Innate Immune Protection (#2) Flashcards

1
Q

List the 3 pathways that activate complement

A
  1. Classical
  2. MBL
  3. Alternative
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2
Q

Describe the classical pathway that activates complement

A
  • antigen-antibody complex binds to pathogen

- causes C3 convertase to which cleaves C3 to C3a (small) + C3b (large)

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3
Q

Describe the MBL pathway that activates complement

A
  • MBL binds to mannose on pathogen

- causes C3 convertase to which cleaves C3 to C3a (small) + C3b (large)

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4
Q

Describe the alt pathway that activates complement

A
  • pathogen causes spontaneous activation of complement

- causes C3 convertase to which cleaves C3 to C3a (small) + C3b (large)

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5
Q

What is function of C3a + C3b?

A
  • C3a diffuses away + binds to macrophages and neutrophils and recruits them to site of inflammation for phagocytosis
  • C3b causes opsonisation = coats surface of pathogens + makes pathogen attractive for phagocytosis
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6
Q

What is function of terminal components of C3 (mem attack complex)?

A
  • terminal comp assemble together to form MAC

- insert + make hole in bacterial cell wall - disrupts osmotic pot + causes lysis of bacteria

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7
Q

Which of the pathways that activate complement are activated by pathogen itself?

A
  • MBL

- alternative

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8
Q

What is a monocyte and macrophage?

A
  • monocyte = in bloodstream

- macrophage = in tissues

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9
Q

How are macrophages formed, where are they found and how long do they survive?

A
  • mature from circ monocytes
  • found in large no.s in GI tract, lung, liver, spleen
  • Rel long lived
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10
Q

Where are neutrophils found and how long do they survive?

A
  • found only in blood unless receive signal to go to infection site in tissues
  • short lived
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11
Q

What is pus?

A

dead neutrophils and bacteria

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12
Q

Describe killing mech of neutrophils

A
  1. after phagocytosis, there’s inc in O2 uptake by cell = resp burst
  2. signal for NADPH oxidase complex to assemble on phagosome surface - 2 components in mem + rest is in cytoplasm
  3. O2 red —> hydroxyl radicals + hypochlorite by NADPH oxidase complex on surface of phagosome
  4. DNA damage + alterations in bacterial mem by O2 radicals
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13
Q

When is NADPH oxidase a complex?

A

only when cell activated

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14
Q

How is killing mech of neutrophils tightly controlled?

A
  • O2 radicals rapidly form H2O + O2 which prevents damage

- assembly of NADPH oxidase on phagosomal mem in close proximity to pathogen

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15
Q

Describe killing mech of macrophages

A
  1. O2 + L-arg —> L-cit + NO radicals
  2. catalysed by inducible NO synthase (iNOS, NOS2) induced by cytokines + bacterial components
  3. Interferon gamma + tumor necrosis factor on macrophage mem send signals to upreg iNOS (cofactor: tetrahydrobiopterin)
  4. NO radicals cause DNA damage + alterations in bacterial mem
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16
Q

What happens if bacteria enter skin through breach?

A
  • recognise pathogen by recognition mech
  • recruit macrophages + neutrophils to site of infection helped by C3a
  • ingest bacteria + helped by C3b which coats bacteria to make it attractive for uptake + lysis
17
Q

What are cytokines and their functions?

A
  • sol proteins
  • IC messengers
  • bind to specific receptors + only instruct cells that express those receptors
  • can be activating/deactivating immune responses
18
Q

In innate immune response, what are cytokines mainly activating?

A
  • IL-1
  • IL-6
  • TNF alpha
  • all induce inflammation
19
Q

What are chemokines and their function and a special property they have?

A
  • contain cysteine residues which classify them into 4 families (CXC, CC, CX3C, XC)
  • class of cytokines with chemoattractant properties to attract cells to infection site
  • pleiotropic = can bind to more than 1 receptor
20
Q

What are functions of chemokines?

A
  • promote inflammation by enabling cells to adhere to surface of blood vessels + migrate to infected tissue
21
Q

Give an e.g. of a chemokine

A

IL-8 prod by macrophages + endo cells (recruits neutrophils to infection site) monocyte chemotactic protein (MCP)

22
Q

What are interferons, when are they prod and their function?

A
  • also cytokines

- prod in response to virally infected cells + activates NK cells

23
Q

List type 1 interferons

A
  • IFN alpha

- IFN beta

24
Q

What are functions of NK cells and what do they respond to + prod?

A
  • kill virally infected + tumor cells
  • responsive to TNF alpha, IL-12
  • prod IFN gamma - activates macrophages
  • upreg MHC mol
  • together with IL-12 stim diff of CD4 Th1 cells
25
Q

Why are cytokines + chemokines important?

A

direct cells to where bacteria are in infected tissues + then activates cells for killing bacteria

26
Q

Describe activation of T cells

A
  1. APC presents part of pathogen to T cell
  2. MHC on APC provides 1st signal to activate naive T cell
  3. signal 2 gen following recognition of pathogens by PRRs
  4. TLR on APC recognise PAMPs + sends signals to nucleus of APC to upreg syn + prod of co-stim mol
  5. cytokines (IL-12, IL-6, TNF alpha) determine type of effector T cell the naive cell becomes
27
Q

List APCs

A
  • macrophage
  • B cell
  • DC
28
Q

What is mature DC?

A
  • present antigen to activate T cells
  • has many dendrites + mol involved in T cell activation with many MHC + co-stim mol
  • most important cell for activating naive T cell
29
Q

What is immature DC?

A
  • round
  • mol important for presenting antigen to T cells not yet displayed on surface
  • do display PRR + recognition of pathogen by PRR on surface causes maturation
30
Q

How does innate immune system recognise pathogen?

A
  • PRR to determine self from non-self + identify type of pathogen
  • PAMPs
31
Q

How does the innate immune system recruit cells?

A
  • complement (lysis, opsonisation, recruitment of macrophages + neutrophils)
  • inflammation
  • cytokine/chemokine prod
32
Q

How does innate immune system ingest pathogen?

A
  • phagocytosis

- opsonisation by complement

33
Q

How does the innate immune system induce specific immune response?

A
  • prod of IL-12, 1FN gamma

- antigen processing

34
Q

Describe the 1st stage of phagocytosis (recognition + engulfing)

A
  • chemotaxis
  • recognition of pathogen by PRR on surface of phagocyte
  • prod of mem-bound pseudopodium which engulfs pathogen
35
Q

Describe the 2nd stage of phagocytosis (phagosome + phagolysome)

A
  • formation of phagosome/phagocytic vesicle - dec pH inside
  • recruitment of small mol onto surface of phagosome is signal for lysosmes to fuse with phagosome + form phagolysome
  • lysosomes contain enz activated at lower pH for digestion
  • digestion of ingested microbe by enz
36
Q

Describe the 3rd stage of phagocytosis (residual body)

A
  • formation of residual body containing indigestible material e.g. FA, peptides
  • some peptides + proteins immunogenic + important for new immune response + therefore displayed on surface of cells
37
Q

Describe the 4th stage of phagocytosis (exocytosis)

A

discharge of waste materials by exocytosis