Viral immune evasion

Question 1

What are the main functions of antibodies?

Answer 1

Antibody neutralizes extracellular virus blocks viral attachment proteins (Glycoproteins, capsid proteins); destablises viral structure
Antibodies opsonize virus for identification for phagocytosis; promotes lysis and destruction of the target cell through the complement cascade, and antibody-dependent cellular cytotoxicity; resolves lytic viral infections; blocks the viraemic spread of target tissue.

Question 2

What is the function of IgM in terms of viral infections?

Answer 2

IgM indicator of recent/current infections

Question 3

Which Ig type is the most effective antiviral?

Answer 3

IgG

Question 4

Which Ig is cardinal for the protection of mucosal surfaces?

Answer 4

IgA

Question 5

How is a viral infection resolved?

Answer 5

Resolution of infection requires elimination of free virus (antibody agglutination), and the virus-producing cell (immune-cell mediated lysis)

Question 6

How do rhinoviruses evade antibodies?

Answer 6

Rhinoviruses display antigenically distinct serotypes; multivalent required

Question 7

How does HIV evade antibodies?

Answer 7

Exist as multiple clades/quasispecies

Question 8

How does Hepatitis B virus (HBV) and Ebola evade antibodies?

Answer 8

`Encode secreted surface antigens, that remove associated antibody, preventing it from reaching viral particles/infected cells

Question 9

How many serotypes are present for the Dengue virus?

Answer 9

4

Question 10

How does serotyping cause antibody evasion for Dengue virus?

Answer 10

1) Previous infection with one serotype followed by infection with different serotype results in antibody-dependent enhancement of disease
2) Virus enters immune cells via antibody & Fc-receptor.
3) Triggers Dengue hemorrhagic fever. Antibodies present from primary DENV infection bind to infecting DENV particle - primary antibodies cannot neutralize the virus
AB-Virus complex attaches tp Fcy receptors on monocytes, assisting in infection mechanism

Question 11

How do DENV particles enter into immune cells?

Answer 11

Antibody via Fc receptor

Question 12

Which type of fever is triggered by DENV?

Answer 12

Hemorrhagic fever

Question 13

How does the influenza virus evade antibodies?

Answer 13

Influenza viruses mutate frequency evolving, attributing to antigenic drift
Influenza viruses acquire new antigens by reassortment with animal viruses (Antigenic shift) - leads to pandemics,
Alters neuraminidase and haemaglglutinin structure

Question 14

What is antigenic drift?

Answer 14

Mutations causes changes in antigenic viral structure

Question 15

What is the antigenic shift?

Answer 15

Influenza viruses acquire new antigens by reassortment with animal viruses.

Question 16

Which antiviral agents are produced from virally infected cells?

Answer 16

Interferons (IFN)

Question 17

Which viral molecules induces the synthesis of interferons?

Answer 17

Double-stranded RNA
RNA that lacks a 5’ cap
Cytoplasmic DNA

Question 18

Which receptors to interferons bind to?

Answer 18

Interferon receptors

Question 19

What response is initiated upon interferon binding on surrounding cells?

Answer 19

Induces antiviral state

Question 20

Which cell cannot induce an antiviral state?

Answer 20

The infected host cell secreting interferons

Question 21

Which genes are activated and transcribed upon activation of antiviral state?

Answer 21

Genes that are transcribed inhibit viral replication (2’5’ oligoadenylate synthetase and protein kinase R - this degrades viral & host RNA

Question 22

What function is performed by 2’5’oligoadenylate synthetase?

Answer 22

Degrades viral and host RNA

Question 23

Which immune cell is mainly activated by interferons?

Answer 23

Natural killer cells

Question 24

What are the three types 1 IFNs?

Answer 24

IFN-alpha
betab
Beta

Question 25

Which cells secreted type 1 IFNs?

Answer 25

All cells

Question 26

Which IFN receptor is present on all tissues?

Answer 26

IFN-alpha Receptor

Question 27

Which cells are specialized IFN-alpha secreting?

Answer 27

Plasmacytoid dendritic cells

Question 28

How many genes exist for IFN-B?

Answer 28

1

Question 29

How many isotypes exist for IFN-a?

Answer 29

13/14 isotypes

Question 30

Which IFN type is IFN-y?

Answer 30

Type II

Question 31

Which cells secrete IFN-y?

Answer 31

NK cells and activated T cells

Question 32

Which receptor is activated by IFN-y?

Answer 32

IFN-yR

Question 33

Which type of interferon is IFN-lambda?

Answer 33

Type III

Question 34

Which receptors are IFN-Lambda signaled through?

Answer 34

IL28R IL10-B These are known as IFN-delta receptors, mainly present on epithelial surfaces

Question 35

How do HBV and influence develop resistance to interferon action?

Answer 35

Blocks the production of interferon by inhibition of IFN transcription Produce protein NS1 that counters RNA sensing and prevents polyA processing

Question 36

How are NK cells activated in terms of an antiviral response?

Answer 36

IFN-alpha | Interleukin-12

Question 37

How are macrophages activated in terms of an antiviral response?

Answer 37

Activated NK cells secrete IFN-y binds to macrophage IFNyRs

Question 38

What is the function performed by activated NK cells during an antiviral response?

Answer 38

NK cells target and kill virus-infected cells (enveloped viruses) Secrete IFN-y to activate macrophages

Question 39

A reduction in which cell surface molecules results in NK cytotoxic response?

Answer 39

Reduction in the number of functional MHC-iu molecules

Question 40

Which viruses are responsible for reducing MHC-I surface molecules in infected cells?

Answer 40

Cytomegalovirus | Herpes Simplex Virus

Question 41

Which type of lymphocytes are NK cells classified as?

Answer 41

Group 1 innate lymphocytes (ILCs)

Question 42

Which type of NK receptors regulate cytotoxicity?

Answer 42

Inhibitory receptors

Question 43

What is the function performed by inhibitory receptors?

Answer 43

Recognizing cognate MHC-I, and inactivates NK cells- preventing cell lysis

Question 44

What happens to cells which lose MHC-I?

Answer 44

Vulnerable to cytotoxic granules containing perforin and granzymes being secreted- lysis of target cell

Question 45

What is the function performed by macrophages during an anti-viral response?

Answer 45

Macrophages filter viral particles from blood; inactivate opsonized virus particles

Question 46

What is the function performed by dendritic cells during an anti-viral response?

Answer 46

Plasmocytoid dendritic cells produce IFN-alpha and other cytokines Initiate and determine nature of CD4 and CD8 T-cell response Dendritic cells undergo antigen presentation - presents antigen to CD4 T cells 

Question 47

Which type of viral infections are controlled by T-cells?

Answer 47

Controls enveloped and noncytolytic viral infections, recognize viral peptides presented by MHC molecules associated on cell surface membrane

Question 48

What are linear epitopes?

Answer 48

Antigenic viral peptides derive from viral proteins (Glycoproteins and nucleoproteins)

Question 49

What T cells are cytotoxic?

Answer 49

CD8, responds to MHC1 protein complexes on infected cells

Question 50

What are Th2 responses?

Answer 50

Required for humoral immunity- can be detrimental if they prematurely limit the Th1 inflammatory and cytolytic response

Question 51

How do viruses evade T cells?

Answer 51

Herpes Simplex HSV, and cytomegalovirus CMV encode proteins that interfere with MHC antigen processing pathway Viruses impair lymphocyte function: HIV kills CD4 T cells, and alters macrophage function HSV prevents CD8 T cell lysis