Blk 3 Flashcards

1
Q

what are the two types of selection of alpha/beta Tcells in thymus

A

Positive selection and negative selection

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2
Q

what can CD8 tcell recognize?

A

MHC1

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3
Q

what happens to the cells that survive positive selection?

A

move to medulla of thymus for negative selection

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4
Q

what happens to tcells that bind with too high of affinity to mhc?

A

die

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5
Q

most important part of negative selection

A

tcells are exposed to AIRE gene product in the medulla of the thymus.

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6
Q

what does the exposure of tcells to AIRE gene products allow for

A

allows epithelial cells that express theses genes to turn on tissue restricted genes

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7
Q

what is the relevance of the tcells to be exposed to AIRE gene products in the medulla of the thymus

A

the AIRE gene expresses genes from all over the body, this allows the tcells to be tested against self reaction to many parts of the body at the same place. the ones that are reactive to these genes are killed.

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8
Q

in negative selection, why isnt only the thymus protected against self reacting Thymocytes?

A

because in the medulla of the thymus the AIRE product gene is expressed, which expresses genes from all over the body.

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9
Q

why TCRs dont undergo somatic hypermutation?

A

because unlike BCR which does somatic hypermutation, TCRs need to remain specific to a particular MHC molecule.

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10
Q

thymic education

A

positive and negative selection.

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11
Q

what are the 2 types of TCRs?

A

alpha/beta (95%). and gamma/delta (5%)

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12
Q

what are the structures that form a TCR?

A
1 heterodimers (alpha/beta, or gamma/delta)
2 Ig family domains
3 transmembrane region
4 short cytoplasmic transduction tails
5 C terminus constant region
6 N terminus variable domain that contain Complementary Determining Regions (CDRs) CDR1, 2, 3,
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13
Q

where are CDR1 and CDR2 encoded

A

in the same V gene segments

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14
Q

how is CDR3 generated?

A

it is generated during joining of the segments, this makes it by far the most diverse segment

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15
Q

how is CDR3 generated?

A

it is generated during joining of the segments, this makes it by far the most diverse segment

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16
Q

how are the interactions vary btw different CDRs?

A

CDR 1 and CDR2 make contact with the shoulder of the MHC molecules and CDR3 with the antigen peptide

17
Q

there are about 10^7 TCRs on a given Tcell, how do they differ?

A

they do not differ. they are exactly the same due to alellic exclusion after a successful chain is made

18
Q

how do the binding with antigen differ btw Bcells and Tcells in terms of affinity for the peptide?

A

Bcells binds with several orders of magnitude more than Tcells to antigens

19
Q

what is the signigicance of the weak interaction btw TCRs and antigens?

A

they will need co-receptors CD4 and CD8 to help hold the cells together during signal transmission

20
Q

what is the reason for CD4 to bind to MHC2 and CD8 to MHC 1?

A

the co-receptors. CD4 binds to beta invatient region of MHC 1, and CD8 binds alpha chain of alpha invarient region of MHC1

21
Q

where do tcell receptors concentrate their diversity?

A

in the 3rd hyperviable region. CD3

22
Q

where CD1 and CD2 bind to?

A

to the MHC

23
Q

TCR gene rearrangements results in what?

A

diversity within CDR 1, 2, and 3

24
Q

when is the alpha locus rearranged?

A

after the beta locus is good

25
Q

how many chances are there to rearrange a Beta chain?

A

4, e on each of the chormosomes

26
Q

how many chances to rearrange the alpha chain?

A

many many chances unlike the 4 times of the beta chains

27
Q

what are the ezymes respostible for rearrangement of VJ and VDJ in TCRs?

A

RAG 1, RAG 2 and TdT

28
Q

what is the first rearrangement in the Beta locus?

A

D to J

29
Q

what happens if the D and J rearrangement is successful in the beta lucus?

A

rearrange V segment into it to make a VDJ segment

30
Q

how is the rearrangement in the alpha locus

A

more straight forward then the beta locus, only VJ rearrangement

31
Q

when are beta and alpha chains rearranged?

A

beta rearranged first, tested, if good, then move on to rearrange alpha chain

32
Q

what is the germline configuration in the beta and alpha locus?

A

VDJ in beta and

VJ in the alpha

33
Q

when the constant segments rearrange?

A

never, just like in BCRs

34
Q

when constant gene segments rearrange in B cell development?

A

during isotype switching, but this does not happen with TCRs

35
Q

what happens after gene rearrangement?

A

transcription and translation of the polypeptide receptors.

36
Q

combinatorial diversity?

A

any combination of VDJ and any combination of VJ in the beta and alpha chains

37
Q

thymocytes

A

tcells name before they leave the thymus

38
Q

what is a considered a functional beta chain polypeptide?

A

one that can interact with an alpha chain and form a functional TCR

39
Q

how is beta chain tested

A

associate with a sorrogate alpha chain forming a pre-Tcell receptor.