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CMOD- Block1 > Immuno 6: T Cell Diversity and Development > Flashcards

Immuno 6: T Cell Diversity and Development Flashcards

1
Q

What are the two type of T cell receptors?

A

alpha-beta (more common)

gamma-delta

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2
Q

At the extreme end of the ____ region of each TCR chain is a hinge-like region followed by a ____ region and a short tail that extends into the cell ____.

A

carboxyterminal; transmembrane; cytoplasm

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3
Q

What is the mechanism that generates a huge T cell receptor repertoire?

A

somatic recombination with cassette genes

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4
Q

With what do T cells recognize specific antigens?

A

with their TCR

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5
Q

In what tissue are the less common gamma-delta TCRs found?

A

mucosal epithelium

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6
Q

γ/δ T cells have a limited TCR repertoire and it is believed that they primarily recognize what kind of antigenic determinants?

A

non-protein antigenic determinants

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7
Q

Where do α/β and γ/δ T cells mature?

A 
α/β = thymus
γ/δ = extrathymically
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8
Q

True or false: γ/δ T cells only recognize antigens bound to MHC class molecules.

A

False. γ/δ T cells are not MHC restricted in their recognition of antigen. However, α/β TCRs recognize peptide antigens only when presented in context with the MHC proteins.

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9
Q

What are the two distinct populations of α/β T cells?

A

CD4+ and CD8+

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10
Q

Generally speaking, what are CD4 and CD8 proteins?

A

they are proteins expressed on the surface of T cells that serve as co-receptors for the TCR to facilitate interaction with the MHC complex on antigen-presenting cells

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11
Q

CD4 is present on ____ T cells.

CD8 is present on ____ T cells.

A

helper; killer

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12
Q

CD4-associated TCRs binds MHC Class ____.

CD8-associated TCRs binds MHC Class ____.

A

CD4-associated TCRs - MHC II

CD8-associated TCRs - MHC I

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13
Q

What are the functions of CD4-associated TCRs?

A

bind MHC class II; produce cytokines; help B cells; stimulate cells of the innate immune system

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14
Q

What is the function of CD8?

A

to kill cells that are presenting their cognate peptide antigen using the MHC Class I molecule (i.e., intracellular infection)

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15
Q

Name 6 types of surface markers expressed on the surfaces of T cells.

A
  1. T Cell receptors
  2. CD4/CD8
  3. CD3
  4. Accessory molecules
  5. Adhesion molecules
  6. Lymphokine receptors
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16
Q

What is the signal transduction complex for the T cell receptor, and what does it use to cause intracellular cascades??

A

CD3; uses tyrosine kinases to cause phosphorylation cascades and other events leading to T cell activation

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17
Q

Each of the TCR chains has a single ___ domain and a single ___ domain.

A

variable; immunoglobulin

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18
Q

Are γ/δ a component of the acquired immune response?

A

no - they appear to be a primitive cell type

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19
Q

Unlike the α/β T cells, the γ/δ T cells are usually double negative. What does this mean?

A

α/β cells express CD4+/CD8+ whereas γ/δ T cells express CD4-/CD8-

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20
Q

What are ITAMs?

A

immunoreceptor tyrosine-based activation motifs; located on cytoplasmic domains of CD3 complex, and are critical for initiating the signal cascade

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21
Q

True or false: a single mature α or β T cell can express CD4, CD8, or both on its surface.

A

False - can express one or the other, but NOT both

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22
Q

CD28 is a molecule that binds to the co-stimulator molecule, known as ___, expressed on antigen-presenting cells that have encountered pathogens.

A

B7

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23
Q

Fas ligand (FasL) is a homotrimeric molecule that can bind what on target cells? Binding then results in signaling that initiates what?

A

binds 3 copies of Fas on target cells; binding results in signaling that can then initiate programmed cell death of the target cell

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24
Q

What do adhesion molecules do? (in the context of immune cells)

A

facilitate the cell-to-cell interactions between immune cells

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25
Q

What are T cell precursors called?

