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
Notch 1
Import for reg of TCD Cell surface red on thymocytes Bind to thymic epith Drive TC differentiation Analogous to Pax-5
26
TC lineage
Rearrangement now at gamma , delta, beta loci occur at the same time G:D compete with B
27
If rearrangement at g:d then what type of cell?
G:d TC
28
If b develop from rearrangement then what kind of cell?
Dev to Pre TCR No commitment yet
29
Now that we have b chain production why happens?
Gene rearrangement stops Cd4 cd8 receptors are formed Now it is a double positive thymocytes
30
After B rearrangement now what occurs after becoming a double thymocytes ?
Now rearrangement of alpha chain | Rearrangement of g:d continue
31
What does a uncommitted progenitor cell express?
CD34 - stem cell surface marker and CD44 -adhesion
32
What does a double neg thymocyte committed to the TC lineage express?
CD2 CD5 IL-7 CD1A- MHC class one molecule
33
What does double neg thymocyte Not have?
CD34 CD44 Because after a week the cells have lost these markers and have become thymocytes CD4 CD8
34
CD2 and CD5 do what?
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
35
CD 34 is on what type of cell?
Uncommitted progenitor
36
What type of cell is CD2 expressed on?
Committed double neg TC progenitor
37
What happens after cd2 expressed in double neg TC progen?
Cell can determine pathway by sequence in which TCr genes make productive rearrangement So could be g:d or a:b
38
If g:d is made before B what happens?
G:d is a heterodimer assembly of CD3 Signals stop of B chain rearrangement Then g:d leaves thymus and enter circulation
39
If B chain is produced then what?
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
The invariant alpha chain pta is analogous to what in the BC
VpreB and lambada 5
41
If a b chain gene rearrangement is made then what will be made next?
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
Thymocytes can make how many attempts to rearrange the beta chain?
Four attempts Two times on each Cb genes
43
Also more infor on B chain | Once b chain is made then there will be suppression of what?
RAG 1 and 2 because this ensures that only one B chain gene has a productive rearrangement and expressed
44
RAG 1 and 2 suppression this ensures that only one B chain gene has a productive rearrangement and expressed what is this called??
Allelic exclusion
45
Where are doub pos thymocytes found?
Inner cortex Of thymus
46
What are the TCR a chains comparable to in the Ig?
Kappa and lambada light chains They do not have D segments Are rearranged only after their partner chain receptor has been expressed
47
A chains have what gene segments?
V-J
48
A chain be arranged how many times?
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
Why when rearranging the alpha chain does it exclude delta?
The delta chain is in the middle and is cut out
50
What is really the summary of TCD?
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
Why is the pta made?
So that the new b chain can quickly become the Pre-TC
52
What does the RAG 1&2 do?
Essential for gene rearrangement and are selectively expressed
53
What enzyme is in involved for somatic recomb?
TdT- inserts N nucleotides and are expressed thought the TCD phase
54
What signals does the Pre TC depend on?
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
What is Th-POK?
Expressed in late in development and is required for development of Single pos CD4 from the doub pos thymocytes
56
What are the two types of screening that the a:b double positive thymocyte undergoes?
Positive selection Neg selec
57
Pos selection is what??
Favors TC that can recognize peptides presented by a self MHC
58
Neg selection does what?
It eliminates potentially auotreactive cells that could be activated by the peptides normally presented by mHc molecules on the surface is healthy cells
59
Pos selec outcomes
No binding/weak binding to MHC peptide then : alpha chain rearrangement If still no binding the undergoes apop
60
Pos selc outcome
If TCR binds strongly then =pos selection Turn off RAG
61
What chain is allelic exclusion used on?
Only B chain A not subject too
62
If the TCR can bind to MHC why does this mean?
Can now present by the body's set of MHC Thymocyte is restricted
63
What does mHC restricted mean?
That the TCR can only respond against peptides being presented by those MHC in that persons body The thymocyte is restricted
64
MHC selection
Only one of the two co receptors will be selected for
65
If interaction bw CD4 & MHC II then what happens to CD8
CD8 is down regulated and disappears from the cell surface only expressing CD4 now a single pos thymocyte
66
What does MHC II respond to and have displayed?
Displays CD4 | T helper can only respond
67
MHC I cells express/respond to
CD8 - single pos T cytotoxic cells can only respond
68
Pos selection means what will be selected?
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
Positive selection is regulated by what type of cells?
Cortical epithelial cells
70
What do cortical epithelial cells express?
Both types is MHC Self-peptides TCR double positive thymocytes
71
What type of cells does negative selection use to regulate a:b TC?
DC and macrophages not pt of the original thymus structure They are the BM dervived
72
Neg selec does what when there is engagement of the mHc of one of these specialized thymic antigen present cells by the receptor?
The rec of the auotreactive TC induces the TC to undergo apoptosis
73
Neg selection main pts
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
Repertoire of peripheral TC that have survived both pos and neg selection is both
Self MHC restricted Self - tolerant
75
Neg selec is specific to what proteins and cell types
Insulin and B cells
76
What are AIRE?
TF Expression of tissue specific genes of epith in thymus medulla Bound to MHC I Participate in Neg selection
77
Def of AIRe
APECeD Type I diabetes Addison's disease Gonadal dysfunction
78
How does the immune as deal with self specific TC?
1. primining of mature TC- peripheral tolerance | 2. TCR suppresses immune response
79
What is AIRE?
Basically a systemic auto imm disease
80
CD4 T cells are also called
T reg
81
CD 4 T-reg cell facts
``` 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
What does only T reg cells have?
FoxP3 transcription factor
83
What is CD4 T reg cells activated by?
Specific MHC class II peptide
84
Do CD4 T reg | Cells proliferate?
No they don't they suppress proliferation of naive TC responding to self antigen
85
Cd4 T reg require what?
On same ApC Requires contact between two TC Needs cytokines IL-10 and TGF-beta
86
Actions of CD T reg?
Suppress APC By respon by helper T or t-cytotoxic Some response agains tumors suppress or other imm response
87
Def of Foxp3 means what?
IPEX Autoimmune directed towards variety of tissue
88
Treatment of IPEX?
BM trans from health HLA- identical sibling
89
T cells undergo further diff in what lymph ?
Secondary lymphoid tissue
90
Effector T cells are what?
``` Cd8 Cd4 -reg TC -helper T *TH1 *TH2 ```
91
Which is more in the periphery? Cd4 or 8?
Twice as many CD4
92
TCR summary
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
Class I deficiency
Cd4+ | Cd8 -no
94
Class II def
No cd4 | Yes CD8
95
Are TC long or short lived?
After thymic atrophy or theymextong TC in the periphery self Renew by cell division and are long lived