Host Response to Viral Infection

Question 1

Physical barriers are part of which type of immunity?

Answer 1

innate

Question 2

Which cells produce the mucociliary blanket and what does it do?

Answer 2

goblet cells; innate physical defense that traps larger particles so they can be swallowed or coughed out

Question 3

What 2 things do cytoplasmic granules of NK cells contain?

Answer 3

perforin: produce pores in plasma membranes
granzymes: initiate apoptosis

Question 4

What activates NK cells?

Answer 4

in virus infected cells, MHC I expression reduced so inhibitory receptors aren’t engaged and ligands for activating receptors are expressed

Question 5

PAMPs

Answer 5

macromolecules present in viruses and other microbes but not host cells -> recognized by PRRs

Question 6

PRR

Answer 6

expressed on a variety of cells including macs, DC, neutrophils, NK cells, endothelial cells, mucosal epithelial cells

Question 7

Binding of PAMP to a TLR on a macrophage results in what?

Answer 7

phagocytosis
chemotaxis
inflammatory mediators
IFN

Question 8

Which important interleukins are relased when PRRs are ligated by PAMPs?

Answer 8

IL1 and IL12

Question 9

Do interferons show virus specificity?

Answer 9

NAH

Question 10

T/F RNA viruses are stronger inducers of IFN than DNAviruses

Answer 10

troooo

Question 11

How should interferons be administered to a patient?

Answer 11

parenteral route (injection) since they are orally inactive

Question 12

Type 1 IFN

Answer 12

IFN a

IFN B

Question 13

IFN a

Answer 13

leukocyte interferon

• produced in large quantities by plasmacytoid DC
• produced in smaller amounts by macs, monocytes and lymphocytes
• not host specific

Question 14

IFN B

Answer 14

• fibroblast interferon secreted by virus-infected fibroblast
• generally host species specific

Question 15

roles of type 1 IFNs

Answer 15

• inhibit virus replication
• activate NK cells
• increase MHC I expression
• stimulate differentiation of monocytes into DC
• maturation of DC
• stimulates memory T cell proliferation

Question 16

How do Type I IFNs inhibit virus replication?

Answer 16

• activate RNAse L -> degrades viral RNA
• induce synthesis of MX proteins that bind and trap viral nucleocapsid and inhibit virus assembly
• induce synthesis of PKR which prevents initiation of translation of viral RNA

Question 17

Type II IFN

Answer 17

• IFN gamma
• mostly immunoregulatory
• produced by antigen-stimulated T cells and NK cells
• labile at pH 2
• host specific

Question 18

functions of IFN gamma

Answer 18

• increased MHC expression
• mac activation
• TH1 effector cells
• isotype switching to opsonizing and complement-fixing antibodies

Question 19

Type III IFN

Answer 19

• IFN lambda1, IFN lambda2, IFN lambda3
• expressed in response to viral infections and activation of TLR
• mainly immunoregulator
• recently discovered

Question 20

gene silencing

Answer 20

RNAi-endonuclease complex binds to mRNA complementary to RNAi and chops off viral mRNA into small pieces
*can disrupt viral replication

Question 21

granulocytosis

Answer 21

presence in peripheral blood of an increased # of granulocytes (neutrophils, eosinophils, basophils, mast cells)
*usually not provoked by viral infections

Question 22

T/F antibodies may be directed against viral proteins on free virions (capsid or envelope) or against viral proteins expressed on surface of infected cells

Answer 22

T

Question 23

virus neutralization

Answer 23

neutralizing antibodies prevent virus attachment and entry into host cells; bind to viral capsid or host envelope

Question 24

opsonization

Answer 24

coating of virions with antibodies so its more easily recognized and phagocytosed by macs and sometimes neutrophils

Question 25

IC formation

Answer 25

clumping of viruses; reduced # of viral particles available for cell invasion

Question 26

chemotaxis

Answer 26

attracting macs and neutrophils

Question 27

lysis

Answer 27

rupturing membranes of foreign cells/pathogens

Question 28

agglutination

Answer 28

clustering and binding of pathogens together

Question 29

ADCC

Answer 29

- antibodies bind antigens on target cells - NK cell CD16 Fc receptors recognize cell-bound antibodies - cross-linking of CD16 triggers degranulation into lytic synapse - infected cells die by apoptosis

Question 30

antigenic plasticity

Answer 30

rapid changes in structure of viral antigen that may be the result of mutation, reassortment or recombination -> virus may become resistant to immunity generated by previous infection

Question 31

antigenic multiplicity

Answer 31

antigenic variants with little or no cross-reactivity -> immunity against one serotype may not work against other variants

Question 32

negative cytokine regulation

Answer 32

- blocking IFN receptor signal - virokines - viroreceptors

Question 33

virokines

Answer 33

some viruses synthesize proteins which are homologs of cytokines e.g. E-B has vIL10 which suppresses cytokine production by TH1 CD4 cells

Question 34

viroreceptors

Answer 34

some viruses encode proteins that are homologous to receptors for cytokines; secreted cytokine receptor homologs bind to cytokines and serve as competitive agonist (poxviruses)

Question 35

down-regulation of MHC I pathway

Answer 35

interfere with expression of MHC I molecules and inhibit antigen presentation *form of evasion

Question 36

inhibition of complement activation

Answer 36

- vaccinia virus has VAP which binds C4b to inhibit classical complement pathway - glycoprotein of herpes simplex virus binds C3b inhibiting both classical and alternative complement pathways

Question 37

evasion of neutralizing antibodies

Answer 37

- soluble proteinsthat soak up antibody - variation in viral antigens - antibodies incapable of neutralization (caprine arthritis-encephalitis of goats) - slow production of antibodies compared to fast infection of cells by virus

Question 38

latency

Answer 38

- transcription of viral genes that encode antigenic proteins are blocked - integration of viral genome in host cell genome (retroviruses)

Question 39

cell-to-cell spread

Answer 39

not exposed to host immune mediators

Question 40

inhibition of apoptosis

Answer 40

poxvirus and herpesvirus produce caspase inhibitors that protect infected cells against death and allow completion of viral replication