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Host Defense > T Cell Development Lecture 8 > Flashcards

T Cell Development Lecture 8 Flashcards

1
Q

By the time the baby is born is the peripheral T cell repertoire established?

A

Yes

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2
Q

Is the functional maturation of thymic epithelial cells required for the development of normal thymic architecture and normal development of T cell subtypes and initial establishment of tcell pool?

A

yes

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3
Q

What are two forms of evidence that the thymus is responsible for thymopoiesis?

A
  1. DiGeorge syndrome–>No thymus and T-cells not detectable–>thyrus implants gives rise to T cell number and restores immune response
  2. FOXN1-mutation in FOXN1 No hair, no thymus
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4
Q

What cells is the thymus responsible for develop?

A
  1. CD4 T helper
  2. CD8 T cytotoxic
  3. regulator T cells (Tregs)
  4. natural killer T cells
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5
Q

When do mature T cells egress the thymus?

A

13-14 th week

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6
Q

What do you find in the capsule of the thymus?

A

fibroblasts

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7
Q

What is in the cortex?

A

Developing T cells

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8
Q

What is in the medulla?

A

Fewer mature T cells

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9
Q

What happens in the corticomedullary junction?

A

Where HSC and T cells come and leave the thymus-where blood vessels are

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10
Q

What is the hassal body?

A

mature epithelial cell

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11
Q

The thymic stroma is made of two types of cells, what parts of the thymus do these two types of cells make up?

A

Fibroblasts: capsule, septa with blood vessels

Epithelial cells: cortical, medullary and hassall’s body

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12
Q

What are the 3 types of cellular composition in the thymus?

A

thymic stroma

macrophages and dendritic cells

lymphoid compartment

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13
Q

What are all thymic epithelial cells derived from?

A

Endoderm

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14
Q

What is the cell surface ligand on thymic epithelial cells?

A

Delta like 1,4

-ligand for the notch receptor

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15
Q

Do thymic endothelial cells express major histocompatiblity comple, and express peripheral tissue antigens?

A

Yes
MHC 1 and 2
Yes

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16
Q

Where are macrophages and dentritic cells concentrated in the medulla?

A

Cortico-medullary junction

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17
Q

What do the macrophages in the thymus do?

A

Deletion of autoreactive T cells, macrophages will kill these through negative selection

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18
Q

What is the most immature t cell?

A

double negative

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19
Q

Are there more CD4 pos or CD 8 pos?

A

CD 4

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20
Q

What happens to your thymus when you get older? What does this mean for your t-cell production?

A

Thymus gets fatty

older you get the less t-cells you make

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21
Q

What type of HSCs go to the thymus?

A

CD34+

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22
Q

Do few mature T cells ever go back to the bone marrow or thymus?

A

yes

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23
Q

What are the 4 developmental steps that occur in the maturation of T cells

A

T lineage commitment: restricted of lineage choices
Proliferation: expansion of commited cells
Differentiation: gaining of new surface markers
Maturation: selection and gaining of immune functions

24
Q

What induces T lineage commitment and terminates lineage plasticity?

A

Delta like 1 or 4 ligand on TEC with notch receptor on HSC

25
Q

What is the first step of the Pre T cell?

A

TCR B gene rearrangement
using RAG 1 and RAG2 and IL7R gamma
(without IL7Rgamma–>SCID)

26
Q

What is expressed with the rearranged beta chain on the PreTCR complex?

A

Surrogate alpha chain
rearranged betta chain
CD3

27
Q

After TCR B gene rearrangement what occurs to select for the functionally rearranged TCR beta?

A

Beta Selection

28
Q

What happens during beta selection?

A
  • Allelic occlusion–>degrading RAG proteins
  • rapid proliferation
  • increased expression of CD3 complex
29
Q

What does signaling through the pre-TCR induce and what does this create a bias for?

A
  • induces significant proliferation of ISP cells

- bias the ISP toward TCR alpha beta lineage over gamma delta

30
Q

What happens to ISP cells after beta selection what type of cells do they develop into?

