T Cells, Effector Functions & the MHC #1 Flashcards

1
Q

What does TCR recognise?

A

foreign mol bound to self protein

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2
Q

What do T cells display?

A

peptides derived from foreign antigens in context of highly polymorphic MHC mol

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3
Q

What is structure of MHC I?

A
  • single chain

- ass non-covalently with beta 2 microglobulin

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4
Q

Where does MHC I express?

A

endogenously derived peptides on all nucleated cells (currently being syn in that cell)

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5
Q

What is structure of MHC II?

A
  • alpha beta heterodimer
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6
Q

Where does MHC II express?

A
  • peptides from exogenous antigens taken up by receptor mediated uptake/endo fro outside on specialised APC
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7
Q

List APC ass with MHC II

A
  • monocytes
  • macrophages
  • DC
  • B lymphocytes
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8
Q

What is function of MHC mol?

A

display foreign peptides to T cells

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9
Q

What does peptide consist of?

A

8-15 aa

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10
Q

What happens when virus infects cell?

A

hijacks host cell’s protein production machinery in order to replicate

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11
Q

How does MHC I present peptides?

A
  • host cell break down sample of all proteins currently being made in cell using proteosome mol
  • take peptides + transport to ER where loaded into newly syn MHC I
  • loaded to cell surface, displaying peptides to immune system
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12
Q

What can the MHC I show?

A
  • sample of all proteins being made in cell at the time
  • mostly normal self-proteins which immune system ignores
  • sometimes show peptides derived from viral antigens
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13
Q

How does MHC II present peptides?

A
  • DC takes up antigen by endo
  • vesicles contain protelytic enz which degrade peptide
  • MHC II syn + assembled in ER + migrate to late endosomes + fuse with vesicles
  • peptides loaded into MHC II mol which are transported to cell surface
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14
Q

Where are genes encoding MHC I + II found + sig?

A
  • on short arm of Chr 6
  • aka human leukocyte antigen
  • most polymorphic/genic region of human genome - sev MHC I + II genes encoding sep mol
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15
Q

How many + what are genes encoding MHC I?

A
  • 3 genes encoding for 3 diff but related HLA proteins (HLA-A, B + C)
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16
Q

How many + what are genes encoding MHC II?

A

3 pairs of genes encoding for 3 diff HLA class II mol (HLA-DR, DQ + DP)

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17
Q

Why is genes of MHC mol being highly polymorphic sig?

A
  • many diff alleles/variants of each gene exist within pop
  • 600+ alleles/variants of HLA I-B
  • great diversity of HLA proteins on cell surface of human pop
    unlikely 2 indiv display same HLA mol on APCs
18
Q

How are genes of MHC mol inherited?

A
  • co-dom expressed

- inherit 1 allele from M + F - express both

19
Q

Where are polymorphisms in HLA found?

A

aa that form peptide binding groove

20
Q

What do aa that form peptide binding groove determine?

A

which peptides from foreign antigen presented to immune system

21
Q

What is polygenic + polymorphic nature of HLA sig for?

A
  • make it imposs for pathogen to evolve antigen that can’t bind to any HLA mol + so can’t trigger immune response
  • as diff HLA in pop, always at least 1 mol that can bind any peptide from antigen of any pathogen
22
Q

What are T cells defined by?

A

expression of TCR

23
Q

Describe structure of TCR

A
  • mem-bound heterodimer
  • 2 chains encoded by diff genes joined by disulphide bonds
  • 2 subtypes (1-alpha + 1-beta chain) + (1-gamma + 1-delta chain)
  • consist of variable + constant domains
24
Q

What do TCR undergo?

A

rearrangements from germline before translation from 1 config expressed in each cell

25
What is gene encoding TCR alpha chain formed by?
recombining 1 V + J segment linked to alpha constant region
26
How many poss combos are there for alpha chain?
~ 2500
27
How is gene encoding TCR beta chain made?
recombining segments from V,D + J segments + can combine with 2 diff constant regions
28
How is diversity of alpha + beta chain inc + no. of poss combos?
imprecise joining so total no. of combos of TCR inc so 1000s of poss combos
29
What happens once TCR rearrangement finished?
can't change config
30
Where do diff MHC mol have greatest variability?
peptide binding groove
31
Where is greatest variability in TCR?
bit which makes contact with peptide + MHC mol
32
List 2 main classes of alpha-beta T cell
1. CD8 | 2. CD4
33
What is CD8 T cell?
T cell express CD8 co-receptor - interacts with conserved part of MHC I mol
34
What is CD4 T cell?
T cell express CD4 co-receptor - interacts with conserved part of MHC II mol
35
What do CD8 T cells see?
mainly endo prod peptides presented by MHC I mol
36
What do CD4 T cells see?
mainly peptides presented by MHC II mol with antigens taken up from exo sources into APC
37
What is signal 1?
interaction between TCR + peptide MHC complex
38
How can you get sustained signalling in T cell?
T cell must encounter APC with MHC complex able to bind to TCR present on T cell strongly enough to cause sustained signalling in T cell
39
What does signal 1 provide?
specificity to T cell immune response
40
What happens to T cell with specificity for peptide MHC mol?
becomes activated by APC