode proteins to
evade the immune response.
•BUT their RNA genome tends to mutate,
RNA virus antigenic proteins change
continually evade immunologic memory.
• HIV this can happen within an individual.
over just a few months of infection.
•Influenza mutates more slowly across a
population rather than in an individual.
DNA viruses are larger and have capacity in
their genomes for evasion tools.
•Some DNA viruses (members of the herpes virus
family)evade the adaptive immune response
by downregulating (MHC) expression, and the
innate response is required for their control 2
(natural killer [NK] cells).
Bacterial pathogens different strategies to evade:
Extracellular : Pneumococcus (Streptococcus pneumoniae)
and Haemophilus sp. evade the innate response (opsonization by
complement and phagocytosis) by producing
a polysaccharide capsule
successful pathogens of the respiratory tract.
Intracellular:
• Mycobacteria, such as M. tuberculosis,
have waxy coats that block the effects
of phagocyte enzymes.
They also secrete catalase, which
inhibits the effects of the respiratory burst.
• Listeria
cause meningitis, particularly in pregnant women.
Listeria secrete listeriolysin, which punches holes
in the phagolysosome walls.
The bacteria can then escape into the cytoplasm, where they are not
exposed to the toxic products of the metabolic burst or to proteolytic
enzymes. 3
Ch1.Infections and Vaccines
Mechanism of Immunity
• Most primary infections ( except TB, HIV, herpes viruses)are completely
cleared by the immune system sterilizing immunity.
• Immunologic memory develops subsequent exposure to the same pathogen
elicits a memory response by the adaptive immune system so
infection is prevented or symptoms reduced.
• After maternal antibody lost early childhood a series of primary infections
while effective immunologic memory is developed.
• Vaccination can act as a substitute for primary infection allowing
immunologic memory to develop without a symptomatic primary infection.
• Vaccines are a success story; smallpox completely eradicated .
• Many other infections (polio, diphtheria & pertussis) become relatively rare.
• Passive immunotherapy the transfer of adaptive immunity-usually
antibodies-from one individual to another give protective antibodies to an
individual exposed to a pathogen.
• Some cases might need both
- passive immunotherapy (to reduce the immediate risk of infection) and
- the vaccine (to induce immunologic memory and reduce the risk for future
Ch1.Infections and Vaccines 4
infection).
Ch1.Infections and Vaccines 5
Strategies for vaccine development
http://www.susanahalpine.com/anim/KubyHTML/vaccine.htm
Recombinant Virus
Hepatitis B vaccine is a subunit antigen that has been produced
using recombinant techniques (made up of recombinant virus
surface peptide)
Antibodies raised against surface peptide will prevent the virus
attaching to and then entering liver cells.
Up to now, hepatitis B vaccine has been very effective.
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DNA vaccine:
In this experimental approach, the gene for the
immunogenic protein is coated onto gold microspheres
and injected directly into cells (e.g., of the skin).
In mice, this has resulted in antibody production,
indicating that the genes were transcribed
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Ch1.Infections and Vaccines
Ch1.Infections and Vaccines
Adjuvants
• Weaker antigens or subunits vaccines may be rendered more immunogenic by
the addition of other chemicals. Such chemicals are known as adjuvants.
• They provide the danger signal required for the innate immune system to
release signals to drive antibody and T-cell responses.
• Live vaccines generally do not require adjuvants because they are capable of
providing danger signals and stimulating Toll-like receptors (TLRs) themselves.
• Immunostimulatory complexes
(ISCOMs) promotes CTL responses.
• ISCOMs are micelles of lipid and subunit antigen that
are lipophilic and able to penetrate cell membranes.
• ISCOMS have two special advantages over
conventional vaccines:
The antigen penetrates the cell membrane
and is delivered to the antigen-presenting
pathways.
• SO stimulate T cells, including CTL.
• ISCOMs can be used for mucosal vaccines (e.g.,
through the nose) and induce widespread mucosal
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immunity in the gut and respiratory tract Ch1.Infections and Vaccines
VACCINE SCHEDULES
• Vaccine schedules take into account the clinical implications
of each type of infection.
• For example, the main purpose of
rubella vaccine is to prevent
intrauterine infection (which can cause
birth deformities), so there is
little point in giving it before puberty.
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Ch1.Infections and Vaccines
Ch1.Infections and Vaccines 18
•Vaccine schedules also vary in different parts of the world
in the developing world, measles is a major cause of death in
infants and so the vaccine is given as early as possible.
In the developed world, measles has become rare and tends to
affect school age children, so the vaccine can be given slightly
later.
•The main factor affecting the use of vaccines in the developing world
is, however, cost.
http://pathology2.jhu.edu/pancreas/vac_anim.htm