Practical Immunity

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Practical Immunity

• Some diseases and how we are fighting them.

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Principal Vaccines Used in the United States to
Prevent Bacterial Diseases in Humans

• DtaP
• 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

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Principal Vaccines Used in the United States to
Prevent Viral Diseases in Humans

• 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)

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Enzyme-Linked Immunosorbent Assay(Direct ELISA)
Figure 18.12a
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Enzyme-Linked Immunosorbent Assay (Indirect
ELISA)
Figure 18.12b
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Serological Tests
Figure 18.13
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We will look at a number of things and how they
deal with our immunity.

• Malaria
• HIV
• HepB a subunit vaccine.
• Tissue Transplant
• Asthma
• Leishmaniasis
• Botfly Larvae MYIASIS

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Malaria

• 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

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The Biology of Malaria
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Outline of Infection.

• Organism Apicomplexan genus of Plasmodium
• Infective stage is sporozoite moves from mosquito
  to human blood.
• 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)

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• Cyclically rupture RBCs 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.

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• Why do these species usually rupture and cause
  fever in 24 hr cycles???
• Why are humans considered an intermediate host?

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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?

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Why does the US not Vaccinate for TB, if a
vaccine exists?

• Risk
• Variable result
• Interferes with testing

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What are we trying to induce with vaccination?

• Herd immunity

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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

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Why does the rest of the world not have the same
vaccination rate as we do?

• Record keeping
• Cannot afford even minimal treatments
• Immunocompramized
• No refrigeration
• No system of distribution
• No profit for drug companies.

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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

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• 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 RBCs
• Antibodies must be created against the malaria
  toxins to reduce the cyclical fever cause by the
  release of merozoites

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• Antibodies to parasite antigens expressed on
  RBCs block adherence to endothelium and
  rupturing.
• Cell mediated immunity can be stimulated to kills
  RBCs containing the parasite.
• Antibodies to gametocytes can block structures
  involved in fertilization which would prevent
  zygote formation in the mosquito.

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Is a malarial Vaccine possible?
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Humoral response to vaccination
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Cell mediated response.
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HIV

• Lentivirus (retrovirus)
• Genome is RNA
• Particle contains the Enzyme Reverse
  transcriptase
• Envelope of cytoplasm has viral protein gp120 and
  others

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• 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

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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 Tcellsgt200/mm3

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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?

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Tissue Transplants

• symptoms
• Biology
• problems

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Asthma

• Symptoms.
• Biology
• Problems

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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

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treatments

• 4 weeks of toxic metal antimony
• Amphotericin B
• Fluconazole

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Look at the change of Promastigote to Amastigote
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Is a vaccine worth making?

• Cost to US?
• Cost world wide.
• Current treatment is toxic.
• How Could we go about making a vaccine?
• Would it necessarily work?

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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?

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• Used antibody knock out mice and found that the
  method still worked.
• Is a T cell mediated response.

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MYIASISIs this a problem?How is damage done?
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Practical vaccination

• Making product that will produce an immune
  response.
• Administering product
• Making sure that product is effective and has low
  side effects.