Chapter 5 Questions

Front 1

The surrogate light chain operating during pre-Bcell development is made up of?

Back 1

1) VpreB:/\5.

Front 2

The surrogate light chains expression with u on the pre-B cell surface represents ?

Back 2

1) an important checkpoint in B-cell maturation

Front 3

Name the T-cell analog of VpreB:/\5.?

Back 3

1) preTa (pTa)

Front 4

pre Tcell receptor consists of ?
pre Bcell receptor consists of?

Back 4

1) Pre Tcell
a) pTa
b) Tcell receptor B-chain,
2) preBcell
a) VpreB:/\5
b) Ig H-chain

Front 5

Tcell receptor B-chain?

Back 5

1) which is the first of the two Tcell receptor chains to be expressed

Front 6

The B chain, is like the Ig ?

Back 6

1) H-chain,
2) 1st to be rearranged
a) contains V, D and J segments.

Front 7

complete complex of pre Tcell receptor?
pre Bcell receptor?

Back 7

1) Pre Tcell
a) pTa
b) B-chain
c) CD3 and zeta components to this complex
2) Pre B cell receptor
a) VpreB:/\5
b) H-chain
c) Iga and IgB

Front 8

and the assembly of the complete complex induces ?

Back 8

1) pre Tcell receptor
a) Tcell proliferation and
b) the cessation of rearrangement at the TCRB loci.
2) Pre B cell receptor
a) similarly prevents further rearrangement of the H-chain loci

Front 9

cessation of rearrangement of TCRB loci and Tcell proliferation leads to ?

Back 9

1) allelic exclusion

Front 10

pre Tcell

Back 10

pre Bcell

Front 11

Tcell receptor

Back 11

Bcell receptor

Front 12

successive gene rearrangements at the Tcell receptor?
the immunoglobiulin?

Back 12

1) a- and B-chain loci can rescue unproductibely rearranged VJ and VDJ segments, respectively.
2) k and /\ L-chain loci can also undergo successive gene rearrangements

Front 13

Ig H-chain genes are only permitted ?

Back 13

1) one rearrangement per locus

Front 14

What aspects of the arrangement of gene segments at these loci make successive gene rearrangements possible for ?

Back 14

1) TCRa,
2) TCRB,
3) light chain k
4) light chain /\ loci
5) but not for the heavy chain locus

Front 15

Successive gene rearrangement is possible at the TCRa locus ?

Back 15

1) because there are numerous V and J gene segments available.
a) As long as there are V segments upstream and J segments downstream of the initial unproductive rearrangement,
(i) a second rearrangement can occur.

Front 16

What does the second rearrangement of TCRa locus involve?

Back 16

1) deletion of the unproductive rearrangement.

Front 17

If the second rearrangement is productive?

Back 17

1) then rearrangement at this locus terminates

Front 18

If second rearrangement is unproductive?

Back 18

1) then another rearrangement is permitted,
a) providing there are V and J segments still available.

Front 19

If the V and/ or J segment pool is depleted at one locus?

Back 19

then the other TCRa locus can begin to rearrange

Front 20

a-chain rearrangements

Back 20

1) because there are numerous V and J gene segments available.
a) As long as there are V segments upstream and J segments downstream of the initial unproductive rearrangement,
(i) a second rearrangement can occur.

Front 21

Successive gene rearrangement is poss. At the TCRB locus because ?

Back 21

1) there are two sets of D, J, and C gene segments down stream of the cluster of V gene segments:
a) (VB)n…DB1…(JB1)n…CB1…DB2…(JB2)n…CB2.

Front 22

if a first rearrangement involving DB1 and JB1 segment is unproductive?

Back 22

1) upstream V gene segment can rearrange to the second D gene segment and an associated J segment.

Front 23

If this is unproductive?

Back 23

1) no more rearrangements can be made

Front 24

B chain rearr

Back 24

1) there are two sets of D, J, and C gene segments down stream of the cluster of V gene segments:
a) (VB)n…DB1…(JB1)n…CB1…DB2…(JB2)n…CB2.

Front 25

successive gene rearrangement is possible at the k L-chain locus b/c ?