A

thymocytes

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26
Q

Where do thymocytes develop?

A

thymus

27
Q

What are the 2 regions of the thymus, and what primary cell types are located in each?

A 
cortex:
- cortical epithelial cells
- thymocytes
- macrophages (few)
medulla:
- medullary epithelial cells
- dendritic cells
- macrophages
- developing, near-mature thymocytes
- Hassel's corpuscles
28
Q

The junction between the cortex and medulla of thymus is called the corticomedullary junction. What important step in thymocyte development happens here?

A

positive selection of the cells that bind MHC Class I or II, and differentiation into CD8+ or CD4+ T cells; this process involves up-regulation of the CD protein that binds with greater affinity to its MHC

29
Q

Tingible body macrophages play a large role in what part of the thymus? What do they do there, and what causes their unique staining pattern?

A

in the cortex: they phagocytize and remove dead thymocytes; the large amount of chromatin taken up from eating the thymocytes causes their unique staining pattern

30
Q

Once the T cell repertoire is formed during normal development, are new T cells required to sustain T cell mediated immunity?

A

No - thus the thymus shrinks after puberty

31
Q

What is the process of T cell ontogeny in the thymus?

A
  1. Thymocytes arrive in cortex, proliferate
  2. Positive selection: those that can’t bind self-MHC undergo apoptosis.
  3. Survivors move to medulla where negative selection occurs: those that bind too tightly to self-MHC:self peptide (self-antigens) will undergo apoptosis
32
Q

All thymocytes enter the thymus as CD4/CD8 positive or negative?

A

negative

33
Q

Double positive CD4+/CD8+ T cells that survive positive selection differentiate to ____ ____ T cells.

A

single positive, by up or down regulating the other, non-preferred TCR

34
Q

CD4-/CD8+ T cells bind which MHC class?

A

Class I - because they are now known as CD8+ cells

35
Q

CD4+/CD8- T cells bind which MHC class?

A

Class II - because they are now known as CD4+ cells

36
Q

Where do the self-peptides come from in thymus for use in the negative selection process of maturing T cells?

A

autoimmune regulator (AIRE) is a TF that produces the expression of hundreds of host-tissue specific peptides in a subset of epithelial cells in the thymic medulla where they are uptaken by medullary APCs for presentation with MHC molecules

37
Q

What happens if a patient lacks a functional AIRE gene?

A

they’ll have broad spectrum autoimmune disease

38
Q

In TCR genes, the coding region for the variable region of the ____ chain is produced by rearrangement of V and J gene segments. (analogous to light chain rearrangement)

A

alpha

39
Q

In TCR genes, the coding region for the variable region of the ____ chain is produced by rearrangement of V, J, and D gene segments. (analogous to heavy chain rearrangement)

A

beta

40
Q

How does a T cell become either alpha-beta or gamma-delta?

A

depend on which chain is the first to rearrange:

  1. start rearranging beta, gamma delta
  2. if either gamma or delta is successful first, the T cell will become gamma-delta
  3. if beta wins, it will become alpha-beta
41
Q

What is the utility of the pTalpha chain?

A

it’s an invariant chain that serves as a surrogate alpha chain to associate with the beta chain and create the pre-T cell receptor complex while awaiting the alpha chain to finish rearranging; without a friend the beta chain is too unstable and will die of loneliness

42
Q

When would gamma-delta rearrangement cease if the T cell is going to become an alpha-beta TCR cell?

A

when the pre-TCR complex is formed using a successful beta chain and a pTalpha chain; this happens before alpha chain rearrangement begins

43
Q

Why should we remember Hassall’s corpuscles today?

A

this cell type may play a critical role in the development of T regulatory cells, which have an important role in preventing autoimmune disease, by producing a cytokine that drives some self-reactive T cells to differentiate into T regs instead of apoptosing

44
Q

Where do mature naive T cells hang out?

