Linking Innate and Adaptive Immunity 3 Flashcards

1
Q

what do TCRs recognize? where?

A

peptide-MHC complexes on the surface of APCs

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2
Q

what is an immunological synapse?

A

T cell:APC contact, with the TCR complex

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3
Q

what are the 4 components of the TCR complex? describe each component’s location in the complex

A
  1. TCR –> in the middle
  2. CD3 –> 1 on either side of TCR
  3. zeta chain –> 2 inside cell
  4. ITAM –> on intracellular part of CD3 and zeta chains
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4
Q

what is ITAM?

A

Immunoreceptor Tyrosine-based Activation Motif

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5
Q

what does the TCR complex trigger?

A

intracellular signaling

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6
Q

what type of molecule is TCR?

A

HETERODIMER

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7
Q

what type of proteins are involved in TCR?

A

transmembrane proteins

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8
Q

is TCR secreted?

A

no, it is membrane-bound

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9
Q

what are the 2 main types of TCR? which is most common?

A
  1. alpha-beta TCR (most common)
  2. gamma-delta TCR (<10%)
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10
Q

what are the 2 types of chains on the most common TCR?

A
  1. ALPHA
  2. BETA
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11
Q

what does clonotypic mean?

A

the cells of a given clone all have identical receptors

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12
Q

what are the 2 main subunits of each chain?

A
  1. Variable (V)
  2. Constant (C)
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13
Q

how many TCR and BCR are possible? why?

A

billions! to allow for increased specificity

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14
Q

how does the number of adaptive immune receptors compare to the number of innate immune receptors? why?

A

there are <100 innate immune receptors (PRRs) because they don’t need to be very specific

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15
Q

BCR and TCR genes undergo __________

A

BCR and TCR genes undergo DNA rearrangement

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16
Q

what are the 4 gene segments of BCR and TCRs?

A
  1. Variable (V)
  2. Diversity (D)
  3. Joining (J)
  4. Constant (C)
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17
Q

what are gene segments?

A

short DNA sequences

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18
Q

what domains are in the alpha chain?

A

V, J, C

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19
Q

what domains are in the beta chain?

A

V, D, J, C

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20
Q

where does TCR rearrangement occur?

A

in the thymus

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21
Q

what is another term for gene rearrangement?

A

somatic recombination

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22
Q

what is somatic recombination/gene rearrangement?

A

recombination of gene segments in TCR genetic loci to make a functional gene

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23
Q

describe gene rearrangement for alpha chain

A

1 V, J, and C are selected in the DNA to be transcribed and translated into an alpha chain

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24
Q

describe gene rearrangement for beta chain

A

1 V, D, J, and C are selected in the DNA to be transcribed and translated into a beta chain

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25
Q

how many variations of TCRs are possible? how is this variability achieved?

A

billions of variations possible

many combos of each subunit are possible, and many combos of alpha and beta chains are possible

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26
Q

why don’t TCRs recognize the peptide by itself?

A

TCRs only recognize the peptide when MHC is present –> TCR interacts with both peptide and MHC

27
Q

what are the 2 types of APCs?

A
  1. Professional APC
  2. Non-professional APC
28
Q

what 3 types of cells are professional APC?

A
  1. DCs
  2. macrophages
  3. activated B cells
29
Q

what type of cells are non-professional APC?

A

all nucleated cells in the body

30
Q

what type of MHCs do professional APC express?

A
  1. MHC Class I
  2. MHC Class II
31
Q

what do professional APCs express when activated?

A

express costimulatory molecules when activated

32
Q

what type of MHCs do non-professional APC express?

A

MHC Class I only

33
Q

when do non-professional APC express MHC Class I?

A

under normal conditions to show that they are healthy

34
Q

do non-professional APC express costimulatory molecules?

A

no

35
Q

what do MHC Class I molecules bind and present?

A

bind and present peptides generated within the cell –> endogenous proteins, self proteins

36
Q

what do MHC Class II molecules bind and present?

A

bind and present peptides of extracellular origin –> exogenous peptides

37
Q

what type of cells do MHC Class I molecules activate?

A

CD8+ T cells

38
Q

what do CD8+ T cells become when they become effector cells?

A

cytotoxic T cells

39
Q

what type of cells do MHC Class II molecules activate?

A

CD4+ T cells

40
Q

what do CD4+ T cells become when they become effector cells?

A

T helper cells

41
Q

what subunits are in the MHC Class I molecule?

A
  • 1 transmembrane alpha protein
  • 1 beta-microglobulin protein
  • 2 alpha proteins that make up the peptide-binding cleft
42
Q

what subunits are in the MHC Class II molecule?

A
  • 1 beta, 1 alpha transmembrane proteins
  • 1 beta, 1 alpha proteins that make up the peptide-binding cleft
43
Q

what subunit of MHC Class I molecule is present in every MHC Class I molecule?

A

beta-microglobulin

44
Q

what are the 3 components of the MHC Class I molecule that is required to be stably expressed on the cell surface?

A
  1. peptide
  2. MHC Class I alpha chain (for 3 subunits)
  3. beta-microglobulin
45
Q

what are the 3 components of the MHC Class II molecule that is required to be stably expressed on the cell surface?

A
  1. peptide
  2. MHC Class II alpha chains
  3. MHC Class II beta chains
46
Q

each chain of the MHC has several _____________ domains

A

each chain of the MHC has several IMMUNOGLOBULIN-LIKE domains

47
Q

what are immunoglobulin-like domains?

A

secondary structure in many immune molecules

48
Q

besides TCRs, where are immunoglobulin-like domains found?

A

adhesion molecules

49
Q

what are the 4 components of immunoglobulin-like domains?

A
  1. ~100 amino acids
  2. alpha helices
  3. beta sheets
  4. stabilized by disulfide bond
50
Q

where is the more conserved location of MHC located?

A

closer to cell membrane

51
Q

where are the most variable regions of MHC located?

A

mostly around peptide-binding cleft

52
Q

what is the shape of MHC?

A

MOOSE

53
Q

how is beta-microglobulin bound to the rest of MHC?

A

bound at transmembrane alpha domain by non-covalent bond

54
Q

what length of peptides do MHC Class I molecules bind?

A

short peptides –> 8-10 amino acids

55
Q

what length of peptides do MHC Class II molecules bind?

A

length doesn’t matter

56
Q

what allows for a stable interaction between TCR and peptide-MHC?

A

co-receptors

57
Q

why are co-receptors required?

A

because TCR and peptide-MHC is a low affinity interaction

58
Q

which co-receptor is used for MHC Class I ?

A

CD8

59
Q

which co-receptor is used for MHC Class II?

A

CD4

60
Q

co-receptors physically interact with __________

A

co-receptors physically interact with MHC

61
Q

describe the structure of CD4

A
  • single chain transmembrane protein
  • 4 Ig-like domains (all identical)
62
Q

describe the structure of CD8

A
  • heterodimer linked by disulfide bond
  • each transmembrane chain has 1 Ig-like domain
63
Q

what are the 2 roles of CD4 and CD8 co-receptors?

A
  1. bind MHC molecule and enhance affinity of TCR-pMHC interaction
  2. initiation of intracellular signaling from TCR (signal 1)