A
  • express CD8

- develop into CD8 CD4 DP cells

31
Q

What happens after the cell becomes a DP cell?

A

RAG expression is re-expressed and alpha genes are rearranged
-caused deletion of delta locus

32
Q

Is there allelic exclusion with with alpha rearrangement?

A

No

  • it is possible that there are two different rearranged alpha chains associated with a common beta
  • positive t cell section will ensure each T cell only has one functional specificity-although tow different alpha chains are expressed
33
Q

How many chains does the signaling component have?

A

5 different chains

34
Q

What type of selection do the DP alpha and beta rearranged cells go through? What does this coordiante?

A

Positive Selection

  • must see both antigen and MHC on cortical epithelial cells to survive to survive
  • coordinates either CD4 pos or CD 8 pos
35
Q

What is bare lymphocyte syndrome?

A

defect in MHC 2 expression-the development of CD4 pos T cells is affected

36
Q

TCRs are selected on the basis of self MHC, what does this have the potential to generate?

A

Autoreactive T cells that may affect autoimmune disease

37
Q

What does negative selection do?

A

mechanism for estabilishing central tolerance

38
Q

What if happens if the signal is too strong?

A

Kill them

39
Q

What 2 types of cells induce negative selection? where

A
  • Dendrites and macrophages
  • Epithelial cells
  • corticomedullary junction
40
Q

What do mTEC cells do in negative selection, what induces this expression?

A

express organ specific antigens that mirror peripheral self antigens
expression of these genes are induced by the transcription factor AIRE

41
Q

What happens in a AIRE mutation? APECED

A

declined immune response fungal will form

  1. oral candidiasis
  2. candidal onychomycosis
  3. vitiligo with halo naevi-kill malanocytes
42
Q

TCR gamma delta tcells are derrived from what cells and are they DP or DN and what do they bind to?

A
  • Derived from: ISP cells
  • DN
  • Bind self lipid antigens
43
Q

What are the two major types of gamma delta t cells?

A

mucosal tissue associated with epithelial tissue and circulatory

44
Q

What are two functions of gamma delta cells?

A
  1. kill stressed epithelial cells

2. anti-microbial immunosurveillance (leprae, Tuburculosis)

45
Q

WHat type of cytokines do gamma delta cells use?

A

INF gamma which acts on NK and NKT and Th1 cells

46
Q

What are the cell makers for NKT cells?

A

Cd56 (NK) and CD3 (Tcell)

47
Q

What do cells that develop into NKT cells recognize during development?

A

CD1d/glycolipids on cortical thymocytes

48
Q

Are NKT cells CD4 pos? CD 8 Pos?

A

CD4 pos or DN

49
Q

What 4 places do NKT cells populate?

A

-liver, spleen, BM, lymph nodes

.2% in peripheral T cell pool

50
Q

What type of cell markers do Tregs have? What od they do?

A

CD4 pos and cd25 pos

  • have suppressor activity agians autoreactive tcells that may have escaped the negative selction process
  • establish dominat tolerance
51
Q

What type of cell markers do Tregs have? What od they do?

A

CD4 pos and cd25 pos

  • have suppressor activity agians autoreactive tcells that may have escaped the negative selction process
  • establish dominat tolerance
52
Q

What does the development of Treg require?

A

Thymic stroma lymphopoietin TSLP of hassll’s bodies

53
Q

What TF is necessary for TREg?

A

FOXP3

54
Q

What is an increased level of Treg associated with?

A

cancer

55
Q

How are periphery Tregs developed?

A
  • TGF beta induces Treg from CD4 pos cells
  • T regulatory type 1: IL10
  • T helper 3: oral tolerance induction
56
Q

What diesase is associated with with mutation of FOXP3 gene?

A

Immune dysregulation polyendocrinopathy and x linked inheritance
(IPEX)

Host Defense (11 decks)

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