Viral immune evasion Flashcards
What are the main functions of antibodies?
Antibody neutralizes extracellular virus blocks viral attachment proteins (Glycoproteins, capsid proteins); destablises viral structure
Antibodies opsonize virus for identification for phagocytosis; promotes lysis and destruction of the target cell through the complement cascade, and antibody-dependent cellular cytotoxicity; resolves lytic viral infections; blocks the viraemic spread of target tissue.
What is the function of IgM in terms of viral infections?
IgM indicator of recent/current infections
Which Ig type is the most effective antiviral?
IgG
Which Ig is cardinal for the protection of mucosal surfaces?
IgA
How is a viral infection resolved?
Resolution of infection requires elimination of free virus (antibody agglutination), and the virus-producing cell (immune-cell mediated lysis)
How do rhinoviruses evade antibodies?
Rhinoviruses display antigenically distinct serotypes; multivalent required
How does HIV evade antibodies?
Exist as multiple clades/quasispecies
How does Hepatitis B virus (HBV) and Ebola evade antibodies?
`Encode secreted surface antigens, that remove associated antibody, preventing it from reaching viral particles/infected cells
How many serotypes are present for the Dengue virus?
4
How does serotyping cause antibody evasion for Dengue virus?
1) Previous infection with one serotype followed by infection with different serotype results in antibody-dependent enhancement of disease
2) Virus enters immune cells via antibody & Fc-receptor.
3) Triggers Dengue hemorrhagic fever. Antibodies present from primary DENV infection bind to infecting DENV particle - primary antibodies cannot neutralize the virus
AB-Virus complex attaches tp Fcy receptors on monocytes, assisting in infection mechanism
How do DENV particles enter into immune cells?
Antibody via Fc receptor
Which type of fever is triggered by DENV?
Hemorrhagic fever
How does the influenza virus evade antibodies?
Influenza viruses mutate frequency evolving, attributing to antigenic drift
Influenza viruses acquire new antigens by reassortment with animal viruses (Antigenic shift) - leads to pandemics,
Alters neuraminidase and haemaglglutinin structure
What is antigenic drift?
Mutations causes changes in antigenic viral structure
What is the antigenic shift?
Influenza viruses acquire new antigens by reassortment with animal viruses.
Which antiviral agents are produced from virally infected cells?
Interferons (IFN)
Which viral molecules induces the synthesis of interferons?
Double-stranded RNA
RNA that lacks a 5’ cap
Cytoplasmic DNA
Which receptors to interferons bind to?
Interferon receptors
What response is initiated upon interferon binding on surrounding cells?
Induces antiviral state
Which cell cannot induce an antiviral state?
The infected host cell secreting interferons
Which genes are activated and transcribed upon activation of antiviral state?
Genes that are transcribed inhibit viral replication (2’5’ oligoadenylate synthetase and protein kinase R - this degrades viral & host RNA
What function is performed by 2’5’oligoadenylate synthetase?
Degrades viral and host RNA
Which immune cell is mainly activated by interferons?
Natural killer cells
What are the three types 1 IFNs?
IFN-alpha
betab
Beta
Which cells secreted type 1 IFNs?
All cells
Which IFN receptor is present on all tissues?
IFN-alpha Receptor
Which cells are specialized IFN-alpha secreting?
Plasmacytoid dendritic cells
How many genes exist for IFN-B?
1
How many isotypes exist for IFN-a?
13/14 isotypes
Which IFN type is IFN-y?
Type II
Which cells secrete IFN-y?
NK cells and activated T cells
Which receptor is activated by IFN-y?
IFN-yR
Which type of interferon is IFN-lambda?
Type III
Which receptors are IFN-Lambda signaled through?
IL28R
IL10-B
These are known as IFN-delta receptors, mainly present on epithelial surfaces
How do HBV and influence develop resistance to interferon action?
Blocks the production of interferon by inhibition of IFN transcription
Produce protein NS1 that counters RNA sensing and prevents polyA processing
How are NK cells activated in terms of an antiviral response?
IFN-alpha
Interleukin-12
How are macrophages activated in terms of an antiviral response?
Activated NK cells secrete IFN-y binds to macrophage IFNyRs
What is the function performed by activated NK cells during an antiviral response?
NK cells target and kill virus-infected cells (enveloped viruses)
Secrete IFN-y to activate macrophages
A reduction in which cell surface molecules results in NK cytotoxic response?
Reduction in the number of functional MHCI molecules
Which viruses are responsible for reducing MHC-I surface molecules in infected cells?
Cytomegalovirus
Herpes Simplex Virus
Which type of lymphocytes are NK cells classified as?
Group 1 innate lymphocytes (ILCs)
Which type of NK receptors regulate cytotoxicity?
Inhibitory receptors
What is the function performed by inhibitory receptors?
Recognizing cognate MHC-I, and inactivates NK cells- preventing cell lysis
What happens to cells which lose MHC-I?
Vulnerable to cytotoxic granules containing perforin and granzymes being secreted- lysis of target cell
What is the function performed by macrophages during an anti-viral response?
Macrophages filter viral particles from blood; inactivate opsonized virus particles
What is the function performed by dendritic cells during an anti-viral response?
Plasmocytoid dendritic cells produce IFN-alpha and other cytokines
Initiate and determine nature of CD4 and CD8 T-cell response
Dendritic cells undergo antigen presentation - presents antigen to CD4 T cells
Which type of viral infections are controlled by T-cells?
Controls enveloped and noncytolytic viral infections, recognize viral peptides presented by MHC molecules associated on cell surface membrane
What are linear epitopes?
Antigenic viral peptides derive from viral proteins (Glycoproteins and nucleoproteins)
What T cells are cytotoxic?
CD8, responds to MHC1 protein complexes on infected cells
What are Th2 responses?
Required for humoral immunity- can be detrimental if they prematurely limit the Th1 inflammatory and cytolytic response
How do viruses evade T cells?
Herpes Simplex HSV, and cytomegalovirus CMV encode proteins that interfere with MHC antigen processing pathway
Viruses impair lymphocyte function: HIV kills CD4 T cells, and alters macrophage function
HSV prevents CD8 T cell lysis
