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IMMUNE RESPONSES TO INFLUENZA VIRUS
IMMUNE RESPONSES TO INFLUENZA VIRUS
3 to 5 millionSevere illness3 to 5 millionSevere illness
3 to 5 millionSevere illness
250,000 to 500,000 deaths
Outline1. Introduction2. Innate Immune Response3. Adaptive Immune Response4. Evading5. Vaccination
1. Introduction
Family of Orthomyxoviridae
3 types
◦ Influenza A virus
◦ Influenza B virus
◦ Influenza C virus
Epidemic
Respiratorydiseases
Pandemic
Spanish flu (1918-1920)50-100 million deaths (subtype of H1N1)
Asian flu (1956-1958)4 million deaths (H2N2)
Hong Kong flu (1968-1969)35,000 deaths (H3N2)
http://www.cdc.gov/flu/images/h1n1/3D_Influenza_transparent_key_pieslice_lrg.gif
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2. Innate response to influenza virus
Recognize pathogens through PAMPs (pathogen-associated molecular patterns)
- Body recognizes unique molecules of microorganism that are not associated with human cells
(carbohydrates, proteins, lipids, nucleic acids)
- PAMPs recognized by PRRs (pathogen recognition receptors)
3 classes of PRRs:- Retinoic acid inducible gene-I (RIG-I) Found in most cell types in cytosol Recognize ssRNA bearing 5’ triphosphate Induction of type I interferons
- Toll-like receptors (TLR-7) Recognize genomic RNA in endosomes of dendritic cells Both live & killed virus can induce type I IFN through TLR-7 Plays important role in development of adaptive immunity
-NOD-like receptors (NLRP3) Inflammasome senses damaged cells Involve an increase in disease tolerance
Induction of type I interferons & proinflammatory cytokines
- Infected epithelial cells produce type I interferons (IFN-α/β)
- PAMP-PRR interactions (TLR-7) induce macrophages & immature DCs at site of infection to produce:
+ Type I interferons
+ Proinflammatory cytokines (IL-1, IL-6, IL-12, TNF- α)
+ Chemokines (MIP-1alpha/beta, MCP-1, IL-8)
- Leads to amplification of the inflammatory response.
Type I interferons (INF-α/β)◦ Bind to IFNR triggers antiviral functions in the cell
-> Protect uninfected cells from virus infection
◦ Induce the influx and activation of NK cells
-> Kill infected epithelial cells before virus release
◦ Upregulate MHC class I expression
-> Make cells better targets for lysis
Role of natural killer cell- Can directly recognize & bind virus-infected cells through receptorsNatural cytotoxicity receptors (NKp46) recognizes HA
- Activated NK cells: + Produce a variety of cytokines (INF-gamma), chemokines + Important bridge between innate and adaptive immunity
Roles of dendritic cells
CONVENTIONAL DENDRITIC CELLS (CDC)
+ Main function: antigen presentation
+ Response to virus in TLR-independent manner
PLASMACYTOID DENDRITIC CELLS (PDC)
+ Main function: IFN-type I producing cells
+ Ability to retain RNA & DNA in TLR-containing endosomes
-> better interaction of viral nucleic acid and TLR
- 2 subsets:
- DCs are central to initiation and regulation of adaptive immune response
3. Adaptive Immunity
Humoral Immunity1. Viral HA:◦ Ab directed to globular head of HA => sterilize immunity to virus infection.
◦ Ab block receptor-mediated endocytosis.
