Lecture 9 and 10: Dendritic Cells, MHC and Antigen Presentation Flashcards

1
Q

What presents antigen to CD4+ helper T cells ?

A

Antigen presentation cells

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2
Q

What are the most efficient antigen presenting cells ?

A

Dendritic cells

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3
Q

What does antigen uptake by a dendritic cell result in?

A

Naive T cella activation; clonal expansion and differentiation into effector T cells

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4
Q

What does antigen uptake to macrophage result in ?

A

Effector T cell activation; activation of macrophages

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5
Q

What does antigen uptake in B cells result in ?

A

Effector T cell activation; B cell activation and antibody production

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6
Q

What are the different ways in which pathogens can replicate ?

A
  1. Cytosolic
  2. Intravesicular
  3. Extracellular
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7
Q

How do dendritic cells present peptide antigen to CD4 T cells ?

A

Through MHC II receptors

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8
Q

What allows it to bind and present antigen at cell surface ?

A

MHC structure

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9
Q

Where are MHC II molecules synthesised ?

A

ER

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10
Q

What prevents binding of MHC II in the ER ?

A

Ii

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11
Q

What does the invariant chain form ?

A

A complex with MHC II, blocking the binding of peptides and misfolded proteins

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12
Q

Where is Ii cleaved ?

A

In an acidified endosome

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13
Q

What is left in an acidified enzyme ?

A

Leaving a short peptide fragment, CLIP, still bound to the MHC II molecule

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14
Q

Where is the exogenous antigen processed ?

A

Endosomes

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15
Q

What binds to the MHC II releasing CLIP ?

A

HLA-DM

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16
Q

What is HLA-DM ?

A

Class II like molecule encoded for MHC region

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17
Q

Where is HLA-DM found ?

A

MIIC

18
Q

What is the function of HLA-DM ?

A
  1. Binds and stabilises empty class II molecules which would otherwise aggregate
  2. Catalyses release of MHC from MHC CLIP complex
  3. Catalyses binding of peptide to empty MHC II
  4. Peptide edits
19
Q

What sort of chains does HLA-DM have ?

A

Alpha and beta

20
Q

What does HLA-DO do ?

A

Inhibits HLA-DM catalysed reaction

21
Q

What increases HLA-DM expression ?

A

IFN-gamma

22
Q

What happens during inflammation (to do with HLA-DM)

A

HLA-DM overcomes HLA-DO

23
Q

What is APC activation of CD4 T cells good for ?

A

Cell mediated immunity and production of antibodies to fight extracellular bacteria or intravesicular infections

24
Q

What are the three signals required for antigen presentation ?

A
  1. MHC specificity
  2. Costimulation
  3. Cytokines
25
Q

What is costimulation ?

A

Control check to avoid over activation

26
Q

What is anergy ?

A

Try to activate cells but do not have the right signal

27
Q

How do viruses replicate ?

A

Intracellularly in the cytosol using endogenous protein synthesis machinery

28
Q

What can kill virally infected cells ?

A

Activation of CD8 T lymphocytes

29
Q

Where is MHC II only expressed ?

A

antigen presenting cells

30
Q

Where is MHC I expressed ?

A

On all nucleated cells

31
Q

What domain binds to CD8 co-receptor ?

A

Alpha 3 domain

32
Q

What are the domains in the MHC I molecule ?

A
  1. Alpha 2
  2. Alpha 3
  3. Alpha 1
  4. Beta microglobulin
33
Q

How do you get pathogen derived peptie loaded into MHC I ?

A
  1. Partly folded MHC I alpha chains bind to calnexin until Beta 2 microglobulin binds
  2. MHC I alpha: Beta2m complex is released from calnexin, binds a complex of chaperone proteins and binds to TAP via tapasin
  3. Cytosolic proteins are degraded to peptide fragments by the proteasome
  4. TAP delivers a peptide that binds to MHC I and completes its folding
  5. The fully folded MHC I is released from TAP and exported
34
Q

What size peptides to MHC I bind ?

A

Short 8-10 amino acids long

35
Q

What is binding of a peptide stabilised by ?

A

Contacts between atoms at carboxy and amino terminal ends of peptide and invariant sites on end of MHC I peptide binding groove

36
Q

What does MHC I bind ?

A

Many different peptides but with common anchor residues

37
Q

What is needed for efficient activation of CTL ?

A

APC co-stimulation

38
Q

Where do naive CTL see viral antigen presented by MHC I ?

A

Cross presentation of viral antigen to CD8 T cells by APC

39
Q

What is peptide loading in the ER targeted by ?

A

Viral immunoevasions

40
Q

How do viral evasions US6 and ICP 47 block antigen presentation ?

A

By preventing peptide movement through TAP peptide transporter

41
Q

What type of genes does MHC have ?

A

Polygenic and polymorphic

42
Q

What type of specificity do TCRs have ?

A

Dual specificcity for MHC and peptide