Infection Pathogenesis

Question 1

Give 3 immunopathologies

Answer 1

Influenza and ARDS symptoms from cytokines

Organ damage from ctl killing

Immune agab complex deposition

Question 2

What organ is damaged by ctl killing in chronic hep b

Answer 2

Liver

Question 3

What do immune complexes trigger in blood eg in yellow fever

Answer 3

Clotting, vascular permeability

Question 4

How can they cause organ dysfunction

Answer 4

Glomerular nephritis

Question 5

Which sensory neurones in the periphery sense pain through lipid mediators and cytokines

Answer 5

Nociceptors

Question 6

What occurs eg when TNFa or pg/ lt trigger nociceptors

Answer 6

Action potential through spinal cord dorsal horn up to brain to be perceived as pain

Question 7

How can pre and post synaptic dorsal neurones also be stimulated by cytokines

Answer 7

Release by cns cells like microglua Astrocytes and t cells

Question 8

What happens then

Answer 8

Nt transmission and signal transduction to brain for pain

Question 9

What are things called than cause fever

Answer 9

Endogenous pyrogens

Question 10

What is the most potent cytokines to do this

Answer 10

Il1

Question 11

Which others

Answer 11

Tnf , il6 and ifn

Question 12

How do they do this

Answer 12

They induce production of pge2 whcih raises temp ser point in hypothalamus

Question 13

How do tnf and il1 do this indirectly

Answer 13

Induce il6 production which then induces pge2

Question 14

How do Ifn do it indirectly

Answer 14

Stimulate production of TNFa and il1 in first place

Question 15

What do pge2 delay

Answer 15

The adaptive response (immunosuppressive which can be an issue eg in cancers)

Question 16

How can they promote Mac and neutrophil attraction but can’t have effect

Answer 16

Mcp-1 and il8

Attenuated phagocytosis though

Question 17

Which cytokines decrease by pge2 which recruit th1 ctl and NK

Answer 17

Cxcl9,10,11

Question 18

How do they suppress NK and th1 effector function

Answer 18

Reduces il12 production and responsiveness

Question 19

How does it inhibit T cell proliferation

Answer 19

Il2

Question 20

What 3 things does it promote which don’t help immunity

Answer 20

Mast cell defranulation
Th2 response
Treg development and activity

Question 21

How has ido which is triggered by inflammation via ifn cause depression

Answer 21

Trp metabolised to kynurenine rather than serotonins
Further metabolised to QUIN which is an agonist of nmda receptor causing depression
Low kyn acid/QUIN ratio = depression
Because kyn acid is an antagonist of nmda

Question 22

How does QUIN agonise nmda

Answer 22

Induces glutamate release into synapse and blocks it’s uptake so it binds more

Question 23

Reminder of how Ifn is immunosuppressive

Answer 23

Induces pdl1, il10 tregs , ido etc

Question 24

Despite this, it is important in fighting hiv. Which cell releases ifn

Answer 24

pDCs

Question 25

How does Ifn stop ctl killed by NK

Answer 25

Upregulate MHC expression

Question 26

What does isg apobec3 do to stop hiv

Answer 26

Mutagenesis of hiv cDNA

Question 27

Which immune cell triggered by cytokines in covid can cause ards which is major immunopathology

Answer 27

Neutrophils

Question 28

How

Answer 28

Elastases, proteinases, mmp, ros = damage to epi and endothelial barrier and cause oedema

Question 29

Which hpv subtypes are cancerous

Answer 29

16 and 18

Question 30

What are the 2 oncogenes

Answer 30

E6 and 7

Question 31

What does e6 do to p53

Answer 31

Causes it’s degradation

Question 32

How does e7 cause cell cycle progression

Answer 32

Binds rb and displaces e2f

Question 33

What types of cells do they invade first

Answer 33

The keratinocyte basal cells at uterine cervix area (need an insult to get to the BM)

Question 34

Which 2 ways do they evade host immune system

Answer 34

Block ifn 1 and MHC 1

Question 35

Why is it controversial that blocking ifn is bad

Answer 35

Because it is suggested ifnb can cause hpv 16 txn persistence as it binds ire on the viral promoter for

Question 36

Which types of macrophages link inflammation with cancer in hpv

Answer 36

Tam

Question 37

Increased risk when what occurs at the cervix before hpv infection

Answer 37

Inflammation eg through BV

Question 38

In tumour initiation, what do tams characterise as which is protumorigenic

Answer 38

Pro-inflam eg releasing cytokines and ros and no = mutations

Question 39

After tumours, what can tam secrete for cancer cell proliferation

Answer 39

Egf

Question 40

What does it secrete for angiogenesis

Answer 40

Vegf, pdgf, some specialised cytokines

Question 41

Once tumours developed, how does tam become immunosuppressive

Answer 41

Il10, pge2, tgfb

Question 42

Which mmp is proangiogenic released by tams

Answer 42

Mmp9

Question 43

Tam doesn’t fit into the m1 or m2 category. What are these

Answer 43

M1 are pro inflam macrophages which are induced eg by ifny and TNFa to release proinflam cytokines M2 are anti inflam which are upreg by il4 and release il10 and tgfb instead