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Antigen Recognition By T Lymphocytes > Chapter 7 > Flashcards

Chapter 7 Flashcards

1
Q

Double neg thymocytes initiate rearrangement at the

A

B, gamma , gamma loci before all other T cell receptor genes

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2
Q

Function of neg selec in the thymus is to elimate

A

Autoreactive thymocytes

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3
Q

If TCR on a double pos thymocyte binds to a self peptide : self MHC I complex with LOW AFFINiTY

A

Results in pos selec of CD8 TC

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4
Q

In adults the mature TC repertoire is self renewing and does not require a thymus for provision of new TC

A

Correct

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5
Q

AIRE def

A

Exhibit APECED

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6
Q

TC analog of VpreB: lambada 5

A

Protein preTa (pTa)

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7
Q

Pta

A

Also binds like imm heavy chain binds to CD3 an zeta - assemble indices TC prolif and rearrangement of TCR beta leading to allelic exclusion

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8
Q

TC k pt

A
  1. Occurs after the rearrangement of the beta chain locus which test the ability of the beta chain to ass with pta, the surrogate light chain, and for the Pre -TCR on the surface
  2. After rearrangement of alpha chain locus test the ability of the alpha chain to associate with the b chain and for the TCR on the surface
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9
Q

MHC II expression

A

APC cells

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10
Q

To produce an antibody

A

Require TC in the form of cytokines produced by CD4 TH2 cells

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11
Q

Role of regulatory CD4 cell

T reg

A

They suppress the proliferation of naive auto-reactive CD4 TC by secreting inhibitory cytokines.

Require both Treg and the other CD4 are interacting with the same APC

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12
Q

TC are derived from

A

BM stem cells

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13
Q

Lymphoid progenitor cells in the

A

Thymus- initiation of TC devel

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14
Q

Things we have to select for in TCD

A

Host MHC

CD4 or CD8

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15
Q

Overview of TC devl

A 
Thymus unit of TCD
TCR speciality -VDJ recom
MHC restriction-pos selec
Selection of -TH or cytoxic
Elimination of self spec TC-neg sele
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16
Q

TC linage

A

A:b

G:d

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17
Q

Thymus contain what precursor

A

Contains thymocytes =precursors

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18
Q

Thymus organization

A

Cortex = immature thymocytes
-enter by HEV then start in cortex

Medulla= mature thymocytes
-selection occurs, mature TC

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19
Q

No thymus means what cells

A

No T cells but yes BC but they would not function bcuz BC need helper TC

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20
Q

No thymus what syndrome

A

DiGeoegr
No thymus dev
Normal BC
Symptoms of SCID

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21
Q

Removal of thymus

A

A thymectomy
-only in adults
Auto imm

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22
Q

TC lineage

A

Interaction bw stromal cells
Signaled to divide
Committed
Double neg- bcuz they do not have CD4 or CD8

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23
Q

What regulates TCD

A

IL-7

Notch 1

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24
Q

What is IL-7

A

Binds to receptor on cd34

Import for reg of TCD

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25
Q

Notch 1

A

Import for reg of TCD

Cell surface red on thymocytes
Bind to thymic epith
Drive TC differentiation

Analogous to Pax-5

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26
Q

TC lineage

A

Rearrangement now at gamma , delta, beta loci occur at the same time

G:D compete with B

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27
Q

If rearrangement at g:d then what type of cell?

A

G:d TC

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28
Q

If b develop from rearrangement then what kind of cell?

A

Dev to Pre TCR

No commitment yet

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29
Q

Now that we have b chain production why happens?

A

Gene rearrangement stops

Cd4 cd8 receptors are formed
Now it is a double positive thymocytes

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30
Q

After B rearrangement now what occurs after becoming a double thymocytes ?

A

Now rearrangement of alpha chain

Rearrangement of g:d continue

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31
Q

What does a uncommitted progenitor cell express?

A

CD34 - stem cell surface marker and

CD44 -adhesion

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32
Q

What does a double neg thymocyte committed to the TC lineage express?

A

CD2
CD5
IL-7
CD1A- MHC class one molecule

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33
Q

What does double neg thymocyte Not have?

A

CD34
CD44
Because after a week the cells have lost these markers and have become thymocytes

CD4
CD8

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34
Q

CD2 and CD5 do what?

A

Present on a double neg thymocytes remember that after becoming a thymocyte they are committed to the TC lineage so the. They express CD2- an adhesion molecule and CD5

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35
Q

CD 34 is on what type of cell?

