Transcript Immunology --- prevention and treatment of infectious diseases

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
--- what immunology can do for us
Innate Immunity
--- the new frontier of immunology
The Two Arms of Immune System
Innate
Adaptive
Jansson, Eugène Fredrik
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
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
Virus DNA
Bacterial cell wall
Do lower-rank animals have
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
LPS (lipopolysaccharide)
• Produced by Gram-negative bacteria
• Causes septic shock in human
A mouse strain that is susceptible to Gramnegative bacterial infection was found to bear a
mutation in Toll-like receptor 4.
Identification of the family of Toll-like receptors
Tapping R
Pattern recognition
Pattern
Recognition
Receptors
•TLRs
•NLRs
•CLRs
•RLRs
PAMPs
DAMPs
The importance of innate
immunity
• A first line of defense
• A means of directing adaptive immunity
Direct defense by innate immunity
Phagocytosis
Direct defense by innate immunity
Anti-microbial peptides
Direct defense by innate immunity
Anti-viral response
Regulate adaptive immunity by innate immunity
Activation of dendritic cells
Dendritic cells
present antigens to
T lymphocytes
Regulate adaptive immunity by innate immunity
Enhance antibody response
B cells, which generate adaptive immunity, also express innate
immune receptors. Simultaneous activation of both antigenrecognition and PAMP-recognition receptors induces strong antibody
response.
The innate and adaptive immunity work
together to defense our body.
Evolution of innate and adaptive immunity
Viral infection and antibody
--- a lesson from HIV elite controller
A scientist’s view of AIDS
• Prevention: vaccine
• Treatment: anti-viral cocktail
HIV attacks immune system
HIV elite controller
•Scott Wafrock (top left) has
lived with HIV for 26 years,
•Bob Massie (top right) for 34
years,
•Loreen Willenberg (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.
Antibodies protect us from virus
Surface proteins of viruses are
targeted by antibodies
Discovery of broadly-neutralizing
antibodies in HIV elite controller
The diversity of immunoglobulin
Membrane Ig:
B cell signaling
Soluble Ig:
antibody
Ig gene contains many gene segments which can form many different
combinations.
B cells need to expand before
producing antibodies
Antibody production needs the
cooperation of many cell types
Can we design vaccines to induce broadlyneutralizing antibodies for HIV?
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
•
•
•
•
Anti-viral therapy ✔
Stem-cell transplant ?
HIV vaccine ?
Passive antibody therapy ?
Mucosal immunity
--- why we are what we eat
We are what we eat
What we eat determines the bacterial flora
(microbiota) in our gut.
An experiment by Jeffery Gordon’s lab
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?
Three major “enterotypes” were found in human, they are
Bacteroides, Prevotella and Ruminococcus.
Diet
microbiota
metabolism
Commensals maintain immunity at
epithelial borders
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.
Commensal bacteria are required to generate proper mucosal immunity.
Different subsets of T cells play a variety of
functions in immune surveillance
Are there probiotics?
No clinical proof yet!
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.
Future Challenge
--- what immunology can do for us
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
• 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
Interdisciplinary approach to tackle the problem
Stem cell technique
DNA sequencing
vaccine
prevention
Structural biology
diagnosis
treatment
Drug screening
bioinformatics
Monoclonal antibody
Technology development reduces the cost
of DNA sequencing and synthesis
Genome diagnosis is possible now
Genetic diagnosis of immune deficiency
H7N9 viral evolution was solved quickly by
sequencing and bioinformatic study
Intellectual vaccine design
Vaccines are not only for prevention, but
can also be used for therapeutic purposes.
Drug screening ---where modern
science meets traditions
Artemisinin (青蒿素）
--- for drug-resistant malaria
Drug screening --- from small
molecules to natural products
Collaboration, collaboration, collaboration
•Health issue is important for both
economic and politic reasons.
•New techniques promote scientific
discoveries.
•Scientific collaborations create new
opportunities.