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Bio 4650 Midterm 2 > Lymphocyte Receptor Genetics > Flashcards

Lymphocyte Receptor Genetics Flashcards

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1
Q

In order for the immune system to recognize a vast array of rapidly evolving microorganisms to provide protection, they must?

A
  1. Generate a diverse repertoire of receptor molecules capable of recognizing microbial pathogens
  2. Minimizing the expression of receptors that recognize self-antigens (no self-harming receptors)
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2
Q

Immune responses rely on recognition molecules

A
  1. Germ-line encoded PRR

2. Randomly generated (BCRs and TCRs)

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3
Q

PRRs

A
  • Germ-line encoded
  • Bind to pathogen-associated molecular patterns
  • generic molecules found on many different types of pathogens
  • Many invertebrates have these same PRRs
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4
Q

BCRs and TCRs

A
  • Randomly generated
  • Bind to very specific antigens, rather than generic molecules found on many pathogens
  • BCRS: structural or soluble antigen
  • TCRS: antigen that has been degraded and put on an MHC molecule
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5
Q

B-cell receptor

A
  • present exclusively on B lymphocytes

- Contains an antibody of defined specificity

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6
Q

T-cell receptor

A
  • present on t lymphocytes

- specific for peptides derived from APC-degraded antigen presented on MHC molecules

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7
Q

When BCR or TCR bind to their corresponding antigens

A

B and T lymphocytes proliferate and differentiate into effector cells that eliminate the microbial threat

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8
Q

Immunoglobulin gene segments

A

V- variable
D- Diversity
J- Joining
C- constant

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9
Q

Where does recombination happen?

A

thymus or bone marrow

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10
Q

Where does recombination occur?

A
  • somatic cells

- randomly generate T and B cells

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11
Q

Variable region

A
  • interacting with antigen

- creating diversity

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12
Q

Light chain

A

encoded by the V, J, and C gene segments

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13
Q

Heavy chain

A

encoded by the V, D, J, and C gene segments

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14
Q

How does the immune system generate a diverse repertoire of receptor molecules capable of recognizing microbial pathogens

A

Partially by the ability of developing B cells to recombine the V,D, and J gene segments

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15
Q

Proteins involved in V(D)J recombination

A
  • RAG1/2
  • TdT
  • Artemis
  • ATM
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16
Q

RAG 1/2

A
  • Responsible for recognizing and cutting DNA at the immunoglobulin-encoding region and the RSS
  • Recognizes RSS
17
Q

TdT (Terminal deoxyribonucleotidyl transferase)

A
  • Adds non-templated nucleotides to the coding joint

- only in the heavy chain

18
Q

Artemis

A

Cuts hairpin loops on DNA

19
Q

ATM (ataxia telangiectasia mutate)

A

Used in cell-cycle, blocks cell cycle until DNA is all repaired

20
Q

How are the different V, D, J, and C gene sequences selected for recombination?

A
  • Recombination is directed by signal sequences
  • Each gene is flanked by recombination signal sequences (RSSs)
  • One RSS with a 12bp spacer sequence and other RSS with a 23bp sequence are randomly selected
21
Q

RSS

A
  • Has a nonamer and heptameter

- 12 or 23 bp spacer

22
Q

After selection what recombines the different V,D,J, and C gene sequences?

A

Gene segments are joined by the RAG 1/2 recombinase

23
Q

12/23 rule

A

One RSS with a 12bp spacer sequence and other RSS with a 23bp sequence are randomly selected

24
Q

V(D)J recombination

A
  1. RAG proteins bind to RSSs and cleaves the DNA
  2. Other proteins process the hairpin loops that form after RAG reacts
  3. Products include a recombined coding joint and a leftover signal joint that is later degraded
    - Can occur in any direction as long as the correct RSSs are lined up
25
Q

Hairpin loop

A
  • cut by artemis
  • Can cut in three ways
  • 5’ overhang
  • blunt end
  • 3’ overhang
  • Creates cites for P nucleotide addition
26
Q

What are the various mechanisms that generate antibody diversity in naive B cells?

A
  1. Multiple gene segments (which segments are put together)
  2. Combinational diversity (between light and heavy chain)
  3. P-nucleotide addition (templated nucleotide addition between joints, resulting from asymmetrical cleaving of hairpin structures)
  4. Exonuclease trimming (sometimes occurs at junctions, losing and changing reading frames)
  5. Nontemplated (N) nucleotide addition (mediated by TdT activity, adding in random nucleotides between joints)
27
Q

Mature B cells express what antibodies

A
  • express both IgM and IgD
28
Q

mRNA splicing

A
  • determines whether the BCR is IgM or IgD

- control whether the cell produces membrane-bound or secreted IgM

29
Q

TCR proteins consist of

A
  • 2 subunits

- alpha and beta

30
Q

Ig heavy chain

A
  • V(D)J recombination
  • 12/23 rule obeyed
  • N- nucleotide addition
  • more than one C region
31
Q

Ig light chain

A
  • V-J recombination
  • 12/23 rule obeyed
  • N- nucleotide addition
  • one C region
32
Q

TCRalpha

A
  • V-J recombination
  • 12/23 rule obeyed
  • N- nucleotide addition
  • one C region
33
Q

TCRbeta

A
  • V(D)J recombination
  • 12/23 rule obeyed
  • N- nucleotide addition
  • one C region

Bio 4650 Midterm 2 (6 decks)

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