Innate Immune System Flashcards

1
Q

May be the most important complement pathway

A

Lectin

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2
Q

Most common complement protein; continually being spontaneously cleaved to two components: C3a and C3b

A

C3

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3
Q

C3b binds…

A

covalently to hydroxyl (-OH) and amino (-NH2) groups on foreign surfaces

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4
Q

What happens if C3b doesn’t find something to bind to in 60 microseconds

A

neutralized by a water molecule

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5
Q

What happens after C3b binds to a foreign body?

A

B sees this and will attach to C3b and then protein D will come along to cleave part of protein B to mke C3bBb = active enzyme; saw-like

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6
Q

BbC3b

A

converts more C3 into C3b; AKA C3 convertase

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7
Q

C3 convertase can also cleave ANOTHER complement protein

A
  • C5 = C5a and C5b
  • C5b attaches to bacterial cell and recruits other complement proteins (C6-9)
  • together, form a pore (MAC)
  • lysis of organism
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8
Q

proteins in our cells that prevent complement from blowing up our own cells

A

MCP, DAF, CD59

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9
Q

MBL

A

mannose-binding lectin

  • made in the liver
  • mannose is a sugar found in complex molecules on many pathogens; mannose in our cells have different patterns so MBL does not bind to them
  • MBL in serum binds to mannose-binding lectin associated serine proteases (MASPs)
  • directed, not spontaneous
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10
Q

Lectin pathway procedure

A
  • MBL binds target mannose group on an organism
  • MASPs bind to MBL
  • activated MASP-2 cleaves C4 to C4a and C4b- some C4b covalently binds to microbial surface
  • MASP-2 also cleaves C2 into C2a and C2b
  • C2a binds to C4b = classical convertase C4b2a
  • C4b2a binds C3 and cleaves it into C3a and C3b; C3b binds covalently to microbial surface
  • rest of the cascade is like alternative pathway; leads to formation of MACs
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11
Q

Two other important functions of complement

A
  • C3b on a bacterium can be clipped by a serum protein to form iC3b; can no longer contribute to forming MAC but can opsonize
  • C3a and C5a act as chemoattractants for professional phagocytes
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12
Q

Three states of Macrophages

A
  1. Resting = garbage collectors
  2. Primed = can become APCs
  3. Hyperactivated = stop dividing and focus on killing invaders
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13
Q

Professional Phagocytes

A

Dendritic cells, Neutrophils and Macrophages

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14
Q

Neutrophils

A
  • found in bloodstream
  • short-lived (days) bc toxic and can damage tissue
  • NOT APCs
  • kill the ndie by apoptosis
  • produce cytokines (TNF); enhances inflammatory response
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15
Q

How do phagocytic sentinel cells recognize invaders (PAMPs or DAMPs)

A
  • macs and dendritic cells
  • PRRs (TLRs = specific)
  • some found on outside of cell; some inside (walls of phagosomes to detect PAMPs released from organisms digested in phagolysosome)
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16
Q

PAMPs have _________ characteristics that are unlikely to mutate.

A

conserved

17
Q

TLR4 recognizes

A

LPS found on all gram -

18
Q

When PRRs on macs and pDC detect a virus, the cells produce these ‘warning proteins’

A

interferon alpha and beta

= type 1 interferons

19
Q

NK cells

A
  • innate
  • short-lived (1 week) lymphocytes
  • like neutrophils, “on call” from the blood; use same exit mechanism
  • in tissue, they divide to boost their numbers
  • receive cytokine signals (like IFN alpha & beta) or LPS to boost secretion of cytokines like IFN-gamma
  • destroy cells through suicide (interaction of Fas with Fas ligand OR injecting granzymes using perforin proteins)
20
Q

how do NK cells identify their target cells?

A
  • inhibitory (MHC I) = signals the NK NOT to kill

- activating = surface proteins or carbs expressed when cell is stressed (virus) = kill!

21
Q

interaction between macs and NK cells

A
  • once NK cells and macs bind to LPS, NK cells will produce IFN-gamma which signals macs to make TNF
  • TNF makes mac produce IL-12
  • TNF makes NK cells release more IFN-gamma to stimulate more macs
  • IL-12 makes NK cells express IL-2 for proliferation
  • ALSO, iC3b on target organisms can stimulate macs to make more C3, B, D = replenishing key complement proteins
  • macs also increase blood vessel permeability to allow more complement to enter site of infection
22
Q

these 2 are produced by a hyperactivated macrophage

A

TNF and IL-12

23
Q

T or F. Innate response is proportional

A

T!