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Immunology Exam 2 > Lecture 10 > Flashcards

Lecture 10 Flashcards

1
Q

What cytokine stimulates T cells to develop from stem cells?

A

IL-7

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2
Q

What cytokine stimulates NK cells to develop from stem cells?

A

IL-15

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3
Q

What stimulates B cells to develop from stem cells?

A

Unknown

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4
Q

What 3 things can B cells develop into?

A

Follicular B cells
Marginal zone
B-1 cells

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5
Q

What 2 things can T cells develop into?

A

Alpha-Beta

Gamma-Delta

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6
Q

Prolymphocytes create large pools with ___ _____

A

high diversity

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7
Q

Describe T cell development. What is activated in T cells. What does this open up? What does that cause?

A

Signals activate the Notch1 or GATA3
-GATA3 for alpha-Beta T cells

Opens the TCR Beta gene locus

  • Can now undergo rearrangement
  • Genes that encode pre-TCR undergo VDJ recombination
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8
Q

Describe B cell development. What do the activating signals activate?

A

Signals activate Pax-5 and EBF

Genes for B cell development are activated

  • RAG-1 and RAG-2
  • Surrogate light chains (Pre-BCR)
  • Igalpha and IgBeta

H-chain – Chr 14
Kappa-chain (light) – Chr2
Gamma-chain (light)- Chr 22

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9
Q

What are the 3 stages of maturation? Describe each stage.

A

Prelymphocyte

  • Each cell created will have a unique receptor!
  • Undergo rearrangement of Ag receptors and selection events
  • Pre-BCRs only have IgM heavy chain
  • Pre-TCRs only have Beta chain

Immature lymphocyte

  • Fully developed
  • Naïve (no Ag encountered yet)

Mature lymphocyte
-Ready to go!

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10
Q

For epigenetics, describe Euchromatin, Heterochromatin, Methylation, and Non-coding RNAs (miRNA) and their effects on genes.

A

Euchromatin- loosely packed and active transcription

Heterochromatin- tightly packed and silenced

Methylation- silence genes

Non-coding RNAs (miRNA)- silence genes

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11
Q

What is Allelic Exclusion? Where does it occur?

A

Term for how B cells heavy and light chains are expressed

Occurs in bone marrow

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12
Q

What is the inheritance pattern for allelic exclusion? Which one will be used? Which chain is decided first.

A

Inherited from both maternal and paternal for each
-But only one is expressed

ONLY ONE will be used

  • Ex. Maternal H/Paternal L
  • Paternal H/Maternal L
  • Both Maternal/Both Paternal

H chain is decided first

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13
Q

What are the 3 mechanisms for Ag diversity? Describe the 1st one and the 3rd one.

A

Somatic Recombination

  • Major method
  • VDJ rearrangement

mRNA splicing

Junctional diversity

  • Loss of nucleotides
  • Addition of N and P nucleotides
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14
Q

How many heavy chains are found in the BCR’s? What are they?

How many will be deleted and what will you end up with?

A

Heavy chains have 4 segments- V, J, D, C
-Multiples of EACH on the heavy chain

All but ONE of these copies deleted

Will end with a singular VDJ sequence

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15
Q

What is the mechism of action for BCR’s?

A

Single J and single D chosen and DNA deleted between them (done by RAG-1/2)

V segment is chosen and DNA between V and DJ are deleted

Finally, C is chosen (remember inherited not combined)

Pre-mRNA

Will then undergo splicing –> mRNA –> protein of BCR

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16
Q

____ is only expressed form Pro-B to mature B cells (Not in plasma cells)

A

RAG (Recombination Activating Genes)

17
Q

During Ig class switching, what do you always start with?

A

Always start with µ or delta heavy chain –> IgM or IgD formed

18
Q

What is the mechanism of action for Ig class switching?

A

Constant region of heavy chains is spliced to another type of Ig gene downstream

Spliced together

Requires AID breaking DNA at Switch regions

19
Q

During B cell light chain recombination, no matter what the heavy chain is (µ or delta), the light chain will be the ____

A

Same

20
Q

Do light chains have D segments?

A

NO they do not have Diversity segments

21
Q

What does light chain recombination cause?

A

A huge amount of diversity

22
Q

During TCR recombination, describe the alpha chains.

A

Do not have D segments

23
Q

During TCR recombination, describe the beta chains.

A

Have V, D, J and C segments

Are made first

24
Q

What is the mechanism of action for TCR recombination?

A

Region between D and J deleted
Region between V and DJ are deleted
Region between VDJ and C are deleted
Uses RAG-1/2

25
Q

When is Junctional Diversity needed? Describe how it works.

A

VDJ not enough to combat a strong enough immune response needs Junctional Diversity.

Loss of nucleotides via exonucleases and addition of N and P nucleotides (DURING VDJ recombination)

P nucleotides fill in sites from hairpin cleavage

N nucleotides bind two sections together

26
Q

What adds P nucleotides and N nucleotides during Junctional Diversity?

A

P nucleotides- added by RAG

N nucleotides- added by TDT

27
Q

During the selection process describe checkpoint 1. What is being checked? What is rearranged for B and T cells, respectively? What happens if the rearrangement provides a functional protein? If not, what happens?

A

Checking of Pre-BCR/TCR

Pro-lymphocytes are rearranged at the heavy chain (B cell) or Beta chain (T cell)

30% rearrangements give functional protein receptor
-Receive survival signals –> Continue to CP2

Those with non-functional receptors–> no survival signal=APOPTOSIS

28
Q

Describe checkpoint 2 positive selection.

A

Self-MHC present to T cells with self Ag

Of B cells take up self-Ag

No reaction Maturation

29
Q

Describe checkpoint 2 negative selection.

A

Self- Ag presented or taken up by lymphocyte
Reaction to self-Ag
In T cells Immediate response
In B cells –> Undergo receptor editing again
-No reaction –> Immature B cell
-Reaction again to self Ag –> Clonal deletion

30
Q

What are the 2 types of B cell subtypes?

A

B1

B2

31
Q

Describe B1 Characteristics. Where does it develop? What is it limited in? Why?

Where is it found?

What can it secrete?

A

Develop in fetal liver

Have limited BCR (no TDT in the fetal liver –> no junctional diversity)

Self-renewing

In mucosal sites

Can secrete IgM spontaneously or in rxn to polysaccharides (G+) and lipids
-Contributes to early phases of infection

32
Q

Describe B2 characteristics. What does it develop from and when?

What are the 2 types? Where are each found?

A

Arise from bone marrow after birth

Follicular- T cell development

  • In circulation and LNs
  • Use protein AGs

MZ-independent of T cells, self-renewing

  • In spleen (blood-borne path)
  • Limited diversity
33
Q

What are the T cell subtypes? Describe the one that is not commonly found.

A

Alpha- Beta cells= Typical

If Gamma or Delta is rearranged before Beta is Will become delta-gamma T cell

  • Only 1-% of T cells
  • Limited diversity (fewer V, J, and D segments)
  • In epithelium

Immunology Exam 2 (10 decks)

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