Immunology 11 Lynphocyte Maturatation

Front 1

maturation of T cells takes place where? B? are these primatry or secondyr

Back 1

T: thymus
B: BM

PRIMARY

Front 2

Recombine heavy chain randomly without the influnece of AG

Back 2

done in the process of making pro B a pre b

Front 3

so before we can make T and B what lineage must cells commit to

Back 3

lymphoid

IL3
IL7

Front 4

what are teh 5 bid picture things to make T and B cells

Back 4

1. commit to ltmphoid lineage. IL3 IL7

2. Proliforate

3. create/express new AG receptors

4. Selection to eliminate self reactivity

5. Differentiation into distinct populations

Front 5

what are the stages of lymphocytes when we are communting them to lymphoid and using growth factors to proliforate

Back 5

stem
Pro lymph

Front 6

at what level of maturation can lymph respong to foerign Ag

Back 6

mature niaeve undifferentiated

Front 7

what are the 2 mian checkpoints for lymph maturation

Back 7

1. Express Ag Receptor
2. Non reactive to self

Front 8

where in the tissue do lymph pass through the checkpoints

Back 8

primary
Thymus or BM

Front 9

if a lymphocyte cannon express an AG receptor will it continue to mature

Back 9

nope

this is one of the 2 check points, the other is to be non reactive to self

Front 10

what happens if lymphycytes cant pass the checkpoints

Back 10

they cant be made and the person is susceptible to opprotunistic infections

Front 11

someone with depressed immunity and numerour opprotunistic infections likely has what

Back 11

impaired ability to make lymphocytes

Front 12

what type of recombination makes the variable region of TCR and BCR

Back 12

SOMATIC RANDOM

during development

Front 13

when is the specificity of a TCR or BCR determined

Back 13

in maturation, random somatic recombination of the variable regions

Front 14

what is the structural ID of TCR and BCR

Back 14

TCR: 1a and 1 b

BCR: 2 IDentical heavy and 2 identical light chains

Front 15

wht defines the stages of lymphocyte matureation

Back 15

the proteins being displayed

Front 16

what has CD 19 and CD10

Back 16

pro B cell

Front 17

pro B cells are defined as having what

Back 17

CD 19
CD10

Front 18

what stage of B cell development has rearranged heavy chains? what does the light chain look like in this case

Back 18

Pre B

**there is a temproy light chain

Front 19

when is there a temorry light chain

Back 19

pre B

**the heavy chain has rearranged and there is a surrogate light chain to keep it stable

Front 20

what is the isotype of the initial heavy chain displayed on pre B

Back 20

IgM

Front 21

what does a pre B look like

Back 21

rearranged heavy chain
surrogate light chain

*heavy chain isotype is IgM

Front 22

what does an immature B cell look like

Back 22

heavy and light chain have rearranged
membrane bound IgM is expressed
has gone through negatine selsction
released from BM and goes to the spleen to mature

Front 23

where would you find an immature B cell

Back 23

spleen for final maturation

Front 24

what type of cell (B) has BOTH the heavy and light chain rearranged? what are other characteristics

Back 24

Immature B

**also has undergone (-) selection, has membrane bound IgM, and its found in the spleen

Front 25

at what stage does the B have heavy chain rearrangement,
light?

Back 25

Pre B: good heavy, temporary light

Immature B: has good heavy and light

Front 26

a b cell in the spleen will be what kind?

Back 26

immature B

Front 27

how can we ID a mature B from immature B based on the membrane bound receptor that it has

Back 27

mature B can have IgD heavy chain (igM also)

Immature B ONLY had IgM

Front 28

wht is the first constant region to be added to be cells, at what stage in developemnt

Back 28

heavy chain, IgM

*pre B

Front 29

when mature B cells class switch how it is done?

Back 29

at the level of the RNA, the specificity doesnt change

Front 30

when immature B --> B and isotypoe switch into IgM or IgD does the specificity change

Back 30

no way!

