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
Q

What is gene encoding TCR alpha chain formed by?

A

recombining 1 V + J segment linked to alpha constant region

26
Q

How many poss combos are there for alpha chain?

A

~ 2500

27
Q

How is gene encoding TCR beta chain made?

A

recombining segments from V,D + J segments + can combine with 2 diff constant regions

28
Q

How is diversity of alpha + beta chain inc + no. of poss combos?

A

imprecise joining so total no. of combos of TCR inc so 1000s of poss combos

29
Q

What happens once TCR rearrangement finished?

A

can’t change config

30
Q

Where do diff MHC mol have greatest variability?

A

peptide binding groove

31
Q

Where is greatest variability in TCR?

A

bit which makes contact with peptide + MHC mol

32
Q

List 2 main classes of alpha-beta T cell

A
  1. CD8

2. CD4

33
Q

What is CD8 T cell?

A

T cell express CD8 co-receptor - interacts with conserved part of MHC I mol

34
Q

What is CD4 T cell?

A

T cell express CD4 co-receptor - interacts with conserved part of MHC II mol

35
Q

What do CD8 T cells see?

A

mainly endo prod peptides presented by MHC I mol

36
Q

What do CD4 T cells see?

A

mainly peptides presented by MHC II mol with antigens taken up from exo sources into APC

37
Q

What is signal 1?

A

interaction between TCR + peptide MHC complex

38
Q

How can you get sustained signalling in T cell?

A

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
Q

What does signal 1 provide?

A

specificity to T cell immune response

40
Q

What happens to T cell with specificity for peptide MHC mol?

A

becomes activated by APC