atypical immune response

Question 1

tuberculosis basic info

Answer 1

very slow growing -> colonies will take several weeks to appear in culture
infection of the lung (predominantly)
apical destruction
growth at higher pO2
- higher at top of the lungs
can lie dormant

Question 2

what is the normal spongy architecture of the lung replaced by in TB

Answer 2

caseous necrosis

Question 3

what are granulomas and where are they found

Answer 3

flecked, sand-like, grain appearance
surface of the lungs
surrounded by activated macrophages and multinucleate cells

Question 4

what type of infection is TB

Answer 4

respiratory infection (droplets

Question 5

what is the immunity response to tb

Answer 5

cell mediated is crucial
macrophages are key to controlling cell
T cell production of interferon gamma
cytokines involved in this process
may still fail to clear it

Question 6

what are the two ways that tb evades lysosomes

Answer 6

subverts intracellular trafficking following phagocytosis
resistance to phagosomal acidification

Question 7

how does tb subvert trafficking following phagocytosis

Answer 7

bacteria alters phagosome so that it becomes covered in coronin (actin associated protein)
inhibits the ability of the phagosome to fuse with the lysosome

Question 8

how does tb resist phagosomal acidification

Answer 8

lysosomes operate at low pH, which increases closer to neutral when the phagosome fuses
- allows the lysosome to function
tb pumps out protons (H+) to reverse this change
prevents lysosome functioning

Question 9

describe the pathway to disseminated disease with tb

Answer 9

BCG (live vaccine) -> lack of interferon-gamma/ lack of interferon-gamma receptor -> disseminated disease
- mutation in some families

Question 10

what are some key cytokines in tb clearance and what do they do

Answer 10

il12 / il12 in dendritic cell
leads to increased production of interferon gamma by T cell -> increased activation of macrophages

Question 11

how can we determine if people have/ have had tb

Answer 11

Mantoux reaction
also T spot test (similar to ELISA test)

Question 12

describe the CD8 response to HIV

Answer 12

keeps HIV in check
when CD8 calls are depleted, the viral load peaks
- CD8 is bringing virus under control
- not final response
many mutations
- epitomes don’t bind to CD8
- allows evasion

Question 13

what is the plateau of mutation for HIV

Answer 13

set point
any more mutation would have a negative impact on the virus
increases chances of survival

Question 14

describe the antibody response to HIV

Answer 14

after ~3months - a year antibody response is observed
similar issue to CD8

Question 15

what vector is dengue spread by

Answer 15

mosquitoes

Question 16

what are the symptoms of dengue

Answer 16

fever, rash, extreme myalgia

Question 17

how does dengue fever destroy the epithelial cell-capillary barrier

Answer 17

variety of inflammatory cytokines produced by viral-infected macrophages can eventually lead to the barrier being broken down
allows fluid from capillary to enter the tissues

Question 18

what is oedima

Answer 18

fill up lungs/ areas of the brain
can proceed to extreme illness or death

Question 19

what does severe dengue cause

Answer 19

severe plasma leakage, haemorrhage
multi system organ failure
brain impairment
congentival haemorrhage

Question 20

what causes severe dengue

Answer 20

4 more serious types across the globe - distinct but related
not non-sterilising but still atypical
recovery from one gives lifelong immunity to that strain
a secondary infection by one of the different strains can lead to dengue haemorrhagic fever (DHV)

Question 21

what is different about the immune response to DHV

Answer 21

antibody combines with the virus but doesn’t neutralise it
acts as opsonin - enhances uptake of virus into monocytes and macrophages
increases cytokine activation and infection of epithelial cells
more complications

Question 22

what is the risk with the dengue vaccine

Answer 22

risk of immune enhancement with antibodies (DHV)
when it was introduced in Indonesia, could give good protection if you’ve had a previous infection with the same strain
- if they hadn’t been exposed to Dengue, then the vaccine made it a lot worse
young children that haven’t lived long enough
vaccine has been withdrawn