Back 25

1) there are numerous V and J gene segments available.
a) As with the TCRa locus,
b) as long as there are available V and J segments,
(i) further rearrangements can take place

Front 26

further rearrangments of k L-chain result in ?

Back 26

1) the excision of the unproductive rearrangement product.

Front 27

Each k locus has the potential of rearranging a maximum of ?

Back 27

1) five times
a) because there are five J segments

Front 28

k L-chain rearrangements

Back 28

1) there are numerous V and J gene segments available.
a) As with the TCRa locus,
b) as long as there are available V and J segments,
(i) further rearrangements can take place

Front 29

successive gene rearrangement is possible at the /\ L-chain locus b/c ?

Back 29

1) there are four sets of one J and one C gene segment cluster:
a) (V/\)-29…J/\1…C/\1…J/\2…C/\2…J/\3…C/\3…J/\4…C/\4.

Front 30

each /\ locus thus has the potential to make a max. of ?

Back 30

1) four rearrangements

Front 31

/\ L-chain rearrangments

Back 31

1) there are four sets of one J and one C gene segment cluster:
a) (V/\)-29…J/\1…C/\1…J/\2…C/\2…J/\3…C/\3…J/\4…C/\4.

Front 32

H- chain locus has the following configuration: ?

Back 32

1) (V)n-heptamer…23 spacer..nonamer…nonamer…12 spacer…heptamer-(D)n-heptamer…12spacer…nonamer…nonamer…23spacer…haptamer(j)n…Cu.

Front 33

After the first DJ rearrangement, ?

Back 33

1) the intervening D segments b/t the chosen D and J will be deleted

Front 34

Following VDJ rearrangements?

Back 34

1) the D segments that lie b/t the chosen V and DJ will be deleted.
2) Therefore, no un-rearranged D segments remain following these two rearrangement events

Front 35

V and J cannot rearrange directly b/c ?

Back 35

1) the recombination signal sequences are not paired appropriately and do not follow the 23/12 rule,
a) but rather they both contain 23-spacers with their recombination signal sequences.
b) Successive gene rearrangement is thus not possible at a H-chain locus

Front 36

H--chain rearrangement

Back 36

1) (V)n-heptamer…23 spacer..nonamer…nonamer…12 spacer…heptamer-(D)n-heptamer…12spacer…nonamer…nonamer…23spacer…haptamer(j)n…Cu.

Front 37

MHCclass II expression is restricted to?

Back 37

a limited number of cell types

Front 38

what are the MHC class II expression cell types?

Back 38

a) the professional antigen presenting cells
b) thymic epithelial cells,
c) neural microglia, and
d) activated Tcells (in humans)

Front 39

the professional antigen presenting cells?

Back 39

1) Bcells,
2) macrophages and
3) dentritic cell

Front 40

which of these cell types populate the thymus or ciculate through it?

Back 40

1) Macrophages,
2) dendritic cells, and
3) thymic epethialial cells

Front 41

what role do MHC class II expression cell types play in mediating positive and/or negative slection?

Back 41

1) positive selection
a) Cortical thymic epithelial cells participate
b) Only Tcells that have Tcell receptors that can interact with self MHC are positively selected
2) Negative selection
a) Cortical and
b) medullary thymic epithelium may also participate
c) Thymic epithelium,
d) circulating macrophages and
e) dendritic cells

Front 42

How do Cortical thymic epithelial cells participate in positive selection ?

Back 42

1) by presenting MHC class I and II molecules w/ self peptides to double positive (CD4+/CD8+) thymocytes

Front 43

What is a double positive thymocytes?

Back 43

1) These are developing T cells that have successfully rearranged the TCRa and TCRB genes.
2) Express CD4, CD8 and the a:B Tcell receptor in assoc w/ CD3

Front 44

Only Tcells that have ? are positively selected?

Back 44

1) Tcell receptors that can interact with self MHC
a) thus shaping a tcell repertoire that is specific for self-MHC molecules.

Front 45

if the affinity for self MHC:self peptide is too weak?

Back 45

1) the Tcells will die by neglect through apop.

