T-cell maturation/development/differentiation

Question 1

Selecting TCRs are reactive to

Answer 1

foreign peptide-self MHC but not to self-peptide/self MHC- central tolerance becasue it occurs in thymus and not in periphery.

Question 2

Thymic epithelial cells serve as

Answer 2

antigen presenting cells expressing MHC class I/ self peptide or MHC class II/ self peptide for thymocyte TCR’s to scrutinize

Question 3

TCR’s structure

Answer 3

Two polypeptide chains Alpha/Beta or Gamma/Delta each with variable and constant domains

Question 4

TCR alpha variable domain

Answer 4

VJ segments

Question 5

TCR beta variable domain

Answer 5

VDJ segments

Question 6

somatic recombination is the process y which

Answer 6

gene segments are selected and combined to form unique variable region in the TCR alph and TCR beta changes

Question 7

Somatic recombination is initiated by

Answer 7

recombinases which are products of RAG(recombination activating gene)-1 and RAG-2 genes

Question 8

V’s D’s and J’s are randomly selected and combined to form

Answer 8

variable region of TCR alpha and TCR Beta

Question 9

Rearranged genes are transcrbied to

Answer 9

mRNA genes whech are translated into an alpha and beta polypeptide chain to become a T cell receptor.

Question 10

allelic exclusion

Answer 10

successful recombination of somatic recombination inhibits other allele recombination

Question 11

unsuccessful rearrangement of DNA on one allele leads to

Answer 11

attempted recombination on another allele.

Question 12

diversity of T cell is the result of

Answer 12

–multiple copies of germline V,D, and J segments, – Random selection and combination of V, d, and J segments, – Juncation diverstity generated by addition and deletion of bases. –random assortment of TCR alph and beta chains

Question 13

junctional diversity is created when

Answer 13

DNA nucleotide are deleted or inserted at V,D, or J, gene segment junctions in order to maintain an open reading frame.

Question 14

each TCR s expressed in assoction with

Answer 14

five invariant polypeptides called CD3

Question 15

CD3 serves to link

Answer 15

the antigen binding receptor of the T-cell signaling pathway.

Question 16

variable regions are constructed from

Answer 16

segments termed Variable(V), Diversity(D), or Joining(J)

Question 17

during activation of recombination the locus that encodes V, D, and J is

Answer 17

cut and recombined to make an intact gene encoding varible regions in TCR alpha and beta polypeptide chains.

Question 18

during recombination process intervening unselected V, D, J are

Answer 18

deleted.

Question 19

when the recombination has not resulte dn open reading frame, nucleotids are

Answer 19

incorporated by a template indipendent of DNA poymerase, terminal deoxynucleotidyl transverase (Tdt) which allows the transcription and transition to form the polypeptide

Question 20

thymic cortex processes

Answer 20

-entry of bone marrow derivee of lymphoid progenitors in the thymus corticomeduallary junction – expresion of preTCR rcomplex(rearranged beta chain, CD3, and pre T Alpha) –expression of both CD4 and CD8 and +pre TCR complex – Expression of TCR complex (rarranged alpha and beta chain) +CD3,4,8) –Selection of DP thymocytes that express TCR’s useful to the immune system –Lineage determination

Question 21

thymic medulla processes

Answer 21

-Expression of AIRE gene in mTEC to allow expression of tissue proteins in the thymic medulla –interaction of SP thymocytes with mTEC’s to select autoreactive cells. –negative selection– export of three lineages of Tcells CD4+nTREG, CD4+Thp and CD8+ pCTL

Question 22

AIRE protein is a

Answer 22

transcription regulator

Question 23

lymphoid progenitors enter the thymus at

Answer 23

the corticomedullary junction

Question 24

lymphoid progenitors migrate through the parenchyma to

Answer 24

the outer regions of the thymic cortex

Question 25

lymphoid progenitors interact with

Answer 25

the thymic epithelial cells, which intiations differentation of the progenitors.

Question 26

CD2 is one of the first

Answer 26

molecules to be expressed on the T cell surface and remains for the life of the cell

Question 27

Thymic tolerance begins with

Answer 27

allelic exclusion of the TCR beta chain and expression of CD3 and pre T alpha to form a pre TCR complex

Question 28

double positive thymocyes are

Answer 28

characterized by the cell surface expression of both CD4 and CD8 and also preTCR complex this may signal somatic recombination of TCR alpha chain.

Question 29

after double positive thymocytes are there the TCR alpha polypeptide

Answer 29

is transcritbed follwoing somatic recombination and allelic exclusion. during this preTalpha chain is downregulated for the cell surface expresion of TCR-CD3 complex.

Question 30

double positive thymocytes are selected to

Answer 30

live or die depending on interactive avidty of their TCR self antigen/self MHC on thymic epithelial cells and other molecules expressed on the two cells

Question 31

interactive avidity depends on

Answer 31

intrinsic affinity of TCR for self antigen/MHC complex, –Density of TCR – Density of self antigen/MHC complexes on the thymic epithelium – the density of antagonist peptide complexs – interactino of a variety of accessory molecules and adhesion molecules with thier counterparts on the thymic epithelium.

Question 32

Death by neclect.

Answer 32

insignificant interactive avidity of the thymocyte with thymic epithelial cells

Question 33

negative selection

Answer 33

recognition exceeds a pre-determined threshold and thymocytes are clonally eliminated or functionally inactived by an active process.

Question 34

negative selection occurs whenever

Answer 34

triggering threshold avidity for Tcells is exceeded.

Question 35

the initial elimination of potential self reactie cells occurs in

Answer 35

the thymic cortex.

Question 36

negative selection is a consequence of

Answer 36

high avidity interactions of the TCR for self antigen/self MHC occuring in the absence of CD4/CD8 interactions with MHC

Question 37

positive selection

Answer 37

occurs in the medulla, the avidity of recognition is intermediate and results in preferntial expansion of T cells.

Question 38

after selection there is

Answer 38

transition from double positive thymocytes to single positive,

Question 39

function of T-cell is determined at

Answer 39

lineage determination when double postive becomes a single positive.

Question 40

Aire exprssion leads to

Answer 40

extopic expression of tissue restricted proteins in mTECS

Question 41

Interactive avidity in the medula includes

Answer 41

CD8 and CD4 interaction with MHC class I or Class II on mTEC and tissue restricted proteins/MHC comlexes are displayed on mTECs

Question 42

medullary negative selection

Answer 42

destruction of potentially autoreactive Tcells

Question 43

Lympohcytes leave maturation sites via blod and

Answer 43

either seed the secondary lymphoid tissue or recirculate in immuno surveillance

Question 44

migration of naive lymphocytes from blood into lymph occurs at

Answer 44

specialized post capillary venules called high endothelial venules

Question 45

lymphocyte rolling is induced by

Answer 45

interactino of L-selectin on lynpohcytes with ligand on endothelial cells.

Question 46

integrins(LFA1) on lymphcytes increases

Answer 46

adhesiveness and stable binding to HEV

Question 47

lymphocytes secerete

Answer 47

matrix metalloproteinases which degrades cologen to generate channells into the basement membrane

Question 48

lymphocytes enter teh tissue through

Answer 48

transendothelial migration

Question 49

if the lymphocyte doesn’t encounter an antige in the lymph node

Answer 49

it starts immunosurveillance in the lymphatics.