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Practical Immunity
Some diseases and how we are
fighting them.
Principal Vaccines Used in the
United States to Prevent Bacterial
• DtaP Diseases in Humans
– Diphtheria: Purified diphtheria toxoid
– Pertussis: Acellular fragments of B. pertussis
– Tetanus: Purified tetanus toxoid
• Meningococcal meningitis: Purified
polysaccharide from N. meningitidis
• Haemophilus influenzae type b meningitis:
Polysaccharides conjugated with protein
• Pneumococcal conjugate vaccine: S.
pneumoniae antigens conjugated with
protein
Principal Vaccines Used in the United States to
Prevent Viral Diseases in Humans
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Smallpox: Live vaccinia virus
Poliomyelitis: Inactivated virus
Rabies: Inactivated virus
Hepatitis A: Inactivated virus
Influenza: Inactivated or attenuated virus
Measles: Attenuated virus
Mumps: Attenuated virus
Rubella: Attenuated virus
Chickenpox: Attenuated virus
Hepatitis B: Antigenic fragments (recombinant
vaccine)
Enzyme-Linked Immunosorbent
Assay
(Direct ELISA)
Figure 18.12a
Enzyme-Linked Immunosorbent
Assay
(Indirect ELISA)
Figure 18.12b
Serological Tests
Figure 18.13
We will look at a number of things
and how they deal with our
immunity.
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Malaria
HIV
HepB a subunit vaccine.
Tissue Transplant
Asthma
Leishmaniasis
Botfly Larvae: MYIASIS
Malaria
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Kills 1-3 million people a year.
Hundreds of millions of clinical infections
Mostly in sub-Saharan Africa
Anopheles control is the major way.
What happens if we loose this control?
In 1985 the mortality rate for Malaria
increased to almost 15% from 5% of
hospitalized cases in Zaire
The Biology of Malaria
Outline of Infection.
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Organism: Apicomplexan genus of
Plasmodium
1. Infective stage is sporozoite moves from
mosquito to human blood.
2. Carried to liver, move into cells change to
merozoites that move into blood stream
and become merozoites (form ring
structure in RBC, how can be identified)
• Cyclically rupture RBC’s and release more
infective particles as well as waste
products that cause fever.
• Merozoites change into gametocytes
where they can be picked up by
Mosquitoes.
• Gametocytes unite in the mosquito and
can produce sporozoites.
• Why do these species usually rupture and
cause fever in 24 hr cycles???
• Why are humans considered an
intermediate host?
Problems with Vaccination
• Many diseases do not occur in the US for
1999
– 0 rabies
– 8 plague
– 58 botulism
– 0 Yellow fever
– 0 small pox
• Is the risk and the expense worth the
effort?
Why does the US not Vaccinate for
TB, if a vaccine exists?
• Risk
• Variable result
• Interferes with testing
What are we trying to induce with
vaccination?
• Herd immunity
Recent studies
• 1993 Childhood Immunization Initiative
(CII) increase coverage levels to 90%.
• 1997 best year with 78% 1 million children
under the age of 2 still have not received
immunizations.
• Other countries?
– Measles still accounts for 10% mortality
among children aged less than 5 years
Why does the rest of the world not
have the same vaccination rate as
we do?
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Record keeping
Cannot afford even minimal treatments
Immunocompramized
No refrigeration
No system of distribution
No profit for drug companies……….
Do you think that Malaria can be
cured by only one type of vaccine?
• No
• We are in the process of developing
different antigens that will lead to
protective immunity at each state
• Vaccine against the sporozoites must produce
antibodies that work within 30 minutes to block
invasion of hepatocites.
• CD4 and CD8 cells must be trained to kill cells
with the intrahepatic parasites
• A vaccine against merozoites will block the
cyclical invasion of RBC’s
• Antibodies must be created against the malaria
toxins to reduce the cyclical fever cause by the
release of merozoites
• Antibodies to parasite antigens expressed
on RBC’s block adherence to endothelium
and rupturing.
• Cell mediated immunity can be stimulated
to kills RBC’s containing the parasite.
• Antibodies to gametocytes can block
structures involved in fertilization which
would prevent zygote formation in the
mosquito.
Is a malarial Vaccine possible?
Humoral response to vaccination
Cell mediated response.
HIV
• Lentivirus (retrovirus)
• Genome is RNA
• Particle contains the Enzyme Reverse
transcriptase
• Envelope of cytoplasm has viral protein
gp120 and others
• Spikes allow virus to attaches to CD4
receptor on host cells.
• Receptor is found on Helper T cells,
Macrophages and dendritic cells
• Following attachment is absorption and
infection
• Infection can be latent or active
Stages of HIV infection
• Clinical stages include
Category A. Asymptomatic
Category B. persistent infections of Candida
albicans denote early indication of
immune failure infections that one does
not normally get but one gets over it.
Category C. C.a. of esophagus and lung
other more serious infections typical AIDS
indicator condition. CD4 Tcells>200/mm3
HIV vaccine
• Probably most realistic way to control
epidemic
• Problems because we lack an animal test
model. How do we know this works?
• Rapid mutation rate of GP120 makes it
difficult to target.
• Why does HIV have a rapid mutation rate?
Tissue Transplants
• symptoms
• Biology
• problems
Asthma
• Symptoms.
• Biology
• Problems
Leishmaniasis
• 20 different forms of protozoan pathogens.
• Transmitted by bite of female sand flies
found in the tropics and deserts.
• Unaffected reservoir of small mammals
• Promastigote in salvia of insect from
vector
• Amastigote in phagocyticic cells to vector
treatments
• 4 weeks of toxic metal antimony
• Amphotericin B
• Fluconazole
Look at the change of Promastigote
to Amastigote
Is a vaccine worth making?
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Cost to US?
Cost world wide.
Current treatment is toxic.
How Could we go about making a
vaccine?
• Would it necessarily work?
One method
• Rather than target the pathogen, scientists
at the U.S. National Institute of Allergy and
Infectious Diseases (NIAID) use fly slava.
• Isolated saliva protein 15 and cloned the
gene.
• Made a DNA vaccine
• Provided some protection
• Is this T cell or antibody mediated?
• Used antibody knock out mice and found
that the method still worked.
• Is a T cell mediated response.
MYIASIS
Is this a problem?
How is damage done?
Practical vaccination
• Making product that will produce an
immune response.
• Administering product
• Making sure that product is effective and
has low side effects.