Front 31

in VDJ recombination what is the order of recombination

Back 31

VD join first then the VD segment will bind a J segment

Front 32

what facilitates VD and VD J joining

Back 32

RAG

Front 33

what happens to lymphocytes in the BM that recognize AG

Back 33

DIE

**this is the time when B cells undergo - selection. if they dont die they become immature B cells: IgM bound BCR, heavy and light chain, not self reactive, released from BM to enter spleen

Front 34

do TCR or BCR have a Fx Fc domain

Back 34

TCR

in the constant region

Front 35

with VDJ and B cells who does first

Back 35

heavy chain VD combine

Front 36

constant regions determine what

Back 36

isotype of heavy chain

Front 37

what is the surrogate light chain like? when is it expressed?are the Iga and Igb also expressed

Back 37

structurally similiar to kappa and lambda light chains but this is not variable

pre B

yes

Front 38

what does having the heavy chain and fake light chain on pre b allow (4)

Back 38

1. lets B continue, proliforate
2. prevents second heavy chain gene from recombining if first was successful
3. stim K and inhibit fake light chain

Front 39

what light chain is always made first

Back 39

kappa

Front 40

IgM is in what form when bound? free

Back 40

bound is monomer (always the first one made on heavy chain)

pentamer

Front 41

why do we want the Pre B to express that silly recombined heavy chain with the fake surrogate

Back 41

this prevents the other heavy gene to recombine, we want only ONE specificity :)

Front 42

when does - selction of B cells occue

Back 42

as cells move from the pre to teh immaure stage

**once immature that are NOT self reactive

Front 43

what cells are killed in negative selsection of b cells

Back 43

cells whos BCR bind TIGHTLY to AG

**this means they really recognize self AG and they are eliminated

Front 44

so lets say a pre B binds REALLY tightly to AG, will it immediatly be killed

Back 44

well be just worked SO hard so we try "light chain editing" to try to rearrange the light chain adn decrease binding

Front 45

what is light chain editing

Back 45

A pre B undergoes (-) selection before becoming an immature B cell.

**if the pre B binds to self AG it will be killed, BUT it takes a long time to make the BCR so its given one chance, if it can edit its light chain to decrease the affinity of binding it will become immature B :)

Front 46

what is (+) selection
what is (-) selection

Back 46

(+) keep low affinity pre B --> immature B

(-) high affinityy pre B ---> apoptosis (light chain rearrangement can spare them)

Front 47

is specificity of TCR created that same way as the specificity for BCR

Back 47

sure thing

VDJ, make variable heavy first and then make the light

Front 48

what is the cell surface marker for...

stem cell for lymphoid
pro B
Pre B
Immature b
Mature B

Back 48

stem: CD43
Pro: CD19, CD10
Pre: Heave chain with surrogate light
Immature: IgM, good heavy AND light
Mature: IgM or IgD

Front 49

in what stages of B cell matrueation do we see proliforation

Back 49

1. from stem to pro B, duh

2, From Pre B to immature B

3. Immature to mature after they saw AG in the periphery

Front 50

is the entire process of B maturation in the BM?

Back 50

nope,

**immature go to spleen and become mature. When they see AG they differentiate nad proliforate

Front 51

how does the resonse to AG in the maturation of B depending on what atructure we are in

Back 51

Pre B in BM die if they see AG (self AG(

Mature/Immature PROLIFORATE when they see AG in SPLEEN

Front 52

wht is the stem cell marker for T, B

Back 52

T: CD25 CD 44
B: CD43

Front 53

the stages of a b cell were stem, pro, pre, immature, mature. what are the stages for a t

Back 53

1. stem
2. Pro
3. Pre
4. Double + (CD8 AND CD4)
5. Single +
6 Niaeve Mature

Front 54

how deos the locatin of T cell matureation differ than BM

Back 54

B: immature leave

T: after they get to Pre T they go to T cell university! they then enter the periphery as niave mature T

Front 55

the cell surface markers for the first few stages of TCR maturation are... when does this change

Back 55

Stem, Pre, Pro: CD25 CD 44

at the double + stage we get CD4 an CD8

Front 56

what happens in the proT cell

Back 56

CD 25, CD44

**b chain begins to undergo somatic recombination

Front 57

wht stage of cell is ID by CD 25, Cd44. what else?