A

Uncommitted progenitor

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36
Q

What type of cell is CD2 expressed on?

A

Committed double neg TC progenitor

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37
Q

What happens after cd2 expressed in double neg TC progen?

A

Cell can determine pathway by sequence in which TCr genes make productive rearrangement

So could be g:d or a:b

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38
Q

If g:d is made before B what happens?

A

G:d is a heterodimer
assembly of CD3

Signals stop of B chain rearrangement

Then g:d leaves thymus and enter circulation

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39
Q

If B chain is produced then what?

A

B chain moves to ER

Test ability to bind of invariant alpha chain pta

If b chain binds then this heterodimer assembles with the CD3 and zeta chain to for PRe-TCR

40
Q

The invariant alpha chain pta is analogous to what in the BC

A

VpreB and lambada 5

41
Q

If a b chain gene rearrangement is made then what will be made next?

A

A Pre-TCR is assembled if B chain binds to pta

Then Pre-TCR signals the cell to proliferate expressing cd4 & cd8 and become Pre TC

42
Q

Thymocytes can make how many attempts to rearrange the beta chain?

A

Four attempts

Two times on each Cb genes

43
Q

Also more infor on B chain

Once b chain is made then there will be suppression of what?

A

RAG 1 and 2 because this ensures that only one B chain gene has a productive rearrangement and expressed

44
Q

RAG 1 and 2 suppression this ensures that only one B chain gene has a productive rearrangement and expressed what is this called??

A

Allelic exclusion

45
Q

Where are doub pos thymocytes found?

A

Inner cortex Of thymus

46
Q

What are the TCR a chains comparable to in the Ig?

A

Kappa and lambada light chains

They do not have D segments
Are rearranged only after their partner chain receptor has been expressed

47
Q

A chains have what gene segments?

A

V-J

48
Q

A chain be arranged how many times?

A

The alpha chain can has as many rearrangements until either:

a productive rearrangement occurs
Or the supply of VJ gene segments is exhausted -whereupon the cell dies

49
Q

Why when rearranging the alpha chain does it exclude delta?

A

The delta chain is in the middle and is cut out

50
Q

What is really the summary of TCD?

A

Uncommitted progen expresses CD34

Then CD2 is expressed now committed doub neg TC progenitor
Then makes a decision as to what direction the cell will go

If B chain is made first (4attempts) then Pre-TC stops gene rearrangement an sends signals o get CD4 CD8 and now becomes a double pos thymocytes still uncommitted at this point.
Rag 1&2 halted allelic exclusion

Now Pre-TC turns back on the recombination to arrange a g d

Now a chain is being made

But b chain moves to ER and binds to an invariant alpha chain pTa

Then once successful a chain it translocates to ER and test for ability to bind B chain

If it binds then it survives
If not then further alpha chain gene rearrangement

51
Q

Why is the pta made?

A

So that the new b chain can quickly become the Pre-TC

52
Q

What does the RAG 1&2 do?

A

Essential for gene rearrangement and are selectively expressed

53
Q

What enzyme is in involved for somatic recomb?

A

TdT- inserts N nucleotides and are expressed thought the TCD phase

54
Q

What signals does the Pre TC depend on?

A

CD4/8- co receptors

CD3- the signaling complex

ZAP-70- involved in relaying signals from the co-receptors
CD2- adhesion molecule on TC the interact with CD58

CD58- cell surface protein generates signals

GATA-3: expressed in early TC progenitors and are essential for TCD

55
Q

What is Th-POK?

A

Expressed in late in development and is required for development of

Single pos CD4 from the doub pos thymocytes

56
Q

What are the two types of screening that the a:b double positive thymocyte undergoes?

A

Positive selection

Neg selec

57
Q

Pos selection is what??

A

Favors TC that can recognize peptides presented by a self MHC

58
Q

Neg selection does what?

A

It eliminates potentially auotreactive cells that could be activated by the peptides normally presented by mHc molecules on the surface is healthy cells

59
Q

Pos selec outcomes

A

No binding/weak binding to MHC peptide then : alpha chain rearrangement

If still no binding the undergoes apop

60
Q

Pos selc outcome

A

If TCR binds strongly then =pos selection

Turn off RAG

61
Q

What chain is allelic exclusion used on?

A

Only B chain

A not subject too

62
Q

If the TCR can bind to MHC why does this mean?

