Practical Immunity

Some diseases and how we are fighting them.

• 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

Principal Vaccines Used in the United States to Prevent Bacterial

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)

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

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.

• Malaria

• HIV

• HepB a subunit vaccine.

• Tissue Transplant

• Asthma

• Leishmaniasis

• Botfly Larvae: MYIASIS

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

The Biology of Malaria

Outline of Infection.

• 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?• 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 includeCategory A. AsymptomaticCategory 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?

• 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.

MYIASISIs 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.