Virology 4 &5 Flashcards
- Explain what Type I and Type II interferons are and how they act in host defense against viruses.
most cells respond to infection by releasing type I IFN and there are two subclasses of type I IFN, a and B (bind to same host cell), immune cells secrete type II IFN or INF-gamma,
both IFN have direct antiviral activity and act synergistically against viruses
IFN is not specific for a virus but is species specific
- Explain how viruses inhibit interferon activity.
block IFN signaling pathways:
bind to signaling components
bind to transcription factors
degrade signaling components or transcription factors
interfere with double stranded RNA activating signal
ind to IFN induced proteins but don’t activate them
phosphorylatation of PKR (inactivating)
- Describe the roles played by the following cells in a viral infection: CD4+, CD8+.
T-cells are activated and migrate to site of infection and reaction varies with type of virus
CD4+ migrate to site of infection and secrete cytokines such as IFN-y (direct antiviral effects)
CD8+ migrate to site of infection and begin attacking cells (only those expressing MHC class I with viral epitope) and can release perforins and granzymes (apoptotic pathways)
- Describe the roles played by the following cells in a viral infection: NK cells and neutrophils.
PMN infiltrate (earliest cell) the infection site in response to cytokines and release more cytokines to attract T-cells, also phagocytose at site of infection; both are attracted by IL-6
NK look for normal MHC class I expression (blocked binding by glycoproteins or down regulate co-stimulatory factors), NK activity peaks early
- Describe the roles played by the following cells in a viral infection: macrophages and APC.
APC pick up viral antigens and traffic to local draining lymph nodes, cytokine release can activate the antigen presenting cell, macrophages are also activated and act as APC cells as well as endocytose virally infected debris
- Describe the roles played by the following cells in a viral infection: B cells.
activated by APC and produce antigen specific antibodies
- Describe the ways in which antibodies contribute to the defense against viruses.
overlap the binding sites for viral attachment
bind two protein molecules on the virus surface preventing conformational change
can trigger permanent conformational changes in viruses
neutralize by aggregation (promotes phagocytosis)
- Describe how viral neutralization and opsonization involved in viral defense.
complement recognizes exposed Fc portion of viral or bound antibodies and triggers activation, resulting in membrane attack complex (punch holes in infected cells)
- Which classes of antibodies are involved in viral defense?
IgM secreted first during infection, acutely only, (can be dx) and then isotope switching where IgA or IgG subclasses are generated (viral infections can lead to IgE production)
- How can enhancing antibodies make disease worse?
viral infections elicit synthesis of antibodies that do not neutralize the virus particles, especially if there is more than one serotype (ie. Dengue fever initiates antibodies to one serotype, but when it cross reacts with another serotype it is not neutralizing)
**additionally infection of macrophages by Dengue fever leads to release of large amounts of TNF-a
- Describe the mechanisms by which viruses interfere with immune responses.
destroy or modify the signal transduction system: target Stat proteins (transcription factors of IFN)
blocking enzymes in pathway, digested by viral proteases, phosphorylated by viral kinases, produce small RNAs that bind to effector proteins
soluble cytokine receptors (decoy)
some viral glycoproteins act as Fc receptors, bind opposite end of antibodies or bind complement
direct infection of T cells (measles or HIV)
suppression of antigen processing presentation and recognition (HCMV prevents transport from ER, HIV endocytosis and destruction of class 1 molecules)
- Describe the roll of innate and cellular resistance mechanisms such as Toll-like receptors, RIG-I, MDA5 and APOBEC proteins in viral infection.
TLRs (3, 7,8,9 are intracellular) recognize nucleic acid structures of viruses and trigger synthesis of type 1 interferon, pro-inflammatory cytokines and antimicrobial peptides (most common pathway involves MyD88 activation of NFkB- enters nucleus and turns on genes), up regulation of genes encoding cheekiness and cytokines
Describe some of the innate defense factors of skin and mucosal surfaces.
keratinized skin, skin secretions (inactivating and acidic) and skin microbiota
mucous: long chain carb polymers that contain large amounts of silica (sticky)
salicylic acid can act as a receptor trap
defensins (a-defensins, B-defensins and cathelecidins)
lactoferrin interfere with attachment of some viruses to cells and can be veridical
saliva continues proteins that bind and inactivate viruses (HIV in particular)
some mucosal surfaces are ciliated and many slough frequently
Name innate defenses of the GI tract.
low pH (low pH prior to attachment)
proteases inactivate (some require protease for activation)
bile salts: dissolve viral envelopes
lipases: attack lipid envelopes
peptide secretion that prevents attachment
mucosal layer and peristaltic action
Describe how age effects severity of viral infection.
measles, polio and mumps more severe in adults (acute illnesses)
infants infected with HVB or EBV have longer chronic infection, or associated cancer (persistent infection)
neonates are particularly susceptible to sever infection with a number of viruses because their immune systems are not fully functional
differences du to the functional status of the immune system
