Trigger 6: Viral involvement in IPF Flashcards
incidence of acute exacerbation in IPF patients is estimated at
5-19%/ patient / year
some patients have slow disease progression, some patients have
quick
increasing evidence to show that ……… initiate IPF as well as cause AE
viral and bacterial infection
animal models have shown that
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
Acute exacerbation causes
disease progression to significantly increase in rate
how many will die within a month of AE
80%
which types of virus’ have been detected in the lung son IPF patients using PCR of lung tissue
herpes virus’
name the herpes virus’ found in IPF lungs using PCR
- Herpes simplex virus
- Epstein-Barr
- Human herpes virus 7 and 8 (HHV7 and HHV8)
- Cytomegalovirus
which types of virus’ have been detected using immunohistochemsitry of lung tissue
Epstein-Barr virus
Human Herpes Virus 8
–> localised in airway epithelial cells
how else can virus’ be detected
by looking for viral antibodies (IgG and IgM)- ELISA
the herpes virus has how many members
8
herpes virus are
ubiquitous
DNA structure of herpes virus
dsDNA
structure of herpes virus
- dsDNA
- Toroidal
- Icosahedral nucleocapsid
- Tegument
toroidal
donut shape
life cycle of herpes virus
has both latent and lytic cycles
after infection by herpes
the virus hides from the immune response by entering the cell bodies of neurones
people with herpes experience
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
how does the herpes virus evade the immune systems
interfere with antigen presentation
what causes reactivation of herpes virus
- UV
- infection
- stress
- immunosuppression
site of recurrent infection
epithelial cells
what is used to prevent the herpes lytic cycle
Ganciclovir
what does the drug Ganciclovir do
inhibits thymidine kinase- blocking viral replication
- inhibits viral DNA polymerases more than cellular DNA polymerases.
MHC I
CD8- cytotoxic
- expressed on all nucleated cells
- presnets pathogenic peptides to CD8+ cytotoxic T cells
MHC II
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.
MHC III
Encodes secreted proteins that have various immune function- complement and inflammation
Th0
naive helper cell- not activated
when do Th0 cells become activated
when antigen is presented on MHC II
activated Th0 cell becomes
Th1 ad Th2 cells
Th1
immunity against virally infected cells- apoptosis
Th1 cells release cytokines which
activate cytotoxic T cells ( CTL) which can then kill virally infected cells.
Th2 cells
stimulate antibody production (to neutralise virus)
B cells differentiate into memory B cells (for future attacks) or plasma cells, which secrete antibodies
the viral response summary
- Virus infected cell present viral antigen to pre-cytotoxic CD8+ cell via MHC class I.
- This cell becomes activated and releases perforins and granzymes to induce apoptosis of the infected cell.
- Viral antigens are also phagocytosed by APCs which present viral antigen to CD4+ cells via MHC class II.
- 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.
- 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.
- 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.
indirect methods of viral testing are
easiest to retrieve but have the lowest specificity
direct methods of viral testing at
very specific but hard to retrieve
least specific
e.g. retrieving IgM or IgG
most specific method
virus isolation
acute exacerbation definition
Acute exacerbation of IPF has been defined as an acute clinically significant deterioration of unidentifiable cause.
