Immunology prevention and treatment of infectious diseases
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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

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Immunology prevention and treatment of infectious diseases

Immunology --- prevention and treatment of infectious diseases

Zhaolin Hua

Institute of Biophysics, CAS


Immunology prevention and treatment of infectious diseases

  • 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

Innate Immunity--- the new frontier of immunology


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


Do lower rank animals have immunity

Do lower-rank animals have immunity?


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.


Identification of the family of toll like receptors

Identification of the family of Toll-like receptors

Tapping R


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


Direct defense by innate immunity phagocytosis

Direct defense by innate immunityPhagocytosis


Direct defense by innate immunity anti microbial peptides

Direct defense by innate immunityAnti-microbial peptides


Direct defense by innate immunity anti viral response

Direct defense by innate immunityAnti-viral response


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.


The innate and adaptive immunity work together to defense our body

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


Immunology prevention and treatment of infectious diseases

Evolution of innate and adaptive immunity


Viral infection and antibody a lesson from hiv elite controller

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


A scientist s view of aids

A scientist’s view of AIDS

  • Prevention: vaccine

  • Treatment: anti-viral cocktail


Hiv attacks immune system

HIV attacks immune system


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.


Antibodies protect us from virus

Antibodies protect us from virus


Surface proteins of viruses are targeted by antibodies

Surface proteins of viruses are targeted by antibodies


Discovery of broadly neutralizing antibodies in hiv elite controller

Discovery of broadly-neutralizing antibodies in HIV elite controller


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.


B cells need to expand before producing antibodies

B cells need to expand before producing antibodies


Antibody production needs the cooperation of many cell types

Antibody production needs the cooperation of many cell types


Can we design vaccines to induce broadly neutralizing antibodies for hiv

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


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 ?


Mucosal immunity why we are what we eat

Mucosal immunity--- why we are what we eat


We are what we eat

We are what we eat


Immunology prevention and treatment of infectious diseases

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


An experiment by jeffery gordon s lab

An experiment by Jeffery Gordon’s lab


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.


Immunology prevention and treatment of infectious diseases

Diet

microbiota

metabolism


Commensals maintain immunity at epithelial borders

Commensals maintain immunity at epithelial borders


Immunology prevention and treatment of infectious diseases

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.


Immunology prevention and treatment of infectious diseases

Commensal bacteria are required to generate proper mucosal immunity.


Different subsets of t cells play a variety of functions in immune surveillance

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


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.


Future challenge what immunology can do for us

Future Challenge--- what immunology can do for us


Immunology prevention and treatment of infectious diseases

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


Immunology prevention and treatment of infectious diseases

Interdisciplinary approach to tackle the problem

Stem cell technique

DNA sequencing

vaccine

bioinformatics

Structural biology

Monoclonal antibody

Drug screening


Technology development reduces the cost of dna sequencing and synthesis

Technology development reduces the cost of DNA sequencing and synthesis


Genome diagnosis is possible now

Genome diagnosis is possible now


Genetic diagnosis of immune deficiency

Genetic diagnosis of immune deficiency


H7n9 viral evolution was solved quickly by sequencing and bioinformatic study

H7N9 viral evolution was solved quickly by sequencing and bioinformatic study


Intellectual vaccine design

Intellectual vaccine design


Vaccines are not only for prevention but can also be used for therapeutic purposes

Vaccines are not only for prevention, but can also be used for therapeutic purposes.


Drug screening where modern science meets traditions

Drug screening ---where modern science meets traditions


Artemisinin for drug resistant malaria

Artemisinin (青蒿素)--- for drug-resistant malaria


Drug screening from small molecules to natural products

Drug screening --- from small molecules to natural products


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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