A

secondary lymphoid tissue

45
Q

What chromosomes are TCR alpha and beta chain genes located on?

A 
alpha = 14
beta = 6
46
Q

As was the case for somatic recombination of the B cell immunoglobulin genes, somatic recombination of the TCR Ig genes is catalyzed by ___ and ___.

A

RAG-1 and RAG-2

47
Q

Genetic deficiency of one or both RAG genes would result in what?

A

an almost TOTAL lack of B and T cells, and SCID #suckstoSCID

48
Q

A deficiency of TdT will result in ____ ____ of both the T cell and B cell repertoire because there will be no ____ ____ of the beta and heavy chain, respectively.

A

reduced diversity; junctional diversity

49
Q

Based on the ____ ____ of the T cell tumors, it can be determined at what point in the development of the T cell that the neoplastic event took place.

A

surface phenotype

50
Q

Common acute lymphoblastic leukemia (C-ALL or B-ALL): the neoplastic event for this tumor type took place in what cell?

A

a lymphoid progenitor cell

51
Q

These tumor cells arise from thymic stromal cells, therefore the do not express any lymphocyte-specific surface markers.

A

Thymoma

52
Q

Acute lymphoblastic leukemia (T-ALL): neoplastic event took place in a ____, as evidenced by its surface expression of ____.

A

thymocyte; CD1

53
Q

Adult T cell leukemia; chronic lymphocytic leukemia (CLL); or T prolymphocytic leukemia (TPLL): the neoplastic event took place in a T cell that was at what stage of development, and how is that known?

A

nearing or was a mature T cell; known because there is already a complete TCR and it’s a single positive cell

54
Q

CD34 is a ____ cell surface marker.

A

stem cell (hemopoietic progenitor)

55
Q

How do self-reactive T cells sometimes get through positive selection?

A

because all MHC molecules must be loaded with a peptide (otherwise they get degraded), there’s a chance that a TCR could end up passing positive selection because it has strong affinity for the loaded peptide, which would appear in this process as being affinity for the MHC molecule.

56
Q

When pathogens are presented to T cells in a lymph node, which protein mediates T cell receptor signaling?

A

CD3

*Note: the TCR will bind the MHC:antigen. Then CD3 will then mediate the signaling pathway.

57
Q

Which T cell surface marker has affinity for B7 co-stimulator molecules located on APCs?

A

CD28. This reaction is critical because B7 is what makes a cell a “professional antigen presenting” cell.

58
Q

Immature thymocytes generated in the bone marrow migrate to the thymus to undergo their development. What compartment of the thymus do they initially populate once they arrive?

A

cortex

59
Q

What happens to thymocytes once they reach the thymic cortex, prior to any repertoire selection?

A
  1. proliferate as double positive CD4/CD8-associated TCR cells; also express CD3
  2. beta, gamma, delta chain rearrangement
  3. gamma/delta rearrangement occurs first, that cell leaves the thymus to mature extrathymically. If beta rearrangement occurs first it will be an alpha-beta cell
  4. beta pairs with pTalpha chain (pre-TCR) until alpha chain is generated
60
Q

Positive selection is driven by the TCR’s affinity for what?

A

MHC class of molecule

61
Q

True or false: TCR selection of CD4+ or CD8+ thymocytes is complete by time the T cells arrive at the medulla.

A

true - they arrive at the medulla as single-positive TCRs already

62
Q

What’s a good reason that self-reactive T cells make it through negative selection and leave the thymus as mature members of the T cell repertoire?

A

there are so many self-peptides they can’t all be expressed

63
Q

If a patient has few B and T cells due to an inherited genetic deficiency, a non-sense mutation of what enzyme dysfunction would be suspected?

A

RAG-1 and RAG-2, because lack of these is what would cause lack of B cell antibodies and T cell receptors. TDT, while involved, would simply decrease the variety of the repertoire.

CMOD- Block1 (36 decks)

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