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Immunology > L9 > Flashcards

L9 Flashcards

1
Q

Where are immune cells tested for self reactivity?

A

Primary lymph organs - bone marrow & thymus

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2
Q

Name the early stages of B and T cell development.

A 
Common lymphoid progenitor 
Pro T/B
Pre T/B
Immature T/B
Mature T/B
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3
Q

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

A

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

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4
Q

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

A

CD19 1st as proB

Igm low as immature –> high as mature

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5
Q

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

A

T cell - NOTCH receptor-ligand interactions

B cells - induce EBF (early B cell factors) & Pax5 TFs

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6
Q

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

A

Chromosome translocations and point mutations to NOTCH or Pax5/EBF

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7
Q

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

A

Unique expression of RAG1/2 & Tdt

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8
Q

List the order in which T cell genes are rearranged.

A

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

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9
Q

List the order in which B cell genes are rearranged.

A

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

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10
Q

Where do you find gamma-delta T cells?

A

Small intestine
Epidermis
Uterine epithelium

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11
Q

What is allelic exclusion?

A

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

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12
Q

Why do you do allelic exclusion?

A

Ensure monoclonal expression in the beta or heavy chain

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13
Q

What are the 2 requirements for allelic exclusion?

A

Sequential rearrangement

Pre T/BCR signaling to feedback to V gene accessibility

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14
Q

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

A

Aka weak/no TCR signal to self

Kill cell

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15
Q

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

A

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

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16
Q

What avidity does a TCR need to mature completely?

A

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

17
Q

What is the goal of self selection?

A

NOT about peptide recognition

About MHC matching!

18
Q

What is AIRE? Fxn, location, etc.

A

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

19
Q

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

A 
GOAL = humoral tolerance
- Ab that binds monovalently 
- Undergoes clonal expansion
- Immature IgMlo --> mature IgMhi
Unknown or multivalent binding --> anergy or apoptosis
20
Q

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

A

Tested in bone marrow

Secondary rearrangement of LIGHT CHAIN only

21
Q

Why are self reactive Abs common?

A

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

22
Q

What is receptor editing?

A

TCR alpha and gamma & light chains (B cells)

Increases the chances of lymphocyte selection

23
Q

Is clonality kept in allelic exclusion? In receptor editing?

A

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

24
Q

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

A 
1st = positive (alpha chain rearrange) @ thymus cortex 
2nd = negative (interaction with medullary epithelium) @ medulla
25
Q

What are the mechanisms of central vs peripheral tolerance?

A

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
Q

Describe autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome.

A

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

27
Q

What happens if Foxp3 is mutated?

A

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

Immunology (25 decks)

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