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

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immunology prevention and treatment of infectious diseases

Immunology --- prevention and treatment of infectious diseases

Zhaolin Hua

Institute of Biophysics, CAS

slide2

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

the two arms of immune system
The Two Arms of Immune System

Innate

Adaptive

Jansson, Eugène Fredrik

adaptive immune system
Adaptive immune system

B cell

T cell

  • Immunoglobulin (antibody)
  • T cell receptor
  • recognition of fast evolved virus or bacteria
a prediction by immunologist dr janeway
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)

some examples of pamps
Some Examples of PAMPs

Virus DNA

Bacterial cell wall

flies also need immunity
Flies also need immunity

Hoffmann JA

Normal

Mutant

Mutation of a single gene called “Toll” make the flies susceptible to fungal infection.

toll like receptor can recognize lps
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.

pattern recognition
Pattern recognition
  • Pattern Recognition Receptors
  • TLRs
  • NLRs
  • CLRs
  • RLRs
  • PAMPs
  • DAMPs
the importance of innate immunity
The importance of innate immunity
  • A first line of defense
  • A means of directing adaptive immunity
regulate adaptive immunity by innate immunity activation of dendritic cells
Regulate adaptive immunity by innate immunityActivation of dendritic cells

Dendritic cells present antigens to T lymphocytes

regulate adaptive immunity by innate immunity enhance antibody response
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.

a scientist s view of aids
A scientist’s view of AIDS
  • Prevention: vaccine
  • Treatment: anti-viral cocktail
hiv elite controller
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.

the diversity of immunoglobulin
The diversity of immunoglobulin

Membrane Ig: B cell signaling

Soluble Ig: antibody

Ig gene contains many gene segments which can form many different combinations.

can we cure aids
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.

towards the future of aids
Towards the future of AIDS
  • Anti-viral therapy ✔
  • Stem-cell transplant ?
  • HIV vaccine ?
  • Passive antibody therapy ?
human gut microbiota
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.
what s your gut type
What’s your gut type?

Three major “enterotypes” were found in human, they are Bacteroides, Prevotella and Ruminococcus.

slide41

Diet

microbiota

metabolism

slide43

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.

are there probiotics
Are there probiotics?

No clinical proof yet!

take home message
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.
slide49

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

challenges for prevention and treatment of infectious diseases
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

slide51

Interdisciplinary approach to tackle the problem

Stem cell technique

DNA sequencing

vaccine

bioinformatics

Structural biology

Monoclonal antibody

Drug screening

collaboration collaboration collaboration
Collaboration, collaboration, collaboration
  • Health issue is important for both economic and politic reasons.
  • New techniques promote scientific discoveries.
  • Scientific collaborations create new opportunities.
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