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PARA438 > L12, T cell development and activation > Flashcards

L12, T cell development and activation Flashcards

1
Q

recap: where do T cells develop?

A

in the thymus

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2
Q

where do the T cells originate from?

A

bone marrow

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3
Q

T cells that travel from the bone marrow into the thymus are known as …

A

thymic settling precursors

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4
Q

precursor cells are not committed to …

A

becoming a T cell yet

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5
Q

what are developing T cells called?

A

thymocytes

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6
Q

what do microenvironments provide within the thymus?

A

membrane-bound and soluble signals that regulate maturation during the development of T cells

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7
Q

what are the two phases of T cell development?

A
  1. early thymocyte development
  2. selection events
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8
Q

early thymocyte development is …

A

largely TCR-independent

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9
Q

what are the 3 specific events during early thymocyte development?

A
  1. commitment of hematopoietic precursors to the T cell lineage
  2. initiation of antigen receptor gene rearrangements (TCR)
  3. expansion of cells that successfully rearrange one of their TCR gene = beta selection
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10
Q

what are double negative stages? and how many are there?

A

absence of expression of CD4 and CD8 molecules
4 double negative stages

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11
Q

what markers can be used to identify different DN stages?

A
  1. c-Kit: also known as CD117 = receptor for stem cell factor
  2. CD44: adhesion molecule
  3. CD25: IL-2 receptor alpha chain
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12
Q

what do DN1 thymocytes do?

A

migration to thymus

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13
Q

DN1 markers = …

A

c-Kit++CD44+CD25-

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14
Q

what do DN2 thymocytes do?

A

rearrangement of TCR, sigma- and beta chain; fully committed to T-cell lineage

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15
Q

DN2 markers = …

A

c-Kit++CD44+CD25+

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16
Q

what do DN3 thymocytes do?

A

make a major decision: join the ysigma or alpha-beta T cell lineage / expression of pre-TCR; beta-selection

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17
Q

what do most of the ysigma T cells do?

A

leave the thymus as mature DN y-sigma T cells

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18
Q

DN3 markers = …

A

c-Kit+CD44-CD25-

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19
Q

formation of the pre-TCR involves …

A
  1. a successfully rearranged beta-chain
  2. pre-T alpha-chain
  3. CD3 molecules
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20
Q

what does signaling through the pre-TCR trigger?

A

a cascade of events that starts with the maturation of DN3 into DN4

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21
Q

DN4 markers =…

A

c-Kit(low/+) CD44-CD25-

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22
Q

what is the function of DN4 thymocytes?

A

proliferation, allelic exclusion of beta chain locus; alpha chain locus rearrangement begins; becomes DP thymocyte

development of CD4+CD8+ double-positive stage

23
Q

selection events are ….

A

largely TCR-dependent

24
Q

double positive thymocytes are characterized by …

A

the expression of both CD4 and CD8 markers

25
Q

what percentage of cells do DP contribute to in the thymic cortex?

A

80%

26
Q

what do DP thymocytes express at their surface?

A

a fully mature alpha-beta TCR/CD3 complex

27
Q

what are the distinct selection processes that DP thymocytes go through?

A

positive and negative selection

28
Q

positive selection = …

A

selection of thymocytes bearing receptors capable of binding self-MHC molecules (MHC restriction)

29
Q

negative selection = …

A

selection against thymocytes bearing high-affinity receptors for self-MHC/peptide complexes (self tolerance)

30
Q

what are self-antigens presented by?

A

cortical thymic epithelial cells (cTECs), to mediate positive selection

31
Q

what triggers maturation of T cells?

A

low/intermediate affinity interaction between the TCR and MHC

32
Q

what does maturation of T-cells trigger?

A

commitment to CD4+ or CD8+ single-positive (SP) T cell lineages

33
Q

how many T cells are not selected?

A

about 90-96%

34
Q

what are the 3 different models of T-cell lineage commitment?

A
  1. instructive model
  2. stochastic model (random)
  3. kinetic signalling model
35
Q

what other lymphocyte types can DP thymocytes commit to?

A
  1. NKT (natural killer T cells)
  2. intraepithelial lymphocytes (IEL) - most of which are CD8+
  3. Regulatory T cells (TREG) - another CD4+ subset different from CD4+ Th cells
36
Q

what transcription factor do medullary thymic epithelial cells express?

A

autoimmune regulator - allows cells to express tissue-specific antigens (TSA) from all organs

37
Q

what do high affinity TCR-MHC/peptide interactions result in?

A

negative selection = clonal deletion

38
Q

what are the 3 signals in T cell activation?

A
  1. TCR signaling
  2. costimulatory interaction
  3. cytokine signaling
39
Q

What happens with T cells in order to mount a response that is appropriate against a given pathogen?

A

T cells can be polarized towards different subsets with specialized functions

40
Q

what are the 3 factors influencing polarization?

A
  1. polarizing cytokines
  2. master gene regulators
  3. effector cytokines
41
Q

What kind of pathogens are detected in type 1 response (Th1 polarization)?

A

intracellular pathogens inducing cell-mediated immunity (most viruses, some bacteria and fungi)

42
Q

what happens in the type 2 response (Th2 polarization)?

A

pathogens inducing humoral immunity, particularly extracellular parasites

43
Q

what is the polarizing cytokine in the type 1 response?

A

IL-12

44
Q

what is the polarizing cytokine in the type 2 response?

A

IL-4

45
Q

what are the master regulators in Type 1 response?

A

STAT4 –> T-Bet

46
Q

what are the master regulators in Type 2 Response?

A

STAT6 –> GATA-3

47
Q

what is the effector cytokine produced in Type 1 response?

A

IFN-y

48
Q

what are the effector cytokines produced in Type 2 response?

A

IL-4, IL-5, IL-13

49
Q

what are the distinct microenvironments in the thymus?

A
  1. subscapular cortex
  2. cortex and cTECs
  3. Corticomedullary junction
  4. Medulla and mTECs
50
Q

description of DN1 development

A

migration to thymus

51
Q

description of DN2 development

A

TCR gamma, sigma, and Beta-chain rearrangement; T-cell lineage commitment

52
Q

what do DN3 thymocytes express?

A

pre-TCR

53
Q

description of DN4 development

A

proliferation, allelic exclusion of beta-chain locus; alpha-chain locus rearrangement begins; becomes DP thymocyte

PARA438 (14 decks)

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