viral evasion of host immunity

Question 1

what are viruses and what are they represented by?

Answer 1

• intracellular pathogens

- represented by MHC 1 mech

Question 2

what clears viral infection? What can be targets?

Answer 2

• cellular immunity clears viral infections but short lived

- interval viral proteins can be targets of this as they vary less than surface antigens

Question 3

name an evading virus

Answer 3

herpes simplex virus

Question 4

state 3 ways a virus can evade MHC

Answer 4

• evasion of antigen loading to TAP
• modulation of tapasin function and prevention of MHC transport
• interfering with MHC presentation at cell surface

Question 5

explain how 3 viruses evade their antigen being loaded to TAP (transporter associated with antigen processing)

Answer 5

• EBV: EBNA1 cannot be proteasome
• HSV: ICP47 blocks access of processes peptide to TAP
• CMV: US6 stops ATP binding to TAP so prevents translocation

Question 6

explain how 2 viruses modulate tapasin function and prevent MHC transport

Answer 6

CMV: US3 binds tapasin and prevents peptides being loaded to MHC
Adenovirus: E3-19K prevents recruitment of TAP to Tapasin, retains MHC in ER

Question 7

what does tapasin do?

Answer 7

• plays important role in stable assembly of class I molecules with peptide

Question 8

explain how 1 virus interfere with MHC presentation at cell surface

Answer 8

• KSHV: kK3 protein induces polyubiquitinylation at internalization of MHC
• from internalized endosome, MHC is passed to lysosomes

Question 9

describe the NK killing evasion

Answer 9

• normal healthy cell display MHC at surface
• cells that don’t display MHC are detected by NK cells –> killed
• viruses that disrupt MHC presentation would end up being killed by NK cells
• viruses can encode MHC analogues or upregulate MHC

Question 10

who does CMV infect?

Answer 10

• only immunocompromised
• problem for transplant recipients
• virus needs to be eliminated from bone marrow cells of transplant recipient before transplantaion

Question 11

what does antigenic variation occur due to?

Answer 11

• continued rapid evolution driven by antigenic pressure from host
• introduction of new subtypes from animal sources
• existing as a different stable serotypes that co-circulate in humans
• consequence of vaccination

Question 12

give an example when continued rapid evolution driven by antigenic pressure from host leads to variation

Answer 12

influenza antigenic drift

Question 13

what is antigenic drift?

Answer 13

change of antigens on a virus picked up from an infected cell that give it immunity to antibodies formed against old self

Question 14

give an example when introduction of new subtypes from animal sources cause variation

Answer 14

influenza antigenic shift

Question 15

name 2 viruses that exist as different stable serotypes

Answer 15

• rhinovirus (100s of serotypes): common cold, impossible to make vaccine
• Poliovirus (3 serotypes): one serotype completely eradicated, vaccine still trivalent
• dengue (4 serotypes)

Question 16

what are broadly neutralizing antibodies?

Answer 16

• produced as biological therapies
• can control viral load
• controls viral load but mutants do appear over time if used individually

Question 17

what does dengue fever cause?

Answer 17

• leakage of blood plasma from capillaries
• leads to inc. haematocrit and RBC count
• dec. protein count in blood
• causes severe bruising and bleeding
• patietns deteriorate even after fever due to shock

Question 18

how do you treat dengue fever?

Answer 18

IV fluids

Question 19

what is antibody dependent enhancement?

Answer 19

• dengue exists as 4 serotypes
• antibodies generated against previous infection can bind but not neutralise
• leads to ADE
• causes dengue haemorrhagic fever
• dengue viruses use ab as an access into monocyte and reproduce inside them

Question 20

state the 3 mechanisms of evasion of antibody response

Answer 20

• glycoprotein antigens
• apoptotic body disguise
• viral filaments

Question 21

describe how glycoprotein antigens leas to evasion of antibody response

Answer 21

heavily glycosylated that antibody access is hindered e.g. HIV

Question 22

describe how apoptotic body disguise leads to evasion of antibody response

Answer 22

• ebola virus particle membranes have high phosphatidl serien lipid content
• makes them look like apoptotic bodies
• taken up by micropinocytosis
• hidden from immune system

Question 23

how does ebola evade innate immune system?

Answer 23

VP35 and VP24 stops innate immune system from seeing Ebola

Question 24

how does ebola evade acquired immune sstem?

Answer 24

• ebola acts as apoptoptic bodies
• taken up and hidden
• also synthesizes soluble GPS to act as antibody decoys (sGPs)
• sGPs are immunosuppressive and inhibit neutrophils

Question 25

what does measles infect?

Answer 25

• CD150+ cells and memory lymphocytes

- erase immunological memory

Question 26

what can a measles infection result in?

Answer 26

2-3 year dec. in immunological memory

morbidity and mortality from other diseases

Question 27

what could the structure of the universal influenza vaccine?

Answer 27

• if we can make an antibody against haemagglutin 2 regions (conserved region)
• then we could theoretically be immune as it’s just the variable region that mutates
  = broadly neutralizing antibody