IMI7: immune responses to intracellular pathogens

Question 1

what are the 2 main classes of intracellular microbes?

Answer 1

obligate intracellular pathogens

facultative intracellular pathogens

Question 2

what are the 2 phases for dealing with an intracellular pathogen?

Answer 2

1. detecting

2. destroying, inactivating or incapacitating the pathogen once it has been found

Question 3

what are virions?

Answer 3

virus particles

Question 4

what are the 3 elements that almost all virions have?

Answer 4

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

Question 5

what are the 3 characteristics that vary between viruses?

Answer 5

DNA or RNA
whether they have a lipid envelop surrounding their packaged genome
if they explicate their genome in the cytoplasm or nucleus

Question 6

how do non-envolopped viruses enter a cell?

Answer 6

endocytic route: Cathrin-mediated endocytosis and penetration

Question 7

how do enveloped viruses enter a cell?

Answer 7

non-endocytic route: fusion at the cell surface

Question 8

what are the 2 characteristics that help define PAMPs or DAMPs of intracellular pathogens?

Answer 8

nature of substance

location of substance

Question 9

what is the easiest way to recognise nucleic acid?

Answer 9

when they are in a location where they should not be

Question 10

what types of DNA sensor are there?

Answer 10

cGAS/STING, AIM2-like receptors

Question 11

how do we sense eadosomal DNA?

Answer 11

TLRs

Question 12

how do we recognise foreign RNA?

Answer 12

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

Question 13

what are the different types of RNA sensors?

Answer 13

RIG-I-like receptor (RLR) family
retinoic acid-inducible gene-I (RIG-I)
MDA5

Question 14

how can viruses prevent the function of genome sensing innate immune proteins?

Answer 14

blocking the RNA sensing pathway
cap snatching
inhibition of DNA sensors

Question 15

what are the 3 classes of interferons (IFNs)?

Answer 15

type I IFNs
type II IFNs
type III IFNs

Question 16

what ae the roles of IFNs?

Answer 16

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

Question 17

what is the antiviral state?

Answer 17

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

Question 18

what are restriction factors?

Answer 18

cellular gene products that can prevent specific pathogen functions

Question 19

what are the extracellular roles of antibodies?

Answer 19

opsonisation
neutralisation
complement activation

Question 20

what are the functions of the complement system?

Answer 20

opsonisation

lysis

Question 21

what happens to opsonins if the virus is enveloped?

Answer 21

opsonins may be left on the surface pf the cell which marks the infected cell

Question 22

what happens to opsonins if the virus is not enveloped?

Answer 22

opsonins may be carried into the cell

Question 23

what do antibodies do to viruses?

Answer 23

neutralise viruses

Question 24

how do antibodies neutralise non enveloped viruses?

Answer 24

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

Question 25

where are the peptides for MHC class I presentation from?

Answer 25

come from intracellular (cytoplasmic) proteins

Question 26

what is cross presentation?

Answer 26

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)

Question 27

what is the innate immune response to intracellular pathogens?

Answer 27

mediated by NK cells

Question 28

what are the functions of NK cells?

Answer 28

important for the rapid clearance of viral infections

important complement to DC8+ T cells

Question 29

on what does the activation of NK cells dependent on?

Answer 29

balance of inhibitory and activating receptors

Question 30

what is the most important ligand for regulating the function of cytotoxic lymphocytes?

Answer 30

MHC class I

Question 31

what happens when MHC class I interacts with NK cells?

Answer 31

inhibits signals regardless of what peptide is bound

Question 32

what technique do neutrophils use to kill a pathogen?

Answer 32

carpet bombing approach

Question 33

what technique do cytotoxic T cells and NK cells use to kill a pathogen?

Answer 33

demolition by releasing contents of cytotoxic granules and by producing IFN gamma

Question 34

what are 3 ways in which pathogens can avoid the adaptive immune system?

Answer 34

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

Question 35

how do viruses change their antigens?

Answer 35

gradual evolution to avoid previously developed adaptive immunity which is called antigenic drift