Brainscape's Knowledge GenomeTM

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


See full index

Immunology Exam 1 > Lecture 7 - Ab diversity and B cell development > Flashcards

Lecture 7 - Ab diversity and B cell development Flashcards

1
Q

Describe B cell development

A

-B cells start out in bone marrow and fetal liver by rearranging their chromosomal DNA to create exon encoding the Ag binding pocket –> both light and heavy chain undero process

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

What is the only isotype generated at this stage of B cell development?

A

IgM (and a little IgD)

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

What happens after cells commit to being B cells?

A

Ab genes start to rearrange

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

B cells leave bone marrow with what bound?

A

IgM and maybe a little IgD

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

Describe 4 basic steps of B cell development described

A

1) B cell precursor rearranges its Ab genes –> generation of B cell receptors in bone marrow
2) immature B cell bound to self cell-surface Ag is removed –> negative selection in bone marrow
3) mature B cell bound to foreign Ag is activated –> migration of B cells to peripheral lymphoid organs and activation
4) activated B cells give rise to plasma cells and memory cells –> Ab secretion and memory cells in bone marrow and lymphoid tissue

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

What do the heavy and light chain genes consist of?

A

large numbers of variable (V) domain genes, joining (J) genes and (+/-) diversity (D) regions

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

How are variable region genes constructed?

A

by joining one of gene segments from each region (1 V seg + 1 D seg + 1 J seg) to form a continuous piece of DNA

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

What must occur to form a joined gene?

A

somatic rearrangement

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

What is somatic rearrangement?

A

random event which occurs only on one chromosome for each light or heavy chain genes (allelic exclusion)

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

What is the constant region encoded by?

A

separate exons

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

How is the constant and variable region exons joined?

A

by splicing of the primary RNA transcript

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

When can isotype switching occur?

A

following VDJ region recombination

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

What genes does the light chain region not have?

A

diversity region

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

True or False: each b cell develops receptors that can bind to a single epitope that is different than the epitope recognized by other B cells

A

True; does this during development in the bone marrow by splicing its chromosomal DNA to create new coding sequences for the Ag binding pocket exons

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

What part is most variable within Ab

A

AAs that contact the epitope

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

The immune system has the capacity to recognize what?

A

approx 10^10 different antigenic epitopes; each B cell produces Ab of a single specificity

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

The pool of B cells within an individual provides what?

A

universal recognition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What 5 processes aid in Ab diversity?

A

1) multiple germline gene exons
2) H and L chain combination
3) Imprecise joining of segments
4) Random insertion of bases
5) somatic hypermutation

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

During B cell development, what do stromal cells secrete?

A

B cell growth factors

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

As a pre-B cell develops, what happens?

A

Ab genes begin to rearrange –> heavy chain first, then light chain

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

Which cells survive and leave bone marrow?

A

those that successfully rearrange both heavy and light chain genes

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

What is “multiple germline genes”?

A

genomic organization of Ab genes has many different gene segments and permits rearrangement.

  • using multiple gene segments, great diversity can be ahcieved
  • B cells have different VDJ and VJ heavy and light chain rearrangements;
  • B cells also have different combinations of VDJ and/or VJ segments
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is “H-L chain combinations”?

A
  • heavy chain rearranges independently of light chain
  • by combining different H and L chains, each with their own variable region rearrangements –> generate Ag-binding pockets of various specificty
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How are the V, D or J regions selected?

A

randomly

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

What is “imprecise joining (or junctional flexibility)”

A

by arbitrarily splicing nucleic acids together within the region, different reading frames are generated leading to different AA structure at the Ag binding pocket

  • occurs at all V-D-J junctions during recombination
  • what is randomly spliced out changes the nucleic acids spliced together –> changes AA structure
26
Q

What is “random base insertion (or P nucleotide addition)”?

A
  • during recombination of V-D-J segments, nucleic acids can be randomly inserted into the junction
  • generates a different AA structure at Ag binding pocket
27
Q

Do most B cells make it out of bone marrow?

A

no

28
Q

What is allelic exclusion?

A

rearrangement of Ab gene DNA occurring only on one chromosome for each light and heavy chain genes

29
Q

What does allelic exclusion assure?