Back 57

pro T

**also begins somatic recombination of b chain

Front 58

what does the pre T do? is this similar to the pre B

Back 58

pre T: recombine b chain expressed with surrogate a chain

Front 59

what cell has a recombined b and a tempory a

Back 59

Pre T

Front 60

what is a Double Positive T cell

Back 60

has BOTH CD4 and CD8

**positive nad negative selsction
**rearranged b and a chain is expressed

Front 61

why is there a need for double positive T cells

Back 61

the cell doesnt know yet what MHC it will respond to so it needs BOTH

Front 62

what is a single positive

Back 62

either CD4 or Cd8 has been downregulated, this is the last step before mature T

Front 63

heavy ligh b a what are analgoous, who has what

Back 63

heavy (B) b (T)
light (B) a (T)

Front 64

a pre TCR is a pre TCR when what?

Back 64

b is expressed with a surrogate a chain pTa

Front 65

how is VDJ recombination differnent for TCR than BCR

Back 65

its not!

heavy (b) chain is 1st, VD join then get J--> PRE
light chain (a) is next --> immature B/ double ++

Front 66

do double ++ TCR display a recombined b and a chain

Back 66

sure thing

Front 67

so we know a pre TCR has pTa (the b chain with a surrogate light chain) any other markers?

Back 67

CD3
zeta chain (analogous to Iga Igb, signaling)

Front 68

so once we had a pre B there were several things that the expression of the heavy and surrogate light chain did? what were these? what are they for preT

Back 68

BOTH:
-survival/proliforation
-the expression of the receptor inhibited recombination of the heavy or b chain.
-Stim light or a chain recombination

**an additional role of the pTa is to stim expression if CD4 and CD8

Front 69

what stim production of CD8 and CD4 for double + T cells

Back 69

the expression of the recombined b chain and surrogate chain on the pre T cell

Front 70

what is positive selection in T cells

Back 70

WEAK interaction of self peptice nad MHC

**note in T cells it was jsut self AG binding to the variable region on the BCR, here we also have MHC

**the MHC that binds will down regulate the unneeded CD marker

Front 71

what cell type shows death by neglect, what is this

Back 71

T cells

**T cells need to recognize AG and MHC, if NO interaction they are killed by neglect. We need the TCR to recognize one form of MHC

Front 72

what is negative selsction

Back 72

the process that is done before B cells enter the immature stage nad T cells enter the double positive stage (jsut after the PRE stage)

**when AG binds TIGHT to a receptor the TCR is killed bc it is reactive to teh SELF proteins in the BM or thymus respectively

Front 73

if there is NO binding btwn TCR and pepide...

if there is STRIOING binding btwh TCR and peptide

if there is WEAK binding btwn TCR and peptide

Back 73

death by neglect

APOPTOSIS


SURVIVE

Front 74

in general what goes on during the pro lymphocyte stage

Back 74

proliforation
expression of early markers (CD19 CD10: CD25 CD44)

random VDJ recombination of heavy or beta chain

Front 75

in general what goes on during the Pre lymphoctye stage

Back 75

continued proliforation

pre AG receptor (rearranged heavy or beta) with surrogate light or alpha chain

initiate VDJ for the light or alpha chain

Front 76

do B cells undergo Negative selesction

Back 76

??????????//

Front 77

in general what happens in the immatre lymphocyte stage

Back 77

complete AG receptor expression (and CD8 ot CD4 fro TCR)

selection against self
B: negative selsection
T: negative and positive selection

Front 78

what is the difference btwn + and - selsction. what cell type does what

Back 78

?????????????

Front 79

what generaly happens in the mature lymphocyte stage

Back 79

functional T or B cell

**released into circulation