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Host Defense > Lecture 9 > Flashcards

Lecture 9 Flashcards

1
Q

Where is thymus located?

A

On top of heart

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2
Q

What can HSCs become in thymus?

A

CD4
CD8
NKT
Tregs

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3
Q

When is thymus colonized by HSCs?

A

7th week of gestation

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4
Q

When does thymus begin to produce T cells?

A

12-13th week of gestation

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5
Q

What is DiGeorge syndrome?

A
  • Deletion of chromosome 22
  • Present at birth: congenital
  • Recurrent infection due to absence of thymus and T cells
  • Thymus transplant fixes T cell deficiency
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6
Q

Where is FoxN1 located?

A

Chromosome 17

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7
Q

What does FoxN1 code for?

A

TF essential for maturation of thymic epithelial cell progenitors

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8
Q

What does FoxN1 mucation cause?

A
  • Failure of thymus to develop

- Showed thymic epithelial cells were required for normal thymus which was required forT cell development

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9
Q

How can FoxN1 be treated?

A

Thymic implant

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10
Q

What is found in thymic cortex?

A

Developing T cells

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11
Q

What is found in thymic medulla?

A

Mature T cells

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12
Q

What is found in thymic septa?

A

Firbroblasts

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13
Q

What are TECs?

A

Thymic epithelial cells

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14
Q

Function of TECs??

A
  1. Cytokines required for growth/differentiatoin of T cells
  2. Notch cells required for T cell commitmen
  3. Expression of MHC for selecting T celsl
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15
Q

3 types of TECS

A

Cortical
Medullary
Hassals

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16
Q

What do TECs derive from?

A

Endoderm

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17
Q

Where do APCs cluster in thymus?

A

Cortical medullary junction

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18
Q

Functions of APC in thymus?

A

Present antigen for Differentation

Destruction of self reactive T cells

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19
Q

What are thymocytes derived from?

A

Bone marrow HSCs

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20
Q

Tool for distinguishing T cell types?

A

Flow cytometry

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21
Q

Good source of HSC CD34 blood cells for transplant ?

A

Umbilical cord blood

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22
Q

What happens to HSC when it enters thymus?

A

Lineage potential restricted to T cells

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23
Q

Why does immune system decline in elderly?

A

T cell production slows

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24
Q

4 developmental steps in T cells?

A
  1. T lineage commitment
  2. Proliferentiation and differentiation
  3. Pos/neg selection
  4. Maturation
25
Q

What does notch signalling do?

A
  • Causes CD34 cell to move away from myeloid lineage (B, moncyte, DC) where then can now only become T/NK
  • Further notch signaling terminates potential of NK develoment
26
Q

Where does notch signal come from?

A

Notch ligand DL4 & 1

27
Q

What is the Pre T cell?

A
  • Commited to T lineage
  • Expresses CD1A
  • Rearranging Gamma, delta, and beta gens
28
Q

What can pre T cells become?

A

Alpha Beta T cell

Gamma Delta T cell

29
Q

What is necessary for recomination of pre T?

A

RAG1/2

IL7

30
Q

What is IL7 required for?

A

T cell rearrangment

31
Q

Stage after pret T?

A
  • CD4ISP - CD4 immature single positive
  • Exress CD3/4
  • Can become alpha beta or gamma delta
32
Q

What ends rearrangement?

A

ERK

33
Q

What expresses CD3

A

ISP

34
Q

What is beta selection?

A
  • Selects only ISP cells with functional TCR beta genes

- Rest will be signalled to die

35
Q

What cells undergo beta selection?

A

ISP

36
Q

What happens to ISP cells selected for survival in beta selection?

A
  • Become double positive cells

- Express both CD3 and CD4

37
Q

T cell selction generate allelic exclusion?

A
  • No

- Positive seletion will ensure that each cell has only one specificity however

38
Q

What do DP cells rearrange?

A

Alpha chain

39
Q

What does alpha chain rearrangment cause?

A

Delta deletion

40
Q

Can DP cell have two different alpha chains?

A

Yes but positive selction will fix this

41
Q

What can DP cell become?

A

CD4 or CD8

42
Q

What happens in positive selection?

A
  • DP cells presented with self antigen in MHCI/II and if they have low affinity they surive
  • Surviving cells shut down RAG and replicate
43
Q

What happens to DP cells that do not recognize self peptide?

A

Undergo apaptosis

44
Q

What does positive selection skew towards

A

Reaction to self peptide and autoreactive T cells

45
Q

What is negative selection?

A

Deletion of T cell with strong affinity to MHC and antigen

46
Q

What does negative selection establish?

A

Central tollerance

47
Q

Where does negative selection occur?

A

Cortical medullary region where [DC] is high to eat self reactive cell

48
Q

What is AIRE?

A

Gene that allows for expression of peripheral tissue antigen in thymic cells to test for self reactivity

49
Q

Diseases with AIRE deficiency?

A

APECED / APS1

50
Q

What are APECED / APS1?

A

Auto immune deficiency resulting from AIRE deficiency

51
Q

What to TCR gamma delta cells develop from?

A

ISP

52
Q

Gamma delta T cell CD4 or 8 positive?

A

Negative for both

53
Q

Gamma delta T cell CD4 use MHCI or MHCII?

A

Neither - bind antigen directly

54
Q

What do NKT cells develop from ?

A

DP T cell

55
Q

Function of NKT?

A

Rapidly produce cytokines necessary for TH1 & TH2 when triggered

56
Q

What do Tregs develop form?

A

CD3/4 positive T cells

57
Q

What is required for Treg development?

A

FOXP3

58
Q

T reg disease?

A

IPEX

Host Defense (12 decks)

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