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Infection and immunity 2 > Innate immunity 2 > Flashcards

Innate immunity 2 Flashcards

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1
Q

second line of defence

A

mobilisation of innate cellular response

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2
Q

process of events following pathogen invading tissues

A
  1. host cells detect MAMPs via PRRs
  2. produce cytokines
    - > triggers innate immune system
  3. white blood cells e.g. macrophages + neutrophils
    - > induce innate or adaptive immune response
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3
Q

PRRs

  • what are they?
  • examples
A

pattern recognition receptors
= receptors on cell surfaces

e.g. toll-like receptors
TLR4 binds LPS
TLR5 binds Flagellin

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4
Q

innate immune cells

A

different cell types in different tissues

  • > have different roles
  • > deal with particular types of pathogen
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5
Q

innate immune cells

e.g. dendritic cells + macrophages

A

key roles in communication between innate + adaptive immune responses

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6
Q

leukocytes

  • what are they?
  • relative abundance of neutrophils
A

= white blood cells

neutrophils = 40-60%

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7
Q

platelets

- features

A

small, regularly-shaped cell fragments

from fragmentation of precursor megakaryocytes

lifespan 5-9 days

natural source of GFs

blood clotting

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8
Q

phagocytes

  • 2 types focussing on
  • features
A

macrophages

  • 1st innate immune cells encountered by pathogen
  • resident in wide range of tissues

neutrophils

  • make up majority of blood
  • recruited to infection site by macrophage signals
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9
Q

other PMNs

Polymorphonuclear leukocytes

A

basophils + eosinophils

found in blood in lower proportions

not phagocytic

important for parasitic infections + allergies

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10
Q

macrophages

  • location
  • role
A

resident in range of host tissues

primary responders - detect + attack pathogens

signal to other immune cells
- recruit neutrophils to site of infection

communicate with adaptive immune system

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11
Q

bacteria binding to phagocytic receptors on macrophages

- process

A
  1. bacteria engulfed
  2. enters phagosome
  3. phagolysosome forms
  4. bacteria degraded
    5.
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12
Q

bacterial components binding to signalling receptors on macrophages
- process

A
  1. induces transcription of cytokine genes
  2. inflammatory cytokines produced
  3. recruits other phagocytic cells to site
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13
Q

epithelial barrier breached by splinter

- process

A
  1. bacteria on splinter enter deeper tissues
  2. macrophages recruited -> engulf pathogens + release inflammatory cytokines
  3. inflammation
  4. neutrophils exit leaky blood vessels
    - > work with macrophages to destroy pathogens
  5. some cytokines initiate healing
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14
Q

what does inflammation do?

A

increases blood flow (vasodilation) + temp

-> inhibits growth of bacteria

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15
Q

neutrophils

  • where are they stored?
  • what happens when a macrophage recognises invading microbes?
A

large reserves in bone marrow

travel to and enter infected tissue

  • > engulf + kill bacteria
  • > neutrophils die in tissue
  • > engulfed by macrophages
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16
Q

phagocytosis

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A
  1. bacteria bind to receptors
    (can be added by antibodies)
  2. phagocyte pseudopods extend + engulf org
  3. invagination of phagocyte membrane
    = bacteria in phagosome
  4. lysosome fuses (phagolysosome) + deposits enzymes into phagosome
  5. destruction of microbe via O2-dependent or independent killing
  6. release of microbial debris
  7. may present antigens to T-cells
17
Q

oxygen-independent killing

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A

lysozyme
AMPs
lactoferrin

18
Q

oxygen-dependent killing

Study These Flashcards
A

activated by TLRs

production of oxygen radicals

greatly increases O2 consumption
= oxidative burst

19
Q

neutrophils contain many endosomes

- what are these?

Study These Flashcards
A

granules

contain antimicrobial agents
-> fuse with phagosomes

20
Q

2 types of macrophages

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A

resting macrophage

  • no inflammatory signals
  • highly degradative phagosome

activated macrophage

  • inflammatory signals e.g. LPS
  • enhanced antigen presentation
  • > more aggressive response
21
Q

neutrophil extracellular traps

Study These Flashcards
A

neutrophils release their DNA impregnated with antimicrobials into surrounding area
-> traps + kills bacteria

22
Q

NETosis

slow cell death

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A

depleting granules

  • > disassembly of nuclear envelope
  • > chromatin decondensation
  • > plasma membrane ruptures
  • > release of NETs
23
Q

Non-lytic NETosis

rapid release from live cells

Study These Flashcards
A

release of granules through degranulation
+
expulsion of nuclear chromatin

-> extracellular assembly of NET

24
Q

recognition of pathogens

  • how?
  • e.g.
Study These Flashcards
A

specialised PRRs on macrophages + neutrophils
- detect bacteria, viruses, fungi etc..

MAMPs
DAMPs

25
recognition of self cells - how? - e.g.
express signals telling phagocytes to leave them alone CD47 is ubiquitous on human cells -> macrophages identify as self cells
26
DAMPs
damage-associated molecular patterns self-derived host molecules - indicate infection
27
pattern recognition
receptors recognise MAMPs - > induces: - phagocytosis - movement towards infection - production of antimicrobial agents in phagolysosome
28
PRR | - examples + what they recognise
CD14 - cell wall components e.g. LPS + peptidoglycan Dectin-1 - B1,3 linked toucans in fungal cell walls
29
PRRs routinely exposed to bacteria | - 2 most important families
TLRs - on cell surfaces + endosomal membranes NLRs - in cell cytoplasm - contain nucleotide-binding oligomerisation domain
30
TLRs - how many expressed in humans? - what do they detect? - what do those on endoscopes recognise?
10 TLR genes various microbial components e.g. LPS, peptidoglycan, flagellin microbial components only accessibly when microbe is destroyed e.g. CpG DNA, dsRNA
31
TLRs - and other PRRs? - what happens when they're activated?
some work with other PRRS - e.g. TLR4 + CD14 on macrophages to detect LPS direct proaction of cytokines
32
activation of inflammatory cytokine production process | via TLRs
1. TLR4 + MD2 + CD14 + LPS complex at macrophage surface 2. MyD88 binds TLR4 - > activates phosphorylation cascade - > activates IKK 3. IKK phosphorylates IkB - > IkB degraded - > releases NFkB - > enters nucleus 4. NFkB activates transcription of inflammatory cytokine genes
33
NLRs detect MAMPs inside cell
signals from different locations - > phosphorylation cascade - > activate NFkB to generate cytokines OR trigger assembly of inflammasomes
34
secretion of cytokines causing a chemotaxis gradient - what does this lead to in infected tissues?
IL-1beta = induces permeable blood vessels IL-6 = fat + muscle cells metabolise -> make heat -> raises temp CXCL8 = recruits neutrophils from blood + guides them IL-12 = recruits + activates natural killer cells -> secrete cytokines -> strengthen macrophage response

Infection and immunity 2 (13 decks)

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