22 - Immune Responses in Viral Infection Flashcards
(24 cards)
How is viral infection prevented
Type 1 IFN and neutralising antibodies
What is immune response to viruses triggered by
Innate immune sensing of viral nucleic aids
TLR3
In endosome, binds dsRNA and signals via TRIF to induced IFN gene expression
TLR7
In endosome, binds ssRNA and signals via MyD88 to induce IFN gene expression
Viral nucleic acids activate transcription factors (IRF proteins and NFkappaB)
Leads to translocation into the nucleus and activation of the production of IFN alpha and beta
Type 1 IFN
- Induce anti viral state
- Produced by most cell types in response to sensing by PRRs
- Plasmacytoid DCs produce high levels
Production of IFNα/β
- Rapid (within hours), declines by 10h
- IFN binding to IFN receptors leads to synthesis of >1000 cell proteins (IFN stimulated genes)
Example of IFN stimulated gene important in antiviral immunity
Tetherin (CD137)
Global effects of IL-1, IL-6 and TNF alpha
Fever, Fatigue, Sleep
What reflects the communication of innate and adaptive immune defense
- The classic inflammatory response (heat, swelling, redness, pain)
- No inflammatory response leads to ineffective adaptive response (reason for using adjuvants)
NK cell ‘missing self’
- NK Cell cytotoxic functions are inhibited by self antigens presented to them by abudany MHC class 1 on the surface of cells
- When these MHC class 1 molecules are reduced, the inhibitory NK cell receptor is not engaged, triggering NK cells to release effector proteins
ADCC
- Antibody binds antigens on surface of target cell
- FCγRIII (CD10) on NK cell recognise bound antibody
- Cross linking of receptor signals the NK cell to kill target cell by apoptosis
IFN-γ antiviral effects
- Produced by Th1 CD4 and CD8 cells
- Inhibits viral replication directly
- Upregulates expression of MHC and components of antigen processing pathway
- Activates macrophages, recruiting them to sites of infection as both effector cells and APCS
Generation of a primary anti viral T cell response
- Recognition of antigens on activated APCs by naive T cells during viral infection predominately results in the generation of Th1 cells due to the presence of type I IFNs and
IL-12 - Th17, Th2 and TReg cells are also generated to some degree in certain viral infections
Major mechanism for clearing viral infected cells
CD8 CTLs
CD8 CTLs
- Recognise complex of viral peptide with MHC class 1 and kills infected cells
- CTL responses are effective as they eliminate virus infected cells without damaging uninfected cells
- CTL kill infected cells via perforin and granzymes
CTL levels in typical cytopathic virus infection
- Appears within 3-5 days after infections
- Peaks about 1 week, declines thereafter
Bystander CD8 T cells
- Activated by IL-12 and IL-18 made by DCs
- Produce IFN-gamma to activate macrophages (no direct killing)
Viral evasion of MHC-1 presentation
- Producing abundant viral protein that is resistant to degradation by the proteasome, reducing viral epitope display (e.g. EBV)
- Encode proteins that block function of TAP, preventing transport of peptides from proteasome to ER (e.g. herpes)
- Degrade vesicles containing MHC-1 complexes
- Block MHC-1 complexes from leaving golgi body
How does HIV evade neutralising antibodies
- Via glycosylation of surface glycoproteins
- Additional N-linked glycosylation sites in the viral E gene confer escape from neutralisation
Two types of variation that allow repeated infection with Influenza virus
Antigenic drift and antigenic shift
Antigenic drift
Emergence of point mutations with altered binding sites for neutralising antibodies on the surface HA
Antigenic shift
Occurs when RNA segments are exchanged between viral strains in a secondary host (reassortment of segmented RNA genomes)
How can antiviral antibodies enhance infection and disease instead of neutralising it
- FcR mediated enhancement
- Immune complexes and inflammation
