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Basic Immunology > Lecture 14 (8B) - Chronic Viral Hepatitis > Flashcards

Lecture 14 (8B) - Chronic Viral Hepatitis Flashcards

1
Q

Hepatitis B

A

300 million
sex
drug injection
50% of UK drug users

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2
Q

Hepatitis c

A

220 million
drugs - blood to blood
50% of drug users
40% in cairo from british injecting everyone in attempt to eradicate bilharzia

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3
Q

HBV replication

A

3 kilobases (when average gene 4-5 kilobases)
• 4 proteins
• DNA virus - can integrate into own chromosomes, use our body enzymes to replicate
• makes pieces of RNA to make DNA again
= REVERSE TRANSCRIPTASE STEP

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4
Q

HepB prevalence

A
  • highest - africa, E and SE asia, N canada and greenlad
  • intermediate - russia, india, medierranea, brazil, japan
  • low - UK, w Europe, USA, australia, new zealand, scandanavia
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5
Q

HCV

A
  • RNA virus so makes mistakes (1 mutation per 10,000 bases)
  • is 10,000 bases long –> 1 mutation every new strand
  • so many changes that T and B cells can’t get it because it’s changed by the time they’re made
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6
Q

Symptoms

A

liver fibrosis –> cirrhosis
ascites - fluid filled abdomen that can burst
multi-focal HCC - liver carcinoma

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7
Q

HBV has 2 forms

A
  • acute - fightable
  • chronic - worrying one

HepB makes you live long enough to pass it on (mom to kid)

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8
Q

Individuals most at risk of developing chronic hepatitis B infection

A 
• neonatal vertical transmission
• infants less than 3 years old
• immunocompromised individuals
- receiving chemotherapy
- haemodialysis patiens
- transplant recipients
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9
Q

Outcome of HBV infection according to age at time of infection

A

chronic from mom, change during puberty
• HepB smart enough to cause pandemic
• 11 years to form adult response to it

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10
Q

Hepatitis B natural history

A
  • mother tolerizes, so no liver inflammation because no cells against
  • teenage = switches on immune, antigens

alanine transaminase - enzyme commonly assocciated with liver - measures liver health

  1. immunotolerant phase
    - HBsAg+
    - HBeAg+
  2. Immunoactive phase
    - HBsAg +
    - HBeAg+
  3. Immunosurveillance phase
    - HBsAg+
    - HBeAg-
  4. Immunoescape phase
    - HBsAg+
    - HBsAg-
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11
Q

HBV therapy

A

either:
• lamivudine + tenofovir - indefinite therapy of tablets
• pegasys - pegylate interferon - 48 weeks of injections

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12
Q

constant battle between immunology and hepatitis B

A

• low liver inflammation = no T cells from hep B
• passed from mother
• first 20 years of life - 100million per ml of blood
- phase 1
• virus changes in teen year - immune system starts trying to kill it - causes body damage
• disease reactivation in 50s
- phases 2 and 4

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13
Q

Hepatitis C

A
  • transmitted by blood-blood contact
  • causes slowly progressive liver fibrosis
  • cirrhosis and cancer are common
  • in the UK drug users are at greatest risk
  • junkies virus
  • not just a problem in drug users
  • common in immigrant communities
  • therapy is very effective
  • prominent in 3rd world from poor medical practice
  • viral disease - transient, self limiting
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14
Q

Chronic viral hepatitis

A
  • HBV infects 400 million people worldwide

* HCV infects 180 million people worldwide

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15
Q

Viral defences

A
  1. INNATE IMMUNITY - type 1 interferons
  2. antibody response (slow)
  3. cytotoxic T cells (slow)
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16
Q

Interferon and the immune system

A 
IFN-α
• very potent virus killer
• never found a person lacking it
• biggest reason for virus elimination
• induced by viral TLRs in infection
• activates DC - kickstarting active immune response
• good immune booster
• successful virus must switch off IFN
- Hep B and Hep C very good at this
 - 1 in 4 Hep B proteins devoted to killing IFN system
17
Q

The interferons - production

A
  • HBV polymerase inhibits the production of interferon

* HCV protease inhibits the production of IFN - chewed up by rigI

18
Q

The interferons - effects

A

• HBV polymerase inhibits the actions of interferon
• HCV NS5a and E1 inhibit the effects of IFN
• both viruses encode proteins that inhibit production and effects of type I IFN
- virus ttries to make protein to kill IFN and cell tries to make IFN - race, block, rate of production

19
Q

NK cells

A

not clear how HCV and HBV avoid NK cellls

  • host genetic factors?
  • right NK –> less likely to get chronic
20
Q

Once a virus has avoided the innate immune response it needs to avoid the

A

acquired immune response (T and B cells)
• little is known how it avoids
• variable regions mutate so quickly immune system can’t get it

21
Q

HBV uses different strategies to avoid the immune response at different stages of its life
• phase 1 immunotolerant

A

• phase 1 immunotolerant - virus not seen by immune system because it induces tolerance

  • the main immune target against HBV is the HBV core protein
  • E antigen induces tolerance –> no reaction

1st ATG codes precore/core, into ER –> hijacked, excretory program to excrete E that’s like core but small enough to cross placenta (E antigen)

  • induced by HBeAg - crossing placcenta
  • ATG starts coding for core
  • other ATG begins coding for “pre-core” core
  • virus hijacks protein excretory system so produces E antigen by hep

• phase 2 immunoactive
- tries to kill virus - damages liver cells
T cell or antibody kill infected cell and virus
- leads to inflammation

22
Q

HBeAg

A
  • HBV core protein is the major target for immune attack
  • if HBV is acquired perinatally the disease is always chronic
  • HBeAg crosses the placenta and induces tolerance
  • hepB tolerizes, introduces to hepB then gets chronic infection
23
Q

HBV uses different strategies to avoid the immune response at different stages of its life
• phase 2 immunoactive

A

• phase 2 immunoactive
- tries to kill virus - damages liver cells
T cell or antibody kill infected cell and virus
- leads to inflammation
- break tolerance –> get chronic
- the host immune response kills both the virus and the infected cells
- this leads to liver inflammation

24
Q

Immune attack on HBV

A

phase 2 immunoactive
• T cells kill the infected cell
• antibodies kill the infected cell
•

25
Q

How does HBV avoid antibodies

A

• block production
tolerance
• mutate viral proteins

26
Q

Forming HBeAg

A

pre-core/core with a portion before ATG - ATG
E antigen dependent
clip portion of both
enters ER clipped
get HBeAg
• non needed for replication, affects that region
• gene to stop making target for immune system that will stop it

27
Q

HBeAg

HBV can mutate the

A

pre-core gene to stop E antigen being made

28
Q

How does HBV get around the cellular immune system?

A
  • indcue tolerance
  • block immune priming - infect dendritic cells
  • mutate antiviral epitopes
  • block IFN production and thereby stop HLA expression on the surface of the cell
  • kills cells against itself, mutates itself
29
Q

Viral hepatitis and the immune system

A
  • HBV and HCV both cause chronic disease
  • to achieve this they overcome the host defense network
  • multiple defense mechanisms operate and most are improperly understood
30
Q

HBV avoids cytotoxic response

A
  • mutate pre-core to stop E antigen being made
  • induce tolerance
  • block immune priming - infect DC
  • mutate anti-viral epitopes
  • block INF-production and thereby stop HLA expression on the surface of the cell

Basic Immunology (15 decks)

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