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Module 204 MSK & Immune system > T1 L5 Adaptive immune system 2 > Flashcards

T1 L5 Adaptive immune system 2 Flashcards

1
Q

What is ITAM?

A

Immunoreceptor tyrosine-based activation motif

Enables the receptor once engaged with the antigen to signal inside the cell to generate activation signals

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2
Q

Describe the steps from a resting B cell with membrane bound IgG to secretion of immunoglobulins

A

Resting B-cell with membrane bound IgG (IgM, IgD) encounters antigen
Stimulated B cell gives rise to antibody-secreting plasma cells
Secretes immunoglobulins

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3
Q

What are the 7 steps of genetic alteration to immunoglobulin genes?

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

What is the mechanism of V-region assembly from gene fragments and what is the nature of the change to B cells’ genome?

A

Somatic recombination of genomic RNA

Irreversible change

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5
Q

What is the mechanism of generation of junctional diversity and what is the nature of the change to B cells’ genome?

A

Imprecision in joining rearranged DNA segments adds non-germline nucleotides (P and N) and depletes gremlin nucleotides
Irreversible change

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6
Q

What is the mechanism of assembly of transcriptional controlling elements and what is the nature of the change to B cells’ genome?

A

Promoter and enhancer are brought closer together by V-region assembly
Irreversible change

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7
Q

What is the mechanism of transcription activated with co-expression of surface IgM and IgG and what is the nature of the change to B cells’ genome?

A

2 patterns of splicing and processing RNA are used

Reversible and regulated

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8
Q

What is the mechanism of synthesis changes from membrane Ig to secreted antibody and what is the nature of the change to B cells’ genome?

A

2 patterns of splicing and processing RNA are used

Reversible and regulated

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9
Q

What is the mechanism of somatic hypermutation and what is the nature of the change to B cells’ genome?

A

Point mutation of genomic DNA

Irreversible

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10
Q

What is the mechanism of isotype switch and what is the nature of the change to B cells’ genome?

A

Somatic recombination of genomic DNA

Irreversible

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11
Q

What is an irreversible change?

A

Requires changes in base composition within DNA of different loci within cell

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12
Q

What is a reversible change?

A

Requires change in splicing of RNA, doesn’t require change in genetic code

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13
Q

Why is it important that the constant region is changed?

A

Different immunoglobulins perform different functions in the cell

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14
Q

What are the 2 types of light chain in a B cell?

A

Lambda chain on chromosome 22
Kappa chain on chromosome 2
Only one of these is expressed as the 2 light chains are identical

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15
Q

What are the 2 types of heavy chains?

A

Alpha chain on chromosome 14

Beta chain on chromosome 7

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16
Q

What is V(D)J recombination?

A

Genetic recombination of a variable region with diversity region and a joining region
Produces new gene sequences to generate immune cell diversity
Occurs in B cells and T cells

17
Q

What are the key enzymes for V(D)J recombination?

A

Recombination activating genes RAG1 and RAG2

18
Q

How many variable regions, diversity regions and joining regions in a B cell?

A

44 variable regions
27 diversity regions
6 joining regions

19
Q

How many possible combinations are there for B cells?

A

3 x 10^11

20
Q

How many possible combinations are there for T cells?

A

10^18

21
Q

Where does rearrangement occur?

A

Between specific sites on DNA called recombination signal sequences

22
Q

What additional proteins get incorporated into large complexes with RAG proteins?

A

DNA dependent protein kinase
Ku
Artemis
Dimer of DNA ligase / XRCC4

23
Q

What does TdT do?

A

adds additional nucleotides to ends of DNA strands

24
Q

Briefly state the steps of V(D)J recombination

A

1) Generation of junctional diversity
2) RAG complex cleaves heptameter from D and J gene segments to yield DNA hairpins
3) RAG complex opens hairpin by nicking one strand of DNA generating palindromic P-nucleotides
4) N-nucleotide additions by TdT
5) Pairing of strands
6) Unpaired nucleotides are removed by an exonuclease
7) Gaps are filled by DNA synthesis and ligation to form coding joint

25
Q

Describe affinity maturation

A

Only the highest affinity centrocytes remain from variable population after competitive selection
Continue to mutate and divide with range of affinity providing basis for selection by competitive binding
Unsuccessful cells undergo apoptosis which increases the affinity with each generation

26
Q

What is somatic hypermutation?

A

Further refinement of B-cell receptor recognition of antigen

Targets rearranged gene segments encoding variable region

27
Q

What is the critical enzyme involved in somatic hypermutation?

A

Activation induced cytidine deaminase

28
Q

What is class-switch recombination?

A

Last step in B-cells response to antigen

Replaces the constant region of the antibody so it can interact with different effector molecules

29
Q

Why aren’t IgM and IgD produced by class switch recombination?

A

The naive B-cell hasn’t experienced antigen

30
Q

How are IgM and IgD produced instead of class switch recombination?

A

Alternative mRNA splicing due to close proximity of u and delta constant regions in immunoglobulin gene structure

31
Q

Which is the dominant immunoglobulin?

A

IgG

32
Q

What immunoglobulins sensitisation by killing NK cells?

A

IgG1, IgG3

33
Q

What immunoglobulins sensitise by mast cells?

A

IgE

34
Q

What immunoglobulins sensitise by basophils?

A

IgD

35
Q

What immunoglobulins activate the complement system?

A

IgM

IgG3

36
Q

What immunoglobulins transport across epithelium

A

IgA

IgM

37
Q

What immunoglobulins diffuse into extravascular sites?

A

IgG

IgA

Module 204 MSK & Immune system (44 decks)

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