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Immunology > Development of T lymphocytes > Flashcards

Development of T lymphocytes Flashcards

1
Q

Double negative

A

When they do not express any co receptors (thymic immigrant stage)

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2
Q

Double positive

A

Both co receptors are expressed

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3
Q

Single positive

A

Only 1 co receptor is expressed

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4
Q

T cells

A
  • derive from bone marrow stem cells
  • rearrange TCR genes in the thymus (antigen independent)
  • formation of 2 different T cell lineages (majority alpha/beta, and minority gamma/delta)
  • positive selection (alpha/beta)
  • negative selection (gamma/delta)
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5
Q

B cells

A
  • derive from bone marrow stem cells
  • rearrange BCR genes in the BM (antigen independent)
  • somatic hypermutation (antigen dependent)
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6
Q

Thymus

A

Primary lymphoid organ

  • T cell development only
  • blood is only route to enter (T cell progenitors) and to leave (mature T cells)
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7
Q

Hassall’s corpuscle

A

Site of cell destruction, located in the medulla of the thymus

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8
Q

Differences between canine and human thymus

A

There are none

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9
Q

2 types of thymus epithelial cells

A
  • cortical (thymicorigin)

- medullary (thymicorigin)

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10
Q

Other cells presented in the thymus

A
  • thymocyte (bone marrow origin)
  • dendritic cell (bone marrow origin)
  • macrophage (bone marrow origin)
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11
Q

Thymus development

A
  • most active in very young
  • fully developed at birth
  • atrophies with increasing age, thymocytes replaced by fat (involution)
  • involution complete by 30 years
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12
Q

Does involution or a thymectomy compromise T cell immunity?

A

No, T cells are long lived or self-renewing

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13
Q

Thymus involution

A

DiGeorge’s syndrome

  • thymus fails to develop = SCIDS
  • 22q11.2 deletion syndrome
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14
Q

Thymic cortex

A
  • apoptotic cells

- macrophages

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15
Q

A common double negative T cell progenitor gives rise to _______

A

Alpha/beta and gamma/delta T cells

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16
Q

2 major signals for T cell lineage commitment

A
  • IL-7

- Notch 1

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17
Q

CD34

A

Uncommitted progenitor

18
Q

CD2

A

Committed double-negative T cell progenitor

19
Q

Gamma + delta

A

Committed gamma/delta T cell

20
Q

Beta lineage

A

Uncommitted double-positive thymocyte

  • CD8 and CD4 receptors
  • first checkpoint
21
Q

Alpha + beta

A

Committed alpha/beta T cell

  • CD8 and CD4 receptors expressed
  • second checkpoint
  • study chart in ppt*
22
Q

Positive selection

A

Selection of T cells that can recognize peptides presented by a self-MHC molecule

  • small population of T cells is signaled to mature further, leaving majority of double positive cells to die by apoptosis
  • controls expression of CD4 or CD8 co receptor
23
Q

Negative selection

A

Deletion of T cells whose antigen receptors bind too strongly to the complexes of self-peptides and self- MHC molecules presented
- negative selection cannot eliminate T cells whose receptors are specific for self peptides that are present only in tissues other than the thymus

24
Q

Negative selection

A

Deletion of T cells whose antigen receptors bind too strongly to the complexes of self-peptides and self- MHC molecules presented
- negative selection cannot eliminate T cells whose receptors are specific for self peptides that are present only in tissues other than the thymus

25
Q

AIRE

A

Autoimmune regulator

  • mutation causes autoimmune polyglandular syndrome type 1 or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
  • Because of AIRE gene, APCs in the thymus express and present many peptides derived from nonthymic tissues
26
Q

What happens if there are only thymus specific cells in the thymus?

A

T cells will go to periphery and be autoreactive

- AIRE gene is the safety mechanism

27
Q

What is the major mechanism of immunological tolerance in the thymus?

A

Negative selection

28
Q

Thymic epithelial cells and transcription factor

A

Transcription factor causes several hundred of other tissue specific genes to be transcribed by a subpopulation of the thymic epithelial cells

29
Q

Mechanisms that contribute to immunological self-tolerance

A

Central tolerance

  • negative selection in the bone marrow and thymus
  • expression of tissue-specific proteins in the thymus (AIRE)

Peripheral tolerance

  • no lymphocyte access to some tissues
  • suppression of autoimmune responses by regulatory T cells
  • induction of anergy in autoreactive B and T cells (absence of co stimulatory signal)
30
Q

Mechanisms of malignant transformations and generation of lymphomas

A
  • high division rate of maturing lymphocytes

- activity of DNA recombination mechanisms responsible for generating antigen receptor diversity

31
Q

Terminally differentiated T cells retain lifelong capacity for _____

A

Neoplasia

32
Q

Canine X-linked SCIDS

A

<4 weeks: greater number of B cells and CD45RA + T cells

> 8 weeks: increased B cells and T cells, decreased CD45RA+T cells

33
Q

XLSCID in Basset Hounds

A

Cell counts: dramatically fewer T cells, but normal or above number if IgM B cells

34
Q

Immunological analysis

A
  • roles of IL-2 in T cell proliferation in the thymus and proliferation and differentiation in the secondary lymphoid organs
  • roles of IL-4 in differentiation of B and Th2 cells
  • roles of IL-7 in the development of lymphoid progenitor cells in the bone marrow
35
Q

Explanation of clinical evidence

A

Explains severe atrophy of both primary and secondary lymphoid organs and absence of mature B cells
- does not explain the elevated numbers of T cells at the age of 8 weeks

36
Q

What are the 3 functionally distinct types of T cell developed from a common progenitor in the thymus?

A
  • gamma/delta T cells (not MHC restricted)
  • alpha/beta CD4+ T cells (MHC 2 restricted)
  • alpha/beta CD8+ T cells (MHC 1 restricted)
37
Q

Subsequent phases in the thymus only concern _____

A

Alpha/beta T cells

38
Q

Positive selection tests the ability of ______ to interact with ____ expressed in the thymus

A

Alpha/beta TCRs; self-MHC molecules

39
Q

Negative selection eliminates cells whose ________

A

Receptors interact too strongly with self-peptide; self MHC complexes

40
Q

Main difference between thymus and bone marrow

A

Bone marrow continuously turns of B cell repertoire during the person’s lifetime, while the thymus works principally during youth to accumulate a repertoire of T cells that can be used throughout life
* reflects magnitude of body’s investment in development of useful T cells and savings to be made by gradually shutting down the thymus *

Immunology (28 decks)

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