A

assures that each individual B cell generates only a single Ab mol rather than expressing genes from both chromosomes
-every Ab that B cell produces is identical

30
Q

Describe an example

A

an animal with two different alleles for the heavy chain gene loci produces Abs using both chromosomes.
-for each individual B cell, only the blue or yellow chromosome is expressed, not both

31
Q

What does allelic exclusion prevent?

A

B cells from having low avidity receptor interactions with Ag
-ensures each B cell produces identical Ab –> every Ab will bind to target Ag

32
Q

What happens without allelic exclusion?

A

produces heterogeneous B cell receptors (Abs) with low avidity binding

33
Q

In rearrangement of Ab variable region genes, heavy chain gene rearranges first (then light). what happens if first splice event fails?

A

chromosome may attempt to splice further down the gene cluster

34
Q

Does choice of heavy chain VDJ regions influence which light chain V and J regions selected?

A

no, they are independent events

35
Q

What are RAG proteins?

A

recombination activating gene

36
Q

What do RAG proteins/enzymes do?

A

recognize conserved sequences flanking each gene segment, bend the DNA strand such that proteins interact and cleave out the intervening DNA sequences

37
Q

What happens to animals who are deficient in RAG activity?

A

they are severely immunocompromised

38
Q

B cells develop in bone marrow and are released with what?

A

rearranged Ig genes

39
Q

What is found on surface of mature B cells released from marrow?

A

IgM +/- IgD

40
Q

Rearrangement occurs when?

A

in absence of Ag

41
Q

When does heavy chain VDJ region genes start rearranging?

A

Early pro-B cell –> large pre-B cell

42
Q

When does light chain VJ region genes rearrange?

A

small pre-B cell –> immature B cell

43
Q

At what stage of B cell development are surface Ig expressed?

A

Immature B cells

44
Q

Why is IgM the first Ab produced by B cells?

A

it’s encoded immediately adjacent to VDJ genes

45
Q

When is IgD also found on B cell surface?

A

on surface of newly formed B cells due to mRNA splicing artifact

46
Q

After B cells are released from bone marrow, where do they go?

A

circulate through secondary lymphoid tissues - lymph nodes, tonsils, spleens and peyer’s patches

47
Q

B cells that encounter Ag (and T cell help) form what?

A

foci called germinal centers that contain proliferating B cells

48
Q

What happens to some of plasma cells?

A

some leave the germinal center and reenter circulation

-some take up residence in bone marrow and spleen

49
Q

What happens in the periphery for B cells?

A
  • maturation to an Ab secreting cell (plasma cell)
  • isotype switching
  • somatic hypermutation
  • **these events occur following specific antigenic stimulation
50
Q

If mature B cell fails to access secondary lymphoid tissue what happens?

A

cell dies

51
Q

If B cell makes it to secondary lymphoid tissue, but doesn’t interact with Ag, what happens?

A

half life of 3-8 wks

52
Q

What happens if B cell encounters Ag?

A

-longer lived
some mature into plasma cells –> Ab secretion (IgM)
-some form germinal centers

53
Q

B cells start to mature in bone marrow, then move to peripheral tissues ONLY if what happens?

A

light and heavy chains rearrange successfully

54
Q

What happens in periphery?

A

B cell encounters its Ag and receives T cell help (cytokines) –> convert to plasma cells that secrete IgM
-further activation results in isotype switching to secrete IgG or IgA

55
Q

Exposure to Ag in periphery results in what?

A
  • activation and cell division
  • differentiation into plasma cells (Ab)
  • class switching and somatic hypermutation (introduce AA changes)
  • selection for receptor specificity with greater affinity (affinity maturation)
  • differentiation into memory B cells
56
Q

Which processes require exposure to Ag in periphery?

A

all activation of B cells and subsequent changes in DNA (somatic hypermutation and isotype switching) or RNA processing

57
Q

What doesn’t require exposure to Ag?

A

gene conversion events

58
Q

What are germinal centers?

A

specialized areas of secondary lymphoid organs
-if stimulated by antigen-specific T cells, B cells will multiply and start to secrete IgM –> undergo somatic hypermutation and selection for Ag binding in these sites

59
Q

Where do B cells interact with T cells?

A

in secondary lymphoid organs

60
Q

What is the first thing to happen following B cell activation?

A

proliferation and conversion to secretory IgM (plasma cell) –> then somatic hypermutation –> affects exon encoding the Ag binding site

Immunology Exam 1 (7 decks)

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