Chapter 17- Immune response to infectious diseases

1. Chapter 17- Immune response to infectious diseases • Where we're going- • We know most of the mechanisms already- we'll be relating them to certain diseases, and some evasion/virulence mechanism • Big subject- we'll just touch on a few areas: • Viruses- interferon & influenza • Bacterial infections- gonorrhea • Protozoan- malaria, sleeping sickness

2. Viruses- • They bind, enter, (usually) kill, then leave cells • Innate, Antibodies and cell-mediated adaptive all work

4. Interferon: DS RNA stimulates IFN a&b production- leaves infected cells and binds to other cells; a) induces 2-5A synthase, activates RNAseL- degrades mRNA b)Activates kinase that inactivates eIF-2 net result- stops protein synthesis. NK cells are also activated by IFN a&b

5. Influenza-Antigenic drift and shift • Fig. 17-4- enveloped virus, 8 segments, hemagglutinin and neuraminidase on the surface. H key to fusion to cells. N sort of allows virus to not get stuck on mucus.

7. What relevance!

8. Bacterial diseases • Mostly innate and antibody response- phagocytosis, complement, antibodies aiding complement and phagocytosis, toxin neutralization.

11. Protozoa- malaria and trypanosomes • Malaria: Fig 17-11: Sporozoites are in the mosquito, enter, stay for 30 MINUTES, then go into the liver. Developmental change and multiplication to produce MEROZOITES- infect/kill RBC's. Often the infections/releases are synchronous, producing regular fevers. Differentiate into gametes, picked up by another mosquito

12. Antibodies are only partly effective- the best you can hope for is a low, chronic infection. Drugs (quinine, etc) as prophylaxis & treatment work. Insecticides, mosquito nets + insecticides work. Evasion mechanisms: Malaria: inside cells most of the time. The most susceptible stage is the sporozoite stage- but it's only out for 30 min! • Malaria sloughs off its coat, so the antibodies don't stick. • Story of volunteers: infection with inactivated sporozoites administered by irradiated mosquitoes: 6/9 protected; 3 came down with it! • Your book indicates that the cytokine response may, in fact, be responsible for many of the symptoms- TNFα mimics malaria, and Ab’s against TNF protect mice from death by malaria.

13. RBC’s- no ag presentation!

14. African Sleeping Sickness-trypanosomes • Bite of the tsetse fly • Multiplies in the blood • Variable surface glycoproteins are what get us.

15. That’s a LOT of trypanosomes!

17. WORMS! YUCK • They don’t multiply in us, just excrete eggs that make us miserable • Shistosomiasis- Snail- larvae- water (cercariae)- burrow into skin (swimmer’s itch is an unsuccessful entry of other types), migrate to final resting place, where they can torture you. • Lay lots of eggs- some get stuck. • Heavy IgE response, that May be a clever ruse! Mice become immune w/ Th1, NOT Th2 response!

18. Again, some doubt as to the value of the IgE response

19. Things to know- mostly the nefarious ways they succeed: • Viruses: influenza- antigenic shift and drift • Bacteria- capsules, destroying IgA and C3b, no succumbing to phagocytosis • Malaria- sporozoite and merozoite, • Trypanosomes- VSG’s • Worms- controversy over role of IgE, do not replicate in us.