Innate Immunity Flashcards

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1
Q

What are the primary barriers?

A
  • skin
  • ear wax
  • mucus
  • stomach acid
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2
Q

Define phagocytosis

A
  • the engulfing of pathogens by surrounding it and ingesting it.
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3
Q

List 3 phagocytic cells, what receptor do they express to detect pathogens

A
  • macrophage.
  • dendritic cells.
  • neutrophils.
  • Toll-like receptor (TLR)
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4
Q

What type of receptor are TLR’s? What does it recognise? Why don’t pathogens evolve not to express these? What else can they recognise?

A
  • TLR’s = PRR (pattern recognition receptor).
  • They recognise PAMPs (pathogen associated molecular patterns) and DAMPs (danger associated molecular patterns).
  • they are essential for pathogen survival.
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5
Q

What type of chemical are TLRs? What amino acid are they rich in?

A
  • type 1 integral membrane glycoproteins.

- they contain leucine rich repeats.

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6
Q

What do TLRs 1 2 and 6 recognise? You can be more specific with 2 (what disease are these molecules associated with)

A
  • lipids.

- TLR 2 - tuberculosis.

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7
Q

What do TLRs 7 8 and 9 recognise?

A
  • nucleic acids.
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8
Q

What does TLR 4 recognise?

A
  • diverse ligands.
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9
Q

Where are TLRs expressed? Immune and non immune cells

A
  • immune cells: macrophage, dendritic cells, B-cells (some T-cells).
  • non-immune cells: epithelial cells and fibroblasts.
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10
Q

What does TLR 3 bind?

A
  • ds RNA viruses
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11
Q

Where are TLRs on the cell?

A
  • most are extracellular & bind from the cell membrane.
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12
Q

What are the 2 phagocytes?

A
  • macrophages.

- neutrophils.

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13
Q

Where are neutrophils normally?

A
  • circulating in the blood.
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14
Q

Where are macrophages found?

A
  • circulating in the lymph or in lymph nodes in organs.
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15
Q

Where are dendritic cells found?

A
  • found in tissues such as skin.

- they stimulate adaptive immunity by presenting antigens to t-cells.

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16
Q

Where are eosinophils? What do they provide defense against?

A
  • found on mucus membrane.

- against multicellular invaders.

17
Q

Where are Natural Killer cells? What do they release and what does this do? What % of leucocytes are NKs?

A
  • lymph nodes and spleen.
  • release perforin that breaks down cell membranes.
  • 5-10% of leucocytes.
18
Q

How does the lymphatic system aid phagocytosis?

A
  • some macrophages reside in lymph nodes.

- dendritic cells migrate to lymph nodes after interacting with pathogens to stimulate adaptive immunity.

19
Q

Describe the 5 steps of phagocytosis

A
  1. Chemotaxis: chemicals (microbes, WBC, activated complement system) attract phagocytes to site of damage.
  2. Adherence: phagocytes attach to the microbe/non-self material as facilitated by bound complement proteins.
  3. Ingestion: pseudopod (membrane protrusion) extends & surrounds microbe and fuses into a phagosome.
  4. Digestion: phagosome fuses with lysosome = phagolysosome. enzymes in this break down microbe cell wall, proteins & n-acids & oxidants involved with oxidative burst.
  5. Killing: microbe degraded, anything left is kept in residual body.
20
Q

What is a pseudopod?

A
  • a protrusion in the phagocyte membrane which engulfs microbes/non-self cells.
21
Q

What is a phagosome?

A
  • the vesicle containing microbes/non-self material once the pseudopod has fused around it.
22
Q

What are interferons?

A
  • proteins released by cells infected by a virus.

- they prevent replication and thus spread of infection.

23
Q

What is the complement system?

A
  • a process leading to a chemical cascade resulting in lysis of bacteria.
24
Q

What are Iron binding proteins and how do they work?

A
  • bind to iron which are required by bacterial enzyme action.
  • therefore affects bacterial growth.
25
Q

What is the key component of the complement system?

What is this cleaved into? What are the effects of the cleavage products? Which is largest?

A
  • C3 - activation leads to cleavage.
  • cleave products: C3a(small) & C3b(big)
  • C3a: stimulates vascular permeability and helps recruit phagocytes.
  • C3b: become tagged onto microbial membrane to make it become opsonised.
26
Q

What are the 3 pathways of activation for C3b? Describe them?

A
  • Classical pathway: IgG or IgM (antibodies) bind to antigens, especially on the surface on pathogen = antigen-antibody complex.
  • MB-Lectin pathway: MBL binding to pathogen polysaccharide.
  • Alternative (fast): spontaneous C3 cleaving and binding of C3b .
27
Q

What are the results of activation of complement system?

A
  • 3 end results from any one pathway:
  • Inflammation: t-cell attraction = cytokine release = inflammation.
  • Opsonisation: antibody FcR and C3-C3R interaction.
  • MAC activation and cell lysis. (not for gram negative).
28
Q

Describe the classical pathway. What is the convertase?

A
  • antibody-antigen complex initiates pathway leading to binding of C1 q,r,s.
  • this results in C4-C2 complex being deposited a.k.a. C3 convertase.
  • this cleaves C3 into C3a&b.
  • C3b binds to C4-C2 complex which activates MAC leading to cell lysis.
  • C3a activates and attracts phagocytes.
  • C5 cleavage leads to T-cell attraction and cytokine release (inflammation).
  • the binding of the complement and or antibody to pathogen increases chance of phagocytosis (opsonisation) due phagocytes having receptors for these -10 fold.
29
Q

What is MAC made from? What does it do? What type of bacteria is this NOT effective on?

A
  • MAC = membrane attack complex:
  • Binding of C3b to C3 convertase = C5 convertase.
  • C5 cleaved into C5a (inflammation) & C5b.
  • This leads to interaction of C5b-C6-C7 at a second membrane site = deposition of C8 which inserts into the membrane followed by multiple C9 molecules (10-16).
  • C9 molecules insert through the membrane, thus lysing the cell.
  • not effective on Gram positive bacteria.
30
Q

Describe the MBL pathway? What is the convertase?

A
  • formation of MBL = resembles C1 complex leads to C4C2 convertase complex being deposited.
  • leads to C3 being cleaved into a&b.
  • leads to the next steps of the complement system.
31
Q

Describe the Alternative pathway. What factors are involved? What is the convertase?

A
  • Activated by binding of C3b (from classical or MBL pathway) to the bacterial cell surface.
  • C3b binds to serum protein factor B.
  • C3b is then cleaved by factor D = C3bBa & C3Bb.
  • C3bBb complex = C3 convertase which combines with factor P to become attached to the membrane = very stable.
  • This attracts more C3 to be cleaved to start the 3 possible outcomes.