Front 46

Cortical and medullary thymic epithelium may also participate in negative selection by ?

Back 46

1) inducing apop of thymocytes
a) that bear a Tcell receptor w/ high affinity for self MHC, self peptide or a comination of the two.

Front 47

Thymic epithelium, circulating macrophages and dendritic cells that are found primarily at the?
participate in?
aid?

Back 47

1) cortico-medullary junction
2) negative selection and
3) aid in the elimination of potentially self reactive T cells

Front 48

Potentially self reactive Tcells bear?

Back 48

1) high affinity Tcell receptors for complexes of self MHC:self peptides.

Front 49

b/c Potentially self reactive Tcells are circulating b/t tissues, organs and the thymus?

Back 49

1) a heterogenous array of self peptides will be transported to the thymus and displayed

Front 50

why is it important for a heterogenous array of self peptides will be transported to the thymus and displayed ?

Back 50

1) b/c there are some self peptides that are expressed in locations other than the thymus and which may be encountered in secondary lymphoid organs

Front 51

Circulating dentritic cells and macrophages are effective at ?

Back 51

1) endocytosing cellular debris
a) in extra thymic locations and
2) then presenting self peptides (derived from this debris) to thymocytes

Front 52

Although circulating dentritic cells and macrophages are effective at endocytosing cellular debris and then presenting self peptides to thymocytes, there are some self proteins that are

Back 52

1) Excluded from this housekeeping function.
a) these are located in immunologically privileged sites
(i) where leukocytes do not usually circulate.

Front 53

These immunologically privileged sites are

Back 53

1) normally MHC class II negative

Front 54

What is the importance of these immunologically priviledged sites being MHC II negative?

Back 54

1) b/c this avoids the presentation of self peptides with MHC class II
a) that were not presented in the thymus during negative selection.

Front 55

Some of these tissues can be induced to

Back 55

1) express MHC class II molecules
a) under the influence of certain cytokines,

Front 56

example of cytokines that can influence the tissues

Back 56

interferon-y,
a) during an inflammatory response

Front 57

This is believed to be one mechanism by which

Back 57

tolerance can be broken, resulting in autoimmunity

Front 58

can you explain why it would be detrimental for non-circulating cells that populate tissues and glands, to express MHC class II?

Back 58

1) Although cellular debris is usually endocytosed in extra thymic locations and presented as self proteins to thymocytes,
a) some self proteins are excluded from this housekeeping function.
(i) located in immunologically privileged sites
(a) These sites are normally MHC class II negative and
b) this is important b/c this avoids the presentation of self peptides with MHC class II that were not presented in the thymus during negative selection.
2) some of these tissues can be induced to express MHC class II molecules.
resulting in autoimmunity

Front 59

in Tcells allelic exclusion of the a- chain locus ?

Back 59

1) is relatively ineffective,
a) resulting in the production of some Tcells w/ 2 Tcell receptors

Front 60

these two receptors are of ?

Back 60

1) differing antigen specificity on their cell surface

Front 61

will both the Tcell receptors have to pass positive selection for the cell to survive?

Back 61

1) only one of the receptors have to be positively selected
a) Even if the other receptor does not react with self MHC this will have no effect.

Front 62

Will both receptors have to pass negative selection for the cell to survive?

Back 62

1) both receptors will have to pass the negative selection test for the Tcell to survive,
a) if only one of them fails > the cell will die

Front 63

is there a potential problem having T cells with dual specificity surviving these selection processes and being exported to the periphery?

Back 63

1) Yes.
a) Activated effector Tcell
(i) 2nd self peptide
b) Interferon-y
(i) Non-prof. APC

Front 64

how would an tcells with dual specificity become activated?

Back 64

1) during an infection by an APC + foreign antigen 1
a) using Tcell receptor 1

Front 65

how would an activated effector tcells with dual specificity respond to 2nd peptide?

Back 65

1) using tcell receptor 2 (could be self-peptide)
a) without requiring the co-stimulatory signals only professional antigen presenting cells deliver.
2) Thus it could cause a reaction against a self tissue

Front 66

reactions against a self tissue, either ?

