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Year 2 - T3 Theme 1 > L5 - Adaptive immunity 2 > Flashcards

L5 - Adaptive immunity 2 Flashcards

1
Q

What is an immunoreceptor tyrosine-based activation motif

A
  • A conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of certain cell surface proteins of the immune system
  • Found in T-cell receptors for signal transduction
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2
Q

How are B-cells activated

A

1) Resting B cell with membrane bound Ig antibodies
2) Encounter with antigen of a pathogen
3) Stimulated B cell gives rise to antibody-secreting plasma cells

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3
Q

Changes in immunoglobulin genes during a B cell’s life

A

1) V-region assembly from gene fragments
2) Generation of junctional diversity
3) Assembly of transcriptional controlling elements
4) Transcription activated with coexpression of surface IgM and IgD
5) Synthesis changes from membrane Ig to secreted antibody
6) Somatic hypermutation
7) Isotype switch

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4
Q

Mechanism via which V-region assembly from gene fragments occurs

A
  • Somatic recombination of genomic DNA

- Irreversible

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5
Q

Mechanism via which junctional diversity is generated

A
  • Imprecision in joining rearranged DNA segments adds nongermline nucleotides (P and N) and deletes germline nucleotides
  • Irreversible
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6
Q

Mechanism via which transcriptional controlling elements are assembled

A
  • Promoter and enhancer are brought closer by V-region assembly
  • Irreversible
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7
Q

Mechanism via which transcription is activated with coexpression of surface IgM and IgD

A
  • Two patterns of splicing and processing RNA are used

- Reversible and regulated

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8
Q

Mechanism via which synthesis changes from membrane Ig to secreted antibody

A
  • Two patterns of splicing and processing RNA are used

- Reversible and regulated

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9
Q

Mechanism via which somatic hypermutation occurs

A
  • Point mutation of genomic DNA

- Irreversible

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10
Q

Mechanism via which isotype switch occurs

A
  • Somatic recombination of genomic DNA

- Irreversible

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11
Q

How are new gene sequences produced

A
  • Through V(D)J recombination
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12
Q

V(D)J recombination in light chains

A
  • Light chain rearrangement is a single step VJ recombination
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13
Q

V(D)J recombination in heavy chains

A
  • Heavy chain rearrangement involves a DJ recombination event followed by a VDJ rearrangement
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14
Q

Germline configuration order

A

V-segments - D-segments - J-segments - Constant region

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15
Q

Features of V(D)J recombination

A

1) D to J recombination
2) V to DJ recombination

  • 44 variable, 27 diversity, 6 joining
  • 3 x 10^11 possible combinations
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16
Q

How does rearrangement occur

A
  • Rearrangement occurs between specific sites on the DNA called recombination signal sequences (RSSs)
  • Rearrangement is catalysed by two recombination activating genes: RAG-1 and RAG-2
17
Q

Process of V(D)J recombination

A
  • Generation of junctional diversity
  • RAG complex cleaves the heptamer RSSs from the D and J gene segments to yield DNA hairpins
  • RAG complex opens hairpins by nicking one strand of the DNA
  • N-nucleotide additions by TdT
  • Pairing of strands
  • Unpaired nucleotides are removed by an exonuclease
  • Gaps are filled by DNA synthesis and ligation to form coding joint
18
Q

What does somatic hypermutation specifically target

A
  • Somatic hypermutation targets the rearranged gene segments encoding the variable region
19
Q

How does class switch recombination allow for a cell to perform different functions

A
  • Same receptor, different constant region allowing the cell to perform a range of effector functions
  • Alternative splicing results in IgM and IgD in naive B-cells
20
Q

IgM - function

A
  • Neutralisation (weak)
  • Activation of complement system(strong)
  • Transportation across epithelium (weak)
  • Diffusion into extravascular sites (variable)
21
Q

IgD - function

A
  • Sensitisation of basophils (strong)
22
Q

IgG1 - function

A
  • Neutralisation (strong)
  • Opsonisation (strong)
  • Sensitisation for killing by NK cells
  • Sensitisation of mast cells (weak)
  • Activation of complement system
  • Transport across placenta (strong)
  • Diffusion into extravascular sites (strong)
23
Q

IgG2 - function

A
  • Neutralisation (strong)
  • Activation of complement system (weak)
  • Transport across placenta (weak)
  • Diffusion into extravascular sites (strong)
24
Q

IgG3 - function

A
  • Neutralisation (strong)
  • Opsonisation
  • Sensitisation for killing by NK cells
  • Sensitisation of mast cells (weak)
  • Activation of complement system (strong)
  • Transport across placenta
  • Diffusion into extravascular sites (strong)
25
Q

IgG4 - function

A
  • Neutralisation (strong)
  • Opsonisation (weak)
  • Transport across placenta
  • Diffusion into extravascular sites (strong)
26
Q

IgA - function

A
  • Neutralisation (strong)
  • Opsonisation ( weak)
  • Activation of complement system (weak)
  • Transport across epithelium (strong)
  • Diffusion into extravascular sites
27
Q

IgE - function

A
  • Sensitisation of mast cells (strong)
  • Sensitisation of basophils
  • Diffusion into extravascular sites (weak)
28
Q

Process of class switch recombination

A
  • Constant regions are spliced out using switch regions located upstream of each constant region
  • First cut is always just before the Cu region
  • The second cut is determined by the cytokines secreted by follicular T helper cells
29
Q

What is the first targeted switch region during class switch recombination

A
  • The first targeted switch region is always the Su switch region
  • The other, partner, switch region is determined by the cytokines present
  • Activation induced cytidine deaminase (AID) is the critical enzyme in this process

Year 2 - T3 Theme 1 (15 decks)

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