Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology > Humoral immunity(Generation of antibody diversity) > Flashcards

Humoral immunity(Generation of antibody diversity) Flashcards

1
Q

What are antibodies?

A

• Y shaped molecules expressed by immune cells to target pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do antibodies work?

A

• Antibodies work by preventing bacteria entering by binding to the bacteria docking site or neutralizing them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Antibody structure?

A

2 heavy, 2 light chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How many classes does the heavy chain have and what are they divided into?

A

○ Heavy chain has 5 classes: μ,δ,γ,α or ε chain
§ Divided into subclasses: γ1, γ2, γ3, γ4
§ Divided into subclasses: α1, α2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How many domains, constant and variable regions does the heavy chain have?

A

§ Heavy chains have 4 domains: 3 constant and 1 variable region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How many classes does the light chain have?

A

Variable region is very specific – binds to specific epitopes of specific antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How many variable and constant regions does the light chain have?

A

§ 1 variable region and 1 constant region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the variable region and what does it bind to?

A

Variable region is very specific – binds to specific epitopes of specific antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is constant region very responsible for?

A

• Constant region is very responsible for biological activities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How many forms do antibodies have and what are they?

A

○ B cell receptor and secreted form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the final form and whats it used for?

A

The final form is the secreted form – used to fight off pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the final form of antibody anchored to

A

It is anchored to plasma membrane of B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What forms can the antibody be when secreted?

A

§ When antibody is secreted it can be monomeric forms or pentameric forms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is antibody initially secreted as?

A

§ Initially secreted as a monomer and then combined to produce a multimeric form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where do B cells spend its life?

A

• B Cell spends its life in bone marrow, blood, spleen and secondary lymphoid organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What can the life cycle of B cells be divided into?

A

• Life cycle can be divided into antigen dependent and independent stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Steps involved in the lifecycle of B cells

A
  1. Start with stem cell which differentiates into pro B cell
  2. Pro B cell undergoes VDJ recombination which codes in the heavy chain constant and variable region and becomes a pre-B cell
    • Once it makes a functional heavy chain, it becomes a pre-B cell
  3. Then it undergoes another VDJ recombination to code in the light variable and heavy chain regions
  4. B cell continues to mature until it expresses IgM and IgD
  5. Becomes a mature circulating B cell and then becomes activated once it encounters a pathogen
  6. B cell migrates into germinal centre (GC) and will undergo a special selection to hone its variable region to that particular pathogen
  7. Undergoes affinity maturation and class switching
  8. Differentiates into plasma cells which secretes antibodies and memory B cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are somatic recombinations and an example?

A

• Any changes at the DNA level are called somatic recombination e.g. VDJ recombination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is differential splicing?

A

• Changes at the mRNA level are called differential splicing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is each chain of the antibody made of?

A

• Each chain is made of one single polypeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the hinge region between in antibodies?

A

Hinge region is between CH1 and CH2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What makes the antibody flex and so what does this expose?

A

○ These are a stretch of polypeptides that make the antibody flex so that the active site can be exposed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What chain is the hinge region longer in?

A

○ Hinge region is longer in heavy chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are Fv regions?

A

○ Variable regions of light and heavy working together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are Fab regions?

A

○ Variable fragment + first constant domains

26
Q

What are Fc regions?

A

○ Heavy chain CH2 and CH3 working together

27
Q

What does glycan form a part . of and what does it attract?

A

• Glycan (sugar group) forms part of the active site

§ Forms a pocket where the receptors of the other immune cells will be attracted to

28
Q

What stabilises the antibody structure?

A

• Disulphide bonds stabilise the structure

29
Q

What are CDRs?

A

Protrusions that interact with the antigens

30
Q

Where are CDRs located in the antibody?

A

○ Are located in the variable light and variable heavy chains

31
Q

Lifecycle of B cells(Antigen independent stage)

A

• Stem cell differentiates into pro-B cell
• Pro-B cell undergoes DNA recombination
○ First DJ
• Then V region combines with the DJ (VDJ recombination)
○ This codes for the heavy chain variable region
§ Heavy chain variable region is co-expressed with μ constant region – constant region for IgM antibody class (this is the default for all B cells before they encounter pathogens)
• Pre B cell expresses valid functional chains
• This pre B cell expresses placeholder light chain to hold it in place as light chain is not generated yet
• Undergoes third recombination on the light chain – VJ recombination
○ Codes in the variable and constant regions on light chain
• There are also additional processes such as junctional flexibility and P and N nucleotide addition
○ Contributes to the diversity of the antibody
• Once B cell can express IgM and IgD (has capacity to alternatively splice MRNA), it becomes a mature/resting/naïve B cell

32
Q

How many loci are there that encode Ig?

A

There are three genetic loci encoding Ig
• Two for the light chain: kappa (κ) and lambda (λ) locus
• One for heavy chain

33
Q

What chromosome is the λ chain found on?

