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Immunology > Lecture 11-12 - TCR and T cell development > Flashcards

Lecture 11-12 - TCR and T cell development Flashcards

1
Q

Major differences between TCR and Immunoglobulins

A

TCR only act as receptors

(Ig’s are receptors AND effector molecules)

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2
Q

Structure of the TCR complex

A
  1. TCR molecule (alpha and beta)
  2. CD3 molecules (epsilon/delta AND epsilon/gamma)
  3. ς-unit (intracellular)
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3
Q

CD3 chain function

A

transmits signals when TCR is activated

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4
Q

Two classes of TCR

A

alpha beta

gamma delta

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5
Q

Four regions of TCR

A
  1. Variable
  2. Constant
  3. Transmembrane
  4. Cytoplasmic tail
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6
Q

Immature T cells migrate from ___ to ___

Mature cells travel to the ___

A

Bone marrow to thymus

to the circulation as a ‘naive’ Tcell

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7
Q

What happens to T cells after they leave the thymus as mature cells?

A

They go to lymphoid tissue, where if they recognize antigens presented on DC, will mature into memory or effector T cells

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8
Q

Immature (Dp/Dn) thymocytes are found in the ____

Mature thymocytes (single positive) are found in ______

A

Immature = cortex

Mature = Medullary area

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9
Q

Most thymectomized patients still have T cell immunity due to

A

the amound of memory T cells in the periphery

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10
Q

Stem cell surface marker

A

CD34

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11
Q

Progenitor cell adhesion molecule

A

CD44

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12
Q

Surface molecules of a double negative thymocyte

A

CD2, CD5 (adhesion and signaling)

IL-7 receptor

CD1A

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13
Q

The alpha and beta chains differ in that..

A

alpha chain does not have a D segment

(Beta chain germline config is more complex)

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14
Q

TCR segment of the beta chain that rearranges first?

Which is second?

A

DJ first –> VDJ second

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15
Q

Even though the alpha TCR chain has no D segment, it does have _____ that contributes to diversity

A

Many more J segments

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16
Q

Total diversity of TCR’s is [less/greater] than immunoglobulins

A

TCR greater diversity

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17
Q

Which TCR chain is made first?

A

Beta chain

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18
Q

Steps to TCR rearrangement (7)

A
  1. Germline baseline configuration
  2. D-J rearrangement
  3. V- DJ rearrangement
  4. Surface expression of beta chain (cell proliferates!)
  5. alpha transcription starts
  6. Alpha VJ rearrangement
  7. Expression of alpha
  8. SELECTION can begin!
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19
Q

How many attemps at Beta chain rearrangement are possible?

A

2

After that the cell apoptosis-es

20
Q

Successful rearrangemtne of one Beta copy…

A

blocks the other chromosome

21
Q

Junctional diversity of TCR is mediated by __ and ___

How?

A

TdT and RAG enzyme

RAG = Cleaves hairpin and adds P nucleotides

TdT = adds N nucleotides

22
Q

How many chances are there fore successful alpha chain rearrangement?

A

Multiple

23
Q

Successful rearrangement of one of the alpha chains…

A

does not block that at the other

Therefore many T cells express two different alpha chains

24
Q

When does a TCR decide it wants to be a gamma delta

A

anytime before rearrangement of the Beta chain

25
Q

Successful rearrangement of gamma and delta chains before Beta means…

A

it will be a gamma delta T cell

26
Q

Successful rearrangement of a B chain before a gamma delta chain means…

A

it still hasnt committed yet.

The cell HALTS its rearrangements and enters a stage of proliferation

27
Q

What happens after the T cell has rearranged its Beta chain, and entered proliferative phase?

A

Three man race to the finish!!

It starts to rearrange the alpha, gamma, and delta chains to see if it will be an alpha/beta or gamma/delta cell.

First one rearranged successfully determines outcome

28
Q

The two opportunities for a cell to become a delta gamma cell:

A

Gamma/delta’s race with BETA

Gamma delta’s race with ALPHA

29
Q

The successful rearrangement of gamma delta signals…

A

for the cell to stop all rearrangement

30
Q

Rearrangement of Alpha always…

A

eliminates the delta chain locus

(because it is always in between Va and Ja segments that join, and looping out the delta)

31
Q

Most gamma delta T cells do not express..

A

CD4 or CD8

32
Q

Function of gamma delta cells?

A

anti-bacterial / viral / tumor

33
Q

Compared to alpha/beta, the gamma chain locus has ___ diversity

A

Less

34
Q

List some antigens that gamma delta cells recognize

A
  • HMB-PP (tuberculosis and malaria)
  • Host MHC1b
  • Nonprotein alkylamines
  • HSP (TB and host)
  • Superantigens
35
Q

Unique feature of gamma delta function

A

Don’t need antigen processing and presentation via MHC

36
Q

Structures of CD4 and CD8

A

CD4 is a linear monomer (D1-4)

CD8 is a dimer (looks like an 8!)

37
Q

Checkpoint for Pre-TCR is _______

Checkpoint for TCR is _______

A

beta chain rearrangement

alpha rearrangement

38
Q

To survive in thymus, Tcells need to…

A

bind self MHC, but not too strongly

39
Q

Positive selection of T cells is carried out by ________ cells.

What do they express?

A

thymic epithelial

They express self MHC1/2 that are loaded with self pepties

40
Q

Negative selection is carried out by ______ cells

Where are they?

A

Dendritic cells and MQ

In the cortico-medullary junction

41
Q

The proportion of T cells that are positely/negatively selected is determined by…

Mathmatically, what are the effects of changing this?

A

the number of MHC molecules (N)

As (N) increases, positive selection increases arithmetically (N), while negative selection increases geometrically (N2)

42
Q

What is the magic number (N) of MHC that will give the maximum T cell repertoire?

A

N= 13

If you have more isotypes than this, there will be too much negative selection

43
Q

Major issue of mismatched bone marrow transplantation?

A

Positively-selected T cells (recipient) can’t recognize antigens presented by the MHC from donor’s antigen-presenting cells

44
Q

DiGeorge syndrome patients lack

A

functional thymus

*symptoms similar to SCID (no thymic epithial cells for lymphocyte maturation)

45
Q

Expansion of Tcell clones is an _____ process, occuring in secondary lymph tissues

A

antigen-dependent

46
Q

Four major steps of T cell development (Summary)

A
  1. Double negative CD3- cells in subcapsular zone (proliferation)
  2. Double positive CD3+ in cortex – (positive selection)
  3. DP cells negatively selected at CMJ
  4. Mature cells (self restrictive, SP) leave in blood venules

Immunology (10 decks)

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