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Flashcards in L9 Deck (27)
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1

Where are immune cells tested for self reactivity?

Primary lymph organs - bone marrow & thymus

2

Name the early stages of B and T cell development.

Common lymphoid progenitor
Pro T/B
Pre T/B
Immature T/B
Mature T/B

3

Do T cells gain CD4/8 or CD3 markers first? When do each of these happen?

Get both CD4&8 @ immature
Then lose one of those
+ CD3high as mature cell

4

Do B cells get CD19 or IgM markers first? When do each of these happen?

CD19 1st as proB
Igm low as immature --> high as mature

5

What signals determine a CLP daughter cell's fate as a T or B cell?

T cell - NOTCH receptor-ligand interactions
B cells - induce EBF (early B cell factors) & Pax5 TFs

6

What kinds of mutations might lead to adult leukemia and lymphoma?

Chromosome translocations and point mutations to NOTCH or Pax5/EBF

7

What is a way that variable region rearrangement is limited to early T.B cells only?

Unique expression of RAG1/2 & Tdt

8

List the order in which T cell genes are rearranged.

Gamma/delta
Beta
Alpha
Generate mature receptors: alpha-beta, gamma-delta

9

List the order in which B cell genes are rearranged.

Heavy 1st
- DJ
- VDJ
Light (gamma or kappa) second

10

Where do you find gamma-delta T cells?

Small intestine
Epidermis
Uterine epithelium

11

What is allelic exclusion?

For TCR beta gene and heavy chain (B cell)
= expression of only 1 allele's product
If unsuccessful gene rearrangement round 1 of heavy chain (B cell) or beta (T cell)
Non-fxnal pre-receptor
Cell gets to re-try rearrangement on the same gene's allele on the OTHER chromosome
Successful - good to go
Not successful - kill the cell

12

Why do you do allelic exclusion?

Ensure monoclonal expression in the beta or heavy chain

13

What are the 2 requirements for allelic exclusion?

Sequential rearrangement
Pre T/BCR signaling to feedback to V gene accessibility

14

What happens if a TCR has low avidity to self antigen?

Aka weak/no TCR signal to self
Kill cell

15

What happens if a TCR has high avidity to self antigen?

Strong TCR signal
Negative selection:
1. Apoptosis
2. Central colterance via CD4 T reg cell - regulates own immunity

16

What avidity does a TCR need to mature completely?

Intermediate avidity to self
These cells positively selected
Which MHC it reacts with determines CD4 vs CD8 expression

17

What is the goal of self selection?

NOT about peptide recognition
About MHC matching!

18

What is AIRE? Fxn, location, etc.

Autoimmune regulator
= TF
How thymus can express some self antigens from other tissues
How tissue specific genes are test outside that tissue

19

What kind of signal leads to negative selection of mature B cells? What is the goal of this step of B cell selection?

GOAL = humoral tolerance
- Ab that binds monovalently
- Undergoes clonal expansion
- Immature IgMlo --> mature IgMhi
Unknown or multivalent binding --> anergy or apoptosis

20

What happens if B cells produce an Ab that is self reactive?

Tested in bone marrow
Secondary rearrangement of LIGHT CHAIN only

21

Why are self reactive Abs common?

Because so many possibilities between the jointing genes of heavy and light chains

22

What is receptor editing?

TCR alpha and gamma & light chains (B cells)
Increases the chances of lymphocyte selection

23

Is clonality kept in allelic exclusion? In receptor editing?

AE: keep clonality
RE: no - but other mechanisms will likely maintain clonality

24

Does positive or negative selection occur first in T cell development? Where does each step happen?

1st = positive (alpha chain rearrange) @ thymus cortex
2nd = negative (interaction with medullary epithelium) @ medulla

25

What are the mechanisms of central vs peripheral tolerance?

Central - direct deletion of highly reactive T/B cells
Peripheral
1. Clonal anergy of self reactive T/B cells via costimulation
2. Suppression by Treg

26

Describe autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome.

AIRE mutation
No presentation of these tissue's self antigen in the thymus
- Endocrine
- Epithelium

27

What happens if Foxp3 is mutated?

No Treg cells
Higher risk for:
- IBD
- Type 1 diabetes