1. Practical Immunity Some diseases and how we are fighting them.

2. 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

3. 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

4. Enzyme-Linked Immunosorbent Assay (Direct ELISA) Figure 18.12a

5. Enzyme-Linked Immunosorbent Assay (Indirect ELISA) Figure 18.12b

6. Serological Tests Figure 18.13

7. 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

8. 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

9. The Biology of Malaria

11. 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)

12. 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.

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

15. 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?

16. Why does the US not Vaccinate for TB, if a vaccine exists? Risk Variable result Interferes with testing

17. What are we trying to induce with vaccination? Herd immunity

18. 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

19. 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……….

20. 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

21. 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

22. 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.

23. Is a malarial Vaccine possible?

24. Humoral response to vaccination

28. Cell mediated response.

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

32. 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

34. 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/mm 3

36. 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?

37. Tissue Transplants symptoms Biology problems

38. Asthma Symptoms. Biology Problems

39. 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

40. treatments 4 weeks of toxic metal antimony Amphotericin B Fluconazole

41. Look at the change of Promastigote to Amastigote

43. 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?

44. 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 vaccineDNA vaccine Provided some protection Is this T cell or antibody mediated?

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

46. MYIASIS MYIASIS Is this a problem? How is damage done?

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