A

Can now present by the body’s set of MHC

Thymocyte is restricted

63
Q

What does mHC restricted mean?

A

That the TCR can only respond against peptides being presented by those MHC in that persons body

The thymocyte is restricted

64
Q

MHC selection

A

Only one of the two co receptors will be selected for

65
Q

If interaction bw CD4 & MHC II then what happens to CD8

A

CD8 is down regulated and disappears from the cell surface only expressing CD4 now a single pos thymocyte

66
Q

What does MHC II respond to and have displayed?

A

Displays CD4

T helper can only respond

67
Q

MHC I cells express/respond to

A

CD8 - single pos

T cytotoxic cells can only respond

68
Q

Pos selection means what will be selected?

A

That there will be a TCR that binds to a MHC

And that then while interaction occurs only one of the co receptors will be expressed

69
Q

Positive selection is regulated by what type of cells?

A

Cortical epithelial cells

70
Q

What do cortical epithelial cells express?

A

Both types is MHC
Self-peptides
TCR double positive thymocytes

71
Q

What type of cells does negative selection use to regulate a:b TC?

A

DC and macrophages not pt of the original thymus structure

They are the BM dervived

72
Q

Neg selec does what when there is engagement of the mHc of one of these specialized thymic antigen present cells by the receptor?

A

The rec of the auotreactive TC induces the TC to undergo apoptosis

73
Q

Neg selection main pts

A

Through BM DC and macrophages
Present self peptides

Occurs when TCR has high affinity with the MHC leading to apop

Deletes poten self reactive thymocytes generating a repetitive of peripheral TC that is largely self tolerant

74
Q

Repertoire of peripheral TC that have survived both pos and neg selection is both

A

Self MHC restricted

Self - tolerant

75
Q

Neg selec is specific to what proteins and cell types

A

Insulin and B cells

76
Q

What are AIRE?

A

TF
Expression of tissue specific genes of epith in thymus medulla

Bound to MHC I
Participate in Neg selection

77
Q

Def of AIRe

A

APECeD
Type I diabetes
Addison’s disease
Gonadal dysfunction

78
Q

How does the immune as deal with self specific TC?

A
  1. primining of mature TC- peripheral tolerance

2. TCR suppresses immune response

79
Q

What is AIRE?

A

Basically a systemic auto imm disease

80
Q

CD4 T cells are also called

A

T reg

81
Q

CD 4 T-reg cell facts

A 
Present in all people
CD4+
Expression of CD25 on the cell surface
5-10% peripheral CD4 
Thought to ordinate from the thymus
Use transcription factor FoxP3
Express a:b TCR
82
Q

What does only T reg cells have?

A

FoxP3 transcription factor

83
Q

What is CD4 T reg cells activated by?

A

Specific MHC class II peptide

84
Q

Do CD4 T reg

Cells proliferate?

A

No they don’t they suppress proliferation of naive TC responding to self antigen

85
Q

Cd4 T reg require what?

A

On same ApC
Requires contact between two TC
Needs cytokines IL-10 and TGF-beta

86
Q

Actions of CD T reg?

A

Suppress APC
By respon by helper T or t-cytotoxic
Some response agains tumors suppress or other imm response

87
Q

Def of Foxp3 means what?

A

IPEX

Autoimmune directed towards variety of tissue

88
Q

Treatment of IPEX?

A

BM trans from health HLA- identical sibling

89
Q

T cells undergo further diff in what lymph ?

A

Secondary lymphoid tissue

90
Q

Effector T cells are what?

A 
Cd8
Cd4
-reg TC
-helper T 
        *TH1
        *TH2
91
Q

Which is more in the periphery? Cd4 or 8?

A

Twice as many CD4

92
Q

TCR summary

A

Controlled by several genes/ gene products

Somatic recomb -RAG
Junctional diversity
Beta chain -VDJ first
Try several times(4x)

B+ surrogate alpha chain
CD3 flanking molecule signaling 
Apop or success
Cell replication if successful
Then Alpha chain VJ
Try several times

Then we get a:b receptor
Apop or success
Then cell rep if successful

93
Q

Class I deficiency

A

Cd4+

Cd8 -no

94
Q

Class II def

A

No cd4

Yes CD8

95
Q

Are TC long or short lived?

A

After thymic atrophy or theymextong TC in the periphery self Renew by cell division and are long lived

Antigen Recognition By T Lymphocytes (4 decks)

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