A

○ In humans, the λ chain is found on Chr22, κ on Chr2

34
Q

What chromosome is the heavy chain found on?

A

○ Heavy chain: Chr14

35
Q

What genes regarding antibodies are inherited and not inherited?

A

• No antibody genes are inherited

§ Only gene segments are inherited

36
Q

What does arranging gene segments in different combinations generate?

A

○ Arranging these gene segments in different combinations generate many Ig sequences causing the B cell to be unique

37
Q

What segments are there in the light chain?

A

• In the light chain there is variable and J gene segments

38
Q

What regions are there in heavy chain?

A

• In the heavy there is V, D and J regions

39
Q

What do segments code for once they’ve been rearranged?

A

• Once they are rearranged at DNA level, they will code for the CDRs

40
Q

What do the J or DJ regions code for?

A

The J or DJ region codes for CDR3 (3RD CDR) region

41
Q

What is the most variable region?

A

CDR3 region

42
Q

What gene are the kappa light chain genes on?

A

• On chromosome 2

43
Q

How do the segments allign in chromosome 2 for the kappa loci?

A

• In the kappa loci in chromosome 2, there is V1-V40, J1-5 and then constant region segments

44
Q

What is there on front of each V segment?

A

• On front of each V segment there is a leader sequence

45
Q

Steps in VJ recombination

A
  • Within V1-40, one segment will be selected at random
  • At DNA level, it will be recombined together
  • This is transcribed to MRNA
  • In the primary RNA transcript, there will be extra segments and these are spliced out (this change does not affect the DNA)
  • Mature RNA has a stop codon and polyA tail
  • After translation, leader sequence is cleaved off and therefore forms the light chain of BCR or secreted antibody
46
Q

What chromosome is gamma heavy chain genes on?

A

On chromosome 14

47
Q

Steps in VDJ recombination

A
  • D7 and J3 to join at random
  • This is transcribed into mRNA transcript
  • Only the first two constant segments are transcribed
  • B cells can express IGM and IgD when they are mature
  • By alternative splicing, the B cell can make two different classes of cell receptor
48
Q

How is antibody diversity generated?

A
  • In the body there are two copies from each parent and each allele has different polymorphisms to contribute to the diversity
  • Multiple germline V, D and J gene segments
  • Combination V-J and V-D-J joining
  • Junctional flexibility
  • P-nucleotide addition
  • N-nucleotide addition
  • Combinatorial association of heavy and light chains
  • Somatic hypermutation during affinity maturation
49
Q

What is the recombination signal sequence?

A

conserved sequences upstream or downstream of gene segments

50
Q

What does the RSS consist of?

A

• ‘Turns’ consisting heptamer and nonamer with a 12 or 23 bp spacer

51
Q

What is the one turn/two turn rule(12/23 rule)?

A

• Recombination only occurs between a segment with a 12bp spacer and a 23bp spacer

52
Q

Turns in the heavy chain?

A

○ Two turn is located downstream of every V segment and upstream of D segment
○ One turn is located upstream and downstream of D segment

53
Q

What is the mechanism if we want to recombine V and J with their RSS?

A

• Rag 1 and Rag 2 would have to clamp down on the RSS to form a major hairpin
• Create nicks in DNA forming minor hairpin
• Two hairpin structures;
○ Major: between upper and lower DNA strands
• Results in V and J joining and a circular signal joint

54
Q

What does artemis do?

A

Comes in and opens the hairpin by generating a nick

55
Q

Steps involved in antibody diversity?

A

• Exonucleases and tdt perform end processing – adding, deleting BPs before joining
• P and N nucleotides form in between due to exonucleases
• Results in a frame shift due to additions
-This generates antibody diversity as well due to different AAs being produced

56
Q

Steps involved in junctional diversity

A

• Artemis randomly nicks between the BPs
• Because it is nicked it will uncoil
• Results in overhang
○ Repair enzymes add nucleotides to repair this
○ P nucleotides
• Tdt enzyme adds end nucleotides (tdt is only present in the heavy chain)
○ This adds more DNA before the V and J segments join

57
Q

When is there junctional flexibility during?

A

• Junctional flexibility during V(D)J recombination, P and N nucleotide additions

58
Q

Steps in junctional flexibility

A
  • Involves exonucleases

* Remove mismatched nucleotides but sometimes can remove dna of gene segment

59
Q

What does junctional flexibility mean?

A

Junctional flexibility means the coding regions would lose BPs whereas the signal joint is always precise

60
Q

How many copies of Ig genes do we have?

A

• Two copies of each Ig gene – one from mother and one from father

61
Q

What mechanism is in place for the heavy and light strand?

A

Mechanism in place to ensure that there is one heavy chain allele and one light chain allele is expressed

62
Q

What is the order of rearrangement?

A

• Order of rearrangement: Heavy>kappa>lambda; 1st allele then 2nd

Immunology (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions