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Chronic Disease > Infection Pathogenesis > Flashcards

Infection Pathogenesis Flashcards

1
Q

Give 3 immunopathologies

A

Influenza and ARDS symptoms from cytokines

Organ damage from ctl killing

Immune agab complex deposition

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2
Q

What organ is damaged by ctl killing in chronic hep b

A

Liver

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3
Q

What do immune complexes trigger in blood eg in yellow fever

A

Clotting, vascular permeability

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4
Q

How can they cause organ dysfunction

A

Glomerular nephritis

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5
Q

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

A

Nociceptors

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6
Q

What occurs eg when TNFa or pg/ lt trigger nociceptors

A

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

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7
Q

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

A

Release by cns cells like microglua Astrocytes and t cells

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8
Q

What happens then

A

Nt transmission and signal transduction to brain for pain

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9
Q

What are things called than cause fever

A

Endogenous pyrogens

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10
Q

What is the most potent cytokines to do this

A

Il1

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11
Q

Which others

A

Tnf , il6 and ifn

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12
Q

How do they do this

A

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

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13
Q

How do tnf and il1 do this indirectly

A

Induce il6 production which then induces pge2

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14
Q

How do Ifn do it indirectly

A

Stimulate production of TNFa and il1 in first place

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15
Q

What do pge2 delay

A

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

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16
Q

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

A

Mcp-1 and il8

Attenuated phagocytosis though

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17
Q

Which cytokines decrease by pge2 which recruit th1 ctl and NK

A

Cxcl9,10,11

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18
Q

How do they suppress NK and th1 effector function

A

Reduces il12 production and responsiveness

19
Q

How does it inhibit T cell proliferation

A

Il2

20
Q

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

A

Mast cell defranulation
Th2 response
Treg development and activity

21
Q

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

A

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

22
Q

How does QUIN agonise nmda

A

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

23
Q

Reminder of how Ifn is immunosuppressive

A

Induces pdl1, il10 tregs , ido etc

24
Q

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

A

pDCs

25
Q

How does Ifn stop ctl killed by NK

A

Upregulate MHC expression

26
Q

What does isg apobec3 do to stop hiv

A

Mutagenesis of hiv cDNA

27
Q

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

A

Neutrophils

28
Q

How

A

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

29
Q

Which hpv subtypes are cancerous

A

16 and 18

30
Q

What are the 2 oncogenes

A

E6 and 7

31
Q

What does e6 do to p53

A

Causes it’s degradation

32
Q

How does e7 cause cell cycle progression

A

Binds rb and displaces e2f

33
Q

What types of cells do they invade first

A

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

34
Q

Which 2 ways do they evade host immune system

A

Block ifn 1 and MHC 1

35
Q

Why is it controversial that blocking ifn is bad

A

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

36
Q

Which types of macrophages link inflammation with cancer in hpv

A

Tam

37
Q

Increased risk when what occurs at the cervix before hpv infection

A

Inflammation eg through BV

38
Q

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

A

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

39
Q

After tumours, what can tam secrete for cancer cell proliferation

A

Egf

40
Q

What does it secrete for angiogenesis

A

Vegf, pdgf, some specialised cytokines

41
Q

Once tumours developed, how does tam become immunosuppressive

A

Il10, pge2, tgfb

42
Q

Which mmp is proangiogenic released by tams

A

Mmp9

43
Q

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

A

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

Chronic Disease (16 decks)

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