Back 66

1) directly if it is a CD8T cell or
2) indirectly if it is a CD4 Tcell,
a) by activating potentially autoreactive B cells

Front 67

interferon-y produced in the response against foreign antigen 1 could activate?

Back 67

1) nonprofessional antigen-presenting cells nearby,

Front 68

what would activation of nonprofessional antigen-presenting cells induce?

Back 68

expression of MHC class II
a) with presentation of the self peptide above.
b) Effector Tcells with T cell receptor could make an autoimmune response against it.

Front 69

mature B cells undergo?

Back 69

1) somatic hypermutation following activation

Front 70

when somatic hypermutation follows activation which follows affinity maturation, it results in ?

Back 70

1) the production of antibody with higher affinity for antigen than in the primary antibody response

Front 71

Since Tcells drive almost all immune responses, once activated,?

Back 71

1) their receptors must continue to recognize the exact complex of foreign antigen and MHC molecule that activated them.

Front 72

b/c of the requirement for dual recognition, somatic hypermutation would more likely than not ?

Back 72

1) change the Tcell receptor to make it unable to recognize either the peptide or the MHC molecule, or the combination of both,

Front 73

if the Tcell receptor was unable to recognize either the peptide or the MHC molecule, or both, it would render it?

Back 73

1) unable to give help the B cells or to attack infected cells,
a) depending on the type of Tcell.

Front 74

if the Tcell was unable to give help the B cells or to attack infected cells, This would?

Back 74

destroy both the primary immune response and the development of immunity

Front 75

Even changes that simply increased the affinity of the t cell for its antigen ?

Back 75

1) would have no real advantage,
a) as it would not make the immune response any stronger or improve immunological memory in the same way that affinity maturation of Bcell does.

Front 76

if somatic hypermutation changed the specificity of the Tcell receptor so that it now ?recognized a self peptide, this could result in ?

Back 76

1) an autoimmune reaction

Front 77

why do These considerations not apply to B cells?

Back 77

1) they require Tcell help to produce antibody and
2) will only receive it if their Bcell receptor still recognizes the original antigen.

Front 78

MHC class II deficiency is inherited as ?
and involves?

Back 78

1) an autosomal recessive trait and
2) involves a defect in the coordination of transcription factors

Front 79

What are the transcription factors involved in ?

Back 79

1) the regulation of all MHC class II gene expression
a) (HLA-DP, HLA-DQ and HLA-DR)

Front 80

what is the effect of MHCclass II defiency?

Back 80

1) it affects the development of CD4 Tcells in the thymus

Front 81

How does MHCclass II defiency affects the development of CD4 Tcells in the thymus?

Back 81

If the thymic epithelium lacks MHC class II,
a) then positive selection of CD4 Tcells will not take place

Front 82

Why are CD8 Tcells not affected ?

Back 82

1) b/c MHC class I expression is unaffected by this defect.

Front 83

explain why hypogammaglobulinemia is associated with this deficiency?

Back 83

1) in order to produce antibody B cells require tcell help

Front 84

In what form is the Tcell help?

Back 84

1) The form of cytokines
a) produced by CD4 TH2 cells

Front 85

what is hypogammaglobulinemia ?

Back 85

1) Low Ig levels

Front 86

what are the low levels of Ig attributed to?

Back 86

1) the inability of B lymphocytes to p/d into plasma cells
a) in the absence of TH2 cytokines

Front 87

what can be used to treat several types of Tcell tumors, ?

Back 87

1) allogeneic bone marrow transplantation

Front 88

example of a type of Tcell tumors?

Back 88

1) acute lymphoblastic leukemia ((T-ALL)

Front 89

describe in general terms how an allogeneic bone marrow transplant is carried out.?

Back 89

a) Following irradiation and chemotherapy,
b) the patient would be infused with bone marrow
(i) obtained from a donor with the best HLA match possible.

Front 90

we learned in chapter 3 that the benefit of polygeney in the MHC class I and class II genes and the expression of multiple isotypes is the ?

Back 90

1) resulting increase in the number of potential peptide-binding motifs for antigen presentation to Tcells.

