Trigger 6: Viral involvement in IPF

Question 1

incidence of acute exacerbation in IPF patients is estimated at

Answer 1

5-19%/ patient / year

Question 2

some patients have slow disease progression, some patients have

Answer 2

quick

Question 3

increasing evidence to show that ……… initiate IPF as well as cause AE

Answer 3

viral and bacterial infection

Question 4

animal models have shown that

Answer 4

gamma herpesvirus infection can modulate the pathogenesis of lung fibrosis, by ‘reprogramming’ lung epithelial cells during latency so that they produce profibrotic factors, which make them more susceptible to fibrosis

Question 5

Acute exacerbation causes

Answer 5

disease progression to significantly increase in rate

Question 6

how many will die within a month of AE

Answer 6

80%

Question 7

which types of virus’ have been detected in the lung son IPF patients using PCR of lung tissue

Answer 7

herpes virus’

Question 8

name the herpes virus’ found in IPF lungs using PCR

Answer 8

• Herpes simplex virus
• Epstein-Barr
• Human herpes virus 7 and 8 (HHV7 and HHV8)
• Cytomegalovirus

Question 9

which types of virus’ have been detected using immunohistochemsitry of lung tissue

Answer 9

Epstein-Barr virus

Human Herpes Virus 8

–> localised in airway epithelial cells

Question 10

how else can virus’ be detected

Answer 10

by looking for viral antibodies (IgG and IgM)- ELISA

Question 11

the herpes virus has how many members

Answer 11

8

Question 12

herpes virus are

Answer 12

ubiquitous

Question 13

DNA structure of herpes virus

Answer 13

dsDNA

Question 14

structure of herpes virus

Answer 14

• dsDNA
• Toroidal
• Icosahedral nucleocapsid
• Tegument

Question 15

toroidal

Answer 15

donut shape

Question 16

life cycle of herpes virus

Answer 16

has both latent and lytic cycles

Question 17

after infection by herpes

Answer 17

the virus hides from the immune response by entering the cell bodies of neurones

Question 18

people with herpes experience

Answer 18

sporadic episodes of viral activation- when the virus in a nerve becomes active and is transported via the axon of the neurone to the skin where it starts to replicate

Question 19

how does the herpes virus evade the immune systems

Answer 19

interfere with antigen presentation

Question 20

what causes reactivation of herpes virus

Answer 20

• UV
• infection
• stress
• immunosuppression

Question 21

site of recurrent infection

Answer 21

epithelial cells

Question 22

what is used to prevent the herpes lytic cycle

Answer 22

Ganciclovir

Question 23

what does the drug Ganciclovir do

Answer 23

inhibits thymidine kinase- blocking viral replication

• inhibits viral DNA polymerases more than cellular DNA polymerases.

Question 24

MHC I

Answer 24

CD8- cytotoxic
- expressed on all nucleated cells

• presnets pathogenic peptides to CD8+ cytotoxic T cells

Question 25

MHC II

Answer 25

CD4- antibody an stimulation of immune system

-Expressed on antigen presenting immune cells (macrophages, dendritic cells, b cell). Presents peptides to CD4+ T helper Cells.

Question 26

MHC III

Answer 26

Encodes secreted proteins that have various immune function- complement and inflammation

Question 27

Th0

Answer 27

naive helper cell- not activated

Question 28

when do Th0 cells become activated

Answer 28

when antigen is presented on MHC II

Question 29

activated Th0 cell becomes

Answer 29

Th1 ad Th2 cells

Question 30

Th1

Answer 30

immunity against virally infected cells- apoptosis

Question 31

Th1 cells release cytokines which

Answer 31

activate cytotoxic T cells ( CTL) which can then kill virally infected cells.

Question 32

Th2 cells

Answer 32

stimulate antibody production (to neutralise virus)

B cells differentiate into memory B cells (for future attacks) or plasma cells, which secrete antibodies

Question 33

the viral response summary

Answer 33

1. Virus infected cell present viral antigen to pre-cytotoxic CD8+ cell via MHC class I.
2. This cell becomes activated and releases perforins and granzymes to induce apoptosis of the infected cell.
3. Viral antigens are also phagocytosed by APCs which present viral antigen to CD4+ cells via MHC class II.
4. These CD4+ then differentiate into Th1 cells and release cytokines (IL-2, IL-12, IFN-y, TNF-a) which enhance the proliferation of effect CD8+ cells.
5. These CD4+ cells activated by APCs can also differentiate into Th2 cells. which produce cytokines (IL-4, IL-5, IL-6, IL-10, TGF-B) which facilitate differentiation of B cells.
6. Viral antigen can also be detected by B-cells which present these to Th2 cells via MHC class II and co-receptor CD28. These activated B-cells also differentiate into Memory B-cells and Plasma B-cells responsible for immune memory and antibody production respectively.

Question 34

indirect methods of viral testing are

Answer 34

easiest to retrieve but have the lowest specificity

Question 35

direct methods of viral testing at

Answer 35

very specific but hard to retrieve

Question 36

least specific

Answer 36

e.g. retrieving IgM or IgG

Question 37

most specific method

Answer 37

virus isolation

Question 38

acute exacerbation definition

Answer 38

Acute exacerbation of IPF has been defined as an acute clinically significant deterioration of unidentifiable cause.