Immunology --- prevention and treatment of infectious diseases

1. Immunology --- prevention and treatment of infectious diseases Zhaolin Hua Institute of Biophysics, CAS

2. Innate immunity--- the new frontier of immunology • Viral infection and antibody--- a lesson from HIV elite controller • Mucosal immunity--- why we are what we eat • Future challenges --- what immunology can do for us

3. Innate Immunity--- the new frontier of immunology

4. The Two Arms of Immune System Innate Adaptive Jansson, Eugène Fredrik

5. Adaptive immune system B cell T cell • Immunoglobulin (antibody) • T cell receptor • recognition of fast evolved virus or bacteria

6. A Prediction by immunologist Dr. Janeway There must be a mechanism for the immune system to distinguish good and bad. (1989) Pathogen-Associated Molecular Patterns (PAMPs) Charles Janeway (1943-2003)

7. Some Examples of PAMPs Virus DNA Bacterial cell wall

8. Do lower-rank animals have immunity?

9. Flies also need immunity Hoffmann JA Normal Mutant Mutation of a single gene called “Toll” make the flies susceptible to fungal infection.

10. Toll-like receptor can recognize LPS LPS (lipopolysaccharide) • Produced by Gram-negative bacteria • Causes septic shock in human A mouse strain that is susceptible to Gram-negative bacterial infection was found to bear a mutation in Toll-like receptor 4.

11. Identification of the family of Toll-like receptors Tapping R

12. Pattern recognition • Pattern Recognition Receptors • TLRs • NLRs • CLRs • RLRs • PAMPs • DAMPs

13. The importance of innate immunity • A first line of defense • A means of directing adaptive immunity

14. Direct defense by innate immunityPhagocytosis

15. Direct defense by innate immunityAnti-microbial peptides

16. Direct defense by innate immunityAnti-viral response

17. Regulate adaptive immunity by innate immunityActivation of dendritic cells Dendritic cells present antigens to T lymphocytes

18. Regulate adaptive immunity by innate immunityEnhance antibody response B cells, which generate adaptive immunity, also express innate immune receptors. Simultaneous activation of both antigen-recognition and PAMP-recognition receptors induces strong antibody response.

19. The innate and adaptive immunity work together to defense our body.

20. Evolution of innate and adaptive immunity

21. Viral infection and antibody--- a lesson from HIV elite controller

23. A scientist’s view of AIDS • Prevention: vaccine • Treatment: anti-viral cocktail

24. HIV attacks immune system

25. HIV elite controller • Scott Wafrock (top left) has lived with HIV for 26 years, • Bob Massie (top right) for 34 years, • LoreenWillenberg (bottom right) for 20 years, • Doug Robinson (bottom left) learned he was HIV-positive in 2003. One out of 300 people infected with HIV are naturally able to control the virus without having to take antiviral medications.

26. Antibodies protect us from virus

27. Surface proteins of viruses are targeted by antibodies

28. Discovery of broadly-neutralizing antibodies in HIV elite controller

29. The diversity of immunoglobulin Membrane Ig: B cell signaling Soluble Ig: antibody Ig gene contains many gene segments which can form many different combinations.

30. B cells need to expand before producing antibodies

31. Antibody production needs the cooperation of many cell types

32. Can we design vaccines to induce broadly-neutralizing antibodies for HIV?

33. Can we cure AIDS? Timothy Ryan “Berlin Patient” In 2007, an HIV-infected man in Berlin received a transplant of haematopoietic stem cells from a naturally HIV-resistant donor. He has now been free of readily detectable virus in the absence of therapy for more than five years.

34. Towards the future of AIDS • Anti-viral therapy ✔ • Stem-cell transplant ? • HIV vaccine ? • Passive antibody therapy ?

35. Mucosal immunity--- why we are what we eat

36. We are what we eat

37. What we eat determines the bacterial flora (microbiota) in our gut.

38. An experiment by Jeffery Gordon’s lab

39. Human gut microbiota • The human body carries 100 trillion (1014) microorganisms in its intestines, 10 times more than the total number of human cells. • Beneficial roles of gut microbiota include: digestion, provide essential nutrients such as vitamin B and K, metabolize bile acids and xenobiotics.

40. What’s your gut type? Three major “enterotypes” were found in human, they are Bacteroides, Prevotella and Ruminococcus.

41. Diet microbiota metabolism

42. Commensals maintain immunity at epithelial borders

43. Commensal bacteria can provide protection through the creation of a hostile environment for pathogenic bacteria by the production of inhibitory compounds, by competing for adhesion sites, or by modulating the immune response.

44. Commensal bacteria are required to generate proper mucosal immunity.

45. Different subsets of T cells play a variety of functions in immune surveillance

46. Are there probiotics? No clinical proof yet!

47. Take home message • Our gut is not only for food digestion, but also an important immune organ. • We are living with large amount of microorganisms in our body and they shape our metabolism system and our immune responses. • Scientists are trying to find the “real” probiotics which can benefit human health.

48. Future Challenge--- what immunology can do for us

49. Despite remarkable advances in medical research and treatments during the 20th century, infectious diseases remain among the leading causes of death worldwide.

50. Challenges for prevention and treatment of infectious diseases • emergence of new infectious diseases SARS, Bird’s Flu, Super-bacteria • re-emergence of old infectious diseases Polios, Measles, tuberculosis • persistence of intractable infectious diseases AIDS, Hepatitis B, latent infection of Herpes viruses