Front 91

three isotypes for MHC class I ?

Back 91

1) HLA-A,
2) -B and
3) –C

Front 92

three isotypes for MHC class II ?

Back 92

1) HLA-DP,
2) -DQ, and
3) –DR

Front 93

If more is better, then why hasn’t natural selection favored more than three isotypes each for MHC class I and MHC class II
and driven the expansion of polygney further in the MHC?

Back 93

1) Beyond a certain number of isotopes, the t cell repertoire will be decreased,

Front 94

Beyond a certain number of isotopes, the t cell repertoire will be decreased owing to?

Back 94

1) the disproportionate increase in negative selection events as the number of different isotypes increases

Front 95

Each additional isotype will

Back 95

1) decrease the number of t cells exported to the periphery,
2) compromising the diversity of the tcell population

Front 96

see notes about transplantation?

Back 96

chapter 5 questions flashcards

Front 97

discuss why there are Tcell tumors corresponding to early and late Tcell developmental stages but no to intermediate stages?

Back 97

1) Thymocytes do Not undergo significant prolif. b/t early and late progenitor stages
a) and there is little opportunity for maturations to accumulate at intermediate stages

Front 98

Why do thymocytes not undergo significant proliferation between the early and late progenitor stages of development ?

Back 98

1) thymic maturation of tcell occurs within a short time period;
2) thymocytes not rescued promptly during positive selection in the cortex are destined to
a) die by apop

Front 99

When do transformation of tcells occur? examples?

Back 99

either at an early lymphoid progenitor stage of thymocyte differentiation in the thymus or
a) common acute lymphoblastic leukemia (C-ALL)
2) at the post maturation stage in the periphery,
a) chronic lymphocytic leukemia (CLL)

Front 100

explain how southern blotting could be used to identify a Tcell tumor expressing a rearranged Tcell receptor B gene?
Southern blotting is a ?

Back 100

1) molecular technique based on DNA hybridization,

Front 101

Southern blotting can be used to detect and characterize a t cell tumor by?

Back 101

1) by demonstrating that the transformed cells all contain the same rearranged tcell receptor gene.

Front 102

In southern blotting DNA is ?

Back 102

1) endonuclease to generate DNA fragments of varying lengths,
2) electrophoresed in an agarose gel,
3) denatured and
4) transferred to a nitrocellulose filter or nylon membrane

Front 103

b/c the tumor cells all contain the same rearranged B gene, ?

Back 103

1) a distinct band can be visualized
a) corresponding to the rearranged gene,

Front 104

How is the band visualized?

Back 104

1) after hybridizing the nitrocellulose filter with a radioactive, single-stranded probe
a) complementary to the Tcell receptor B-locus C-region
2) followed by autoradiography.

Front 105

What is also visible?

Back 105

1) bands corresponding to the unrearranged B locus

Front 106

what result would you expect when comparing DNA extracted from spermatocytes?

Back 106

1) They will all contain Tcell receptor B-loci in the germline configuration,
2) and so the sample will only give the two bands
a) corresponding to the CB1 and CB2 genes in the unrearranged locus when probed with a C-region probe.

Front 107

what are PBMCs?

Back 107

1) peripheral blood mononuclear cells

Front 108

normal PBMCs?

Back 108

1) contain Tcells in addition to other monoculear cells

Front 109

what result would you expect when comparing DNA extracted from normal (PBMCs)?

Back 109

1) will give the same two bands and
2) a barely detectable smear
a) corresponding to the numerous different rearranged B genes in the heterogenous polyclonal pop. Of T cells

Front 110

what result would you expect when comparing DNA extracted from PBMCs of patient with Tcell leukemia?

Back 110

1) will contain a much larger proportion of T cells than normal,
a) and the majority will harbor the same rearranged B gene,
(i) as a result of outgrowth of a single transformed Tcell.
2) a discrete band migrating at a location distinct from the band s representing the germline configuration.
a) This band represents the numerous identical rearranged B genes in the sample.
b) The intensity of the band will correlate with the proportion of transformed cells in the sample