IMI7: immune responses to intracellular pathogens Flashcards
what are the 2 main classes of intracellular microbes?
obligate intracellular pathogens
facultative intracellular pathogens
what are the 2 phases for dealing with an intracellular pathogen?
- detecting
2. destroying, inactivating or incapacitating the pathogen once it has been found
what are virions?
virus particles
what are the 3 elements that almost all virions have?
genome made of DNA and RNA
protein that packages the genome either like beads on a string (nucleoprotein) or in a protein shell (capsid)
external protein that binds specifically to a cell surface molecule allowing the virus to enter the cell
what are the 3 characteristics that vary between viruses?
DNA or RNA
whether they have a lipid envelop surrounding their packaged genome
if they explicate their genome in the cytoplasm or nucleus
how do non-envolopped viruses enter a cell?
endocytic route: Cathrin-mediated endocytosis and penetration
how do enveloped viruses enter a cell?
non-endocytic route: fusion at the cell surface
what are the 2 characteristics that help define PAMPs or DAMPs of intracellular pathogens?
nature of substance
location of substance
what is the easiest way to recognise nucleic acid?
when they are in a location where they should not be
what types of DNA sensor are there?
cGAS/STING, AIM2-like receptors
how do we sense eadosomal DNA?
TLRs
how do we recognise foreign RNA?
PRRs that recognise viral DNA do NOT rely on location but recognise features of viral RNAs that are NOT shared by cellular RNAs
virus RNA rely on their RNA polymerase to transcribed RNA from DNA which is unnatural in eukaryotic cell
what are the different types of RNA sensors?
RIG-I-like receptor (RLR) family
retinoic acid-inducible gene-I (RIG-I)
MDA5
how can viruses prevent the function of genome sensing innate immune proteins?
blocking the RNA sensing pathway
cap snatching
inhibition of DNA sensors
what are the 3 classes of interferons (IFNs)?
type I IFNs
type II IFNs
type III IFNs
what ae the roles of IFNs?
activate and attract cells of the immune system
establish an antiviral state in non-immune cells to control viral replication
==> do NOT save infected cells but warn all of the other surrounding cells
what is the antiviral state?
when IFN bind to its receptor and induces a signalling cascade that triggers the transcription of a large number of genes that code for proteins that help fight viruses
what are restriction factors?
cellular gene products that can prevent specific pathogen functions
what are the extracellular roles of antibodies?
opsonisation
neutralisation
complement activation
what are the functions of the complement system?
opsonisation
lysis
what happens to opsonins if the virus is enveloped?
opsonins may be left on the surface pf the cell which marks the infected cell
what happens to opsonins if the virus is not enveloped?
opsonins may be carried into the cell
what do antibodies do to viruses?
neutralise viruses
how do antibodies neutralise non enveloped viruses?
non enveloped virus flows through blood where they encounter antibodies and mark it out
the virus then goes into the cytoplasm of a cell then into nucleus
BUT antibody on the surface of the virus binds to TRIM21 (intracellular ab receptor)
TRIM21 catalyses the ligation of ubiquitin to itself which forms poly-ubiquitin chains
these chains are signals that recruit the proteasome (=cellular garbage factory)
proteasome begins to degrade the virus proteins into short peptides which disrupts the structure of the virus particle
the viral DNA left in the cytoplasm will act as PAMPs alerting the cells
where are the peptides for MHC class I presentation from?
come from intracellular (cytoplasmic) proteins
what is cross presentation?
process where extracellular antigen can cross from the extracellular to intracellular antigen presentation which is a way to present the antigen on MHC class I used by APCs (specially DCs)
what is the innate immune response to intracellular pathogens?
mediated by NK cells
what are the functions of NK cells?
important for the rapid clearance of viral infections
important complement to DC8+ T cells
on what does the activation of NK cells dependent on?
balance of inhibitory and activating receptors
what is the most important ligand for regulating the function of cytotoxic lymphocytes?
MHC class I
what happens when MHC class I interacts with NK cells?
inhibits signals regardless of what peptide is bound
what technique do neutrophils use to kill a pathogen?
carpet bombing approach
what technique do cytotoxic T cells and NK cells use to kill a pathogen?
demolition by releasing contents of cytotoxic granules and by producing IFN gamma
what are 3 ways in which pathogens can avoid the adaptive immune system?
changing the pathogen’s antigens so they are different from previous infections
adopting an evasive lifestyle
directly interfering with the generation of an adaptive immune response
how do viruses change their antigens?
gradual evolution to avoid previously developed adaptive immunity which is called antigenic drift