Humoral immunity2. Viral NA:◦ Ab interfere with the last phase of viral replication cycle
◦NA-specific Abs do not neutralize the virusÞLimit the viral spread & shorten duration of illness.Þ contribute to clearance of virus-infected cells
Cellular Immunity1. CD4+ T cells
• Associated with MHC class II
a. Th2: produce IL-4, IL-5, IL-13
=> promote activation of B cells
b. Th1: produce IFN-, IL-2
=> promote CTL response
Cellular immunity2. CD8+
T Cells
◦ Activated after recognition of viral epitopes with MHC class I
=> Subsequently mature into CTLs
3. Regulatory T cells and Th17 cells
a. Tregs: balances the immune response
=>control CD4+ T cells an CTL responses
b. Th17 cells: produce IL-6
=> inhibit the effect of Tregs & promote T helper responses
4. How influenza virus escapes from immunity?
Escape from innate immunity
◦ NS1 protein inhibits type I Interferon ◦ Other proteins interfere with host responses (PB1, PB2, PA)
Escape from Humoral Immune Response
ANTIGENIC DRIFT
◦ Small changes, happend continually
◦ Produce viruses with same antigenic
properties
◦ Small changes accumulated
antigenic difference
ANTIGENIC SHIFT
◦ Abrupt, major changes in influenza A
◦ Results in new influenza A subtype
(different hemagglutinin,
neuraminidase)
◦ People are lack of protection against
the new virus
http://www.organicbestchoices.com/page/333070235
Escape from cellular immune response
Evade recognition by virus-specific T cells:
◦ Viruses with large DNA genome: encode proteins interfering with antigen processing, presentation pathways
◦ RNA viruses : + evade recognition by T cells
+ selective pressure exerted by virus-specific T cells
http://www.mdpi.com/1999-4915/4/9/1438/htm
5. Influenza Virus Vaccination
Influenza Virus Vaccination
Annual Vaccination Can be trivalent or quadrivalent vaccine:
◦ One influenza type A subtype H1N1 virus strain◦ One influenza type A subtype H3N2 virus strain◦ One or two influenza type B virus strains
Can be an injection or a nasal spray.
Time for Influenza Virus Vaccination
Influenza Virus Vaccination should begin ideally by October.
Should continue to be offered throughout the flu season
How Influenza Virus Vaccine Works
Take about two weeks after vaccination Activate the immune system to provide antibodies against influenza virus
For the first time of vaccination, 2 doses are needed. From second time, 1 dose is enough.
Who should get influenza virus vaccination each year
Children aged 6 months until their 5th birthday Pregnant women People ≥ 50 years old People of any age with chronic medical conditions People living in long-stay facilities People who live with or care for those at high risk for complications from flu
Types of Influenza Virus Vaccine
Inactivated vaccine:◦ Intramuscular◦ Split virus and subunit types◦ Duration of immunity of 1 year or less
Live attenuated vaccine:◦ Intranasal◦ Using the technique of cold-adaptation◦ Duration of immunity at least 1 year
Who should not be vaccinated with live attenuated influenza vaccine
Children < 2 years of age
Who should not be vaccinated with live attenuated influenza vaccine
Children < 2 years of age
Who should not be vaccinated with live attenuated influenza vaccine
Children < 2 years of age
People ≥ 50 years old
People with a medical condition that places them at high risk for complications from influenza
Children < 5 years old with a history of recurrent wheezing
Children or adolescent taking aspirin
People with a history of Guillain-Barré syndrome
Pregnant women
People with a severe allergy to chicken eggs or any of the nasal spray vaccine components.
Syndrome after vaccination
Begin within 6-12 hours and persists for 1-2 days◦ Fever◦ Malaise◦ Headache◦ Arthralgia◦ Myalgia◦ Guillain-Barré syndrome (GBS)◦ Immediate allergic reaction
Thanks for your special attention!
Group 7: ◦ Hồ Hoàng Anh
◦ Nguyễn Thị Hồng Hà
◦ Trần Thu Hà
◦ Thái Tuyết Ngân
◦ Đặng Thị Minh Nguyệt
Thanks for your special attention!
Group 7: ◦ Hồ Hoàng Anh
◦ Nguyễn Thị Hồng Hà
◦ Trần Thu Hà
◦ Thái Tuyết Ngân
◦ Đặng Thị Minh Nguyệt
Thanks for your special attention!
Group 7: ◦ Hồ Hoàng Anh
◦ Nguyễn Thị Hồng Hà
◦ Trần Thu Hà
◦ Thái Tuyết Ngân
◦ Đặng Thị Minh Nguyệt
